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Artículos originales (todos) *** Original articles (all)

 

GLIOMAS AND RELATED TUMORS

(Conceptos / Keywords: Gliomas; Glioblastoma multiforme; Oligodendroglioma; Astrocytoma, Ependymoma; Medulloblastoma; etc).

February - March 2013

 

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[1]

TÍTULO / TITLE:  - Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Genet. 2013 Mar;45(3):295-8. doi: 10.1038/ng.2552. Epub 2013 Feb 3.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ng.2552

AUTORES / AUTHORS:  - Smith MJ; O’Sullivan J; Bhaskar SS; Hadfield KD; Poke G; Caird J; Sharif S; Eccles D; Fitzpatrick D; Rawluk D; du Plessis D; Newman WG; Evans DG

INSTITUCIÓN / INSTITUTION:  - Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St. Mary’s  Hospital, University of Manchester, Manchester, UK.

RESUMEN / SUMMARY:  - One-third of all primary central nervous system tumors in adults are meningiomas. Rarely, meningiomas occur at multiple sites, usually occurring in individuals with type 2 neurofibromatosis (NF2). We sequenced the exomes of three unrelated individuals with familial multiple spinal meningiomas without NF2 mutations. We identified two individuals with heterozygous loss-of-function mutations in the SWI/SNF chromatin-remodeling complex subunit gene SMARCE1. Sequencing of SMARCE1  in six further individuals with spinal meningiomas identified two additional heterozygous loss-of-function mutations. Tumors from individuals with SMARCE1 mutations were of clear-cell histological subtype, and all had loss of SMARCE1 protein, consistent with a tumor suppressor mechanism. Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology.

 

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[2]

TÍTULO / TITLE:  - A phase I/II trial of pazopanib in combination with lapatinib in adult patients with relapsed malignant glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Feb 15;19(4):900-8. doi: 10.1158/1078-0432.CCR-12-1707. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-1707

AUTORES / AUTHORS:  - Reardon DA; Groves MD; Wen PY; Nabors L; Mikkelsen T; Rosenfeld S; Raizer J; Barriuso J; McLendon RE; Suttle AB; Ma B; Curtis CM; Dar MM; de Bono J

INSTITUCIÓN / INSTITUTION:  - Dana-Farber Cancer Institute, Boston, MA 02215, USA. David_Reardon@DFCI.harvard.edu

RESUMEN / SUMMARY:  - PURPOSE: Increased mitogenic signaling and angiogenesis, frequently facilitated by somatic activation of EGF receptor (EGFR; ErbB1) and/or loss of PTEN, and VEGF overexpression, respectively, drive malignant glioma growth. We hypothesized that patients with recurrent glioblastoma would exhibit differential antitumor benefit based on tumor PTEN/EGFRvIII status when treated with the antiangiogenic agent pazopanib and the ErbB inhibitor lapatinib. EXPERIMENTAL DESIGN: A phase II study evaluated the antitumor activity of pazopanib 400 mg/d plus lapatinib 1,000 mg/d  in patients with grade 4 malignant glioma and known PTEN/EGFRvIII status not receiving enzyme-inducing anticonvulsants (EIAC). The phase II study used a two-stage Green-Dahlberg design for futility. An independent, parallel phase I component determined the maximum-tolerated regimen (MTR) of pazopanib and lapatinib in patients with grade ¾ glioma receiving EIACs. RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and  15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. Two patients (5%) had a partial response and 14 patients (34%) had stable disease lasting 8 or more weeks. In phase I (n = 34), the MTR was not reached. On the basis of pharmacokinetic and safety review, a regimen of pazopanib 600 mg plus lapatinib 1,000 mg, each twice  daily, was considered safe. Concomitant EIACs reduced exposure to pazopanib and lapatinib. CONCLUSIONS: The antitumor activity of this combination at the phase II dose tested was limited. Pharmacokinetic data indicated that exposure to lapatinib was subtherapeutic in the phase II evaluation. Evaluation of intratumoral drug delivery and activity may be essential for hypothesis-testing trials with targeted agents in malignant glioma.

 

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[3]

TÍTULO / TITLE:  - A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):873-83. doi: 10.3171/2012.12.JNS111970. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS111970

AUTORES / AUTHORS:  - Wu AS; Trinh VT; Suki D; Graham S; Forman A; Weinberg JS; McCutcheon IE; Prabhu SS; Heimberger AB; Sawaya R; Wang X; Qiao W; Hess KR; Lang FF

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery.

RESUMEN / SUMMARY:  - Object Seizures are a potentially devastating complication of resection of brain  tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas. Methods Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection  were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned. Results The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of  0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence  at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of  early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients. Conclusions The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%-18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.

 

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[4]

TÍTULO / TITLE:  - Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric  Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Science. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1126/science.1232245

AUTORES / AUTHORS:  - Lewis PW; Muller MM; Koletsky MS; Cordero F; Lin S; Banaszynski LA; Garcia BA; Muir TW; Becher OJ; Allis CD

INSTITUCIÓN / INSTITUTION:  - Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New  York, NY 10065, USA.

RESUMEN / SUMMARY:  - Sequencing of pediatric gliomas has identified missense mutations Lys27Met (K27M) and Gly34Arg/Val (G34R/V) in genes encoding histone H3.3 (H3F3A) and H3.1 (HIST3H1B). We report that human diffuse intrinsic pontine gliomas (DIPGs) containing the K27M mutation display significantly lower overall H3K27me3 levels, and that histone H3K27M transgenes are sufficient to reduce H3K27me3 levels in vitro and in vivo. We find that H3K27M inhibits the enzymatic activity of the Polycomb repressive complex 2 (PRC2) through interaction with the EZH2 subunit. Additionally, transgenes containing lysine-to-methionine substitutions at other known methylated lysines (H3K9 and H3K36) are sufficient to cause specific reduction in methylation levels through inhibition of SET-domain enzymes. We propose that K-to-M substitutions may represent a mechanism to alter epigenetic states in a variety of pathologies.

 

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[5]

TÍTULO / TITLE:  - Outcome of infants and young children with newly diagnosed ependymoma treated on  the “Head Start” III prospective clinical trial.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1111-9

AUTORES / AUTHORS:  - Venkatramani R; Ji L; Lasky J; Haley K; Judkins A; Zhou S; Sposto R; Olshefski R; Garvin J; Tekautz T; Kennedy G; Rassekh SR; Moore T; Gardner S; Allen J; Shore R; Moertel C; Atlas M; Dhall G; Finlay J

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Oncology, Children’s Hospital Los Angeles, 4650, Sunset Boulevard, Mailstop 54, Los Angeles, CA, 90027, USA, rvenkatramani@chla.usc.edu.

RESUMEN / SUMMARY:  - This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational “Head Start”  III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were  to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was  achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR.  Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 +/- 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 +/- 13 % and 73 +/- 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation.

 

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[6]

TÍTULO / TITLE:  - Prospective evaluation of early treatment outcome in patients with meningiomas treated with particle therapy based on target volume definition with MRI and (68)Ga-DOTATOC-PET.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2013 Apr;52(3):514-20. doi: 10.3109/0284186X.2013.762996. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.762996

AUTORES / AUTHORS:  - Combs SE; Welzel T; Habermehl D; Rieken S; Dittmar JO; Kessel K; Jakel O; Haberkorn U; Debus J

INSTITUCIÓN / INSTITUTION:  - University Hospital of Heidelberg, Department of Radiation Oncology , Heidelberg  , Germany.

RESUMEN / SUMMARY:  - Abstract Purpose. To evaluate early treatment results and toxicity in patients with meningiomas treated with particle therapy. Material and methods. Seventy patients with meningiomas were treated with protons (n = 38) or carbon ion radiotherapy (n = 26). Median age was 49 years. Median age at treatment was 55 years, 24 were male (34%), and 46 were female (66%). Histology was benign meningioma in 26 patients (37%), atypical in 23 patients (33%) and anaplastic in  four patients (6%). In 17 patients (24%) with skull base meningiomas diagnosis was based on the typical appearance of a meningioma. For benign meningiomas, total doses of 52.2-57.6 GyE were applied with protons. For high-grade lesions, the boost volume was 18 GyE carbon ions, with a median dose of 50 GyE applied as  highly conformal radiation therapy. Nineteen patients were treated as re-irradiation. Treatment planning with MRI and 68-Ga-DOTATOC-PET was evaluated.  Results. Very low rates of side effects developed, including headaches, nausea and dizziness. No severe treatment-related toxicity was observed. Local control for benign meningiomas was 100%. Five of 27 patients (19%) developed tumor recurrence during follow-up. Of these, four patients had been treated as re-irradiation for recurrent high-risk meningiomas. Actuarial local control after re-irradiation of high-risk meningiomas was therefore 67% at six and 12 months. In patients treated with primary radiotherapy, only one of 13 patients (8%) developed tumor recurrence 17 months after radiation therapy (photon and carbon ion boost). Conclusion. Continuous prospective follow-up and development of novel study concepts are required to fully exploit the long-term clinical data after particle therapy for meningiomas. To date, it may be concluded that when proton therapy is available, meningioma patients can be offered a treatment at least comparable to high-end photon therapy.

 

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[7]

TÍTULO / TITLE:  - Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Toxicol Appl Pharmacol. 2013 May 1;268(3):318-30. doi: 10.1016/j.taap.2013.02.001. Epub 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.taap.2013.02.001

AUTORES / AUTHORS:  - Puntel M; A K M GM; Farrokhi C; Vanderveen N; Paran C; Appelhans A; Kroeger KM; Salem A; Lacayo L; Pechnick RN; Kelson KR; Kaur S; Kennedy S; Palmer D; Ng P; Liu C; Krasinkiewicz J; Lowenstein PR; Castro MG

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

RESUMEN / SUMMARY:  - Adenoviral vectors (Ads) are promising gene delivery vehicles due to their high transduction efficiency; however, their clinical usefulness has been hampered by  their immunogenicity and the presence of anti-Ad immunity in humans. We reported  the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L). Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression “on” or “off” according to clinical need. The inclusion of two therapeutic transgenes within a  single vector enables a reduction of the total vector load without adversely impacting efficacy. Because clinically the vectors will be delivered into the surgical cavity, normal regions of the brain parenchyma are likely to be transduced. Thus, we assessed any potential toxicities elicited by escalating doses of HC-Ad-TK/TetOn-Flt3L (1x10(8), 1x10(9), or 1x10(10) viral particles [vp]) delivered into the rat brain parenchyma. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points. The results indicate that doses up to 1x10(9) vp of HC-Ad-TK/TetOn-Flt3L can be safely delivered into the normal rat brain and  underpin further developments for its implementation in a phase I clinical trial  for glioma.

 

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[8]

TÍTULO / TITLE:  - Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Dev. 2013 Mar 15;27(6):654-69. doi: 10.1101/gad.212662.112.

            ●● Enlace al texto completo (gratuito o de pago) 1101/gad.212662.112

AUTORES / AUTHORS:  - Stricker SH; Feber A; Engstrom PG; Caren H; Kurian KM; Takashima Y; Watts C; Way M; Dirks P; Bertone P; Smith A; Beck S; Pollard SM

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom;

RESUMEN / SUMMARY:  - Epigenetic changes are frequently observed in cancer. However, their role in establishing or sustaining the malignant state has been difficult to determine due to the lack of experimental tools that enable resetting of epigenetic abnormalities. To address this, we applied induced pluripotent stem cell (iPSC) reprogramming techniques to invoke widespread epigenetic resetting of glioblastoma (GBM)-derived neural stem (GNS) cells. GBM iPSCs (GiPSCs) were subsequently redifferentiated to the neural lineage to assess the impact of cancer-specific epigenetic abnormalities on tumorigenicity. GiPSCs and their differentiating derivatives display widespread resetting of common GBM-associated changes, such as DNA hypermethylation of promoter regions of the cell motility regulator TES (testis-derived transcript), the tumor suppressor cyclin-dependent  kinase inhibitor 1C (CDKN1C; p57KIP2), and many polycomb-repressive complex 2 (PRC2) target genes (e.g., SFRP2). Surprisingly, despite such global epigenetic reconfiguration, GiPSC-derived neural progenitors remained highly malignant upon  xenotransplantation. Only when GiPSCs were directed to nonneural cell types did we observe sustained expression of reactivated tumor suppressors and reduced infiltrative behavior. These data suggest that imposing an epigenome associated with an alternative developmental lineage can suppress malignant behavior. However, in the context of the neural lineage, widespread resetting of GBM-associated epigenetic abnormalities is not sufficient to override the cancer  genome.

 

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[9]

TÍTULO / TITLE:  - The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Invest. 2013 Feb;31(2):140-4. doi: 10.3109/07357907.2012.762780.

            ●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2012.762780

AUTORES / AUTHORS:  - Yovino S; Kleinberg L; Grossman SA; Narayanan M; Ford E

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

RESUMEN / SUMMARY:  - PURPOSE: Severe treatment-related lymphopenia (TRL) occurs in 40% of patients with high grade gliomas (HGG) receiving glucocorticoids, temozolomide, and radiation. This occurs following radiation, persists for months, and is associated with reduced survival. As all three treatment modalities are lymphotoxic, this study was conducted to estimate the radiation dose that lymphocytes receive passing through the radiation field and if this could explain the observed TRL. MATERIALS AND METHODS: A typical glioblastoma plan (8-cm tumor, 60 Gy/30 fractions) was constructed using the Pinnacle radiation planning system. Radiation doses to circulating cells (DCC) were analyzed using MatLab. The primary endpoints were mean DCC and percent of circulating cells receiving >/=0.5 Gy. The model was also used to study how changes in target volumes (PTV), dose rates, and delivery techniques affect DCC. RESULTS: The modeling determined that  while a single radiation fraction delivered 0.5 Gy to 5% of circulating cells, after 30 fractions 99% of circulating blood had received >/=0.5 Gy. The mean DCC  was 2.2 Gy and was similar for IMRT, 3D-conformal techniques, and different dose  rates. Major changes in PTV size affected mean DCC and percent of circulating cells receiving >/=0.5 Gy. CONCLUSIONS: Standard treatment plans for brain tumors deliver potentially lymphotoxic radiation doses to the entire circulating blood pool. Altering dose rates or delivery techniques are unlikely to significantly affect DCC by the end of treatment. Novel approaches are needed to limit radiation to circulating lymphocytes given the association of lymphopenia with poorer survival in patients with HGG.

 

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[10]

TÍTULO / TITLE:  - Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell. 2013 Feb 28;152(5):1065-76. doi: 10.1016/j.cell.2013.01.036.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cell.2013.01.036

AUTORES / AUTHORS:  - Snuderl M; Batista A; Kirkpatrick ND; Ruiz de Almodovar C; Riedemann L; Walsh EC; Anolik R; Huang Y; Martin JD; Kamoun W; Knevels E; Schmidt T; Farrar CT; Vakoc BJ; Mohan N; Chung E; Roberge S; Peterson T; Bais C; Zhelyazkova BH; Yip S; Hasselblatt M; Rossig C; Niemeyer E; Ferrara N; Klagsbrun M; Duda DG; Fukumura D; Xu L; Carmeliet P; Jain RK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.

RESUMEN / SUMMARY:  - Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic  hedgehog (Shh) and show that PlGF acts through Nrp1-and not vascular endothelial  growth factor receptor 1-to promote tumor cell survival. This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway.

 

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[11]

TÍTULO / TITLE:  - Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar 12. doi: 10.3892/ijo.2013.1856.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1856

AUTORES / AUTHORS:  - Kong BH; Shin HD; Kim SH; Mok HS; Shim JK; Lee JH; Shin HJ; Huh YM; Kim EH; Park EK; Chang JH; Kim DS; Hong YK; Kim SH; Lee SJ; Kang SG

INSTITUCIÓN / INSTITUTION:  - Department of Medical Science, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - The presence of glioma stromal mesenchymal stemlike cells (GS-MSLCs) in tumors from glioma patients has been previously reported. The mechanisms through which these cells function as a part of the glioma microenvironment, however, remain incompletely understood. We investigated the biological effects of GS-MSLCs on glioma cancer stem cells (gCSCs), testing the hypothesis that GS-MSLCs alter the  biological characteristics of gCSCs. GS-MSLCs and gCSCs were isolated from different glioblastoma (GBM) specimens obtained from patients. In in vitro experiments, gCSCs were cultured alone or co-cultured with GS-MSLCs, and gCSCs cell counts were compared between the two groups. In addition, two groups of orthotopic GBM xenografts in mice were created, one using gCSCs from the monoculture group and one using gCSCs isolated from the co-culture group, and tumor volume and survival were analyzed. Furthermore, in vivo proliferation, apoptosis and vessel formation were examined using immunohistochemical analyses.  In vitro cell counts for gCSCs co-cultured with GS-MSLCs increased 3-fold compared to gCSCs cultured alone. In orthotopic xenograft experiments, mice injected with gCSCs isolated from the co-culture group had significantly larger tumor volume, measured on day 40 after injection, and their survival times were shorter. Immunohistochemical analysis showed increased tumor expression of CD31,  indicative of enhanced microvessel formation in mice injected with gCSCs co-cultured with GS-MSLCs compared to mice injected with gCSCs cultured alone. However, proliferation (PCNA) and apoptosis (TUNEL) markers showed no significant difference between the two groups. In conclusion, GS-MSLCs may influence the biological properties of gCSCs, shifting them towards a more aggressive status; moreover, increased angiogenesis may be a critical component of this mechanism.

 

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[12]

TÍTULO / TITLE:  - The treatment of glioblastomas: A systematic update on clinical Phase III trials.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Crit Rev Oncol Hematol. 2013 Feb 27. pii: S1040-8428(13)00033-4. doi: 10.1016/j.critrevonc.2013.01.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.critrevonc.2013.01.007

AUTORES / AUTHORS:  - Yin AA; Cheng JX; Zhang X; Liu BL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province 710032, PR  China.

RESUMEN / SUMMARY:  - Glioblastomas (GBMs) are invariably associated with unavoidable tumor recurrence  and overall poor prognosis. The present study is to summarize the results of clinical Phase III studies on GBMs over the past seven years. A systematic literature search was performed using major electronic databases and by screening meeting abstracts. Totally, 16 studies of patients with newly diagnosed GBMs, recurrent GBMs, and elderly patients with GBMs were selected for this review. Although the outcomes of the experimental therapies were not encouraging, these studies produced a considerable amount of potentially clinically relevant information. Such aspects as surgical outcomes, radiation schedules, temozolomide (TMZ) schedules, methylation status of the O6-methylguanine DNA methyltransferase (MGMT) gene, combination of therapies, novel drug delivery methods and use of targeted agents have come to light and are being addressed here. In addition, we  discuss the existing controversies of (1) surgical studies, (2) evaluations of recurrence, (3) salvage treatment bias, and (4) studies on elderly patients.

 

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[13]

TÍTULO / TITLE:  - Threatening internal carotid artery floating thrombus: left middle cerebral artery stroke in a patient with lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Circulation. 2013 Feb 26;127(8):e463. doi: 10.1161/CIRCULATIONAHA.112.155689.

            ●● Enlace al texto completo (gratuito o de pago) 1161/CIRCULATIONAHA.112.155689

AUTORES / AUTHORS:  - Delgado MG; Velasco A; Calleja S

INSTITUCIÓN / INSTITUTION:  - Neurology, Hospital Universitario Central de Asturias, Oviedo, España. mglezdelgado@yahoo.es

 

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[14]

TÍTULO / TITLE:  - Phase I Trial, Pharmacokinetics, and Pharmacodynamics of Vandetanib and Dasatinib in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-13-0306

AUTORES / AUTHORS:  - Broniscer A; Baker SD; Wetmore C; Pai Panandiker A; Huang J; Davidoff AM; Onar-Thomas A; Panetta JC; Chin TK; Merchant TE; Baker JN; Kaste SC; Gajjar A; Stewart CF

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, St. Jude Children’s Research Hospital.

RESUMEN / SUMMARY:  - PURPOSE: Testing of promising drug combinations is crucial in the treatment of diffuse intrinsic pontine glioma (DIPG). Since the VEGF and PDGF pathways are critical in gliomas, we evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of vandetanib, a VEGFR-2 inhibitor, combined with dasatinib, a potent PDGFR inhibitor, during and after radiotherapy  in children with newly diagnosed DIPG. EXPERIMENTAL DESIGN: Dasatinib was started concurrently with radiotherapy. Vandetanib was started 8 days later. We tested increasing doses of vandetanib (65 and 85 mg/m2 once daily) and dasatinib (65 and 85 mg/m2 twice daily). Dose-limiting toxicities were evaluated during the first six weeks of therapy. Plasma pharmacokinetics was obtained on days 8 and 42+/-3 in all patients and concomitantly with cerebrospinal fluid (CSF) when possible. Inhibition of targets of dasatinib in peripheral blood mononuclear cells (PBMCs)  was evaluated. RESULTS: Twenty-five patients were treated. Treatment was well tolerated. The median duration of treatment was 184 days. Diarrhea was the most significant toxicity. Three patients experienced substantial myelosuppression. The steady-state plasma pharmacokinetics of vandetanib was comparable to previous studies. Although the plasma exposure to dasatinib decreased from days 8 to 42, it remained similar to adult studies. CSF to plasma exposure of vandetanib and dasatinib were approximately 2% in 2 patients. Phosphorylated 70S6K decreased during therapy in PBMCs. CONCLUSIONS: The MTD of vandetanib and dasatinib in combination was 65 mg/m2 for each drug. Other studies are underway to test dasatinib and other PDGFR inhibitors alone or in combination for this deadly cancer.

 

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[15]

TÍTULO / TITLE:  - Erratum to: Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1118-2

AUTORES / AUTHORS:  - Grossmann KF; Colman H; Akerley WA; Glantz M; Matsuoko Y; Beelen AP; Yu M; De Groot JF; Aiken RD; Olson JJ; Evans BA; Jensen RL

INSTITUCIÓN / INSTITUTION:  - Division of Oncology, Huntsman Cancer Institute, University of Utah, 2000 Circle  of Hope Drive, Salt Lake City, UT, 84112, USA.

 

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[16]

TÍTULO / TITLE:  - Can Elderly Patients With Newly Diagnosed Glioblastoma be Enrolled in Radiochemotherapy Trials?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e3182868ea2

AUTORES / AUTHORS:  - Fiorentino A; Balducci M; De Bonis P; Chiesa S; De Filippo L; Mangiola A; De Rose F; Autorino R; Rinaldi C; Fersino S; Diletto B; Matteucci P; Ciurlia E; Fusco V; Anile C; Valentini V

INSTITUCIÓN / INSTITUTION:  - *Department of Radiation Oncology, IRCCS/CROB, Rionero in Vulture (PZ) Departments of daggerRadiation Oncology double daggerNeurosurgery, Catholic University of Sacred Heart, Rome, Italy.

RESUMEN / SUMMARY:  - OBJECTIVES:: Age is an unfavorable prognostic factor in glioblastoma multiforme (GBM). To assess the possibility and the advantage of radiotherapy (RT) plus concomitant/sequential temozolomide (TMZ) in patients over 65 years with GBM, we  analyzed 4 prospective trials in terms of compliance and outcomes. METHODS:: Elderly patients with histologically proven GBM, included in 4 prospective phase  II studies with a Karnofsky Performance Status (KPS) >70 and a Charlson Comorbidity Index (CCI) <3, were selected for these analyses. Patients were treated by 3D-conformal RT (60 Gy), fractionated stereotactic conformal-RT (69.4  Gy), or intensity-modulated RT with simultaneous integrated boost (63 Gy). Concomitant (standard modality, first and last week, or from the Monday to Friday) and adjuvant chemotherapy with TMZ was administered. To stratify patients, recursive partitioning analysis was used. Safety and tolerability were  measured by the National Cancer Institute Common Criteria. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method.  RESULTS:: From 2001 to 2011, 201 patients were enrolled in 4 trials and 111 elderly patients were recruited for this analysis. Compliance was 96.4%: 4/111 patients discontinued treatment, prevalently for disease progression. During radiochemotherapy, acute toxicity was mild. At a median follow-up of 64 months (range, 9 to 122 mo), median PFS and OS were 10 and 13 months, respectively. Extent of surgery (P=0.009) and radiation dose (P=0.01) significantly improved survival. CONCLUSIONS:: Radiochemotherapy is effective and well tolerated by elderly patients when KPS >70 and CCI <3; therefore these criterions should be considered to enroll elderly patients in combined prospective study.

 

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[17]

TÍTULO / TITLE:  - Expression of HAUSP in gliomas correlates with disease progression and survival of patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar 12. doi: 10.3892/or.2013.2342.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2342

AUTORES / AUTHORS:  - Cheng C; Niu C; Yang Y; Wang Y; Lu M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230001, P.R. China.

RESUMEN / SUMMARY:  - The human herpesvirus-associated ubiquitin-specific protease (HAUSP) deubiquitinating enzyme has been shown to regulate many proteins involved in the  cell cycle, as well as tumor suppressors and oncogenes. However, the expression pattern of HAUSP in glioma patients is still unclear. The purpose of the present  study was to investigate the expression pattern and prognostic significance of HAUSP in patients with glioma. Eighty glioma specimens and 10 normal control samples were obtained. Immunohistochemical assay, quantitative real-time PCR and  western blot analysis were carried out to explore the expression of HAUSP. Additionally, the association of HAUSP expression with clinicopathological parameters and the survival of glioma patients were analyzed. Our results showed  that HAUSP expression levels were increased from grade I to grade IV in the tumors of the glioma patients. Moreover, the survival rate of patients with HAUSP-positive tumors was lower when compared to that of patients with HAUSP-negative tumors. We further confirmed that high expression of HAUSP was a significant and independent prognostic indicator in glioma by multivariate analysis. Our data provide convincing evidence for the first time that the overexpression of HAUSP at the gene and protein levels is correlated with poor outcome in patients with glioma in China. HAUSP may play an important oncogenic role in glioma progression, and it is a potential diagnostic and therapeutic target.

 

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[18]

TÍTULO / TITLE:  - Local MEG networks: The missing link between protein expression and epilepsy in glioma patients?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuroimage. 2013 Mar 16;75C:203-211. doi: 10.1016/j.neuroimage.2013.02.067.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neuroimage.2013.02.067

AUTORES / AUTHORS:  - Douw L; de Groot M; van Dellen E; Aronica E; Heimans JJ; Klein M; Stam CJ; Reijneveld JC; Hillebrand A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of  Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02134, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA. Electronic address: douw@nmr.mgh.harvard.edu.

RESUMEN / SUMMARY:  - Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate  the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role  of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology  in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics.

 

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[19]

TÍTULO / TITLE:  - TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1303607110

AUTORES / AUTHORS:  - Killela PJ; Reitman ZJ; Jiao Y; Bettegowda C; Agrawal N; Diaz LA Jr; Friedman AH; Friedman H; Gallia GL; Giovanella BC; Grollman AP; He TC; He Y; Hruban RH; Jallo GI; Mandahl N; Meeker AK; Mertens F; Netto GJ; Rasheed BA; Riggins GJ; Rosenquist TA; Schiffman M; Shih IM; Theodorescu D; Torbenson MS; Velculescu VE; Wang TL; Wentzensen N; Wood LD; Zhang M; McLendon RE; Bigner DD; Kinzler KW; Vogelstein B; Papadopoulos N; Yan H

INSTITUCIÓN / INSTITUTION:  - The Preston Robert Tisch Brain Tumor Center at Duke, Pediatric Brain Tumor Foundation Institute at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC 27710.

RESUMEN / SUMMARY:  - Malignant cells, like all actively growing cells, must maintain their telomeres,  but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low  (<15%) and high (>/=15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding  the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

 

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[20]

TÍTULO / TITLE:  - Survival in patients with newly diagnosed conventional glioblastoma: a modified prognostic score based on a single-institution series.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumori. 2012 Nov;98(6):756-61. doi: 10.1700/1217.13500.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1217.13500

AUTORES / AUTHORS:  - Bertolini F; Zunarelli E; Baraldi C; Valentini A; Del Giovane C; Depenni R; Falasca A; Giacobazzi P; Malagoli M; Meletti S; Fontana A; Conte P

INSTITUCIÓN / INSTITUTION:  - Division of Oncology, University Hospital, Via del Pozzo 71, Modena, Italy. bertolini.federica@policlinico.mo.it

RESUMEN / SUMMARY:  - AIMS AND BACKGROUND: Recursive partioning analysis (RPA) is commonly used to define the stratification of patients with glioblastoma. Epigenetic silencing of  the O6-methylguanine methyltransferase (MGMT) gene by promoter methylation plays  an important role in regulating MGMT expression in gliomas and this is an established independent prognostic factor. We tested a prognostic scoring system  including all clinical variables used by RPA classification (age, ECOG performance status and type of surgery) and MGMT gene promoter methylation status. METHODS: Seventy-eight consecutive patients with newly diagnosed, histopathologically confirmed conventional glioblastoma were included. Information about MGMT promoter methylation status was available for all of them. Based on the patients’ age (<50 vs >/=50 years), ECOG performance status (0 vs >/=1), type of surgery (gross tumor resection versus partial resection/biopsy) and MGMT promoter methylation status (methylated versus unmethylated), three classes of risk were generated where the prognostic score was defined assigning 1 point to every favorable parameter (Class I: >/=3; Class II: 2; Class III: 0-1).  All classes were correlated with overall survival. RESULTS: The median survival times were 32.4, 8.6 and 8.8 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 69%, 13.5% and <1%. The same analysis was performed on 54 patients treated with postoperative concomitant chemoradiotherapy. The median survival times were 32.5, 13.4 and 8.9 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 68.6%, 26.9% and <1%. In both groups of 78 and 54 patients the differences in survival between Class I and III were statistically significant ( P <0.0001). CONCLUSIONS: The proposed prognostic scoring system including clinical variables  and MGMT promoter methylation status proved valuable in patients with primary conventional glioblastoma, especially those treated with postoperative chemoradiotherapy.

 

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[21]

TÍTULO / TITLE:  - Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: A randomized, double-blind, hypothesis-generating study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Feb 13. doi: 10.1002/ijc.28111.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28111

AUTORES / AUTHORS:  - Stragliotto G; Rahbar A; Solberg NW; Lilja A; Taher C; Orrego A; Bjurman B; Tammik C; Skarman P; Peredo I; Soderberg-Naucler C

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Karolinska University Hospital, Sweden.

RESUMEN / SUMMARY:  - Cytomegalovirus is highly prevalent in glioblastomas. In 2006, we initiated a randomized, double-blind, placebo-controlled, hypothesis-generating study to examine the safety and potential efficacy of Valganciclovir as an add-on therapy  for glioblastoma. Forty-two glioblastoma patients were randomized in double-blind fashion to receive Valganciclovir or placebo in addition to standard therapy for  6 months. Magnetic resonance images were obtained before and immediately and 3 and 6 months after surgery to evaluate treatment efficacy by measuring contrast enhancing tumor volume (primary end point). Survival data were analyzed for patients and controls in explorative analyses to aid the design of future randomized trials. Trends but no significant differences were observed in tumor volumes in Valganciclovir and placebo patients at 3 (3.58 vs. 7.44 cm3 , respectively, p = 0.2881) and 6 (3.31 vs. 13.75 cm3 , p = 0.2120) months. Median  overall survival (OS) was similar in both groups (17.9 vs. 17.4 months, p = 0.430). Patients could take Valganciclovir for compassionate use after the study  phase. Explorative analyses showed an OS of 24.1 months (95% CI, 17.4-40.3) in patients receiving >6 months of Valganciclovir (Val > 6M) versus 13.1 months (95% CI, 7.9-17.7, p < 0.0001) in patients receiving Valganciclovir for 0 or <6 months, and 13.7 months (95% CI, 6.9-17.3, p = 0.0031) in contemporary controls.  OS at 4 years was 27.3% in Val>6M patients versus 5.9% in controls (p = 0.0466).  Prolonged OS in Val>6M patients suggest that future randomized trials are warranted and should evaluate whether continuous antiviral treatment can improve  outcome in glioblastoma patients.

 

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[22]

TÍTULO / TITLE:  - TGF-beta Mediates Homing of Bone Marrow-Derived Human Mesenchymal Stem Cells to Glioma Stem Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Apr 1;73(7):2333-44. doi: 10.1158/0008-5472.CAN-12-3086. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3086

AUTORES / AUTHORS:  - Shinojima N; Hossain A; Takezaki T; Fueyo J; Gumin J; Gao F; Nwajei F; Marini FC; Andreeff M; Kuratsu J; Lang FF

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Neurosurgery Neuro-Oncology, and Molecular  Hematology and Therapy, The Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Neurosurgery, Graduate  School of Life Sciences, Kumamoto University, Kumamoto, Japan.

RESUMEN / SUMMARY:  - Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cancer stem cells, including glioma stem cells (GSC), which are the tumor-initiating cells responsible for treatment  failures. Using standard glioma models, we identify TGF-beta as a tumor factor that attracts BM-hMSCs via TGF-beta receptors (TGFbetaR) on BM-hMSCs. Using human and rat GSCs, we then show for the first time that intravascularly administered BM-hMSCs home to GSC-xenografts that express TGF-beta. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-beta-secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFbetaR on BM-hMSCs. These findings reveal the TGF-beta/TGFbetaR axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-beta predicts patients in whom BM-hMSC delivery will be effective. Cancer Res; 73(7); 2333-44. ©2012 AACR.

 

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[23]

TÍTULO / TITLE:  - Differential molecular genetic analysis in glioblastoma multiforme of long- and short-term survivors: a clinical study in Chinese patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1102-x

AUTORES / AUTHORS:  - Zhang GB; Cui XL; Sui DL; Ren XH; Zhang Z; Wang ZC; Lin S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People’s Republic of China.

RESUMEN / SUMMARY:  - This study was designed to find whether long-term survivors (LTSs) exhibit molecular genetic differences compared with short-term survivors (STSs) in patients with GBM. Tumors from 12 patients initially diagnosed with GBM and survived longer than 36 months (LTSs) were compared with 30 patients with GBM and STSs (survival <18 months) for detecting of MGMT promoter methylation, 1p/19q LOH and IDH1 mutation. IDH1 mutation and MGMT promoter methylation were significantly more frequent in the LTSs group (P = 0.039 and 0.017, respectively). The incidence of 1p/19q co-deletion was not significantly different (P = 1.0). IDH1 mutation and MGMT promoter methylation might be independent, significant, and favorable factors for LTSs with GBM.

 

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[24]

TÍTULO / TITLE:  - Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219232110

AUTORES / AUTHORS:  - Sievert AJ; Lang SS; Boucher KL; Madsen PJ; Slaunwhite E; Choudhari N; Kellet M; Storm PB; Resnick AC

INSTITUCIÓN / INSTITUTION:  - Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104.

RESUMEN / SUMMARY:  - Astrocytomas are the most common type of brain tumors in children. Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and V600EBRAF alterations characterizing distinct or higher-grade tumors. Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-dependent melanomas. Like V600EBRAF, BRAF fusion kinases activate  MAPK signaling and are sufficient for malignant transformation; however, here we  characterized the distinct mechanisms of action of KIAA1549-BRAF and its differential responsiveness to PLX4720, a first-generation BRAF inhibitor and research analog of vemurafenib. We found that in cells expressing KIAA1549-BRAF,  the fusion kinase functions as a homodimer that is resistant to PLX4720 and accordingly is associated with CRAF-independent paradoxical activation of MAPK signaling. Mutagenesis studies demonstrated that KIAA1549-BRAF fusion-mediated signaling is diminished with disruption of the BRAF kinase dimer interface. In addition, the KIAA1549-BRAF fusion displays increased binding affinity to kinase  suppressor of RAS (KSR), an RAF relative recently demonstrated to facilitate MEK  phosphorylation by BRAF. Despite its resistance to PLX4720, the KIAA1549-BRAF fusion is responsive to a second-generation selective BRAF inhibitor that, unlike vemurafenib, does not induce activation of wild-type BRAF. Our data support the development of targeted treatment paradigms for BRAF-altered pediatric astrocytomas and also demonstrate that therapies must be tailored to the specific mutational context and distinct mechanisms of action of the mutant kinase.

 

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[25]

TÍTULO / TITLE:  - PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4339-44. doi: 10.1073/pnas.1217602110. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1217602110

AUTORES / AUTHORS:  - Iwanami A; Gini B; Zanca C; Matsutani T; Assuncao A; Nael A; Dang J; Yang H; Zhu S; Kohyama J; Kitabayashi I; Cavenee WK; Cloughesy TF; Furnari FB; Nakamura M; Toyama Y; Okano H; Mischel PS

INSTITUCIÓN / INSTITUTION:  - Departments of Orthopaedic Surgery and Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.

RESUMEN / SUMMARY:  - Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy  to overcome it.

 

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[26]

TÍTULO / TITLE:  - Headache as a risk factor for neurovascular events in pediatric brain tumor patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurology. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1212/WNL.0b013e31828cf81e

AUTORES / AUTHORS:  - Kranick SM; Campen CJ; Kasner SE; Kessler SK; Zimmerman RA; Lustig RA; Phillips PC; Beslow LA; Ichord R; Fisher MJ

INSTITUCIÓN / INSTITUTION:  - From the Departments of Neurology (S.M.K., S.E.K., R.I.), Pediatrics (P.C.P., M.J.F.), and Radiation Oncology (R.A.L.), The Perelman School of Medicine at The  University of Pennsylvania, Philadelphia; and the Divisions of Neurology (C.J.C., S.K.K., L.A.B., R.I.), Neuroradiology (R.A.Z.), and Oncology (P.C.P., M.J.F.), Children’s Hospital of Philadelphia, Philadelphia, PA.

RESUMEN / SUMMARY:  - OBJECTIVE: To determine whether severe recurrent headache is a risk factor for neurovascular events in children who received radiation for brain tumors. METHODS: This is a retrospective cohort study of children with brain tumors who received cranial irradiation at a large tertiary care center, aged 0-21 years at  diagnosis, with initial treatment between January 1, 1993 and December 31, 2002,  and 2 or more follow-up visits. Patients were considered to have severe recurrent headache if this appeared as a complaint on 2 or more visits. Headaches attributed to tumor progression, shunt malfunction, or infection, or appearing at the end of life, were excluded. Medical records were reviewed for events of stroke or TIA. RESULTS: Of 265 subjects followed for a median of 6.0 years (interquartile range 1.7-9.2 years), stroke or TIA occurred in 7/37 (19%) with severe headaches compared to 6/228 (3%) without these symptoms (hazard ratio 5.3, 95% confidence interval 1.8-15.9, p = 0.003). Adjusting for multiple variables did not remove the significance of this risk. Median time to first neurovascular  event for the entire cohort was 4.9 years (interquartile range 1.7-5.5 years). CONCLUSIONS: Severe recurrent headache appears to be a risk factor or predictor for subsequent cerebral ischemia in pediatric brain tumor survivors treated with  radiation. This finding has clinical implications for both monitoring survivors and targeting a specific population for primary stroke prevention.

 

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[27]

TÍTULO / TITLE:  - Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS  disorders.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Neurosci. 2013 Apr;14(4):293-304. doi: 10.1038/nrn3464.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrn3464

AUTORES / AUTHORS:  - Tabares-Seisdedos R; Rubenstein JL

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Valencia, CIBERSAM, INCLIVA, Blasco-Ibez 15, Valencia 46010, España.

RESUMEN / SUMMARY:  - Inverse comorbidity is a lower-than-expected probability of disease occuring in individuals who have been diagnosed with other medical conditions. Emerging evidence points to inverse cancer comorbidity in people with certain CNS disorders. In this Opinion article, we discuss the evidence for this intriguing association and possible underlying mechanisms. We believe that this association  is an invaluable opportunity to gain insight into the pathogenesis of these diseases, and understanding why certain individuals with CNS disorders are protected against many different types of cancer could help to develop new and improved treatments.

 

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[28]

TÍTULO / TITLE:  - Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):520. doi: 10.1007/s12032-013-0520-0. Epub 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0520-0

AUTORES / AUTHORS:  - Aviles A; Jesus Nambo M; Neri N

INSTITUCIÓN / INSTITUTION:  - Oncology Research Oncology Diseases, Ave. Cuauhtemoc 330, Colonia Doctores, 06725 Mexico, DF, Mexico. aamiranda12@gmail.com

RESUMEN / SUMMARY:  - Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has  not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was  similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive  or did not receive prophylaxis was not statistically significant: 49 % versus 53  % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies  are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised.

 

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[29]

TÍTULO / TITLE:  - Deaths Among Adult Patients with Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4059

AUTORES / AUTHORS:  - Burman P; Mattsson AF; Johannsson G; Hoybye C; Holmer H; Dahlqvist P; Berinder K; Engstrom BE; Ekman B; Erfurth EM; Svensson J; Wahlberg J; Karlsson FA

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology (P.B., E.M.E.), Skanes University Hospital Malmo/Lund, SE-205 02 Malmo, Sweden; Pfizer Health AB (A.F.M.), Endocrine Care, SE-190 91 Sollentuna, Sweden; Department of Endocrinology (G.J.), and Center for  Bone and Arthritis Research (J.S.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Department of Endocrinology, Metabolism, and Diabetology (C.H., K.B.), Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Department of Internal Medicine (H.H.), Central Hospital, SE-291 85 Kristianstad, Sweden; Department of Public Health and Clinical Medicine (P.D.), Umea University, SE-901 87 Umea, Sweden; Department of  Endocrinology, Diabetes, and Metabolism (B.E.E., F.A.K.), University Hospital, Uppsala University, SE-751 85 Uppsala, Sweden; and Division of Cardiovascular Medicine (B.E., J.W.), Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, Sweden.

RESUMEN / SUMMARY:  - Context:Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.Objective:To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.Design and Methods:All-cause and cause-specific  mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.Main Outcome Measures:Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.Results:An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.Conclusion:Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

 

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[30]

TÍTULO / TITLE:  - Somatic uniparental isodisomy explains multifocality of glomuvenous malformations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Hum Genet. 2013 Feb 7;92(2):188-96. doi: 10.1016/j.ajhg.2012.12.017. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajhg.2012.12.017

AUTORES / AUTHORS:  - Amyere M; Aerts V; Brouillard P; McIntyre BA; Duhoux FP; Wassef M; Enjolras O; Mulliken JB; Devuyst O; Antoine-Poirel H; Boon LM; Vikkula M

INSTITUCIÓN / INSTITUTION:  - Laboratory of Human Molecular Genetics, de Duve Institute, Universite catholique  de Louvain, Brussels, Belgium.

RESUMEN / SUMMARY:  - Inherited vascular malformations are commonly autosomal dominantly inherited with high, but incomplete, penetrance; they often present as multiple lesions. We hypothesized that Knudson’s two-hit model could explain this multifocality and partial penetrance. We performed a systematic analysis of inherited glomuvenous malformations (GVMs) by using multiple approaches, including a sensitive allele-specific pairwise SNP-chip method. Overall, we identified 16 somatic mutations, most of which were not intragenic but were cases of acquired uniparental isodisomy (aUPID) involving chromosome 1p. The breakpoint of each aUPID is located in an A- and T-rich, high-DNA-flexibility region (1p13.1-1p12).  This region corresponds to a possible new fragile site. Occurrences of these mutations render the inherited glomulin variant in 1p22.1 homozygous in the affected tissues without loss of genetic material. This finding demonstrates that a double hit is needed to trigger formation of a GVM. It also suggests that somatic UPID, only detectable by sensitive pairwise analysis in heterogeneous tissues, might be a common phenomenon in human cells. Thus, aUPID might play a role in the pathogenesis of various nonmalignant disorders and might explain local impaired function and/or clinical variability. Furthermore, these data suggest that pairwise analysis of blood and tissue, even on heterogeneous tissue, can be used for localizing double-hit mutations in disease-causing genes.

 

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[31]

TÍTULO / TITLE:  - Progressive neurolymphomatosis with cutaneous disease: Response in a patient with mycosis fungoides.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Skeletal Radiol. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00256-013-1595-6

AUTORES / AUTHORS:  - Hanna R; Di Primio GA; Schweitzer M; Torres C; Sheikh A; Chakraborty S

INSTITUCIÓN / INSTITUTION:  - Department of Medical Imaging, The Ottawa Hospital - General Campus, 501 Smyth Road, Ottawa, ON, Canada, K1H 8L6, rhanna@toh.on.ca.

RESUMEN / SUMMARY:  - Peripheral neurolymphomatosis is a rare manifestation of advanced lymphoproliferative disorders. It is often associated with B cell lymphomas and rarely with cutaneous T cell lymphomas, such as mycosis fungoides and Sezary syndrome. In this case report, we present a 78-year-old male with a long-standing history of mycosis fungoides. The patient initially presented with chronic peripheral neuropathy in an ulnar nerve distribution. After an unsuccessful ulnar nerve transposition, the ulnar nerve was re-explored and a mass consistent with diffuse lymphomatous infiltration was diagnosed. Magnetic resonance (MR) imaging  of the left brachial plexus and later of the sacral plexus demonstrated diffuse thickening and peripheral nodularity in keeping with neurolymphomatosis. The patient’s clinical course rapidly deteriorated thereafter and the patient succumbed to his disease. Although uncommon, neurolymphomatosis may be considered in patients with chronic peripheral neuropathy and an underlying history of a lymphoproliferative disorder. US and MR may serve as helpful non-invasive adjuncts in making the diagnosis and identifying sites for biopsy.

 

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[32]

TÍTULO / TITLE:  - Response classification based on a minimal model of glioblastoma growth is prognostic for clinical outcomes and distinguishes progression from pseudoprogression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3588

AUTORES / AUTHORS:  - Neal ML; Trister AD; Ahn S; Baldock A; Bridge CA; Guyman L; Lange J; Sodt R; Cloke T; Lai A; Cloughesy TF; Mrugala MM; Rockhill JK; Rockne RC; Swanson KR

INSTITUCIÓN / INSTITUTION:  - Pathology, University of Washington.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. GBM growth dynamics vary widely across patients, making it difficult to accurately gauge their response to treatment. We developed a model-based metric of therapy response called Days Gained that accounts for this heterogeneity. Here we demonstrate in 63 newly diagnosed GBM patients that Days Gained scores from a  simple GBM growth model computed at the time of the first post-radiation therapy  MRI scan are prognostic for time to tumor recurrence and overall patient survival. After radiation treatment, Days Gained also distinguished patients with pseudoprogression from those with true progression. Since Days Gained scores can  be easily computed with routinely available clinical imaging devices, it offers immediate potential to be used in ongoing prospective studies.

 

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[33]

TÍTULO / TITLE:  - Medulloblastoma: Fuelling the debate.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Cancer. 2013 Apr;13(4):222-3. doi: 10.1038/nrc3494. Epub 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrc3494

AUTORES / AUTHORS:  - Seton-Rogers S

 

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[34]

TÍTULO / TITLE:  - GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain. 2013 Mar;136(Pt 3):918-25. doi: 10.1093/brain/aws368. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/brain/aws368

AUTORES / AUTHORS:  - Violante IR; Ribeiro MJ; Edden RA; Guimaraes P; Bernardino I; Rebola J; Cunha G; Silva E; Castelo-Branco M

INSTITUCIÓN / INSTITUTION:  - IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

RESUMEN / SUMMARY:  - Alterations in the balance between excitatory and inhibitory neurotransmission have been implicated in several neurodevelopmental disorders. Neurofibromatosis type 1 is one of the most common monogenic disorders causing cognitive deficits for which studies on a mouse model (Nfl(+/-)) proposed increased gamma-aminobutyric acid-mediated inhibitory neurotransmission as the neural mechanism underlying these deficits. To test whether a similar mechanism translates to the human disorder, we used magnetic resonance spectroscopy to measure gamma-aminobutyric acid levels in the visual cortex of children and adolescents with neurofibromatosis type 1 (n = 20) and matched control subjects (n = 26). We found that patients with neurofibromatosis type 1 have significantly lower gamma-aminobutyric acid levels than control subjects, and that neurofibromatosis type 1 mutation type significantly predicted cortical gamma-aminobutyric acid. Moreover, functional imaging of the visual cortex indicated that blood oxygen level-dependent signal was correlated with gamma-aminobutyric acid levels both in patients and control subjects. Our results provide in vivo evidence of gamma-aminobutyric acidergic dysfunction in neurofibromatosis type 1 by showing a reduction in gamma-aminobutyric acid levels in human patients. This finding is relevant to understand the physiological profile of the disorder and has implications for the identification of targets for therapeutic strategies.

 

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[35]

TÍTULO / TITLE:  - Inherited Mutations in Pheochromocytoma and Paraganglioma: Why All Patients Should Be Offered Genetic Testing.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Surg Oncol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2942-5

AUTORES / AUTHORS:  - Fishbein L; Merrill S; Fraker DL; Cohen DL; Nathanson KL

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA,  USA.

RESUMEN / SUMMARY:  - BACKGROUND: Pheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumors that, although rare, are an important cause of secondary hypertension because of the high morbidity and mortality. PCC/PGL are still thought of as the  “tumor of tens,” with 10 % being hereditary; however, recent population based studies suggest that up to 32 % of patients have a germline mutation in one of the known common susceptibility genes (including NF1, VHL, RET, SDHB, SDHD, and SDHC). Despite this, most patients in the United States are not referred for clinical genetic testing by their physicians. We aimed to examine the mutation prevalence in a clinic-based population in the United States. METHODS: We performed a retrospective chart review of 139 consecutive patients with PCC/PGL from the medical genetics clinic at the hospital of the University of Pennsylvania from January 2004 through February 2012. RESULTS: We found a 41 % overall mutation detection rate. Twenty-six percent of the cohort had a mutation  in the SDHB or SDHD genes. Of patients with at least one PGL tumor outside the adrenal gland, 53 % had an identified mutation. CONCLUSIONS: Forty-one percent of the cohort had a heritable mutation. The most commonly mutated gene was SDHB, which carries the highest risk of malignancy. These data, together with American  Society of Clinical Oncology guidelines suggesting that genetic testing be performed if the risk of a hereditable mutation is at least 10 % or if it will affect medical management, strongly suggest that all patients with PCC/PGL should undergo clinical genetic testing.

 

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[36]

TÍTULO / TITLE:  - Central neurocytoma: Radiological and clinico-pathological findings in 18 patients and one additional MRS case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuroradiol. 2013 Feb 11. pii: S0150-9861(12)00198-8. doi: 10.1016/j.neurad.2012.05.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neurad.2012.05.007

AUTORES / AUTHORS:  - Ramsahye H; He H; Feng X; Li S; Xiong J

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China.

RESUMEN / SUMMARY:  - OBJECTIVES: To evaluate clinical findings and radiological characteristics of central neurocytoma (CN) in 18patients and magnetic resonance spectroscopy (MRS)  features in one additional case. MATERIALS AND METHODS: Clinical and imaging findings of 18patients (nine female and nine male; age range, 18-37 years old (27.8+/-5.7)) with histopathological diagnosis of CN were evaluated retrospectively. Eight patients underwent CT and eight had MR imaging. Both MR and CT images were acquired for other two patients. We also assessed the tumour NADC values. Clinical data, such as presenting symptoms and medical histories were collected. MRS was also obtained for one additional case. RESULTS: Clinical  symptoms at the time of presentation were headaches (n=11), dizziness (n=6), visual disturbances (n=2), etc. Eight lesions were unilateral ventricle (44%) and ten were located in both lateral ventricles. Three tumours continued towards the  foramen of Monro and one to the third ventricle. The maximum diameter of the CNs  varied from 3.4 to 9.2cm (5.2+/-1.5cm). On CT, diffuse and diverse calcifications were observed in nine cases and cysts varying in sizes were revealed in all. On MRI, the solid parts of the tumours were mainly hypo- to isointense on all T1WI and isointense to grey matter on T2WI. Clusters of cysts gave the tumours a “swiss cheese/soap bubble” inhomogeneous hyperintense appearance on T2WI and FLAIR images. Heterogeneous moderate enhancement (5/8) was present on T1 postcontrast images. On DWI, the tumours had heterogeneous hyperintense appearances and the tumour NADC values were 0.93+/-0.21.On MRS, elevated Cho and  Gly peaks and reduced Cr and NAA peaks were obtained. CONCLUSION: CN is almost exclusively located in the body of lateral ventricle in young adults. It is discovered due to symptoms of raised intracranial pressure. The distinct radiological features such as: (1) diffuse and diverse calcifications on CT images; (2) clusters of cysts of varying sizes resulting in the “swiss cheese/soap bubble” appearance on T2WI and heterogeneous moderate enhancement on  MR images; (3) the incorporation of the septum pellucidum in bilateral tumours and abutting of the septum pellucidum in unilateral tumours together with the attachment of the wall of the ventricles can help in the diagnosis of preoperative central neurocytoma.

 

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[37]

TÍTULO / TITLE:  - A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Feb 4. pii: S0959-8049(13)00005-1. doi: 10.1016/j.ejca.2013.01.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.001

AUTORES / AUTHORS:  - Portnow J; Badie B; Markel S; Liu A; D’Apuzzo M; Frankel P; Jandial R; Synold TW

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, City of Hope/Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, United States. Electronic address: jportnow@coh.org.

RESUMEN / SUMMARY:  - PURPOSE: The primary objective of this study was to use intracerebral microdialysis (ICMD) to determine the neuropharmacokinetics of bafetinib, a dual  BCR-Abl/Lyn tyrosine kinase inhibitor that may have activity against gliomas. METHODS: A microdialysis catheter was placed into either peritumoural or enhancing brain tissue of seven patients at the time of tumour resection or biopsy. Twenty-four hours later, bafetinib was administered, 240 or 360mg po, repeating the same dose 12h later. Dialysate samples were continuously collected  for 24h, with plasma samples obtained in parallel. One to two weeks after finishing ICMD, patients were allowed to resume taking bafetinib continuously while being observed for toxicity and tumour response. RESULTS: Twenty-six dialysate samples per patient were collected (n=6) and analysed for bafetinib by  tandem mass spectrometry. Bafetinib concentrations in the brain were below the lower limit of detection of the assay (0.1ng/ml) in all samples except one from a single subject that was 0.52ng/ml. The mean plasma bafetinib maximum concentrations after dose 1 and 2 were 143+/-99 and 247+/-73ng/ml, respectively.  Only one patient remained on treatment past two cycles, and no radiographic responses were seen. CONCLUSIONS: Bafetinib does not sufficiently cross intact or disrupted blood-brain barrier, and therefore, systemic administration of bafetinib is not recommended when investigating this drug as a treatment for brain tumours. ICMD can be a valuable research tool in early drug development. Lead-in ICMD studies can be performed relatively quickly, requiring only a small  number of patients, and without significantly disrupting standard cancer care.

 

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[38]

TÍTULO / TITLE:  - High-resolution steady-state cerebral blood volume maps in patients with central  nervous system neoplasms using ferumoxytol, a superparamagnetic iron oxide nanoparticle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cereb Blood Flow Metab. 2013 Mar 13. doi: 10.1038/jcbfm.2013.36.

            ●● Enlace al texto completo (gratuito o de pago) 1038/jcbfm.2013.36

AUTORES / AUTHORS:  - Varallyay CG; Nesbit E; Fu R; Gahramanov S; Moloney B; Earl E; Muldoon LL; Li X; Rooney WD; Neuwelt EA

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Oregon Health and Science University, Portland, Oregon,  USA.

RESUMEN / SUMMARY:  - Cerebral blood volume (CBV) measurement complements conventional magnetic resonance imaging (MRI) to indicate pathologies in the central nervous system (CNS). Dynamic susceptibility contrast (DSC) perfusion imaging is limited by low  resolution and distortion. Steady-state (SS) imaging may provide higher resolution CBV maps but was not previously possible in patients. We tested the feasibility of clinical SS-CBV measurement using ferumoxytol, a nanoparticle blood pool contrast agent. SS-CBV measurement was analyzed at various ferumoxytol doses and compared with DSC-CBV using gadoteridol. Ninety nine two-day MRI studies were acquired in 65 patients with CNS pathologies. The SS-CBV maps showed improved contrast to noise ratios, decreased motion artifacts at increasing ferumoxytol doses. Relative CBV (rCBV) values obtained in the thalamus and tumor  regions indicated good consistency between the DSC and SS techniques when the higher dose (510 mg) ferumoxytol was used. The SS-CBV maps are feasible using ferumoxytol in a clinical dose of 510 mg, providing higher resolution images with comparable rCBV values to the DSC technique. Physiologic imaging using nanoparticles will be beneficial in visualizing CNS pathologies with high vascularity that may or may not correspond with blood-brain barrier abnormalities.Journal of Cerebral Blood Flow & Metabolism advance online publication, 13 March 2013; doi:10.1038/jcbfm.2013.36.

 

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[39]

TÍTULO / TITLE:  - Bromocriptine-induced Brainstem Angulation in a Patient With Invasive Prolactinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):867-8. doi: 10.1210/jc.2012-3735. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3735

AUTORES / AUTHORS:  - Lou XH; Wu ZB; Zhang YZ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. zyz2004520@163.com.

 

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[40]

TÍTULO / TITLE:  - Free and Total Plasma Cortisol Measured by Immunoassay and Mass Spectrometry Following ACTH1-24 Stimulation in the Assessment of Pituitary Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3576

AUTORES / AUTHORS:  - Burt MG; Mangelsdorf BL; Rogers A; Ho JT; Lewis JG; Inder WJ; Doogue MP

INSTITUCIÓN / INSTITUTION:  - Southern Adelaide Diabetes and Endocrine Services (M.G.B., B.L.M., J.T.H., M.P.D.) and Flinders University (M.G.B., A.R., J.T.H., M.P.D.), Adelaide, Australia 5041; Steroid and Immunobiochemistry Laboratory (J.G.L.), Canterbury Health Laboratories, Christchurch, New Zealand 8140; and Department of Endocrinology and Diabetes (W.J.I.), St Vincent’s Hospital, Melbourne, Australia  3065.

RESUMEN / SUMMARY:  - Context:Measurement of plasma cortisol by immunoassay after ACTH1-24 stimulation  is used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Liquid chromatography-tandem mass spectrometry (LCMS) has greater analytical specificity than immunoassay and equilibrium dialysis allows measurement of free plasma cortisol.Objective:We investigated the use of measuring total and free plasma cortisol by LCMS and total cortisol by immunoassay during an ACTH1-24 stimulation test to define HPA status in pituitary patients.Design and Setting:This was a case control study conducted in a clinical research facility.Participants:We studied 60 controls and 21 patients with pituitary disease in whom HPA sufficiency (n = 8) or deficiency (n = 13) had been previously defined.Intervention:Participants underwent 1 mu g ACTH1-24 intravenous and 250 mu g ACTH1-24 intramuscular ACTH1-24 stimulation tests.Main Outcome Measures:Concordance of ACTH1-24-stimulated total and free plasma cortisol with previous HPA assessment.Results:Total cortisol was 12% lower when measured by immunoassay than by LCMS. Female sex and older age were positively correlated with ACTH1-24-stimulated total and free cortisol, respectively. Measurements of total cortisol by immunoassay and LCMS and free cortisol 30 minutes after 1 mu g  and 30 and 60 minutes after 250 mu g ACTH1-24 were concordant with previous HPA axis assessment in most pituitary patients. However, free cortisol had greater separation from the diagnostic cutoff than total cortisol.Conclusions:Categorization of HPA status by immunoassay and LCMS after ACTH1-24 stimulation was concordant with previous assessment in most pituitary patients. Free cortisol may have greater clinical use in patients near the diagnostic threshold.

 

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[41]

TÍTULO / TITLE:  - Bone Metastases and Skeletal-Related Events in Patients with Malignant Pheochromocytoma and Sympathetic Paraganglioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4231

AUTORES / AUTHORS:  - Ayala-Ramirez M; Palmer JL; Hoffman MC; de la Cruz M; Moon BS; Waguespack SG; Habra MA; Jimenez C

INSTITUCIÓN / INSTITUTION:  - Departments of Endocrine Neoplasia and Hormonal Disorders (M.A.-R., M.-C.H., S.G.W., M.A.H., C.J.), Biostatistics (J.L.P.), Palliative Care and Rehabilitation Medicine (M.d.l.C.), and Orthopaedic Oncology (B.S.M.), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.

RESUMEN / SUMMARY:  - Context:Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and  reduced survival. There is limited information on the clinical effects of BM and  SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL).Objectives:We studied the prevalence and clinical characteristics of  BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE  development.Design:Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011.Results:Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001).Conclusions:BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.

 

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[42]

TÍTULO / TITLE:  - Novel HSP90 inhibitor NVP-HSP990 targets cell cycle regulators to ablate Olig2-positive glioma tumor initiating cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2033

AUTORES / AUTHORS:  - Fu J; Koul D; Yao J; Wang S; Yuan Y; Colman H; Sulman EP; Lang FF; Yung WK

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Center , Department of Neuro-oncology, M.D.Anderson.Cancer Center.

RESUMEN / SUMMARY:  - Genetic heterogeneity and signaling alterations diminish the effectiveness of single-agent therapies in glioblastoma multiforme (GBM). The heat shock protein HSP90 is a molecular chaperone for several signaling proteins that are deregulated in glioma cells. Thus, HSP90 inhibition may offer an approach to coordinately correct multiple signaling pathways as a strategy for GBM therapy. In this study, we evaluated the effects of a novel HSP90 inhibitor, NVP-HSP990, in glioma tumor initiating cell (GIC, hereafter GIC) populations, which are strongly implicated in the root pathobiology of GBM. In GIC cultures, NVP-HSP990  elicited a dose-dependent growth inhibition with IC50 values in the low nanomolar range. Two GIC subgroups with different responses were observed with an Olig2-expressing subset relatively more sensitive to treatment. We also showed that Olig2 is a functional marker associated with cell proliferation and response to NVP-HSP990, as NVP-HSP990 attenuated cell proliferation in Olig2-high GIC lines. Additionally, NVP-HSP990 disrupted cell cycle control mechanism by decreasing CDK2 and CDK4 and elevating apoptosis-related molecules. Mechanistic investigations revealed molecular interactions between CDK2/CDK4 and Olig2. Inhibition of CDK2/CDK4 activity disrupted Olig2-CDK2/CDK4 interactions and attenuated Olig2 protein stability. In vivo evaluation demonstrated a relative prolongation of median survival in an intracranial model of GIC growth. Our results suggest that GBM characterized by high-expressing Olig2 GIC may exhibit greater sensitivity to NVP-HSP990 treatment, establishing a foundation for further investigation of the role of HSP90 signaling in GBM.

 

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[43]

TÍTULO / TITLE:  - Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.773287

AUTORES / AUTHORS:  - Yousaf J; Hills C; Dixit S; Achawal S; O’Brien D; Greenman J; Scott IS

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery, Hull & East Yorkshire Hospitals NHS Trust , Hull Royal Infirmary, Hull , UK.

RESUMEN / SUMMARY:  - Objective. To investigate whether expression of regulatory components of the cell division cycle can be used independently to predict survival and response to adjuvant therapy in glioblastomas. Method. A tissue micro-array, constructed using glioblastomas (n = 66), was stained using antibodies against minichromosome maintenance protein-2 (Mcm-2), expressed throughout the cell-division cycle; geminin, a protein that prevents re-initiation of DNA replication; and cyclin A,  an S-phase cyclin. A semi-quantitative labelling index (LI) was calculated using  an average of 18 high-power fields (hpf) in three replicate cores. The patients were divided into two groups: Group 1 (n = 50) underwent surgery and radiotherapy with 24 patients receiving temozolomide, and Group 2 (n = 16) received surgical treatment only. Results. The LIs (median +/- IQR) for Group 1 were as follows: Mcm-2, 36.7% (22.9%-51.8%); geminin, 7.8% (5.8%-10.5%); and cyclin A, 4.2% (2.4%-6.9%). Elevated LIs, higher than the median, for geminin and cyclin A correlated with prolonged survival when the tumours received adjuvant therapy (Kaplan-Meier curves, p = 0.0046 and p = 0.0063 for geminin and cyclin A, respectively). Linear regression analysis revealed positive correlations with survival for Mcm-2 (p = 0.0376), geminin (p = 0.0006) and cyclin A (p = 0.004). In Group 2, there was no relationship between the patient survival and the LI for any marker. Conclusions. Geminin and cyclin A, each show potential as independent prognostic markers in glioblastomas receiving adjuvant therapy. This may reflect  the fact that both geminin and cyclin A estimate proliferating tumour cell subpopulations sensitive to radio/chemotherapy. These markers could provide valuable prognostic information, even in small biopsies, especially if combined with O6MGMT expression and 1p;19q deletion status.

 

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[44]

TÍTULO / TITLE:  - Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas - Data from the Swedish Brain Tumour Population-based Registry.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.754993

AUTORES / AUTHORS:  - Asklund T; Malmstrom A; Bjor O; Blomquist E; Henriksson R

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Sciences and Oncology, Norrlands University Hospital , Umea , Sweden.

 

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[45]

TÍTULO / TITLE:  - Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4009-14. doi: 10.1073/pnas.1219747110. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219747110

AUTORES / AUTHORS:  - Sottoriva A; Spiteri I; Piccirillo SG; Touloumis A; Collins VP; Marioni JC; Curtis C; Watts C; Tavare S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University of Cambridge, Cambridge CB2 2XZ, United Kingdom.

RESUMEN / SUMMARY:  - Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. However, the extent of intratumor heterogeneity  as a result of tumor evolution is still poorly understood. To address this, we developed a unique surgical multisampling scheme to collect spatially distinct tumor fragments from 11 GB patients. We present an integrated genomic analysis that uncovers extensive intratumor heterogeneity, with most patients displaying different GB subtypes within the same tumor. Moreover, we reconstructed the phylogeny of the fragments for each patient, identifying copy number alterations  in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression. We also characterized the clonal organization of each tumor fragment at the single-molecule level, detecting multiple coexisting cell lineages. Our results reveal the genome-wide architecture of intratumor variability in GB across multiple spatial scales and patient-specific patterns of cancer evolution, with consequences for treatment design.

 

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[46]

TÍTULO / TITLE:  - Acute Toxicity Profile of Patients with Low-grade Gliomas and Meningiomas Receiving Proton Therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827de86b

AUTORES / AUTHORS:  - Maquilan G; Grover S; Alonso-Basanta M; Lustig RA

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA.

RESUMEN / SUMMARY:  - OBJECTIVES:: Proton therapy is an emerging treatment modality. We studied its acute side effects on patients with low-grade gliomas and meningiomas. MATERIALS  AND METHODS:: Twenty-three patients diagnosed with low-grade gliomas or meningiomas enrolled in an Institutional Review Board-approved prospective proton treatment protocol (NCT01024907) were treated and followed between April 2010 and August 2011. Patients received 54 Gy (relative biological effectiveness) in 1.8 Gy (relative biological effectiveness) per fraction and were assessed at the time of consult, weekly during treatment, and at 1, 3, 6, and 9 months posttreatment.  At each clinic visit, nursing completed a “Symptom Assessment/Grading” table. Symptoms were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS:: Fatigue: At on-treatment visit (OTV) week 6, 13 patients had grade 1 and 6 patients had grade 2 fatigue. At 1-month follow-up, 3 patients had grade 1 and 1 patient had grade 2 fatigue. At each timepoint, 1 patient had grade 3 fatigue. Nausea: At OTV week 3, 5 patients  experienced grade 1 nausea. At OTV week 6, 3 patients experienced grade 1 nausea. Headache: At OTV week 3, 10 patients had grade 1 headaches. At OTV week 6, 4 patients experienced grade 1 headaches and 1 patient by follow-up month 1. One to 2 patients experienced grade 2 headaches at each timepoint. At OTV week 3, 1 patient experienced a grade 3 headache. CONCLUSIONS:: Our results suggest that proton therapy for patients with low-grade gliomas and meningiomas has a favorable acute toxicity profile-most patients experienced mild fatigue, headache, and insomnia that largely resolved by 1-month posttreatment.

 

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[47]

TÍTULO / TITLE:  - In vivo Imaging of the Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. 2013 Feb 6. doi: 10.1002/stem.1355.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1355

AUTORES / AUTHORS:  - Martinez-Quintanilla J; Bhere D; Heidari P; He D; Mahmood U; Shah K

INSTITUCIÓN / INSTITUTION:  - Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114.

RESUMEN / SUMMARY:  - Therapeutically engineered stem cells (SC) are emerging as a very effective tumor specific therapeutic approach for different cancer types. However, the assessment of the long-term fate of therapeutic SC post-tumor treatment is critical if such  promising therapies are to be increasingly translated into clinical practice. In  this study, we have developed an efficient stem cell based therapeutic strategy that simultaneously allows killing of tumor cells and assessment and eradication  of SC post highly malignant glioblastoma multiforme (GBM) brain tumor treatment.  Mesenchymal stem cells (MSC) engineered to co-express the prodrug converting enzyme, herpes simplex virus thymidine kinase (HSV-TK) and a potent and secretable variant of tumor necrosis factor apoptosis-inducing ligand (S-TRAIL) induced caspase mediated GBM cell death and showed selective MSC sensitization to the prodrug ganciclovir (GCV). A significant decrease in tumor growth and a subsequent increase in survival were observed when mice bearing a highly aggressive GBM were treated with MSC co-expressing S-TRAIL and HSV-TK. Furthermore, the systemic administration of GCV post-tumor treatment selectively  eliminated therapeutic MSC expressing HSV-TK in vitro and in vivo, which was monitored in real time by positron emission-computed tomography (PET) imaging utilizing 18F-FHBG, a substrate for HSV-TK. These findings demonstrate the development and validation of a novel therapeutic strategy that has implications  in translating stem cell based therapies in cancer patients.

 

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[48]

TÍTULO / TITLE:  - Pre-incubation of Pituitary Tumour Cells with the Epidrugs Zebularine and Trichostatin A are Permissive for Retinoic Acid Augmented Expression of the BMP-4 and D2R genes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinology. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/en.2013-1061

AUTORES / AUTHORS:  - Yacqub-Usman K; Duong CV; Clayton RN; Farrell WE

INSTITUCIÓN / INSTITUTION:  - Institute of Science and Technology in Medicine, Keele University School of Medicine, Stoke-on-Trent, Staffordshire, ST4 7QB. UK.

RESUMEN / SUMMARY:  - Retinoic acid (RA) induced expression of bone morphogenetic protein (BMP-4) inhibits in vitro and in vivo cell proliferation and ACTH synthesis in corticotroph derived tumour cells. Reduced expression of BMP-4 in this adenoma subtype is associated with epigenomic silencing and similar silencing mechanisms  are also associated with the RA responsive dopamine D2 receptor (D2R) in somatolactotroph cells. We now show that pre-incubation with the epidrugs, zebularine and TSA is obligate and permissive for RA induced expression of the BMP-4 and the D2R genes in pituitary tumour cells. Combined epidrug challenges are associated with marginal reduction in CpG island methylation. However, significant change to histone tail modifications toward those associated with expression-competent genes is apparent, whereas RA challenge alone or in combined incubations does not impact on these modifications. Epidrug mediated and RA augmented expression of endogenous BMP-4 increased or decreased cell proliferation and CFE in GH3 and AtT-20 pituitary tumour cells respectively, and  recapitulating recent reports of challenges of these cells with exogenous ligand. The specificity of the BMP-4 mediated effects was further supported by knock-down experiments of the BMP-4 antagonist noggin (siRNA). Knock-down of noggin, in the  absence and the presence of epidrugs, induced and augmented BMP-4 expression respectively. In cell proliferation assays, challenge with either epidrugs or siRNA led to significant increase in cell numbers at the 72hr time point, however, in siRNA treated cells co-incubated with epidrugs a significant increase was apparent at the 48hr time point. These studies show the potential of combined drug challenges as a treatment option, where epidrug renders silenced genes responsive to conventional therapeutic options.

 

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[49]

TÍTULO / TITLE:  - “Ghosts in My Body”: Seizure-like Presentation of Hypocalcemic Tetany Secondary to Hypomagnesemia in a Patient Receiving Cetuximab Therapy for Metastatic Medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318282d99c

AUTORES / AUTHORS:  - Kidwell KS; Kopp WE; Albano EA; Brown AE

INSTITUCIÓN / INSTITUTION:  - *Pediatric Residency Program, University of Colorado Health Sciences Center daggerUniversity of Colorado School of Medicine double daggerCenter for Cancer and Blood Disorders, Children’s Hospital Colorado, Aurora, CO.

RESUMEN / SUMMARY:  - Cetuximab, a monoclonal antibody specific for epidermal growth factor receptor, is increasingly used off-label and in early-phase trials for pediatric malignancies. Here, we report a patient with metastatic medulloblastoma receiving therapy with cyclophosphamide, vinblastine, and cetuximab. During evaluation for  possible seizures, he was noted to be severely hypocalcemic, hypokalemic, and hypomagnesemic, a consequence of the blockade of renal epidermal growth factor receptor expression. His symptoms rapidly abated with intravenous electrolyte repletion. This case highlights the clinical heterogeneity of tetany and the importance of careful laboratory screening for known adverse effects of chemotherapy, particularly when newer biological agents are used off-study in combination chemotherapeutic regimens.

 

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[50]

TÍTULO / TITLE:  - Low triiodothyronine syndrome as a predictor of poor outcomes in patients undergoing brain tumor surgery: a pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121696

AUTORES / AUTHORS:  - Bunevicius A; Deltuva V; Tamasauskas S; Tamasauskas A; Laws ER Jr; Bunevicius R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and.

RESUMEN / SUMMARY:  - Object A low triiodothyronine (T3) state is highly prevalent and is associated with a poor prognosis in critically ill patients. The authors investigated, in patients undergoing brain tumor surgery, the direct association of a perioperative low T3 syndrome with clinical outcomes and also with symptoms of depression and anxiety. Methods Ninety consecutive patients (71% women, median age 55 years), on admission for brain tumor surgery, were evaluated for sociodemographic and clinical characteristics. Their thyroid function profile was assessed on the morning of brain tumor surgery and on the morning after brain tumor surgery. Patients with free T3 concentrations of 3.1 pmol/L or less were considered to have low T3 syndrome. The patients were evaluated for symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) before and after surgery and for clinical outcomes using the Glasgow Outcome Scale (GOS) at discharge. Results After brain tumor surgery, free T3 concentrations decreased (p < 0.001) and the proportion of patients with low T3 levels increased from 38% to 54% (p = 0.02). Lower preoperative (rho = 0.30, p =  0.004) and postoperative (rho = 0.33, p = 0.002) free T3 concentrations correlated with low GOS scores at discharge. Preoperative low T3 syndrome (OR 5.49, 95% CI 1.27-23.69, p = 0.02) and postoperative low T3 syndrome (OR 8.73, 95% CI 1.49-51.21, p = 0.02) both increased risk for unfavorable clinical outcomes (GOS scores < 5) at discharge, after adjusting for age, sex, histological diagnosis of brain tumor, preoperative functional impairment, previous treatment for brain tumor, and depressive symptoms. Preoperative low T3  syndrome increased the risk for preoperative (HADS-depression subscale score >/=  11; OR 4.12, 95% CI 1.16-14.58, p = 0.03) but not postoperative depressive symptoms independently from sociodemographic and clinical factors. Conclusions Low T3 syndrome is a strong independent predictor of unfavorable clinical outcomes and depressive symptoms, and its diagnosis and preoperative management should be considered in patients undergoing neurosurgery for the treatment of brain tumors.

 

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[51]

TÍTULO / TITLE:  - Expression of aquaporin 5 and the AQP5 polymorphism A(-1364)C in association with peritumoral brain edema in meningioma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):297-305. doi: 10.1007/s11060-013-1064-z. Epub 2013  Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1064-z

AUTORES / AUTHORS:  - Lambertz N; Hindy NE; Adler C; Rump K; Adamzik M; Keyvani K; Bankfalvi A; Siffert W; Erol Sandalcioglu I; Bachmann HS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Westdeutsches Tumorzentrum WTZ, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany, nicole.lambertz@uk-essen.de.

RESUMEN / SUMMARY:  - Aquaporins (AQP) are a growing family of water-channel proteins, numbering 13 to  date. Recent studies have reported AQP1 and AQP4 to be involved in the development and resorption of brain edemas of different origin. Other AQPs have also been detected in brain tissue, but their impact on brain edema remains to be shown. To evaluate a possible role of AQP5 in brain edema, we investigated the association of AQP5 expression and the functional AQP5 promoter polymorphism A(-1364)C with occurrence and intensity of peritumoral edema in meningioma patients. Peritumoral edema was classified in three degrees based on preoperative imaging in 89 meningioma patients treated at the University Hospital Essen between 2003 and 2006. AQP5 expression was assessed immunohistochemically in tumor tissue obtained during neurosurgical tumor resection. Genotypes of the A(-1364)C polymorphism were determined using the “slowdown” polymerase chain reaction. Higher levels of AQP5 expression were significantly correlated with the AQP5-1364 AA genotype (P = 0.02). AQP5 expression was positively correlated with  edema (P = 0.04). AQP5 genotypes were not significantly associated with the occurrence, but with the intensity of peritumoral brain edema (P = 0.04). In our  cohort, 40 % of patients with grade I, 66.7 % with grade II, and 76.5 % with grade III edema possessed at least one A allele. Development and intensity of peritumoral edema in meningiomas are associated with AQP5 expression. The intensity of edema correlates with the AQP5 A(-1364)C genotype. This suggests AQP5 as an interesting new candidate involved in peritumoral brain edema in meningioma patients.

 

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[52]

TÍTULO / TITLE:  - Side population in human glioblastoma is non-tumorigenic and characterizes brain  endothelial cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1093/brain/awt025

AUTORES / AUTHORS:  - Golebiewska A; Bougnaud S; Stieber D; Brons NH; Vallar L; Hertel F; Klink B; Schrock E; Bjerkvig R; Niclou SP

INSTITUCIÓN / INSTITUTION:  - 1 NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Sante (CRP-Sante), L-1526 Luxembourg, Luxembourg.

RESUMEN / SUMMARY:  - The identification and significance of cancer stem-like cells in malignant gliomas remains controversial. It has been proposed that cancer stem-like cells display increased drug resistance, through the expression of ATP-binding cassette transporters that detoxify cells by effluxing exogenous compounds. Here, we investigated the ‘side population’ phenotype based on efflux properties of ATP-binding cassette transporters in freshly isolated human glioblastoma samples  and intracranial xenografts derived thereof. Using fluorescence in situ hybridization analysis on sorted cells obtained from glioblastoma biopsies, as well as human tumour xenografts developed in immunodeficient enhanced green fluorescence protein-expressing mice that allow an unequivocal tumour-stroma discrimination, we show that side population cells in human glioblastoma are non-neoplastic and exclusively stroma-derived. Tumour cells were consistently devoid of efflux properties regardless of their genetic background, tumour ploidy or stem cell associated marker expression. Using multi-parameter flow cytometry we identified the stromal side population in human glioblastoma to be brain-derived endothelial cells with a minor contribution of astrocytes. In contrast with their foetal counterpart, neural stem/progenitor cells in the adult brain did not display the side population phenotype. Of note, we show that CD133-positive cells often associated with cancer stem-like cells in glioblastoma biopsies, do not represent a homogenous cell population and include CD31-positive endothelial cells. Interestingly, treatment of brain tumours with the anti-angiogenic agent bevacizumab reduced total vessel density, but did not affect the efflux properties of endothelial cells. In conclusion our findings contribute to an unbiased identification of cancer stem-like cells and stromal cells in brain neoplasms, and provide novel insight into the complex issue of drug delivery to the brain. Since efflux properties of endothelial cells are likely to compromise drug availability, transiently targeting ATP-binding cassette transporters may be a valuable therapeutic strategy to improve treatment effects in brain tumours.

 

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[53]

TÍTULO / TITLE:  - Prognostic Value of Residual Fluorescent Tissue in Glioblastoma Patients After Gross Total Resection in 5-ALA Guided Surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31828c3974

AUTORES / AUTHORS:  - Orzaiz GA; Solis ST; Valverde EP; Sanchez MM; Herruzo BB; Idoate Gastearena MA; Valle RD

INSTITUCIÓN / INSTITUTION:  - 1Department of Neurosurgery. Clinica Universidad de Navarra. Pamplona. España 2Department of Pathology. Clinica Universidad de Navarra. Pamplona. España.

RESUMEN / SUMMARY:  - BACKGROUND:: There is evidence in the literature that supports fluorescent tissue signal in fluorescence guided surgery (FGS) extends farther than tissue highlighted in T1Gd MRI, which is the standard to quantify the extent of resection (EOR). OBJECTIVE:: To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI. METHODS:: A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated using 5-aminolevulinic acid (5-ALA) FGS. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological  complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale (KPS), MGMT methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy. RESULTS:: The median overall survival was 27.0 months (CI= 22.4-31.6) in patients with non-residual fluorescence (n=25) and 17.5 months (CI= 12.5-22.5) for the group with residual fluorescence (n=27) (p= 0.015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, HR= 2.5 (p=0.041).The neurological complication rate was 8% in patients with non-residual fluorescence and 18.5% for the group with residual fluorescence (p=  0.267). CONCLUSION:: GBM patients with CRET in early MRI and no fluorescent residual tissue had longer OS than patients with CRET and residual fluorescent tissue.

 

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[54]

TÍTULO / TITLE:  - Cerebral Venous Sinus Thrombosis in Pediatric Cancer Patients: Long-term Neurological Outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e31827e8dbd

AUTORES / AUTHORS:  - Ross CS; Brown TM; Kotagal S; Rodriguez V

INSTITUCIÓN / INSTITUTION:  - Divisions of daggerChild and Adolescent Psychiatry and Psychology double daggerChild and Adolescent Neurology and *Department of Pediatric and Adolescent  Medicine, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - Cerebral venous sinus thrombosis (CVST) is an uncommon but recognized complication of treatment for leukemia. Our goal was to determine the long-term neurocognitive outcomes in childhood cancer survivors who had CVST during therapy. Nine patients were identified from an institutional database. All had experienced CVST in the setting of L-asparaginase therapy in combination with other chemotherapeutic agents. Four patients completed neuropsychological evaluation. Their neurological examinations were normal. Neuropsychological testing showed that the participants performed well, with average to above-average scores on cognitive and behavioral testing. Three exhibited difficulties on a visual-motor integration task and 1 had difficulty with fine-motor dexterity, nonverbal memory, emotional control, shifting attention, and anxiety. Overall, by patient and parent report, the survivors had few problems. CVST is a known complication associated with treatment for leukemia and non-Hodgkin lymphoma, most commonly observed if asparaginase is used in combination with other chemotherapeutic agents. Although subtle difficulties were noted in survivors on neuropsychological testing, survivors themselves were not aware of the deficits. Further evaluation of leukemia survivors with a history of CVST is needed to assess for deficits and to understand whether further intervention is necessary.

 

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[55]

TÍTULO / TITLE:  - Reversing the warburg effect as a treatment for glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Biol Chem. 2013 Mar 29;288(13):9153-64. doi: 10.1074/jbc.M112.440354. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.440354

AUTORES / AUTHORS:  - Poteet E; Choudhury GR; Winters A; Li W; Ryou MG; Liu R; Tang L; Ghorpade A; Wen Y; Yuan F; Keir ST; Yan H; Bigner DD; Simpkins JW; Yang SH

INSTITUCIÓN / INSTITUTION:  - From the Department of Pharmacology and Neuroscience and.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines. MB decreases GBM cell proliferation and halts the cell cycle in S phase. Through activation of AMP-activated protein kinase, MB inactivates downstream acetyl-CoA  carboxylase and decreases cyclin expression. Structure-activity relationship analysis demonstrated that toluidine blue O, an MB derivative with similar bioenergetic actions, exerts similar action in GBM cell proliferation. In contrast, two other MB derivatives, 2-chlorophenothiazine and promethazine, exert no effect on cellular bioenergetics and do not inhibit GBM cell proliferation. MB inhibits cell proliferation in both temozolomide-sensitive and -insensitive GBM cell lines. In a human GBM xenograft model, a single daily dosage of MB does not  activate AMP-activated protein kinase signaling, and no tumor regression was observed. In summary, the current study provides the first in vitro proof of concept that reversal of Warburg effect might be a novel therapy for GBM.

 

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[56]

TÍTULO / TITLE:  - SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not019

AUTORES / AUTHORS:  - Calaminus G; Kortmann R; Worch J; Nicholson JC; Alapetite C; Garre ML; Patte C; Ricardi U; Saran F; Frappaz D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Therapy and Radio-oncology, University of Leipzig, Leipzig, Germany (R.K.); Department of Paediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany (G.C., J.W.); Department of Paediatric Oncology, Addenbrookes Hospital, Cambridge, UK (J.C.N.); Department for Paediatric Hematology/Oncology, Radiation Oncology Department, Paris & Proton Therapy Center, Orsay, Institut Curie, Paris, France (C.A.); Neuro-Oncology Unit, Department of Pedeatric Hematology and Oncol ogy, G. Gaslini Children’s Hospital, Genova, Italy (M.L.G.); Paediatrics Department, Institut Gustave Roussy, Villejuif, France (C.P.); Department of Medical and Surgical Sciences, Radiation  Oncology Unit, University of Turin, Torino, Italy (U.R.); Department of Radiotherapy, Royal Marsden Hospital, Sutton, Surrey, UK (F.S.); Institute d’Hemato-Oncologie Pediatrique, Centre Leon Berard, Lyon, France (D.F.).

RESUMEN / SUMMARY:  - BackgroundWe conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s).MethodsPatients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy.ResultsPatients with localized germinoma  (n = 190) received either CSI alone (n = 125) or combined therapy (n = 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 +/- 0.02 vs 0.88 +/- 0.04; P = .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n = 45) had 0.98 +/- 0.023 event-free and overall survival.ConclusionsLocalized germinoma can be treated with reduced dose  CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease.

 

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[57]

TÍTULO / TITLE:  - Reduced microglial CX3CR1 expression delays neurofibromatosis-1 glioma formation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Neurol. 2013 Feb;73(2):303-8. doi: 10.1002/ana.23813. Epub 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ana.23813

AUTORES / AUTHORS:  - Pong WW; Higer SB; Gianino SM; Emnett RJ; Gutmann DH

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Washington University School of Medicine, St Louis, MO.

RESUMEN / SUMMARY:  - Although traditional models of carcinogenesis have largely focused on neoplastic  cells, converging data have revealed the importance of non-neoplastic stromal cells in influencing tumor growth and progression. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1)-associated optic glioma, we now demonstrate that stromal microglia express the CX3CR1 chemokine receptor,  such that reduced CX3CR1 expression decreases optic nerve microglia. Moreover, genetic reduction of Cx3cr1 expression in Nf1 optic glioma mice delays optic glioma formation. Coupled with previous findings demonstrating that microglia maintain optic glioma growth, these new findings provide a strong preclinical rationale for the development of future stroma-directed glioma therapies in children. ANN NEUROL 2013;73:303-308.

 

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[58]

TÍTULO / TITLE:  - 68Ga-DOTANOC PET/CT for Baseline Evaluation of Patients with Head and Neck Paraganglioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nucl Med. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.115485

AUTORES / AUTHORS:  - Sharma P; Thakar A; Suman Kc S; Dhull VS; Singh H; Naswa N; Reddy RM; Karunanithi S; Kumar R; Kumar R; Malhotra A; Bal C

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India; and.

RESUMEN / SUMMARY:  - The purpose of this study was to evaluate the role of 68Ga-labeled DOTANOC PET/CT for baseline evaluation of patients with head and neck paragangliomas (HNPs). METHODS: The data for 26 patients (mean age +/- SD, 34.3 +/- 10.4 y; 50% men) with known or suspected HNPs who underwent 68Ga-DOTANOC PET/CT for staging were retrospectively analyzed. PET/CT was performed after intravenous injection of 132-222 MBq of 68Ga-DOTANOC. The images were evaluated by 2 experienced nuclear medicine physicians in consensus, both qualitatively and quantitatively. The PET/CT findings were grouped as HNPs, paraganglioma at other sites (non-HNPs), and metastatic disease. The size and maximum standardized uptake values (SUVmax)  were measured for all lesions. All of the patients also underwent whole-body 131I-metaiodobenzylgunanidine (131I-MIBG) scintigraphy and conventional imaging (CT/MR imaging) of the head and neck region. Their results were compared with those of 68Ga-DOTANOC PET/CT. RESULTS: 68Ga-DOTANOC PET/CT findings were positive in all 26 patients, and 78 lesions were detected. PET/CT imaging demonstrated 45  HNPS, 10 non-HNPs, and 23 metastatic sites. Fifteen patients (57.6%) had more than one site of disease on PET/CT. Among 45 HNPs, 26 were carotid body tumors (CBTs), 15 glomus jugulare, 3 glomus tympanicum, and 1 laryngeal paraganglioma. A positive correlation was seen between size and SUVmax of HNPs (rho = 0.323; P = 0.030). The SUVmax of the CBTs was higher than that of jugulotympanic paragangliomas (P = 0.026). No correlation was seen between size and SUVmax (rho  = 0.069; P = 0.854) of non-HNPs. The size and SUVmax of non-HNPs were significantly less than those of HNPs (P = 0.029 and 0.047, respectively). 131I-MIBG scintigraphy showed only 30 of the 78 lesions and was inferior to PET/CT (P < 0.0001). Conventional imaging (CT/MR imaging) was positive for 42 of  49 head and neck lesions and was inferior to PET/CT on direct comparison (P = 0.015). A combination of CT/MR imaging and 131I-MIBG scintigraphy detected only 53 of 78 (67.9%) lesions and was also inferior to PET/CT (P < 0.0001). CONCLUSION: 68Ga-DOTANOC PET/CT is useful for the baseline evaluation of patients with HNPs and can demonstrate synchronous paragangliomas at other sites and distant metastases. It is superior to 131I-MIBG scintigraphy and conventional imaging (CT/MR imaging) for this purpose.

 

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[59]

TÍTULO / TITLE:  - Vasculogenic mimicry is a prognostic factor for postoperative survival in patients with glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1077-7

AUTORES / AUTHORS:  - Wang SY; Ke YQ; Lu GH; Song ZH; Yu L; Xiao S; Sun XL; Jiang XD; Yang ZL; Hu CC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Department, Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration  of Guangdong, Southern Medical University, Gongye Road 253, Guangzhou, 510282, China.

RESUMEN / SUMMARY:  - A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative  clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.

 

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[60]

TÍTULO / TITLE:  - Focal Cranial Hyperostosis From Meningioma: A Complication From Previous Radiation Treatment for Childhood T-Cell Acute Lymphoblastic Leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e3182830d56

AUTORES / AUTHORS:  - Songdej N

INSTITUCIÓN / INSTITUTION:  - Fox Chase Cancer Center, Temple University, Philadelphia, PA.

RESUMEN / SUMMARY:  - Nearly 75% of childhood cancer survivors will experience an adverse late effect from previous therapy. In patients previously treated with cranial irradiation, the late effect can manifest as secondary central nervous system tumors. Presented is a case of a 20 year man with a history of T-cell lymphoblastic leukemia diagnosed at age 22 months, treated with chemotherapy and cranial irradiation. He had developed increasing prominence of the top of his head over several months. Plain radiograph showed frontal calvarium thickening with focal “hair-on-end” periosteal reaction. Magnetic resonance imaging revealed an enhancing dural-based mass with transcalvarial extension, confirmed after resection to be meningioma (World Health Organization Grade I). This case illustrates an atypical presentation of a late effect of childhood cancer treatment and highlights the need to be informed about prior treatments received  and potential attendant complications.

 

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[61]

TÍTULO / TITLE:  - Preoperative Particle and Glue Embolization of Meningiomas: Indications, Results  and Lessons Learned from 117 Consecutive Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31828e1ffd

AUTORES / AUTHORS:  - Borg A; Ekanayake J; Mair R; Smedley T; Brew S; Kitchen N; Samandouras G; Robertson F

INSTITUCIÓN / INSTITUTION:  - 1Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London 2Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London 3Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London.

RESUMEN / SUMMARY:  - BACKGROUND:: Preoperative embolization of meningiomas remains contentious, with persisting uncertainty over the safety and efficacy of this adjunctive technique. OBJECTIVE:: To evaluate the safety of presurgicalembolization of meningiomas and  its impact on subsequent transfusion requirement, with respect to the extent of embolization and technique used. METHODS:: 117 consecutive patients between 2001  and 2010 were referred for embolization of presumed intracranial meningioma prior to surgical resection. Glue and/or particles were used to devascularize the tumor in 107 patients, all of whom went on to operative resection. The extent and nature of embolization-related complications, degree of angiographic devascularization, and the intraoperative blood transfusion requirements were analyzed. RESULTS:: Mean blood transfusion requirement during surgery was 0.8 units per case (range 1-14 units). Blood transfusion was significantly lower in patients whose meningiomas were completely, angiographicallydevascularized (P= .035). Four patients had complications as a direct result of the embolization procedure. These included intratumoral haemorrhage in two, sixth cranial nerve palsy in one, and scalp necrosis requiring reconstructive surgery in a further patient. CONCLUSION:: The complication rate was 3.7%. No relationship between the embolic agent and the degree of devascularization was observed. Achieving a complete devascularization resulted in a lower blood transfusion requirement, considered an indirect measure of operative blood loss. This series demonstrates  that pre-operative meningiomaembolization is safe and may reduce operative blood  loss. We present distal intratumoral injection of liquid embolic as a safe and effective alternative to more established particle embolization techniques.

 

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[62]

TÍTULO / TITLE:  - Deciphering the 8q24.21 association for glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Mol Genet. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt063

AUTORES / AUTHORS:  - Enciso-Mora V; Hosking FJ; Kinnersley B; Wang Y; Shete S; Zelenika D; Broderick P; Idbaih A; Delattre JY; Hoang-Xuan K; Marie Y; Di Stefano AL; Labussiere M; Dobbins S; Boisselier B; Ciccarino P; Rossetto M; Armstrong G; Liu Y; Gousias K; Schramm J; Lau C; Hepworth SJ; Strauch K; Muller-Nurasyid M; Schreiber S; Franke A; Moebus S; Eisele L; Forsti A; Hemminki K; Tomlinson IP; Swerdlow A; Lathrop M; Simon M; Bondy M; Sanson M; Houlston RS

INSTITUCIÓN / INSTITUTION:  - Division of Genetics and Epidemiology, Institute of Cancer Research, 15 Cotswold  Road, Sutton, Surrey SM2 5NG, UK+

RESUMEN / SUMMARY:  - We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.

 

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[63]

TÍTULO / TITLE:  - Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Endocrinol (Oxf). 2013 Mar 18. doi: 10.1111/cen.12204.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cen.12204

AUTORES / AUTHORS:  - Ciresi A; Amato MC; Guarnotta V; Lo Castro F; Giordano C

INSTITUCIÓN / INSTITUTION:  - Section of Endocrinology, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), University of Palermo, Italy.

RESUMEN / SUMMARY:  - OBJECTIVE: Currently available studies that fully analyze the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and  CAB dosage. DESIGN: This is a retrospective clinical-based therapy analysis. PATIENTS: Forty-three prolactinoma patients (8 men, 35 women), aged 33.65 +/- 11.23 years, were evaluated metabolically at baseline and after 12 months of CAB  treatment. MEASUREMENTS: Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index  (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment. RESULTS: 12 months of CAB reduced WC (p<0.001), total (p=0.001), and low-density lipoprotein cholesterol (p<0.001), triglyderides (p=0.024), fasting insulin (p<0.001), AUCINSULIN (p<0.001), HbA1c (p=0.022), Homa-IR (p<0.001) and VAI (p<0.001), with a concomitant increase in high-density  lipoprotein cholesterol (p<0.001) and in ISI-Matsuda (p<0.001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (> 0.50 mg/week) of CAB showed lower BMI (p=0.009), fasting insulin (p=0.001), Homa-IR (p<0.001) and VAI (p=0.018) and higher ISI-Matsuda (p=0.002) and DIo (p=0.011), compared to those on lower doses. CONCLUSIONS: A significant metabolic improvement was observed in prolactinoma patients after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses. © 2013 Blackwell Publishing Ltd.

 

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[64]

TÍTULO / TITLE:  - Management and survival rates in patients with glioma in China (2004-2010): a retrospective study from a single-institution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1103-9

AUTORES / AUTHORS:  - Yang P; Wang Y; Peng X; You G; Zhang W; Yan W; Bao Z; Wang Y; Qiu X; Jiang T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing, 100050, China.

RESUMEN / SUMMARY:  - To analyze the clinical characteristics and prognostic factors in patients with glioma in an academic institute in China. From October 2004 to August 2010, total 1,285 patients were diagnosed as glioma at the Glioma Center of Beijing Tiantan Hospital. Clinical and molecular pathology features and survival rates were analyzed. The median overall survival (OS) times were 78.1, 37.6 and 14.4 months  for low-grade glioma (WHO grade II), anaplastic glioma (WHO grade III) and glioblastoma (WHO grade IV), respectively. In patients with low-grade glioma, age, preoperative Karnofsky performance scale (KPS), pathological type, radiotherapy, O6-methylguanine-DNA methyltransferase (MGMT) expression and Ki-67  expression, were significantly associated with OS in multivariate analyses; and preoperative KPS and radiotherapy were significantly associated with progression-free survival (PFS). For anaplastic gliomas, age, preoperative KPS, pathological type, extent of resection, radiotherapy, p53 expression and phosphatase and tensin homolog (PTEN) expression were associated with OS. For glioblastomas, age, preoperative KPS, pathology type, extent of resection, radiotherapy and chemotherapy were associated with OS; and age, gender, preoperative KPS, extent of resection, radiotherapy and chemotherapy were associated with PFS. This is the largest survey for glioma management in China to date. We found significant differences in age, presenting symptoms and the expression of p53, MGMT, PTEN, and Ki-67 among patients with different types of glioma. Age, preoperative KPS, tumor grades, radiotherapy, chemotherapy and Ki-67 expression were significantly associated with clinical prognosis.

 

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[65]

TÍTULO / TITLE:  - Screening for major depressive disorder in adults with glioma using the PHQ-9: a  comparison of patient versus proxy reports.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1088-4

AUTORES / AUTHORS:  - Rooney AG; McNamara S; Mackinnon M; Fraser M; Rampling R; Carson A; Grant R

INSTITUCIÓN / INSTITUTION:  - Edinburgh Centre for Neuro-Oncology, Western General Hospital, Edinburgh, Scotland, UK, a.rooney@nhs.net.

RESUMEN / SUMMARY:  - When screening for depression in glioma patients, the utility of proxy carer report is unknown. We studied how patients and proxies differed in the frequency, severity and agreement of reported depressive symptoms, the external validity of  these reports, and whether patient-proxy agreement was associated with cognitive  function. This was a cross-sectional study within a prospective cohort study of depression in glioma. Eligible patients were adults with a new diagnosis of cerebral glioma whose cohabiting partners chose to attend study interviews. Patients completed the Patient Health Questionnaire-9 (PHQ-9, maximum score 27) to screen for major depressive disorder. Proxies independently completed the PHQ-9 ‘for the patient’. A structured clinical interview for MDD was then given.  From 55 couples attending, 41 participated (74 %). Patient-proxy total PHQ-9 score differed by 3 or more points in 26/41 cases (63.4 %). Disagreement within dyads ranged from -7 to +10 points. Proxies observed more individual depressive symptoms than patients reported (mean 2.7 vs 1.8 symptoms respectively, p = 0.013, Wilcoxon Rank Sum Test), and a greater severity of symptom burden (mean PHQ-9 score 8.4 vs 6.8 respectively, p = 0.016, Wilcoxon Rank Sum Test). Proxies  were more reliable than patients on objective behavioural symptoms of depression. Dyadic agreement was not associated with severity of patient cognitive impairment. There was frequent disagreement between glioma patients and proxies reports of depressive symptoms. Proxies reported more depressive symptoms than patients, and were more reliable when reporting observable behavioural symptoms.  When diagnosing depression in glioma, collateral history should be obtained.

 

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[66]

TÍTULO / TITLE:  - Tumoral EPAS1 (HIF2A) mutations explain sporadic pheochromocytoma and paraganglioma in the absence of erythrocytosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Mol Genet. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt069

AUTORES / AUTHORS:  - Comino-Mendez I; de Cubas AA; Bernal C; Alvarez-Escola C; Sanchez-Malo C; Ramirez-Tortosa CL; Pedrinaci S; Rapizzi E; Ercolino T; Bernini G; Bacca A; Leton R; Pita G; Alonso MR; Leandro-Garcia LJ; Gomez-Grana A; Inglada-Perez L; Mancikova V; Rodriguez-Antona C; Mannelli M; Robledo M; Cascon A

INSTITUCIÓN / INSTITUTION:  - Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, España.

RESUMEN / SUMMARY:  - Pheochromocytomas (PCCs) and paragangliomas (PGLs) are chromaffin-cell tumors that arise from the adrenal medulla and extra-adrenal paraganglia, respectively.  The dysfunction of genes involved in the cellular response to hypoxia, such as VHL, EGL nine homolog 1, and the succinate dehydrogenase (SDH) genes, leads to a  direct abrogation of hypoxia inducible factor (HIF) degradation, resulting in a pseudo-hypoxic state implicated in PCC/PGL development. Recently, somatic post-zygotic mutations in EPAS1 (HIF2A) have been found in patients with multiple PGLs and congenital erythrocytosis. We assessed 41 PCCs/PGLs for mutations in EPAS1 and herein describe the clinical, molecular and genetic characteristics of  the 7 patients found to carry somatic EPAS1 mutations; 4 presented with multiple  PGLs (3 of them also had congenital erythrocytosis), whereas 3 were single sporadic PCC/PGL cases. Gene expression analysis of EPAS1-mutated tumors revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Interestingly, single nucleotide polymorphism array analysis revealed an exclusive gain of chromosome 2p in three EPAS1-mutated tumors. Furthermore, multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumor and in three non-EPAS1-mutated cases. The finding  that EPAS1 is involved in the sporadic presentation of the disease not only increases the percentage of PCCs/PGLs with known driver mutations, but also highlights the relevance of studying other hypoxia-related genes in apparently sporadic tumors. Finally, the detection of a specific copy number alteration affecting chromosome 2p in EPAS1-mutated tumors may guide the genetic diagnosis of patients with this disease.

 

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[67]

TÍTULO / TITLE:  - MR Imaging Assessment of Tumor Perfusion and 3D Segmented Volume at Baseline, during Treatment, and at Tumor Progression in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3421

AUTORES / AUTHORS:  - Sedlacik J; Winchell A; Kocak M; Loeffler RB; Broniscer A; Hillenbrand CM

INSTITUCIÓN / INSTITUTION:  - Departments of Radiological Sciences, Biostatistics, and Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee; and Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:DIPG is among the most devastating brain tumors in children, necessitating the development of novel treatment strategies and advanced imaging markers such as perfusion to adequately monitor clinical trials. This study investigated tumor perfusion and 3D segmented tumor volume as predictive markers for outcome in children with newly diagnosed DIPG.METHODS:Imaging data were assessed at baseline, during, and after RT, and every other month thereafter until tumor progression for 35 patients (ages 2-16 years) with newly diagnosed DIPG enrolled in the phase I clinical study, NCT00472017. Patients were treated with conformal RT and vandetanib, a vascular endothelial growth factor receptor 2 inhibitor.RESULTS:Tumor perfusion increased  and tumor volume decreased during combined RT and vandetanib therapy. These changes slowly diminished in follow-up scans until tumor progression. However, increased tumor perfusion and decreased tumor volume during combined therapy were associated with longer PFS. Apart from a longer OS for patients who showed elevated tumor perfusion after RT, there was no association for tumor volume and  other perfusion variables with OS.CONCLUSIONS:Our results suggest that tumor perfusion may be a useful predictive marker for the assessment of treatment response and tumor progression in children with DIPG treated with both RT and vandetanib. The assessment of tumor perfusion yields valuable information about tumor microvascular status and its response to therapy, which may help better understand the biology of DIPGs and monitor novel treatment strategies in future  clinical trials.

 

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[68]

TÍTULO / TITLE:  - Neuregulin 1 enhances cell adhesion molecule l1 expression in human glioma cells  and promotes their migration as a function of malignancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Mar;72(3):244-55. doi: 10.1097/NEN.0b013e3182863dc5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e3182863dc5

AUTORES / AUTHORS:  - Zhao WJ; Schachner M

INSTITUCIÓN / INSTITUTION:  - Center for Neuroscience, Shantou University Medical College, Shantou, Guandong Province, People’s Republic of China.

RESUMEN / SUMMARY:  - Similar functions of L1, a cell adhesion molecule, and the cytokine neuregulin 1  (Nrg1) have been suggested in tumorigenesis and the promotion of metastasis. We studied the relationships of Nrg1 and L1 expression in human gliomas. Using immunofluorescence staining on a human glioma tissue microarray, we found a positive correlation between levels of L1 and Nrg1alpha or Nrg1beta expression; expression tended to increase with increasing WHO (World Health Organization) tumor grade. L1 was also found to colocalize with either Nrg1 isoform. In cultures of U87-MG human glioblastoma and human U251 and SHG-44 glioma cells, the base levels of full-length L1 expression were increased by the 2 Nrg1 molecules in the nanomolar range, and Nrg1 siRNA downregulated full-length L1 expression in these tumor cell lines. U87-MG cells treated with either Nrg1 isoform also showed enhanced migration when compared with that treated with vehicle control. In addition, administration of either lapatinib (a dual inhibitor of both the epidermal growth factor receptor and ErbB-2) or erlotinib (an inhibitor of the epidermal growth factor receptor) in combination with either Nrg1alpha or Nrg1beta inhibited the L1 expression elicited by these cytokines in U87-MG cells. Together, our data suggest that Nrg1 regulates L1 expression in gliomas, and that Nrg1 may contribute to malignancy by upregulating the L1 expression in glioblastoma cells, thereby enhancing their migration.

 

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[69]

TÍTULO / TITLE:  - Seizures during the management of high-grade gliomas: clinical relevance to disease progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1094-6

AUTORES / AUTHORS:  - Kim YH; Park CK; Kim TM; Choi SH; Kim YJ; Choi BS; Han JH; Lee SH; Kim CY; Kim IA; Heo DS; Kim IH; Kim DG; Jung HW

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul National University College of Medicine, 101 Daehang-ro Jongno-gu, Seoul, 110-744, South Korea.

RESUMEN / SUMMARY:  - This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of high-grade gliomas (HGGs). A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizures during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (<1 month), and follow-up (<3 months) MRI. After a median follow-up of 17.4 months (range 0.1-88.3), seizures developed in 127 patients (31 %). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65 %) and the follow-up MRI confirmed progression in 79 patients (62 %). Four other patients (3 %) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24 %); however, 13 patients (10 %) revealed eventual progression. In the patients with a seizure, absence of preoperative seizures (p = 0.003), <95 % tumor resection (p = 0.001), and pre-ictal Karnofsky  Performance Scale score </=70 (p = 0.025) were significantly associated with disease progression. During the management of HGG, 31 % of patients experienced seizures; of these patients, 72 % harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.

 

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[70]

TÍTULO / TITLE:  - Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Immunother. 2013 Feb;36(2):152-7. doi: 10.1097/CJI.0b013e3182811ae4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CJI.0b013e3182811ae4

AUTORES / AUTHORS:  - Prins RM; Wang X; Soto H; Young E; Lisiero DN; Fong B; Everson R; Yong WH; Lai A; Li G; Cloughesy TF; Liau LM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA.

RESUMEN / SUMMARY:  - Dendritic cell (DC) vaccination is emerging as a promising therapeutic option for malignant glioma patients. However, the optimal antigen formulation for loading these cells has yet to be established. The objective of this study was to compare the safety, feasibility, and immune responses of malignant glioma patients on 2 different DC vaccination protocols. Twenty-eight patients were treated with autologous tumor lysate (ATL)-pulsed DC vaccination, whereas 6 patients were treated with glioma-associated antigen (GAA) peptide-pulsed DCs. Safety, toxicity, feasibility, and correlative immune monitoring assay results were compared between patients on each trial. Because of HLA subtype restrictions on the GAA-DC trial, 6/15 screened patients were eligible for treatment, whereas 28/32 patients passed eligibility screening for the ATL-DC trial. Elevated frequencies of activated natural killer cells were observed in the peripheral blood from GAA-DC patients compared with the ATL-DC patients. In addition, a significant correlation was observed between decreased regulatory T lymphocyte (Treg) ratios (postvaccination/prevaccination) and overall survival (P = 0.004) in patients on both trials. In fact, Treg ratios were independently prognostic for overall survival in these patients, whereas tumor pathology was not in multivariate analyses. In conclusion, these results suggest that ATL-DC vaccination is associated with wider patient eligibility compared with GAA-DC vaccination. Decreased postvaccination/prevaccination Treg ratios and decreased frequencies of activated natural killer cells were associated with prolonged survival in patients from both trials, suggesting that these lymphocyte subsets may be relevant immune monitoring endpoints for immunotherapy protocols in malignant glioma patients.

 

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[71]

TÍTULO / TITLE:  - Neoadjuvant chemotherapy may optimize the extent of resection of World Health Organization grade II gliomas: a case series of 17 patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1106-6

AUTORES / AUTHORS:  - Blonski M; Pallud J; Goze C; Mandonnet E; Rigau V; Bauchet L; Fabbro M; Beauchesne P; Baron MH; Fontaine D; Peruzzi P; Darlix A; Duffau H; Taillandier L

INSTITUCIÓN / INSTITUTION:  - Neuro-Oncology Unit, Nancy University Hospital, 29, Avenue du Marechal Lattre de  Tassigny, 54035, Nancy, France, blonski-marie@orange.fr.

RESUMEN / SUMMARY:  - The involvement of eloquent brain areas may preclude the total/subtotal surgical  resection of diffuse low-grade gliomas (DLGGs). The feasibility and functional tolerance of neoadjuvant chemotherapy have been demonstrated in such cases. The present study assesses the clinical and radiological impact of neoadjuvant chemotherapy on the natural course of DLGG. Seventeen patients without feasible surgical resection (infiltration of functional areas and/or large contralateral extension) were retrospectively selected. Temozolomide based neoadjuvant chemotherapy was initiated, inducing a tumor volume decrease and allowing a functional based maximal surgical resection. The median follow-up since initial radiological diagnosis was 5.9 years (range, 1.4-11). The median time to malignant transformation was 5.9 years. Six patients (35 %) had 1p19q codeletion, 12 patients (70 %) with IDH mutation and MGMT promoter methylation, and eight patients (47 %) had p53 overexpression. Chemotherapy reduced tumor volume (median -35.6 %, range -61.6 to -5.1 %) in contralateral hemisphere through the corpus callosum in seven cases (41 %) and in ipsi-lesional functional areas in ten cases (59 %). Chemotherapy significantly decreased the imaging tumor growth (measured by the velocity of diametric expansion VDE) with a median of -3.2 mm/year (range, -29.8 to -0.9 mm/year) (p < 0.001). A tumor volume decrease of more than 20 % was correlated with a lower postoperative residual tumor (median 2 cc, p = 0.04), a greater extent of resection (93.1 vs. 89.5 %), a higher probability of total/subtotal removal. Neoadjuvant chemotherapy with Temozolomide could optimize the surgical resection of DLGGs and could impact their natural history. Further large prospective studies with long-term follow-up are needed.

 

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[72]

TÍTULO / TITLE:  - Vaccination for Invasive Canine Meningioma Induces in Situ Production of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3366

AUTORES / AUTHORS:  - Andersen BM; Pluhar GE; Seiler C; Goulart MR; Santacruz KS; Schutten MM; Meints JP; O’Sullivan G; Bentley RT; Packer RA; Thomovsky SA; Chen AV; Faissler D; Chen W; Hunt MA; Olin MR; Ohlfest JR

INSTITUCIÓN / INSTITUTION:  - Pediatrics, University of Minnesota.

RESUMEN / SUMMARY:  - Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. Interferon gamma elaborating T cells were detected in the peripheral blood  of two cases, but vaccine-induced tumor-reactive antibody responses developed in  all dogs. Antibody responses were polyclonal, recognizing both intracellular and  cell surface antigens, and heat shock protein 60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, demonstrating common antigens across breed and species. Histological analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in post-treatment compared to pre-treatment samples. Tumor-reactive antibodies were capable of inducing antibody dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data demonstrate the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development towards  human trials.

 

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[73]

TÍTULO / TITLE:  - Refining the predictors of risk for central nervous system involvement in patients with mantle cell lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Leuk Lymphoma. 2013 Apr 2.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.777839

AUTORES / AUTHORS:  - Cheah CY; Seymour JF

INSTITUCIÓN / INSTITUTION:  - Department of Haematology, Peter MacCallum Cancer Centre , East Melbourne , Australia.

 

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[74]

TÍTULO / TITLE:  - Antiproliferative, Antiinvasive, and Proapoptotic Activity of Folate Receptor alpha-Targeted Liposomal Doxorubicin in Nonfunctional Pituitary Adenoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinology. 2013 Apr;154(4):1414-23. doi: 10.1210/en.2012-2128. Epub 2013 Mar  5.

            ●● Enlace al texto completo (gratuito o de pago) 1210/en.2012-2128

AUTORES / AUTHORS:  - Liu X; Ma S; Dai C; Cai F; Yao Y; Yang Y; Feng M; Deng K; Li G; Ma W; Xin B; Lian W; Xiang G; Zhang B; Wang R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China. liuxiaohai09@yahoo.com.cn.

RESUMEN / SUMMARY:  - There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)alpha is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRalpha-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRalpha and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9,  and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the  secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition  of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRalpha plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRalpha.

 

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[75]

TÍTULO / TITLE:  - Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lasers Surg Med. 2013 Mar 26. doi: 10.1002/lsm.22126.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lsm.22126

AUTORES / AUTHORS:  - Johansson A; Faber F; Kniebuhler G; Stepp H; Sroka R; Egensperger R; Beyer W; Kreth FW

INSTITUCIÓN / INSTITUTION:  - Laser-Forschungslabor, University Hospital of Munich, Marchioninistrasse 23, 81377 Munich, Germany.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively. MATERIALS AND METHODS: Five patients harbouring non-resectable glioblastomas were included. ALA (20 or 30 mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies were taken throughout the tumour volume for both histological analysis and determination of PpIX concentrations, which were measured by chemical extraction. Cylindrical light diffusors were stereotactically implanted. Prior to and after irradiation, fluorescence measurements were performed. Outcome measurement was based on clinical and neuro-radiological follow up. RESULTS: In three patients, a strong PpIX fluorescence was seen before treatment, which was completely photobleached after iPDT. High concentrations of PpIX could be detected in viable tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 microM). In  the other two patients, however, no or only low PpIX uptake (0-0.6 microM) could  be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilisation (no progression in 29, 30 and 36 months), early  treatment failure was seen in the remaining two patients (death after 3 and 9 months). CONCLUSIONS: Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT. Lasers Surg. Med. © 2013 Wiley Periodicals, Inc.

 

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[76]

TÍTULO / TITLE:  - Atypical Imaging Features of Epstein-Barr Virus—Positive Primary Central Nervous System Lymphomas in Patients without AIDS.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3429

AUTORES / AUTHORS:  - Lee HY; Kim HS; Park JW; Baek HJ; Kim SJ; Choi CG

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; and Department of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Recent clinical experience with EBV-positive PCNSL in patients without acquired immune deficiency syndrome showed that they tended to have atypical features seen on conventional MR imaging. The purpose of our study  was to evaluate the MR imaging features of EBV-positive PCNSL in patients without AIDS and to compare these imaging findings with those of EBV-negative PCNSL.MATERIALS AND METHODS:MR images were obtained in 55 consecutive patients with pathologically proved EBV-positive (n = 10) or EBV-negative (n = 45) PCNSL.  We statistically analyzed the differences between the patient groups regarding the occurrence of tumor necrosis or hemorrhage and ADC, rCBV(max), rCBV®, and the Cho/NAA ratio in the tumor area.RESULTS:Tumor necrosis and hemorrhage were observed in 9 (90%) and 7 (70%), respectively, of the patients with EBV-positive  PCNSL; necrosis was observed in 8 (18%), and hemorrhage, in 3 (7%) patients with  EBV-negative PCNSL (P < .0001 each). The necrotic core was hyperintense relative  to contralateral white matter, as seen on DWI in 4 patients with EBV-positive PCNSL, though the ADC between the 2 patient groups did not differ significantly.  rCBV(max), rCBV®, and the Cho/NAA ratios did not differ significantly between the 2 groups. The sensitivity and specificity of necrosis and hemorrhage for differentiating the 2 groups were 89.2% and 81.7% and 78.5% and 94.1%, respectively.CONCLUSIONS:Our initial clinical experience with a small number of patients suggests that EBV-positive PCNSL in patients without AIDS tends to present with atypical MR imaging features.

 

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[77]

TÍTULO / TITLE:  - Retrospective analysis of the tolerability and activity of lacosamide in patients with brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS12397

AUTORES / AUTHORS:  - Saria MG; Corle C; Hu J; Rudnick JD; Phuphanich S; Mrugala MM; Crew LK; Bota DA; Dan Fu B; Kim RY; Brown T; Feely H; Brechlin J; Brown BD; Drappatz J; Wen PY; Chen CC; Carter B; Lee JW; Kesari S

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosciences and.

RESUMEN / SUMMARY:  - Object The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors. Methods The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide. Results The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities. The majority  of the patients had gliomas (96%). Fifty-five (78%) had partial seizures only, and 12 (17%) had generalized seizures. Most of the patients (74%) were started on lacosamide because of recurrent seizures. Forty-six patients (66%) reported a decrease in seizure frequency, and 21 patients (30%) reported stable seizures. Most of the patients (54 [77%]) placed on lacosamide did not report any toxicities. Conclusions This retrospective analysis demonstrated that lacosamide  was both well tolerated and active as an add-on antiepileptic drug (AED) in patients with brain tumors. Lacosamide’s novel mechanism of action will allow for concurrent use with other AEDs, as documented by its activity across many different types of AEDs used in this patient population. Larger prospective studies are warranted.

 

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[78]

TÍTULO / TITLE:  - Genetic expression profiles of adult and pediatric ependymomas: Molecular pathways, prognostic indicators, and therapeutic targets.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Apr;115(4):388-99. doi: 10.1016/j.clineuro.2012.12.006. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.006

AUTORES / AUTHORS:  - Nagasawa DT; Trang A; Choy W; Spasic M; Yew A; Zarinkhou G; Garcia HM; Yang I

INSTITUCIÓN / INSTITUTION:  - UCLA Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, United States.

RESUMEN / SUMMARY:  - Ependymomas are tumors that can present within either the intracranial or spinal  regions. While 90% of all pediatric ependymomas are intracranial, spinal cord ependymomas are more commonly found in patients 20-40 years old. Treatment for spinal lesions has achieved local control rates up to 100% following gross total  resection, while pediatric intracranial tumors have 40-60% mortality. Given the inability to effectively treat ependymomas with current standard practices, researchers have focused their efforts on evaluating chromosomal alterations, genetic expression profiles, epigenetic events, and molecular pathways. While these studies have provided critical insight into the potential mechanisms underlying ependymoma pathogenesis, understanding of the intricate interplay between the various pathways involved in tumor initiation, development, and progression will require deeper investigation. However, several potential prognostic markers and therapeutic targets have been identified, providing key areas of focus for future research. The utilization of unique genetic expression  profiles based upon patient age, tumor location, tumor grade, and subtype has revealed a multitude of findings warranting further study. Inspection of various  molecular pathways associated with ependymomas may establish the foundation for developing novel therapies capable of achieving significant clinical improvements with individualized regimens specifically designed for personalized treatment strategies.

 

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[79]

TÍTULO / TITLE:  - ‘Elderly’ patients with newly diagnosed glioblastoma deserve optimal care.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1113-7

AUTORES / AUTHORS:  - Holdhoff M; Rosner GL; Alcorn S; Grossman SA

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1550 Orleans Street, 1M16, Baltimore, MD, 21287, USA, mholdho1@jhmi.edu.

 

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[80]

TÍTULO / TITLE:  - Noninvasive language mapping in patients with epilepsy or brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Apr;72(4):555-65. doi: 10.1227/NEU.0b013e318282cdad.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e318282cdad

AUTORES / AUTHORS:  - Genetti M; Grouiller F; Vulliemoz S; Spinelli L; Seeck M; Michel CM; Schaller K

INSTITUCIÓN / INSTITUTION:  - double daggerDepartment of Neurology and Fundamental Neurosciences, Geneva University Hospitals, Geneva, Switzerland section signDepartment of Radiology and Medical Informatics, Geneva University Hospitals, Geneva, Switzerland ||Department of Neurology, Geneva University Hospitals, Geneva, Switzerland paragraph signDepartment of Neurosurgery, Geneva University Hospitals, Geneva, Switzerland.

RESUMEN / SUMMARY:  - BACKGROUND: : Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required. OBJECTIVE: : To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery. METHODS: : fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses  were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available. RESULTS: : fMRI activations concordant with the anterior and posterior language areas were found  in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations. CONCLUSION: : The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical  planning of epileptogenic foci and of brain tumors. ABBREVIATIONS: : ECS, electrocortical stimulationFLI, frontal lateralization indexfMRI, functional magnetic resonance imagingFWE, family-wise errorLI, lateralization indexMNI, Montreal Neurological InstituteSD, standard deviationSEM, standard error of the meanTPLI, temporoparietal lateralization index.

 

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[81]

TÍTULO / TITLE:  - Early Clinical Outcomes Using Proton Radiation for Children With Central Nervous  System Atypical Teratoid Rhabdoid Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Mar 13. pii: S0360-3016(12)03900-4. doi: 10.1016/j.ijrobp.2012.12.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.004

AUTORES / AUTHORS:  - De Amorim Bernstein K; Sethi R; Trofimov A; Zeng C; Fullerton B; Yeap BY; Ebb D; Tarbell NJ; Yock TI; Macdonald SM

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

RESUMEN / SUMMARY:  - PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy. METHODS AND MATERIALS: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT). RESULTS: Ten consecutive patients of a median 2.3 years of age and with a median  follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients  suffered distant relapse; 1 patient was successfully treated with involved field  irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus. CONCLUSIONS: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable.

 

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[82]

TÍTULO / TITLE:  - Dental X-rays and Risk of Meningioma: Anatomy of a Case-Control Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Dent Res. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0022034513484338

AUTORES / AUTHORS:  - Dirksen D; Runte C; Berghoff L; Scheutzel P; Figgener L

INSTITUCIÓN / INSTITUTION:  - Department of Prosthetic Dentistry and Biomaterials, University of Muenster, Waldeyerstr. 30 D-48149 Muenster, Germany.

 

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[83]

TÍTULO / TITLE:  - Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 20;31(9):1182-7. doi: 10.1200/JCO.2012.43.9455. Epub 2013  Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.9455

AUTORES / AUTHORS:  - Recht L; Mechtler LL; Wong ET; O’Connor PC; Rodda BE

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Advanced Medicine Clinic, Stanford University School of  Medicine, 875 Blake Wilbur Dr, Stanford, CA 94305; LRecht@stanford.edu.

RESUMEN / SUMMARY:  - PURPOSE To compare the safety and efficacy of corticorelin acetate (CrA) and placebo in patients with malignant brain tumors requiring chronic administration  of dexamethasone (DEX) to control the signs and symptoms of peritumoral brain edema (PBE). PATIENTS AND METHODS Prospective, randomized, double-blind study of  200 patients with PBE on a stable dose of DEX. Initially, DEX dose was decreased  by 50% over a 2-week period and then held at this level for 3 weeks. The primary  end point was the proportion of patients who responded to treatment-patients who  achieved a >/= 50% DEX reduction from baseline and achieved stable or improved neurologic examination score and Karnofsky performance score at week 2, and then  continued to respond at week 5. Results One hundred patients received subcutaneous injections of 1 mg twice per day of CrA and 100 patients received placebo for the duration of the study period. Although results did not attain statistical significance (at the P < .05 level), a clinically important difference in the proportion of responders between the CrA group (57.0%) and the  placebo group (46.0%; P = .12) was observed. In addition, the maximum percent reduction in DEX dose achieved during the double-blind 12-week study was significantly greater in the CrA group (62.7%) than in placebo group (51.4%; P <  .001). Patients receiving CrA demonstrated an improvement in myopathy and were less likely to develop signs of Cushing syndrome. CONCLUSION CrA enables a reduction in steroid requirement for patients with PBE and is associated with a reduction in the incidence and severity of common steroid adverse effects, including myopathy.

 

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[84]

TÍTULO / TITLE:  - New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.47.1912

AUTORES / AUTHORS:  - Pacak K; Jochmanova I; Prodanov T; Yang C; Merino MJ; Fojo T; Prchal JT; Tischler AS; Lechan RM; Zhuang Z

INSTITUCIÓN / INSTITUTION:  - Karel Pacak, Ivana Jochmanova, and Tamara Prodanov, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maria J. Merino and Tito Fojo, National Cancer Institute; Chunzhang Yang and Zhengping Zhuang, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Josef T. Prchal, University of Utah School of Medicine and  VA Hospital, Salt Lake City, UT; and Arthur S. Tischler and Ronald M. Lechan, Tufts Medical Center, Boston, MA.

RESUMEN / SUMMARY:  - PURPOSEThe occurrence of >/= two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes. PATIENTS AND METHODSFour unrelated patients were investigated,  with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations.  The prolyl hydroxylation and stability of the mutant HIF2alpha protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2alpha was performed on formalin-fixed, paraffin-embedded tumor tissue.ResultsPatients were  found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2A mutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2alpha interaction with the prolyl hydroxylase domain 2-containing protein, decreasing the hydroxylation of HIF2alpha, and reducing HIF2alpha affinity for the von Hippel-Lindau protein and  its degradation. An increase in the half-life of HIF2alpha was associated with upregulation of the hypoxia-related genes EPO, VEGFA, GLUT1, and END1 in tumors.  CONCLUSIONOur findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.

 

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[85]

TÍTULO / TITLE:  - The impact of sequential vs. combined radiochemotherapy with temozolomide, resection and MGMT promoter hypermethylation on survival of patients with primary glioblastoma- a single centre retrospective study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Feb 18.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.767317

AUTORES / AUTHORS:  - Rapp M; Goeppert M; Felsberg J; Steiger HJ; Sabel M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Duesseldorf , Duesseldorf , Germany.

RESUMEN / SUMMARY:  - Background. The benefit of the introduction of alkylating chemotherapy in the treatment of glioblastoma multiforme (GBM) patients has been demonstrated by comparing radiotherapy with concomitant plus intermittent temozolomide (iTMZ) to  radiation therapy. The isolated impact of the concomitant part of this protocol on survival was not investigated. We were therefore interested in the impact of the effect of the concomitant therapy part on survival. Hence, we compared patients treated with open surgery followed by radiotherapy and iTMZ with patients treated with concomitant plus iTMZ chemotherapy regarding overall (OS) and progression-free survival (PFS). Methods. We performed a retrospective database search for the period between 2002 and 2007 and aimed at the identification of patients with primary GBM treated by open resection, radiotherapy (only radiotherapy = Group A and plus concomitant TMZ = Group B) and at least two cycles of TMZ. Patients were stratified for established prognostic markers like extent of resection, MGMT promoter methylation, Karnofsky Performance Scale (KPS), and age. Results. Eighty-five patients were analysed, among which 42 patients (49%) were affiliated with Cohort A and 43 patients (51%) with Cohort B. Between both cohorts there was no significant difference regarding MGMT methylation status (p = 0.929), extend of resection (p = 0.102), KPS (p = 0.197) and age (p = 0.327). For the entire patient population, median OS was 18.6 months and PFS was 5.6 months. The extent of resection was significantly correlated with survival (OS: 21.5 vs. 16.1 months (p = 0.001) and PFS: 11.0 vs.  3.9 months (p = 0.044)). MGMT methylation status revealed a significant impact on OS (p = 0.008). Affiliation to Cohort A or B was neither correlated with PFS (p = 0.168) nor with OS (p = 0.343). Conclusion. Our study demonstrates that PFS and OS are strongly determined by the MGMT status and the extent of resection. Interestingly, concomitant radiochemotherapy was not superior to radiotherapy followed by iTMZ chemotherapy regarding OS and PFS.

 

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[86]

TÍTULO / TITLE:  - Initial Contact of Glioblastoma Cells with Existing Normal Brain Endothelial Cells Strengthen the Barrier Function via Fibroblast Growth Factor 2 Secretion: A New In Vitro Blood-Brain Barrier Model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Mol Neurobiol. 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10571-013-9913-z

AUTORES / AUTHORS:  - Toyoda K; Tanaka K; Nakagawa S; Thuy DH; Ujifuku K; Kamada K; Hayashi K; Matsuo T; Nagata I; Niwa M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries  in brain. Normal capillary endothelial cells function as the blood-brain barrier  (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8  mum pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB  function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited  LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front.

 

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[87]

TÍTULO / TITLE:  - Overexpression of SLC7A7 predicts poor progression-free and overall survival in patients with glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):384. doi: 10.1007/s12032-012-0384-8. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0384-8

AUTORES / AUTHORS:  - Fan S; Meng D; Xu T; Chen Y; Wang J; Li X; Chen H; Lu D; Chen J; Lan Q

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, China.

RESUMEN / SUMMARY:  - The clinical significance of SLC7A7 expression remains unclear. In this study, we aimed to explore whether SLC7A7 expression in tumor tissues could be used to assess subsequent prognosis in patients with glioblastoma (GBM). A total of 119 patients with pathologically confirmed GBM and 16 normal controls were recruited  for this study. The expression of SLC7A7 in GBM and normal tissues was evaluated  by immunohistochemistry in tissue microarrays and quantitative real-time PCR. Kaplan-Meier method and Cox’s proportional hazards model were used in survival analysis. Compared with normal tissues, GBM specimens had significantly increased expression of SLC7A7 at both mRNA and protein levels (both P < 0.05). Moreover, multivariate analysis confirmed that overexpression of SLC7A7 was a significant and independent indicator for predicting poor prognosis. Our results suggest, for the first time, that overexpression of SLC7A7 is correlated with worse outcomes in patients with GBM. SLC7A7 plays a critical role in GBM carcinogenesis and may  be a potential prognosis predictor of GBM.

 

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[88]

TÍTULO / TITLE:  - Central pontine myelinolysis in a patient with non-Hodgkin lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Haematol. 2013 Apr;161(2):156. doi: 10.1111/bjh.12241. Epub 2013 Feb 6.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bjh.12241

AUTORES / AUTHORS:  - Zhou AY; Barnes C; Razzaq R

INSTITUCIÓN / INSTITUTION:  - Department of Haematology, Royal Bolton Hospital, Manchester, UK. anlizhou89@doctors.org.uk.

 

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[89]

TÍTULO / TITLE:  - Do severe headaches portend greater stroke risk following CRT for childhood brain tumor?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurology. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1212/WNL.0b013e31828cfaf5

AUTORES / AUTHORS:  - Heyer GL; Mack KJ

INSTITUCIÓN / INSTITUTION:  - From the Division of Child Neurology (G.L.H.), Nationwide Children’s Hospital and the Ohio State University, Columbus, OH; and Division of Child Neurology (K.J.M.), Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - Children with brain tumors are more likely to survive, with survival rates improving consistently over several decades and well over 70% of patients now surviving 5 years from diagnosis.1 The vast majority of these children will become long-term survivors. As cure rates improve, a greater focus has been placed on enduring patient health after cancer treatment.

 

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[90]

TÍTULO / TITLE:  - Unclear standard of care for pediatric high grade glioma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1104-8

AUTORES / AUTHORS:  - Fangusaro J; Warren KE

INSTITUCIÓN / INSTITUTION:  - Pediatric Neuro-Oncology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 60611, USA, jfangusaro@luriechildrens.org.

 

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[91]

TÍTULO / TITLE:  - Spontaneous and therapeutic prognostic factors in adult hemispheric World Health  Organization Grade II gliomas: a series of 1097 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121

AUTORES / AUTHORS:  - Capelle L; Fontaine D; Mandonnet E; Taillandier L; Golmard JL; Bauchet L; Pallud J; Peruzzi P; Baron MH; Kujas M; Guyotat J; Guillevin R; Frenay M; Taillibert S; Colin P; Rigau V; Vandenbos F; Pinelli C; Duffau H

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery.

RESUMEN / SUMMARY:  - Object The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed. Methods Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age >/= 18 years at diagnosis, histological diagnosis of  WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value </= 0.1) were included in the multivariate  Cox proportional hazard regression model analysis. Results At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were  an age >/= 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a  greater extent of resection. Conclusions This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

 

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[92]

TÍTULO / TITLE:  - Multifunctional mesoporous silica-coated graphene nanosheet used for chemo-photothermal synergistic targeted therapy of glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Am Chem Soc. 2013 Mar 27;135(12):4799-804. doi: 10.1021/ja312221g. Epub 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1021/ja312221g

AUTORES / AUTHORS:  - Wang Y; Wang K; Zhao J; Liu X; Bu J; Yan X; Huang R

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Fudan University , Shanghai 201203, China.

RESUMEN / SUMMARY:  - Current therapy of malignant glioma in clinic is unsatisfactory with poor patient compliance due to low therapeutic efficiency and strong systemic side effects. Herein, we combined chemo-photothermal targeted therapy of glioma within one novel multifunctional drug delivery system. A targeting peptide (IP)-modified mesoporous silica-coated graphene nanosheet (GSPI) was successfully synthesized and characterized, and first introduced to the drug delivery field. A doxorubicin (DOX)-loaded GSPI-based system (GSPID) showed heat-stimulative, pH-responsive, and sustained release properties. Cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of glioma cells compared to that of single chemotherapy or photothermal therapy. Furthermore, the IP modification could significantly enhance the accumulation of GSPID within glioma  cells. These findings provided an excellent drug delivery system for combined therapy of glioma due to the advanced chemo-photothermal synergistic targeted therapy and good drug release properties of GSPID, which could effectively avoid  frequent and invasive dosing and improve patient compliance.

 

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[93]

TÍTULO / TITLE:  - Prolonged survival associated with the use of intraoperative carmustine (Gliadel(®)) in a paediatric patient with recurrent Grade III astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.764970

AUTORES / AUTHORS:  - Pizer B; Salehzadeh A; Brodbelt A; Mallucci C

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Alder Hey Children’s NHS Foundation Trust , Liverpool , UK.

RESUMEN / SUMMARY:  - A 15-year-old female presented with a middle cranial fossa anaplastic astrocytoma that was completely excised. She received local radiotherapy (54 Gy) and oral temozolomide. Five months after therapy, MRI showed local relapse. She underwent  resection of the tumour with implantation of seven carmustine-impregnated wafers  (Gliadel(®)). She then received six cycles of procarbazine and lomustine therapy. Three years later, she is well and disease free. This case supports the  further investigation of Gliadel(®) in children and young people with relapsed  high-grade glioma, particularly in the setting of a second complete resection.

 

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[94]

TÍTULO / TITLE:  - MR Imaging Predictors of Molecular Profile and Survival: Multi-institutional Study of the TCGA Glioblastoma Data Set.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiology. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13120118

AUTORES / AUTHORS:  - Gutman DA; Cooper LA; Hwang SN; Holder CA; Gao J; Aurora TD; Dunn WD Jr; Scarpace L; Mikkelsen T; Jain R; Wintermark M; Jilwan M; Raghavan P; Huang E; Clifford RJ; Mongkolwat P; Kleper V; Freymann J; Kirby J; Zinn PO; Moreno C; Jaffe C; Colen R; Rubin DL; Saltz J; Flanders A; Brat DJ

INSTITUCIÓN / INSTITUTION:  - Departments of Biomedical Informatics, 36 Eagle Row, Room 572 PAIS, Emory University Hospital, Atlanta, GA 30322; Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, Mich; Department of Radiology, University of Virginia, Charlottesville, Va; National Cancer Institute, Bethesda, Md; Department of Radiology, Northwestern University, Chicago, Ill; SAIC-Frederick Inc, Frederick,  Md; Department of Genetics, MD Anderson Cancer Center, Houston, Tex; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Ga; Department of Radiology, Boston University School of Medicine, Boston, Mass; Department of Radiology, Brigham & Women’s Hospital, Harvard University, Boston, Mass; Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa.

RESUMEN / SUMMARY:  - Purpose:To conduct a comprehensive analysis of radiologist-made assessments of glioblastoma (GBM) tumor size and composition by using a community-developed controlled terminology of magnetic resonance (MR) imaging visual features as they relate to genetic alterations, gene expression class, and patient survival.Materials and Methods:Because all study patients had been previously deidentified by the Cancer Genome Atlas (TCGA), a publicly available data set that contains no linkage to patient identifiers and that is HIPAA compliant, no institutional review board approval was required. Presurgical MR images of 75 patients with GBM with genetic data in the TCGA portal were rated by three neuroradiologists for size, location, and tumor morphology by using a standardized feature set. Interrater agreements were analyzed by using the Krippendorff alpha statistic and intraclass correlation coefficient. Associations between survival, tumor size, and morphology were determined by using multivariate Cox regression models; associations between imaging features and genomics were studied by using the Fisher exact test.Results:Interrater analysis  showed significant agreement in terms of contrast material enhancement, nonenhancement, necrosis, edema, and size variables. Contrast-enhanced tumor volume and longest axis length of tumor were strongly associated with poor survival (respectively, hazard ratio: 8.84, P = .0253, and hazard ratio: 1.02, P  = .00973), even after adjusting for Karnofsky performance score (P = .0208). Proneural class GBM had significantly lower levels of contrast enhancement (P = .02) than other subtypes, while mesenchymal GBM showed lower levels of nonenhanced tumor (P < .01).Conclusion:This analysis demonstrates a method for consistent image feature annotation capable of reproducibly characterizing brain  tumors; this study shows that radiologists’ estimations of macroscopic imaging features can be combined with genetic alterations and gene expression subtypes to provide deeper insight to the underlying biologic properties of GBM subsets.© RSNA, 2013.

 

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[95]

TÍTULO / TITLE:  - Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Mar 19. pii: S0360-3016(13)00180-6. doi: 10.1016/j.ijrobp.2013.02.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.02.012

AUTORES / AUTHORS:  - Barker CA; Bishop AJ; Chang M; Beal K; Chan TA

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: barkerc@mskcc.org.

RESUMEN / SUMMARY:  - PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We  investigated whether VA use during RT for GB was associated with overall survival (OS). METHODS AND MATERIALS: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in  patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history. CONCLUSIONS: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

 

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[96]

TÍTULO / TITLE:  - The caregivers’ perspective on the end-of-life phase of glioblastoma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1069-7

AUTORES / AUTHORS:  - Flechl B; Ackerl M; Sax C; Oberndorfer S; Calabek B; Sizoo E; Reijneveld J; Crevenna R; Keilani M; Gaiger A; Dieckmann K; Preusser M; Taphoorn MJ; Marosi C

INSTITUCIÓN / INSTITUTION:  - Department of Medicine I, Medical University of Vienna, Austria Comprehensive Cancer Center, Central Nervous System Tumors Unit (CCC-CNS), Wahringer Gurtel 18-20, 1090, Vienna, Austria, birgit.flechl@gmx.at.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) still harbors a fatal prognosis. The involvement of the neurocognition and psyche poses unique challenges for care provision by relatives. We lack data about the caregivers’ perspective on the end-of-life (EOL) phase of GBM patients to improve counseling and support. In this study we investigated the experiences of 52 caregivers of deceased GBM patients treated in Austria. We used a questionnaire developed by the University Medical Centre of Amsterdam for exploration of the EOL-phase in glioma patients. The caregivers (17 men, 34 women) completed the questionnaire in median three years after the patients’ death. 29 % of caregivers reported that they felt incompletely prepared for their tasks, however, those with higher education levels felt significantly better informed. 29 % suffered from financial difficulties, which was associated  with burnout (60 %) and reduced quality of life (QOL). The patients’ most common  symptoms reported by caregivers were fatigue (87 %), reduced consciousness (81 %) and aphasia (77 %). 22 % of patients were bedbound during their last three months increasing to 80 % in the last week of life. The reported QOL of caregivers was very low and did not differ between caregivers of patients, who died at home (40  %) and caregivers of patients, who died in hospital (46 %). The caregiver reported that their QOL was only slightly better than the QOL they attributed to  the patients. Furthermore, the high frequency of financial difficulties, burnout  symptoms and feelings of insufficient information emphasize the urgent need for support and training dedicated to caregivers.

 

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[97]

TÍTULO / TITLE:  - AMPK activation by oncogenesis is required to maintain cancer cell proliferation  in astrocytic tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-0861

AUTORES / AUTHORS:  - Rios M; Foretz M; Viollet B; Prieto A; Fraga M; Costoya JA; Senaris R

INSTITUCIÓN / INSTITUTION:  - Physiology, University of Santiago de Compostela.

RESUMEN / SUMMARY:  - AMPK is an energy sensor that controls cell metabolism, and it has been related with apoptosis and cell cycle arrest. Although its role in metabolic homeostasis  is well documented, its function in cancer is much less clear. In this study, we  examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion, based upon the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-RasV12 in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosphorylated Rb at Ser804,  which might indicate an AMPK mediated phosphorylation of Rb. We confirmed this AMPK-Rb relationship in human glioblastoma cell lines and xenografts. In clinical specimens of human glioblastoma, elevated levels of activated AMPK appeared especially in areas of high proliferation surrounding the blood vessels. Together, our findings indicate that the initiation and progression of astrocytic tumours relies upon AMPK-dependent control of the cell cycle, thereby identifying AMPK as a candidate therapeutic target in this setting.

 

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[98]

TÍTULO / TITLE:  - Adenomatous polyposis coli regulates oligodendroglial development.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosci. 2013 Feb 13;33(7):3113-30. doi: 10.1523/JNEUROSCI.3467-12.2013.

            ●● Enlace al texto completo (gratuito o de pago) 1523/JNEUROSCI.3467-12.2013

AUTORES / AUTHORS:  - Lang J; Maeda Y; Bannerman P; Xu J; Horiuchi M; Pleasure D; Guo F

INSTITUCIÓN / INSTITUTION:  - Institute for Pediatric Regenerative Medicine, University of California, Davis, School of Medicine and Shriners Hospital, Sacramento, California 95817, USA.

RESUMEN / SUMMARY:  - The expression of the gut tumor suppressor gene adenomatous polyposis coli (Apc)  and its role in the oligodendroglial lineage are poorly understood. We found that immunoreactive APC is transiently induced in the oligodendroglial lineage during  both normal myelination and remyelination following toxin-induced, genetic, or autoimmune demyelination murine models. Using the Cre/loxP system to conditionally ablate APC from the oligodendroglial lineage, we determined that APC enhances proliferation of oligodendroglial progenitor cells (OPCs) and is essential for oligodendrocyte differentiation in a cell-autonomous manner. Biallelic Apc disruption caused translocation of beta-catenin into the nucleus and upregulated beta-catenin-mediated Wnt signaling in early postnatal but not adult oligodendroglial lineage cells. The results of conditional ablation of Apc  or Ctnnb1 (the gene encoding beta-catenin) and of simultaneous conditional ablation of Apc and Ctnnb1 revealed that beta-catenin is dispensable for postnatal oligodendroglial differentiation, that Apc one-allele deficiency is not sufficient to dysregulate beta-catenin-mediated Wnt signaling in oligodendroglial lineage cells, and that APC regulates oligodendrocyte differentiation through beta-catenin-independent, as well as beta-catenin-dependent, mechanisms. Gene ontology analysis of microarray data suggested that the beta-catenin-independent  mechanism involves APC regulation of the cytoskeleton, a result compatible with established APC functions in neural precursors and with our observation that Apc-deleted OPCs develop fewer, shorter processes in vivo. Together, our data support the hypothesis that APC regulates oligodendrocyte differentiation through both beta-catenin-dependent and additional beta-catenin-independent mechanisms.

 

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[99]

TÍTULO / TITLE:  - LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Apr 1;19(7):1816-26. doi: 10.1158/1078-0432.CCR-12-2861. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2861

AUTORES / AUTHORS:  - Yeung JT; Hamilton RL; Ohnishi K; Ikeura M; Potter DM; Nikiforova MN; Ferrone S; Jakacki RI; Pollack IF; Okada H

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Neurological Surgery, Pathology, Surgery and Immunology, and Pediatrics, University of Pittsburgh School of Medicine; Department of Biostatistics, Graduate School of Public Health; and Brain Tumor Program and Biostatistics Facility, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.

RESUMEN / SUMMARY:  - PURPOSE: Glioblastoma (GBM) shows downregulated expression of human leukocyte antigen (HLA) class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. Loss of heterozygosity (LOH) of HLA class I (6p21) and/or beta-2 microglobulin (B2m) (15q21) regions represents irreversible downregulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM. EXPERIMENTAL DESIGN: In a cross-sectional analysis on 60 adult patients with GBM, DNA from formalin-fixed,  paraffin-embedded specimens were evaluated for 10 microsatellite regions of HLA class I, B2m, HLA class II, HLA class III, and 6q by PCR as well as immunohistochemical evaluation of HLA class I expression and CD8(+) T-cell infiltration. RESULTS: LOH in HLA class I, B2m, HLA class II, HLA class III, and  6q regions was present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA class I was associated with shorter overall survival (HR = 4.89, P = 0.0078). HLA class I was downregulated in 22% to 43% of  cases based on immunohistochemistry. Cases that displayed negative staining were  significantly younger. HLA class I expression correlated with intratumoral CD8(+) T-cell infiltration. CONCLUSION: LOH in the HLA class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggests  a crucial role for these genes in immunosurveillance. Clin Cancer Res; 19(7); 1816-26. ©2013 AACR.

 

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[100]

TÍTULO / TITLE:  - Human Glioma-Initiating Cells Show a Distinct Immature Phenotype Resembling but Not Identical to NG2 Glia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Apr;72(4):307-24. doi: 10.1097/NEN.0b013e31828afdbd.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e31828afdbd

AUTORES / AUTHORS:  - Barrantes-Freer A; Kim E; Bielanska J; Giese A; Mortensen LS; Schulz-Schaeffer WJ; Stadelmann C; Bruck W; Pardo LA

INSTITUCIÓN / INSTITUTION:  - Max-Planck-Institute of Experimental Medicine, Molecular Biology of Neuronal Signals, AG Oncophysiology, Gottingen (AB-F, JB, LSM, LAP); Universitatsmedizin Johannes Gutenberg University, Department of Neurosurgery,Translational Neurooncology Research Group, Mainz (EK, AG); and Institute of Neuropathology, University Medical Center, Gottingen (AB-F, WJS-S, CS, WB), Germany.

RESUMEN / SUMMARY:  - Glioma-initiating cells (GICs) represent a potential important therapeutic target because they are likely to account for the frequent recurrence of malignant gliomas; however, their identity remains unsolved. Here, we characterized the cellular lineage fingerprint of GICs through a combination of electrophysiology,  lineage marker expression, and differentiation assays of 5 human patient-derived  primary GIC lines. Most GICs coexpressed nestin, NG2 proteoglycan, platelet-derived growth factor receptor-alpha, and glial fibrillary acidic protein. Glioma-initiating cells could be partially differentiated into astrocytic but not oligodendroglial or neural lineages. We also demonstrate that  GICs have a characteristic electrophysiologic profile distinct from that of well-characterized tumor bulk cells. Together, our results suggest that GICs represent a unique type of cells reminiscent of an immature phenotype that closely resembles but is not identical to NG2 glia with respect to marker expression and functional membrane properties.

 

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[101]

TÍTULO / TITLE:  - Treatment of primary CNS lymphoma (PCNSL) following successful treatment of systemic non-Hodgkin’s lymphoma (NHL): a case series.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1085-7

AUTORES / AUTHORS:  - Chamberlain MC

INSTITUCIÓN / INSTITUTION:  - Division of Neuro-Oncology, Department of Neurology and Neurological Surgery, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, University  of Washington, 825 Eastlake Ave E, MS G-4940, Seattle, WA, 98109, USA, chambemc@u.washington.edu.

RESUMEN / SUMMARY:  - Management of PCNSL occurring after successful treatment of systemic non-Hodgkin’s lymphoma (NHL) is poorly defined. Illustrate a treatment approach for PCNSL following prior treatment of a systemic NHL. A retrospective case series of 6 patients (mean age 60 years; range 46-65) diagnosed with a diffuse large B cell lymphoma of the CNS following prior successful treatment of a systemic NHL (low-grade in 2; high-grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7-18). In 4/6 patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab (immunochemotherapy) followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (ASCT) with total body irradiation (TBI) and multi-agent conditioning chemotherapy (BEAM: carmustine, etoposide, cytarabine, melphalan). 5/6 patients had a radiographic complete response to immunochemotherapy and were treated with ASCT. 4/5 patients were free of disease  following ASCT with a mean follow-up of 3 years (range 0.5-4 years). There were no toxic deaths and all patients transplanted successfully engrafted within 28 days (mean 18). Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by ASCT) for PCNSL occurring metachronously after successful treatment of systemic NHL appears safe and effective.

 

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[102]

TÍTULO / TITLE:  - DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar;98(3):1130-6. doi: 10.1210/jc.2012-2924. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-2924

AUTORES / AUTHORS:  - Hirohata T; Asano K; Ogawa Y; Takano S; Amano K; Isozaki O; Iwai Y; Sakata K; Fukuhara N; Nishioka H; Yamada S; Fujio S; Arita K; Takano K; Tominaga A; Hizuka N; Ikeda H; Osamura RY; Tahara S; Ishii Y; Kawamata T; Shimatsu A; Teramoto A; Matsuno A

INSTITUCIÓN / INSTITUTION:  - MD, Department of Neurosurgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,  Tokyo 113-8655, Japan. hirohata-tky@umin.ac.jp.

RESUMEN / SUMMARY:  - Context: Temozolomide (TMZ) is an alkylating agent and was a first-line chemotherapeutic agent for malignant gliomas. Recently, TMZ has been documented to be effective against atypical pituitary adenomas (APAs) and pituitary carcinomas (PCs). Objective: The clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively. Design: Members of the Japan Society of Hypothalamic and Pituitary Tumors were surveyed regarding the clinical characteristics of APAs and PCs treated with TMZ. Stored tumor samples were gathered from the responders and  were assessed by the immunohistochemistry of Ki-67, O-methyl-guanine-DNA methyltransferase, p53, MSH6, and anterior pituitary hormones. Responses to TMZ treatment were defined as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 2.0. Subjects: Three samples from 3  subjects with APA and 11 samples from 10 subjects with PC were available. Results: The 13 subjects had APAs and PCs consisting of 5 prolactin-producing tumors, 5 ACTH-producing tumors, and 3 null cell adenomas. The clinical response  to TMZ treatment was as follows: 4 cases of CR and PR (31%), 2 cases of SD (15%), 6 cases of recurrence after CR and PR (46%), and 1 case of PD (8%). However, considerable subjects had recurrent disease after a response to TMZ. The immunohistochemical findings of Ki-67, O-methyl-guanine-DNA methyltransferase, and p53 did not show any significant correlation with the efficacy of TMZ. However, the immunopositivity of MSH6 was positively correlated with TMZ response (P = .015, Fisher’s exact test). Conclusions: This study showed that preserving MSH6 function was contributory to the effectiveness of TMZ in malignant pituitary neoplasms. It is necessary to survey more cases and evaluate multifactor analyses.

 

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[103]

TÍTULO / TITLE:  - Chronic Residual Lesions in Metastatic Medulloblastoma Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e3182843b40

AUTORES / AUTHORS:  - Fried I; Huang A; Bartels U; Tabori U; Laperriere N; Dirks P; Bouffet E

INSTITUCIÓN / INSTITUTION:  - *Neuro-Oncology Program, Division of Paediatric Haematology and Oncology, The Hospital for Sick Children, University of Toronto double daggerDepartment of Radiation Oncology, Princess Margaret Hospital section signDepartment of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada daggerDepartment of Pediatrics, Hadassah Medical Center, Division of Pediatric Hematology and Oncology, Jerusalem, Israel.

RESUMEN / SUMMARY:  - In a retrospective review of 24 metastatic medulloblastoma patients whose treatment included craniospinal irradiation, 5 patients presented with gross residual abnormalities at completion of therapy. This report describes 2 medulloblastoma patients with persistent residual abnormalities on serial follow-up imaging studies. The patients aged 2 and 2.5 years old at the time of diagnosis underwent surgery followed by multiagent chemotherapy. One patient progressed on therapy and underwent salvage craniospinal radiation. The second showed residual tumor on end of treatment imaging and received low-dose craniospinal irradiation. Despite persistent magnetic resonance imaging findings, the patients are alive and well 13 and 7 years after diagnosis with no further treatment applied. The nature of these residual abnormalities is discussed.

 

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[104]

TÍTULO / TITLE:  - First Report of Bilateral Pheochromocytoma in the Clinical Spectrum of HIF2A-Related Polycythemia-Paraganglioma Syndrome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2013-1217

AUTORES / AUTHORS:  - Taieb D; Yang C; Delenne B; Zhuang Z; Barlier A; Sebag F; Pacak K

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine (D.T.), La Timone University Hospital, Centre Europeen de Recherche en Imagerie Medicale, Aix-Marseille University, 13005 Marseille, France; Surgical Neurology Branch (C.Y., Z.Z.), National Institute of  Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892; Department of Endocrinology (B.D.), Aix-en-Provence General Hospital, 13616 Aix-en-Provence France; Laboratory of Biochemistry and Molecular  Biology (A.B.), Conception Hospital, Aix-Marseille University, 13005 Marseille, France; Department of Endocrine Surgery (F.S.), La Timone University Hospital, Aix-Marseille University, 13005 Marseille, France; and Program in Reproductive and Adult Endocrinology (K.P.), Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland 20892.

RESUMEN / SUMMARY:  - Context:Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported.Objective:The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia.Patient:A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There  was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype.Results:A heterozygous missense mutation (c.1589C>T) was identified in  exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2alpha protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2alpha and hence a gain-of-function phenotype, as in previously published studies.Conclusion:This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.

 

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[105]

TÍTULO / TITLE:  - GC/MS-based metabolomic analysis of cerebrospinal fluid (CSF) from glioma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1090-x

AUTORES / AUTHORS:  - Nakamizo S; Sasayama T; Shinohara M; Irino Y; Nishiumi S; Nishihara M; Tanaka H; Tanaka K; Mizukawa K; Itoh T; Taniguchi M; Hosoda K; Yoshida M; Kohmura E

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

RESUMEN / SUMMARY:  - Metabolomics has recently undergone rapid development; however, metabolomic analysis in cerebrospinal fluid (CSF) is not a common practice. We analyzed the metabolite profiles of preoperative CSF samples from 32 patients with histologically confirmed glioma using gas chromatography/mass spectrometry (GC/MS). We assessed how alterations in the metabolite levels were related to the World Health Organization (WHO) tumor grades, tumor location, gadolinium enhancement on magnetic resonance imaging (MRI), and the isocitrate dehydrogenase (IDH) mutation status. Sixty-one metabolites were identified in the CSF from glioma patients using targeted, quantitative and non-targeted, semi-quantitative  analysis. The citric and isocitric acid levels were significantly higher in the glioblastoma (GBM) samples than in the grades I-II and grade III glioma samples.  In addition, the lactic and 2-aminopimelic acid levels were relatively higher in  the GBM samples than in the grades I-II glioma samples. The CSF levels of the citric, isocitric, and lactic acids were significantly higher in grade I-III gliomas with mutant IDH than in those with wild-type IDH. The tumor location and  enhancement obtained using MRI did not significantly affect the metabolite profiles. Higher CSF levels of lactic acid were statistically associated with a poorer prognosis in grades III-IV malignant gliomas. Our study suggests that the  metabolomic analysis of CSF from glioma patients may be useful for predicting the glioma grade, metabolic state, and prognosis of gliomas.

 

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[106]

TÍTULO / TITLE:  - Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1122-6

AUTORES / AUTHORS:  - Backes DM; Siddiq A; Cox DG; Calboli FC; Gaziano JM; Ma J; Stampfer M; Hunter DJ; Camargo CA; Michaud DS

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology, Brown Public Health, Brown University, PO Box G-S121-2, Providence, RI, 02912, USA.

RESUMEN / SUMMARY:  - Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine  the association between 166 SNPs of 21 allergy-related genes and glioma risk in a nested case-control study of participants from three large US prospective cohort  studies. Blood collection took place between 1982 and 1994 among the 562 included Caucasian participants (143 cases and 419 matched controls) prior to case diagnosis. Custom Illumina assay chips were used for genotyping. Logistic regression analyses, controlling for age and study cohort, were used to determine associations between each SNP and glioma risk. Statistically significant associations were found between rs2494262 and rs2427824 of the FCER1A gene, which encodes the alpha chain of the high affinity immunoglobulin E receptor, and glioma risk (nominal trend p values 0.01 and 0.03, respectively). Significant associations were also found between SNPs in IL10, ADAM33, NOS1 and IL4R and glioma risk. However, our analyses were not corrected for multiple comparisons and need to be interpreted with caution. Our findings with FCER1A SNPs provide further support for the link between allergies and risk of glioma.

 

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[107]

TÍTULO / TITLE:  - Surgical management of multicentric diffuse low-grade gliomas: functional and oncological outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.2.JNS121747

AUTORES / AUTHORS:  - Terakawa Y; Yordanova YN; Tate MC; Duffau H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier;

RESUMEN / SUMMARY:  - Object Multicentric diffuse low-grade gliomas (DLGGs) are defined as widely separated lesions in different lobes or hemispheres where there is no anatomical  continuity between lesions. This condition is rare and its clinicopathological characteristics have been scarcely described in the literature. Here, the authors report the first consecutive surgical series of multicentric DLGGs with functional and oncological outcomes. Methods A retrospective review of patients surgically treated for histopathologically confirmed multicentric DLGGs between 2000 and 2012 was performed. Information regarding clinical features, surgical procedures, histopathological results, and clinical outcomes was collected and analyzed. Results Five consecutive patients were included in this study. There were 3 men and 2 women, whose mean age was 27.4 years (range 23-35 years). The mean follow-up period after surgery was 46 months (range 11-138 months). Gross-total or subtotal resection was achieved in all cases, using a single surgery in 3 patients and a 2-stage surgery in 2 patients. There was no mortality or permanent morbidity associated with surgery. The Karnofsky Performance Scale score ranged between 90 and 100 in all cases. Adjuvant chemotherapy was administered in 2 patients because of tumor regrowth with no malignant transformation. Conclusions Multicentric DLGGs can be removed safely without inducing severe permanent neurological deficits. Interestingly, a single-stage resection of multiple lesions within different lobes may be performed if tumors are located in the same hemisphere. Therefore, the authors suggest considering surgery as the first therapeutic option for multicentric DLGGs, as in solitary DLGGs.

 

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[108]

TÍTULO / TITLE:  - Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Feb 22. pii: S0360-3016(13)00072-2. doi: 10.1016/j.ijrobp.2013.01.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.01.009

AUTORES / AUTHORS:  - Lee P; Eppinga W; Lagerwaard F; Cloughesy T; Slotman B; Nghiemphu PL; Wang PC; Kupelian P; Agazaryan N; Demarco J; Selch MT; Steinberg M; Kang JJ

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California. Electronic address: percylee@mednet.ucla.edu.

RESUMEN / SUMMARY:  - PURPOSE: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. METHODS AND MATERIALS: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and  OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. RESULTS: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS  and OS on multivariate analysis. CONCLUSION: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

 

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[109]

TÍTULO / TITLE:  - Pituitary Tumor With Gigantism, Acromegaly and Preclinical Cushing’s Disease Diagnosed from the 10th Row.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Med Sci. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MAJ.0b013e3182831919

AUTORES / AUTHORS:  - Tourtelot JB; Vesely DL

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology (JBT), H. Lee Moffitt Cancer Center, Tampa, Florida; Division of Endocrinology (DLV), James A. Haley Veterans Administration Hospital, Tampa, Florida; and Department of Medicine (JBT, DLV), School of Medicine, University of South Florida Morsani, Tampa, Florida.

RESUMEN / SUMMARY:  - : A 7’3” basketball player was noted to have 2 to 3 times thicker tissue in his  hands than 6’10” players by an endocrinologist sitting 10 rows above the player  in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7’3” at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and  insulin-like growth factor 1 (IGF-1) with a 2 x 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing’s disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

 

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[110]

TÍTULO / TITLE:  - miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cdelta

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinology. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1210/en.2012-2070

AUTORES / AUTHORS:  - Gentilin E; Tagliati F; Filieri C; Mole D; Minoia M; Rosaria Ambrosio M; Degli Uberti EC; Zatelli MC

INSTITUCIÓN / INSTITUTION:  - Section of Endocrinology (E.G., F.T., C.F., D.M., M.M., M.R.A., E.C.d.U., M.C.Z.), Department of Medical Sciences, and Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (E.G., E.d.U., M.C.Z.), University of Ferrara, 44100 Ferrara, Italy.

RESUMEN / SUMMARY:  - The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent  an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cdelta (PRKCD) is a direct target  of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing’s disease.

 

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[111]

TÍTULO / TITLE:  - A treatment planning comparison of highly conformal radiation therapy for pediatric low-grade brainstem gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Oncol. 2013 Apr;52(3):594-9. doi: 10.3109/0284186X.2013.767474. Epub 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.767474

AUTORES / AUTHORS:  - Brower JV; Indelicato DJ; Aldana PR; Sandler E; Rotondo R; Mendenhall NP; Marcus RB; Su Z

INSTITUCIÓN / INSTITUTION:  - University of Florida Proton Therapy Institute , Jacksonville, Florida , USA.

 

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[112]

TÍTULO / TITLE:  - Hypo-fractionated IMRT for patients with newly diagnosed glioblastoma multiforme: A 6 year single institutional experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb 26. pii: S0303-8467(13)00054-1. doi: 10.1016/j.clineuro.2013.02.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.02.001

AUTORES / AUTHORS:  - Ciammella P; Galeandro M; D’Abbiero N; Podgornii A; Pisanello A; Botti A; Cagni E; Iori M; Iotti C

INSTITUCIÓN / INSTITUTION:  - Radiation Therapy Unit, Department of Oncology and Advanced Technology, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy. Electronic address: patrizia.ciammella@asmn.re.it.

RESUMEN / SUMMARY:  - OBJECTIVES: Glioblastoma (GBM) is the most common malignant primary brain tumour  in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. PATIENTS AND METHODS: Sixty-seven patients affected by GBM who had previously undergone surgical resection (total,  subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS>/=60, age>/=18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns  of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. RESULTS: All patients have completed the treatment protocol. Median age was 64.5 years (range 41-82 years) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. CONCLUSIONS: The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.

 

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[113]

TÍTULO / TITLE:  - Fronto-cerebellar fiber tractography in pediatric patients following posterior fossa tumor surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2070-3

AUTORES / AUTHORS:  - Gudrunardottir T; Sehested A; Juhler M; Schmiegelow K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The University Hospital Rigshospitalet, 2100, Copenhagen, Denmark.

 

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[114]

TÍTULO / TITLE:  - Spontaneous speech of patients with gliomas in eloquent areas before and early after surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):685-92. doi: 10.1007/s00701-013-1638-8. Epub 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1638-8

AUTORES / AUTHORS:  - Satoer D; Vincent A; Smits M; Dirven C; Visch-Brink E

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Erasmus MC-University Medical Center, Dr. Molewaterplein 50-60, PO Box 2040, 3015 GE, Rotterdam, The Netherlands, d.satoer@erasmusmc.nl.

RESUMEN / SUMMARY:  - BACKGROUND: Glioma patients often complain about problems in daily conversation.  A detailed spontaneous speech analysis could provide more insight in these communicative problems; no previous studies are reported. OBJECTIVE: To select sensitive parameters in spontaneous speech pre- and post-operatively in patients  with gliomas in eloquent areas. METHODS: We included 27 patients and 21 healthy controls. In addition to a naming and category fluency test, spontaneous speech was collected 1 month pre-operatively and 3 months post-operatively, and analysed with the variables: Self-corrections, Repetitions, Lexical Diversity, Incomplete  Sentences and Mean Length of Utterance (MLUw). A correlation analysis was performed between the linguistic variables and tumour characteristics (grade, localisation and volume), treatment related factors, and between the linguistic variables and the language tasks. RESULTS: Pre-operatively, patients produced more Incomplete Sentences than the controls (p < 0.001). Post-operatively, patients’ utterance length (MLUw) (p < 0.05) was also deviant. The quality of the spontaneous speech was influenced by tumour grade and localisation. There was no  influence of tumour volume or treatment-related factors. Pre- and post-operatively, patients’ performance on the naming and the fluency task deviated from normal (p < 0.001). The majority of the linguistic variables did not correlate with the language tasks, pointing to a measurement of distinct linguistic aspects. CONCLUSION: Pre- and post-operatively there was a disorder in naming, category fluency and spontaneous speech, partly influenced by tumour characteristics. A spontaneous speech analysis appeared to be a valuable addition to standardised language tasks. Both measurements are important tools to obtain a complete linguistic profile.

 

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[115]

TÍTULO / TITLE:  - PDGFRA Amplification is Common in Pediatric and Adult High-Grade Astrocytomas and Identifies a Poor Prognostic Group in IDH1 Mutant Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Feb 25. doi: 10.1111/bpa.12043.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12043

AUTORES / AUTHORS:  - Phillips JJ; Aranda D; Ellison DW; Judkins AR; Croul SE; Brat DJ; Ligon KL; Horbinski C; Venneti S; Zadeh G; Santi M; Zhou S; Appin CL; Sioletic S; Sullivan LM; Martinez-Lage M; Robinson AE; Yong WH; Cloughesy T; Lai A; Phillips HS; Marshall R; Mueller S; Haas-Kogan DA; Molinaro AM; Perry A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of California San Francisco, San Francisco, CA; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA; Department of Brain Tumor Research Center, University of California San Francisco, San Francisco, CA.

RESUMEN / SUMMARY:  - High-grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors.  Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)R132H mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.

 

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[116]

TÍTULO / TITLE:  - Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Chem. 2013 Mar 28;56(6):2695-9. doi: 10.1021/jm301782e. Epub 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1021/jm301782e

AUTORES / AUTHORS:  - O’Reilly MC; Scott SA; Brown KA; Oguin TH 3rd; Thomas PG; Daniels JS; Morrison R; Brown HA; Lindsley CW

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and double daggerVanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.

RESUMEN / SUMMARY:  - An iterative parallel synthesis effort identified a PLD2 selective inhibitor, ML298 (PLD1 IC50 > 20 000 nM, PLD2 IC50 = 355 nM) and a dual PLD1/2 inhibitor, ML299 (PLD1 IC50 = 6 nM, PLD2 IC50 = 20 nM). SAR studies revealed that a small structural change (incorporation of a methyl group) increased PLD1 activity within this classically PLD2-preferring core and that the effect was enantiospecific. Both probes decreased invasive migration in U87-MG glioblastoma  cells.

 

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[117]

TÍTULO / TITLE:  - Glioblastoma Resistance to Anti-VEGF Therapy: Has the Challenge Been MET?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Apr 1;19(7):1631-3. doi: 10.1158/1078-0432.CCR-13-0051. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-13-0051

AUTORES / AUTHORS:  - McCarty JH

INSTITUCIÓN / INSTITUTION:  - Author’s Affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - In glioblastoma cells the receptor tyrosine kinase c-Met is upregulated in response to bevacizumab and plays an important role in promoting invasion and tumor recurrence. These data support novel links between VEGF-A and hepatocyte growth factor and suggest that c-Met and its signaling effectors may be effective targets for anti-invasive therapies. Clin Cancer Res; 19(7); 1631-3. ©2013 AACR.

 

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[118]

TÍTULO / TITLE:  - Anaplastic astrocytomas with abundant Rosenthal fibers in elderly patients: A diagnostic pitfall of high-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Feb 25. doi: 10.1111/neup.12025.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12025

AUTORES / AUTHORS:  - Sugita Y; Nakashima S; Ohshima K; Terasaki M; Morioka M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan.

RESUMEN / SUMMARY:  - To investigate the clinicopathological features of anaplastic astrocytoma (AA) with abundant Rosenthal fibers (RFs), this study assessed four cases of AA (elderly patients; age >/=70 years). Histologically, these tumors were composed of diffusely infiltrating astrocytomas with brightly eosinophilic cytoplasmic granules or cork-screw or beaded bundles. Tumor cells showed pleomorphism, bizarre giant cells, and mitotic activity, but no necrosis. The cytoplasmic granules showed negativity on PAS staining. Immunohistochemically, the tumor cells with cytoplasmic granular cells showed a positive reaction for GFAP. The cytoplasmic eosinophilic granules or bundles were positive for alphaB-crystallin, ubiquitin and HSP27. In addition, tumor cells showed strong cytoplasmic positivity for isocitrate dehydrogenase 1 (IDH1)-R132H protein in all cases. The  MIB-l labeling index of these cases ranged from 7% to 10%. In cases 1 and 2, ultrastructurally, the tumor cells had electron-dense, amorphous structures in the cytoplasm and in the processes. These structures were bound to glial intermediate filaments. Based on these microscopic, immunohistochemical and ultrastructural findings, case 1 was diagnosed as AA with abundant, mixed, common type of RFs and miniature (m) RFs, and cases 2,3, and 4 were diagnosed as AA with abundant mRFs. These results indicate that the presence of RFs in astrocytic tumors does not necessarily exclude a diagnosis of high-grade astrocytoma. In addition, AAs with abundant mRFs in elderly patients should be classified as a peculiar variant of AA.

 

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[119]

TÍTULO / TITLE:  - Malignant Emboli on Transcranial Doppler During Carotid Stenting Predict Postprocedure Diffusion-Weighted Imaging Lesions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stroke. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1161/STROKEAHA.111.000659

AUTORES / AUTHORS:  - Almekhlafi MA; Demchuk AM; Mishra S; Bal S; Menon BK; Wiebe S; Clement FM; Wong JH; Hill MD; Goyal M

INSTITUCIÓN / INSTITUTION:  - From the Departments of Clinical Neurosciences.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) has a higher incidence of periprocedural stroke compared with endarterectomy. Identifying CAS  steps with the highest likelihood of embolization may have important implications. We evaluated CAS safety by correlating the findings of procedural transcranial Doppler with postprocedure diffusion-weighted imaging (DWI) lesions. METHODS: In this prospective study, transcranial Doppler monitoring was performed during CAS procedures, which were divided into 11 steps. Embolic signals on transcranial Doppler were counted and classified based on the relative energy index of microembolic signals into microemboli </=1 or malignant macroemboli >1.  Poststenting MRI was performed in all cases. A negative binomial regression model was used to evaluate the predictive value of transcranial Doppler emboli for new  DWI lesions. RESULTS: Thirty subjects were enrolled. Seven of 30 subjects (23.3%) were asymptomatic. The median embolic signal count was 212.5 (108 microemboli and 80 malignant macroemboli). Stent deployment phase showed the highest median embolic signals count at 58, followed by protection device deployment at 30 (P=0.0006). Twenty-four of 30 (80%) had new DWI lesions on post-CAS MRI. The median DWI count was 4 (interquartile range 7). Two of 30 (6.7%) had new or worsening clinical deficits post-CAS. For every malignant embolus, the expected count of DWI lesions increases by 1% ( 95% confidence interval, 0%-2%; P=0.032).  CONCLUSIONS: We observed a high incidence of embolic signals during CAS procedure, especially, when devices were deployed. Most subjects developed new DWI lesions, but only 6.7% had deficits. Malignant macroemboli predicted new DWI  lesions.

 

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[120]

TÍTULO / TITLE:  - Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Rev. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1210/er.2012-1013

AUTORES / AUTHORS:  - Beckers A; Aaltonen LA; Daly AF; Karhu A

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology (A.B., A.F.D.), Centre Hospitalier Universitaire de Liege, University of Liege, 4000 Liege, Belgium; and Genome-Scale Biology Research Program (L.A.A., A.K.), Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00530 Helsinki, Finland.

RESUMEN / SUMMARY:  - Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and  new advances in mouse Aip knockout models demonstrate multiple pathways by which  AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas.

 

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[121]

TÍTULO / TITLE:  - Pilocytic Astrocytoma: A Disease With Evolving Molecular Heterogeneity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Child Neurol. 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0883073813476141

AUTORES / AUTHORS:  - Sadighi Z; Slopis J

INSTITUCIÓN / INSTITUTION:  - 1St. Jude Children’s Research Hospital, Memphis, TN, USA.

RESUMEN / SUMMARY:  - Pilocytic astrocytoma, the most common pediatric brain tumor, is a clinically and molecularly heterogeneous disease that occurs most often in the cerebellum and hypothalamic and chiasmatic regions. Classically, pilocytic astrocytomas are driven by the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Recently described genetic aberrations involving this pathway are critical for tumorigenesis. Tandem duplication of 7q34 encodes BRAF and produces  several KIAA1549-BRAF novel oncogenic fusions. Activating point mutations of BRAF, such as BRAF(V600E), also lead to pilocytic astrocytoma. Loss of the NF1 gene allows hyperactivation of the oncogene KRAS. In this review, we discuss the  current understanding of the novel molecular aberrations described in pilocytic astrocytomas and their clinical relevance for prognosis and treatment. The prognostic indications of these aberrations are discussed with regard to tumor location, tumor pathology, and patient age. A better understanding of the evolving molecular heterogeneity of pilocytic astrocytomas offers hope for developing molecularly targeted therapeutic armamentariums.

 

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[122]

TÍTULO / TITLE:  - Cardiac paraganglioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Am Coll Cardiol. 2013 Mar 7. pii: S0735-1097(13)00931-5. doi: 10.1016/j.jacc.2012.10.061.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jacc.2012.10.061

AUTORES / AUTHORS:  - Xia HM; Jiang Y

INSTITUCIÓN / INSTITUTION:  - Department of Ultrasound, Second Affiliated Hospital, the Third Military Medical  University, Chongqing, 400037 China. Electronic address: digitalheart@163.com.

 

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[123]

TÍTULO / TITLE:  - Double, Synchronous Pituitary Adenomas Causing Acromegaly and Cushing’s Disease.  A Case Report and Review of Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Pathol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12022-013-9237-z

AUTORES / AUTHORS:  - Zielinski G; Maksymowicz M; Podgorski J; Olszewski WT

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Military Institute of Medicine, 128 Szaserow Street., 04-141 Warszawa 44, Warsaw, Poland, gzielinski@wim.mil.pl.

RESUMEN / SUMMARY:  - Double pituitary adenomas are very rare and present up to 1 % of pituitary adenomas in unselected autopsy series and up to 2 % in large surgical series. We  report a case of a 47-year-old man presented slight clinical features of acromegaly with 2 years duration. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia.  Preoperative magnetic resonance imaging of the pituitary demonstrated clearly separated double microadenomas with different intensity. The patient underwent transsphenoidal surgery and both tumors were completely removed and were fixed separately. The histological and ultrastructural examination confirmed coincidence of the double, clearly separated pituitary adenomas in one gland. Postoperative function of the hypothalamo-hypophyseal axis was normalized. We conclude from this case and a literature review that double endocrinologically active pituitary adenomas leading to acromegaly and Cushing’s disease may occur.  Additionally, a review of the literature regarding multiple pituitary adenomas has also been performed.

 

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[124]

TÍTULO / TITLE:  - Four Common Polymorphisms in MicroRNAs and the Risk of Adult Glioma in a Chinese  Case-control Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Mol Neurosci. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12031-013-9980-0

AUTORES / AUTHORS:  - Hu E; Wang D; Zhang X; Li J; Hu Y; Gong H; Liu E

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, First Affiliated Hospital, Harbin Medical University, Number 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, China.

RESUMEN / SUMMARY:  - Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. It has been suggested that four common single nucleotide polymorphisms (SNPs; miR-146aG > C, 149C > T, 196a2C > T, and 499A > G) are associated with susceptibility to numerous malignancies. However, published results are inconsistent and inclusive. To further investigate the role of these loci, we examined the association of the miRNA polymorphisms with the risk of gliomas in a Han population in northeastern China. Both miR-146aG > C and 196a2C > T showed allelic differences between glioma patients and healthy controls in the studied population, with an OR of 1.30 (P = 0.0006) and an odds ratio (OR) of 1.25 (P = 0.003), respectively. Logistic regression analysis also revealed that the 146aG > C and 196a2C > T wild-type homozygous carriers had an increased glioma risk compared to the variant carriers. Besides,  in pairwise comparisons two SNP combinations were associated with the risk of glioma. Among others, carriers of both homozygous risk genotypes, i.e., 146aGG and 196a2CC were associated with a nearly 4-fold increased risk of glioma (OR = 3.77, P = 1.3 x 10(-4)). Overall, glioma risk increased with increasing numbers of risk variant alleles. These results suggest that the miR-146aG > C and 196a2C  > T might influence the risk of developing glioma in a northeastern Han Chinese population.

 

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[125]

TÍTULO / TITLE:  - Similar pyruvate kinase modifications in glioblastoma cells by 7beta-hydroxycholesterol and glutamine withdrawal.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Mar 25. pii: S0006-2952(13)00193-7. doi: 10.1016/j.bcp.2013.03.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.03.012

AUTORES / AUTHORS:  - de Weille J; Fabre C; Gaven C; Bakalara N

INSTITUCIÓN / INSTITUTION:  - Institut des Neurosciences de Montpellier, U1051 INSERM, 80 rue Augustin Fliche,  34295 Montpellier cedex 05, France. Electronic address: Jan.de-Weille@INSERM.fr.

RESUMEN / SUMMARY:  - Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells.  These observations suggested that glycolysis might have been changed. Here we will show that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate. The latter effect is mimicked by glutamine withdrawal.

 

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[126]

TÍTULO / TITLE:  - Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and  risk of glioma: a case-control study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Mar 19;108(5):1189-94. doi: 10.1038/bjc.2013.87. Epub 2013 Feb  28.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.87

AUTORES / AUTHORS:  - Gaist D; Garcia-Rodriguez LA; Sorensen HT; Hallas J; Friis S

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Odense University Hospital, Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Sdr Boulevard 29, Odense C 5000, Denmark.

RESUMEN / SUMMARY:  - Background:Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting.Methods:We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous  use for >/=5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin or of NA-NSAIDs was associated with ORs of 0.80 (95% CI: 0.53-1.21) and 1.11 (0.57-2.17), respectively. We observed no clear patterns of risk in stratified analysis according to estimated doses of low-dose  aspirin (</=100 mg, 150 mg).Conclusion:We did not find any apparent association between aspirin or NA-NSAID use and risk of glioma, although our results may be consistent with a slight reduction in glioma risk with long-term use of low-dose  aspirin.

 

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[127]

TÍTULO / TITLE:  - Transsphenoidal microsurgical results of female patients with prolactinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Mar 13. pii: S0303-8467(13)00069-3. doi: 10.1016/j.clineuro.2013.02.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.02.016

AUTORES / AUTHORS:  - Ikeda H; Watanabe K; Tominaga T; Yoshimoto T

INSTITUCIÓN / INSTITUTION:  - Research Institute for Pituitary Disease, Southern Tohoku General Hospital, Koriyama, Japan. Electronic address: ikeda@nsg.med.tohoku.ac.jp.

RESUMEN / SUMMARY:  - OBJECTIVE: We investigated surgical cure rate and surgical complications of patients with macroprolactinomas who desired pregnancy to evaluate the efficacy of transsphenoidal surgery. METHODS: Surgical cure rate was investigated in 138 female patients who were under 40 years old. RESULTS: We found a significant correlation between serum prolactin levels and adenoma volume (r=0.004; p<0.0001), adenoma volume and age (r=-0.213; p<0.03), and proliferative index of  the adenoma and age (r=-0.15; p<0.007). Seventy-seven out of 81 patients with enclosed macroadenoma were considered cured, and therefore the overall surgical cure rate was 95%. However, during long-term follow-up, recurrence of adenomas with hyperprolactinemia was seen in 5 out of 81 patients (6%), and the long-term  cure rate in patients with enclosed macroadenomas was 89%. Adenomas that did not  invade the cavernous sinus showed a significantly higher surgical curability and  lower serum prolactin levels, and a smaller size than those adenomas that invaded the cavernous sinus. CONCLUSIONS: The long-term surgical cure rate was found to be 89% and this success rate far surpasses the complication rate of 39% during pregnancy by dopamine agonist therapy. Thus, transsphenoidal surgery should be considered as a first-line treatment for female patients who desire pregnancy.

 

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[128]

TÍTULO / TITLE:  - The reliability of topographic measurements from navigated transcranial magnetic  stimulation in healthy volunteers and tumor patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1665-5

AUTORES / AUTHORS:  - Zdunczyk A; Fleischmann R; Schulz J; Vajkoczy P; Picht T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Charite University Hospital, Augustenburger Platz 1,  13353, Berlin, Germany.

RESUMEN / SUMMARY:  - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is increasingly being used for preoperative mapping of the motor cortex. Any new technology should undergo rigorous validation before being widely adopted in routine clinical practice. The aim of this experimental study was to assess the intraexaminer and interexaminer reliability of topographic mapping with nTMS. METHODS: nTMS mapping of the motor cortex for the first dorsal interosseous (FDI) muscle was performed by an expert and a novice examiner, twice in ten healthy volunteers and once in ten tumor patients. The distances between the centers-of-gravity and hotspots were calculated, as were coefficients of variation. This study also compared orthogonal versus variable orientation of the stimulation coil. RESULTS: The mean (range) distance between centers-of-gravity for the expert examiner in the test-retest protocol with healthy volunteers was 4.40 (1.86-7.68) mm. The mean (range) distance between centers-of-gravity for the expert vs. novice examiner was 4.89 (2.39-9.22) mm. There were no significant differences in this result between healthy volunteers and tumor patients. CONCLUSIONS: nTMS is sufficiently reliable for clinical use, but examiners should make efforts to minimize sources of error. The reliability of nTMS in tumor patients appears comparable to healthy subjects.

 

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[129]

TÍTULO / TITLE:  - Maze learning in patients with intracranial arachnoid cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1641-0

AUTORES / AUTHORS:  - Isaksen E; Leet TH; Helland CA; Wester K

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Sciences, University of Bergen, Bergen, Norway, e.isaksen@hotmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: The temporal lobe is of importance for visuospatial orientation. Intracranial arachnoid cysts have a predilection for the temporal fossa, and might therefore affect visuospatial orientation. The aim was to find out whether  temporal cysts affect maze learning and if surgical cyst decompression improves maze performance. METHODS: Forty-five patients with a temporal arachnoid cyst and 17 control patients with cervical disc disease were tested in a labyrinth route in the hospital corridors the day before surgery and at least 3 months postoperatively. RESULTS: Thirty-five cyst patients (78 %) experienced postoperative improvement of their preoperative complaints. The cyst patients spent significantly longer time than the controls navigating through the maze in  the preoperative test, 161 s and 127 s, respectively, but there was no difference in number of errors between the two groups. However, the cyst patients improved significantly in the postoperative test, both with regards to number of errors they made and time spent, contrary to the control patients, whose postoperative performance equalled that of the preoperative test. For the cyst patients, postoperative improvement in the labyrinth test correlated with the clinical outcome-but not the neuroradiological outcome-after the operation. CONCLUSIONS: Thus, temporal arachnoid cysts may affect visuospatial orientation and learning in a reversible manner.

 

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[130]

TÍTULO / TITLE:  - A highly sensitive and specific chemiluminescent enzyme immunoassay for placental alkaline phosphatase in the cerebrospinal fluid of patients with intracranial germinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Neurosurg. 2012;48(3):141-5. doi: 10.1159/000345632. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345632

AUTORES / AUTHORS:  - Watanabe S; Aihara Y; Kikuno A; Sato T; Komoda T; Kubo O; Amano K; Okada Y; Koyamaishi Y

INSTITUCIÓN / INSTITUTION:  - Tokyo PLAP Study Group, Tokyo, Japan.

RESUMEN / SUMMARY:  - Background: Placental alkaline phosphatase (PLAP) in cerebrospinal fluid (CSF) has been proposed as a tumor marker for intracranial germinomas. The purpose of the present study was to develop a sensitive assay for measuring CSF PLAP and to  evaluate the clinical significance of PLAP in patients with germinomas. Methods:  A chemiluminescent enzyme assay for PLAP was developed using an anti-human-PLAP monoclonal antibody. PLAP concentrations were determined in 37 controls, 36 germinomas, 3 nongerminomatous germ cell tumors, 21 gliomas and 12 other brain tumors. Results: The assay detection limit was 5 pg/ml. The median PLAP concentration in the control group was below the detection limit. Significantly higher PLAP levels were detected in all 36 germinoma patients, with values ranging from 16 to 3,700 pg/ml. The high PLAP concentrations of 17 germinoma patients decreased to below the detection limit after complete remission had been achieved with radiochemotherapy. The sensitivity and specificity of PLAP for germinomas were 94 and 97%, respectively, with a cutoff value of 30 pg/ml. Conclusions: The results of this study suggest that the determination of CSF PLAP by the chemiluminescent method described here provides a clinically useful tumor  marker for the diagnosis and monitoring of intracranial germinomas.

 

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[131]

TÍTULO / TITLE:  - Sox21 inhibits glioma progression in vivo by forming complexes with Sox2 and stimulating aberrant differentiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Cancer. 2013 Mar 5. doi: 10.1002/ijc.28147.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28147

AUTORES / AUTHORS:  - Caglayan D; Lundin E; Kastemar M; Westermark B; Ferletta M

INSTITUCIÓN / INSTITUTION:  - Department of Immunology, Genetics and Pathology, Rudbeck laboratory, Uppsala University, Uppsala, Sweden.

RESUMEN / SUMMARY:  - Sox2 is a transcription factor in neural stem cells and keeps the cells immature  and proliferative. Sox2 is expressed in primary human glioma such as glioblastoma multiforme (GBM), primary glioma cells and glioma cell lines and is implicated in signaling pathways in glioma connected to malignancy. Sox21, the counteracting partner of Sox2, has the same expression pattern as Sox2 in glioma but in general induces opposite effects. In this study, Sox21 was overexpressed by using a tetracycline-regulated expression system (tet-on) in glioma cells. The glioma cells were injected subcutaneously into immunodeficient mice. The control tumors  were highly proliferative, contained microvascular proliferation and large necrotic areas typical of human GBM. Induction of Sox21 in the tumor cells resulted in a significant smaller tumor size, and the effect correlated with the  onset of treatment, where earlier treatment gave smaller tumors. Mice injected with glioma cells orthotopically into the brain survived significantly longer when Sox21 expression was induced. Tumors originating from glioma cells with an induced expression of Sox21 exhibited an increased formation of Sox2:Sox21 complexes and an upregulation of S100beta, CNPase and Tuj1. Sox21 appears to decrease the stem-like cell properties of the tumor cells and initiate aberrant differentiation of glioma cells in vivo. Taken together our results indicate that Sox21 can function as a tumor suppressor during gliomagenesis mediated by a shift in the balance between Sox2 and Sox21. The wide distribution of Sox2 and Sox21 in GBM makes the Sox2/Sox21 axis a very interesting target for novel therapy of gliomas.

 

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[132]

TÍTULO / TITLE:  - Successful Treatment of Metastatic Relapse of Medulloblastoma in Childhood With Single Session Stereotactic Radiosurgery: A Report of 3 Cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e3182830fd4

AUTORES / AUTHORS:  - King D; Connolly D; Zaki H; Lee V; Yeomanson D

INSTITUCIÓN / INSTITUTION:  - Departments of *Paediatric Oncology daggerRadiology double daggerNeurosurgical, Sheffield Children’s Hospital NHS Foundation Trust, Western Bank, Sheffield, UK.

RESUMEN / SUMMARY:  - Stereotactic radiosurgery (SRS) is an increasingly used treatment modality in adults, but its use and effectiveness in pediatric brain tumors is still uncertain. We describe 3 patients with metastatic relapse of medulloblastoma, who were treated with SRS, and achieved prolonged, progression-free survival. Tolerability of the treatment was excellent with no adverse effects reported. This work adds to the growing evidence that SRS may have an important role to play in the treatment of pediatric brain tumors.

 

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[133]

TÍTULO / TITLE:  - Longitudinal expression analysis of alphav integrins in human gliomas reveals upregulation of integrin alphavbeta3 as a negative prognostic factor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Mar;72(3):194-210. doi: 10.1097/NEN.0b013e3182851019.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e3182851019

AUTORES / AUTHORS:  - Schittenhelm J; Schwab EI; Sperveslage J; Tatagiba M; Meyermann R; Fend F; Goodman SL; Sipos B

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany. jens.schittenhelm@med.uni-tuebingen.de

RESUMEN / SUMMARY:  - Integrin inhibitors targeting alphav series integrins are being tested for their  therapeutic potential in patients with brain tumors, but pathologic studies have  been limited by lack of antibodies suitable for immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded specimens. We compared the expression of alphav integrins by IHC in brain tumor and normal human brain samples with gene expression data in a public database using new rabbit monoclonal antibodies against alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 complexes using both manual and automated microscopy analyses. Glial tumors usually shared an alphavbeta3-positive/alphavbeta5-positive/alphavbeta8-positive/alphavbeta6-negati ve phenotype. In 94 WHO (World Health Organization) grade II astrocytomas, 85 anaplastic astrocytomas WHO grade III, and 324 glioblastomas from archival sources, expression of integrins generally increased with grade of malignancy. Integrins alphavbeta3 and alphavbeta5 were expressed in many glioma vessels; the  intensity of vascular expression of alphavbeta3 increased with grade of malignancy, whereas alphavbeta8 was absent. Analysis of gene expression in an independent cohort showed a similar increase in integrin expression with tumor grade, particularly of ITGB3 and ITGB8; ITGB6 was not expressed, consistent with  the IHC data. Parenchymal alphavbeta3 expression and ITGB3 gene overexpression in glioblastomas were associated with a poor prognosis, as revealed by survival analysis (Kaplan-Meier logrank, p = 0.016). Together, these data strengthen the rationale for anti-integrin treatment of glial tumors.

 

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[134]

TÍTULO / TITLE:  - Treatment of children with glioblastoma with conformal radiation, temozolomide, and bevacizumab as adjuncts to surgical resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Apr;35(3):e123-6. doi: 10.1097/MPH.0b013e318282cd7f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318282cd7f

AUTORES / AUTHORS:  - Friedman GK; Spiller SE; Harrison DK; Fiveash JB; Reddy AT

INSTITUCIÓN / INSTITUTION:  - Departments of *Pediatrics, Division of Hematology and Oncology daggerPathology double daggerRadiation Oncology, University of Alabama at Birmingham, Birmingham, AL.

RESUMEN / SUMMARY:  - Prognosis for children with glioblastoma is unacceptably poor. Modest improvements in progression-free survival were seen in adults with glioblastoma by combining temozolomide and bevacizumab with conformal radiation. We retrospectively reviewed 3 cases of glioblastoma in children treated using upfront bevacizumab and temozolomide during radiation, followed by 12 cycles of maintenance therapy. All patients completed therapy with minimal toxicity and no  delays in treatment. Two patients remain disease free at 38 and 49 months from diagnosis. One patient recurred 14 months off therapy and currently receives salvage therapy 48 months from diagnosis. These results support further investigation of this regimen.

 

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[135]

TÍTULO / TITLE:  - Pasireotide, a multi-somatostatin receptor ligand with potential efficacy for treatment of pituitary and neuroendocrine tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Drugs Today (Barc). 2013 Feb;49(2):89-103. doi: 10.1358/dot.2013.49.2.1915142.

            ●● Enlace al texto completo (gratuito o de pago) 1358/dot.2013.49.2.1915142

AUTORES / AUTHORS:  - Feelders RA; de Herder WW; Neggers SJ; van der Lely AJ; Hofland LJ

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. r.feelders@erasmusmc.nl

RESUMEN / SUMMARY:  - Somatostatin receptors are an important target for medical treatment of pituitary and neuroendocrine tumors. To date, five somatostatin receptor (sst) subtypes have been identified. The currently available somatostatin analogues octreotide and lanreotide have predominantly affinity for sst. Pasireotide is a sst multireceptor ligand with affinity for sst, sst, sst and sst and this broader binding profile may translate into a higher efficacy with respect to suppression  of hormone production and cell growth in certain tumors. Experimental animal studies and in vitro studies with cultured tumor cells have shown that pasireotide strongly suppresses growth hormone and adrenocorticotropin production. In addition, pasireotide can influence tumor cell growth via effects  on apoptosis and angiogenesis. In this review, the role of somatostatin receptors in pituitary and neuroendocrine tumors is briefly discussed followed by an overview of possible applications of pasireotide based on recent trials in patients with acromegaly, Cushing’s disease and neuroendocrine tumors.

 

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[136]

TÍTULO / TITLE:  - Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Mar;23(2):210-6. doi: 10.1111/bpa.12023.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12023

AUTORES / AUTHORS:  - Fontebasso AM; Liu XY; Sturm D; Jabado N

INSTITUCIÓN / INSTITUTION:  - Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada.

RESUMEN / SUMMARY:  - Primary brain tumors occur in 8 out of 100 000 people and are the leading cause of cancer-related death in children. Among brain tumors, high-grade astrocytomas  (HGAs) including glioblastoma multiforme (GBM) are aggressive and are lethal human cancers. Despite decades of concerted therapeutic efforts, HGAs remain essentially incurable in adults and children. Recent discoveries have revolutionized our understanding of these tumors in children and young adults. Recurrent somatic driver mutations in the tail of histone 3 variant 3 (H3.3), leading to amino acid substitutions at key residues, namely lysine (K) 27 (K27M)  and glycine 34 (G34R/G34V), were identified as a new molecular mechanism in pediatric GBM. These mutations represent the pediatric counterpart of the recurrent mutations in isocitrate dehydrogenases (IDH) identified in young adult  gliomas and provide a much-needed new pathway that can be targeted for therapeutic development. This review will provide an overview of the potential role of these mutations in altering chromatin structure and affecting specific molecular pathways ultimately leading to gliomagenesis. The distinct changes in chromatin structure and the specific downstream events induced by each mutation need characterizing independently if progress is to be made in tackling this devastating cancer.

 

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[137]

TÍTULO / TITLE:  - Oligodendroglioma (WHO grade I) in a young epilepsy patient: A specific entity lying within the spectrum of dysembryoplastic neuroepithelial tumor?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Feb 24. doi: 10.1111/neup.12026.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12026

AUTORES / AUTHORS:  - Takahashi H; Kakita A; Tomikawa M; Okamoto K; Kameyama S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.

RESUMEN / SUMMARY:  - We studied a frontal lobe subcortical cystic tumor that had been resected from a  13-year-old girl with a 3-year history of intractable partial seizure. Currently, more than 13 years after surgery, the patient remains recurrence-free and has no  neurological deficits. Histological examination showed that the tumor was non-infiltrating and paucicellular with a mucinous matrix, and consisted of fairly uniform small cells with round to oval nuclei. Within the mucinous matrix, the tumor cells were often arranged in pseudorosettes around small blood vessels. Mitotic activity and necrosis were absent, with a Ki-67 labeling index of <1%. Based on the immunohistochemical and ultrastructural findings, the constituent tumor cells were considered to be those of oligodendroglioma, including mini-gemistocytes and gliofibrillary oligodendrocytes. No neuronal elements were  identified. Features of cortical dysplasia (FCD Type 1) were evident in the cortex covering the lesion. The surrounding white matter also contained a significant number of ectopic neurons. The entire pathological picture appeared to differ somewhat from that of ordinary oligodendroglioma (WHO grade II). Considering the clinical and pathological features, the present unusual oligodendroglioma appeared to represent a previously undescribed form of oligodendroglioma (WHO grade I) lying within the spectrum of dysembryoplastic neuroepithelial tumor (DNT; WHO grade I). Simultaneously, the present oligodendroglioma also raises the question of whether or not oligodendrocyte-like cells of DNTs truly show neurocytic differentiation.

 

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[138]

TÍTULO / TITLE:  - Optic nerve seeding of atypical meningiomas presenting with subacute visual loss: 2 case reports with genetic characterization.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121533

AUTORES / AUTHORS:  - Kitamura Y; Akiyama T; Sasaki H; Hayashi Y; Yoshida K

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Meningiomas rarely cause CSF dissemination, and CSF seeding to the optic nerve (ON) is extremely rare. This is the first report of 2 cases of atypical meningioma with subacute visual loss due to ON seeding. The authors present the genetic characteristics of these atypical meningiomas with CSF dissemination. The patient in Case 1 was a 36-year-old woman with a 1.5-cm mass within the left ON,  and the patient in Case 2 was a 70-year-old woman with a 0.9-cm mass around the right ON. Both individuals had undergone multiple surgeries for primary lesions and local recurrent lesions. They presented with subacute visual loss, and both tumors were completely resected. The pathological diagnosis was atypical meningioma with high MIB-1 indices and p53-positive cell ratios in each case. Comparative genomic hybridization showed significant chromosomal copy number alterations similar to the results of previous surgeries, confirming that the tumors were disseminated lesions. The present findings suggest that genetic characteristics, such as 1p and 10qcen-23 losses and 17q and 20 gains, shared by  the 2 cases might be associated with CSF dissemination of meningiomas.

 

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[139]

TÍTULO / TITLE:  - Dysembryoplastic Neuroepithelial Tumors Share with Pleomorphic Xanthoastrocytomas and Gangliogliomas BRAF Mutation and Expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Feb 26. doi: 10.1111/bpa.12048.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12048

AUTORES / AUTHORS:  - Chappe C; Padovani L; Scavarda D; Forest F; Nanni-Metellus I; Loundou A; Mercurio S; Fina F; Lena G; Colin C; Figarella-Branger D

INSTITUCIÓN / INSTITUTION:  - INSERM, UMR 911, Marseille, France; Medicine School, Aix-Marseille University, Marseille, France.

RESUMEN / SUMMARY:  - Pediatric cortical glioneuronal benign tumors mainly include gangliogliomas (GG)  [differential diagnoses pilocytic astrocytomas (PA) and pleomorphic xanthoastrocytomas (PXA)] and dysembryoplastic neuroepithelial tumor (DNT). DNT include the specific form and the controversial non-specific form that lack the specific glioneuronal element. Our aims were to search for BRAFV600E mutation and CD34 expression in DNT, PXA, GG and PA to correlate BRAFV600E mutation with BRAFV600E expression and to evaluate their diagnostic and prognostic values. Ninety-six children were included. BRAFV600E mutation was studied by sequencing and immunohistochemistry; CD34 expression was analyzed by immunohistochemistry. BRAFV600E mutation was detected in PXA (60%), GG (38.7%), DNT (30%, including 3/11 specific and 3/9 non-specific forms) and PA (12.5%). BRAFV600E expression was recorded in PXA (60%), GG (45.2%) and DNT (30%). CD34 expression was recorded in PXA (60%), GG (58.1%), DNT (25%) and PA (12.5%). Neither CD34 expression nor BRAFV600E status was predictive of prognosis, except for PA tumors where CD34 expression was associated with a shorter overall survival. In conclusion, DNT shared with PXA and GG, BRAFV600E mutation and/or CD34 expression, which represent molecular markers for these tumors, and we recommend searching for CD34 expression and BRAFV600E mutation in all DNT, especially the non-specific forms.

 

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[140]

TÍTULO / TITLE:  - Encephalocraniocutaneous Lipomatosis: Magnetic Resonance Imaging Findings in a Child.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr. 2013 Feb 26. pii: S0022-3476(13)00115-7. doi: 10.1016/j.jpeds.2013.01.040.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpeds.2013.01.040

AUTORES / AUTHORS:  - Dhouib A; Hanquinet S; La Scala GC

INSTITUCIÓN / INSTITUTION:  - Pediatric Radiology Unit, Department of Radiology, University of Geneva Children’s Hospital, Geneva, Switzerland.

 

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[141]

TÍTULO / TITLE:  - Dopamine D2 receptor activation leads to an up-regulation of glial cell line-derived neurotrophic factor via Gbetagamma-Erk1/2-dependent induction of Zif268.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurochem. 2013 Feb 1. doi: 10.1111/jnc.12178.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jnc.12178

AUTORES / AUTHORS:  - Ahmadiantehrani S; Ron D

INSTITUCIÓN / INSTITUTION:  - Gallo Research Center, Emeryville, California, USA; Graduate Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, California, USA.

RESUMEN / SUMMARY:  - Glial cell line-derived neurotrophic factor (GDNF) is a potent growth factor essential to the development, survival, and function of dopaminergic neurons (Airaksinen and Saarma 2002). The molecular mechanisms underlying GDNF expression remain elusive; thus, we set out to identify a signaling pathway that governs GDNF levels. We found that treatment of both differentiated dopaminergic-like SH-SY5Y cells and rat midbrain slices with the dopamine D2 receptor (D2R) agonist, quinpirole, triggered an increase in the expression of GDNF that was temporally preceded by an increase in the levels of zinc-finger protein 268 (Zif268), a DNA-binding transcription factor encoded by an immediate-early gene.  Moreover, the D2R inhibitor raclopride blocked the increase of both GDNF and Zif268 expression following potassium-evoked dopamine release in SH-SY5Y cells. We used adenoviral delivery of small hairpin RNA (shRNA) targeting Zif268 to down-regulate its expression and found that Zif268 is specifically required for the D2R-mediated up-regulation of GDNF. Furthermore, the D2R-mediated induction of GDNF and Zif268 expression was dependent on Gbetagamma-mediated signaling and  activation of extracellular signal-regulated kinase ½. Importantly, using chromatin immunoprecipitation assay, we identified a direct association of Zif268 with the GDNF promoter. These results suggest that D2R activation induces a Gbetagamma- and extracellular signal-regulated kinase ½-dependent increase in the level of Zif268, which functions to directly up-regulate the expression of GDNF.

 

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[142]

TÍTULO / TITLE:  - Bevacizumab plus irinotecan in recurrent or progressive malign glioma: a multicenter study of the Anatolian Society of Medical Oncology (ASMO).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Clin Oncol. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00432-013-1390-8

AUTORES / AUTHORS:  - Demirci U; Tufan G; Aktas B; Balakan O; Alacacioglu A; Dane F; Engin H; Kaplan MA; Gunaydin Y; Ozdemir NY; Tugba Unek I; Karaca H; Akman T; Sonmez OU; Coskun U; Harputluoglu H; Sevinc A; Tonyali O; Buyukberber S; Benekli M

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Ataturk Training and Research Hospital, Bilkent,  Ankara, 0906800, Turkey, drumutdemirci@gmail.com.

RESUMEN / SUMMARY:  - PURPOSES: The overall prognosis for recurrent malignant glioma (MG) is extremely  poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy. METHODS: A total of 115 patients with grade IV glial tumor (n = 93) and grade III glial tumor (n = 22) were retrospectively evaluated at 14 centers in Turkey. Primary objectives of the study were to evaluate the efficacy and toxicity of the bevacizumab and irinotecan as salvage treatment based on response to therapy, progression-free survival (PFS), 6 months of PFS, overall survival (OS), and 6 months of OS (OS6). RESULTS: Bevacizumab and irinotecan were performed as second line (79.1 %) and third line treatment (20.9 %). Median chemotherapy cycle was 6 (range 1-37), and  median follow-up was 6 months (range 1-36 months). Objective response rate was 39.1 %. Six-month PFS and OS6 were 46.3 % and 67.5 %, respectively. Median PFS was 6 months (95 % CI 2.5-9.5) and 6 months (95 % CI 4.9-7.1) in the grade III and IV groups, respectively (p = 0.773). Median OS was 9 months (95 % CI 7.1-10.9) and 8 months (95 % CI 6.6-9.4) in the grade III and IV groups, respectively (p = 0.450). Serious toxicities were observed in 7.8 % of patients.  Treatment-related toxic death was observed in 3 patients. There was no treatment  related to central nervous system hemorrhage or other serious hemorrhages. CONCLUSIONS: Present study results were consistent with previous studies. In addition, we detected similar outcomes in grade III and IV glial tumors.

 

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[143]

TÍTULO / TITLE:  - Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Apr 1;19(7):1748-59. doi: 10.1158/1078-0432.CCR-12-3066. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3066

AUTORES / AUTHORS:  - Cheng Z; Gong Y; Ma Y; Lu K; Lu X; Pierce LA; Thompson RC; Muller S; Knapp S; Wang J

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Neurological Surgery and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee; Departments of Oncology and Geriatrics, the Second Affiliated Hospital, Department of Oncology,  the First Affiliated Hospital, Nanjing Medical University, Nanjing, China; and Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Oxford, United Kingdom.

RESUMEN / SUMMARY:  - PURPOSE: Glioblastoma is refractory to conventional therapies. The bromodomain and extraterminal domain (BET) proteins are epigenetic readers that selectively bind to acetylated lysine residues on histone tails. These proteins recently emerged as important therapeutic targets in NUT midline carcinoma and several types of hematopoietic cancers. In this study, the therapeutic potential of a novel BET bromodomain inhibitor, JQ1, was assessed in a panel of genetically heterogeneous glioblastoma samples. EXPERIMENTAL DESIGN: The antineoplastic effects of JQ1 were shown using ex vivo cultures derived from primary glioblastoma xenograft lines and surgical specimens of different genetic background. The in vivo efficacy was assessed in orthotopic glioblastoma tumors.  RESULTS: We showed that JQ1 induced marked G1 cell-cycle arrest and apoptosis, which was phenocopied by knockdown of individual BET family members. JQ1 treatment resulted in significant changes in expression of genes that play important roles in glioblastoma such as c-Myc, p21(CIP1/WAF1), hTERT, Bcl-2, and  Bcl-xL. Unlike the observations in some hematopoietic cancer cell lines, exogenous c-Myc did not significantly protect glioblastoma cells against JQ1. In  contrast, ectopically expressed Bcl-xL partially rescued cells from JQ1-induced apoptosis, and knockdown of p21(CIP1/WAF1) attenuated JQ1-induced cell-cycle arrest. Cells genetically engineered for Akt hyperactivation or p53/Rb inactivation did not compromise JQ1 efficacy, suggesting that these frequently mutated signaling pathways may not confer resistance to JQ1. Furthermore, JQ1 significantly repressed growth of orthotopic glioblastoma tumors. CONCLUSION: Our results suggest potentially broad therapeutic use of BET bromodomain inhibitors for treating genetically diverse glioblastoma tumors. Clin Cancer Res; 19(7); 1748-59. ©2013 AACR.

 

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[144]

TÍTULO / TITLE:  - Integrin control of the transforming growth factor-beta pathway in glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain. 2013 Feb;136(Pt 2):564-76. doi: 10.1093/brain/aws351. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1093/brain/aws351

AUTORES / AUTHORS:  - Roth P; Silginer M; Goodman SL; Hasenbach K; Thies S; Maurer G; Schraml P; Tabatabai G; Moch H; Tritschler I; Weller M

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland. patrick.roth@usz.ch

RESUMEN / SUMMARY:  - Transforming growth factor-beta is a central mediator of the malignant phenotype  of glioblastoma, the most common and malignant form of intrinsic brain tumours. Transforming growth factor-beta promotes invasiveness and angiogenesis, maintains cancer cell stemness and induces profound immunosuppression in the host. Integrins regulate cellular adhesion and transmit signals important for cell survival, proliferation, differentiation and motility, and may be involved in the activation of transforming growth factor-beta. We report that alphavbeta3, alphavbeta5 and alphavbeta8 integrins are broadly expressed not only in glioblastoma blood vessels but also in tumour cells. Exposure to alphav, beta3 or beta5 neutralizing antibodies, RNA interference-mediated integrin gene silencing  or pharmacological integrin inhibition using the cyclic RGD peptide EMD 121974 (cilengitide) results in reduced phosphorylation of Smad2 in most glioma cell lines, including glioma-initiating cell lines and reduced transforming growth factor-beta-mediated reporter gene activity, coinciding with reduced transforming growth factor-beta protein levels in the supernatant. Time course experiments indicated that the loss of transforming growth factor-beta bioactivity due to integrin inhibition likely results from two distinct mechanisms: an early effect  on activation of preformed inactive protein, and second, major effect on transforming growth factor-beta gene transcription as confirmed by decreased activity of the transforming growth factor-beta gene promoter and decreased transforming growth factor-beta(1) and transforming growth factor-beta(2) messenger RNA expression levels. In vivo, EMD 121974 (cilengitide), which is currently in late clinical development as an antiangiogenic agent in newly diagnosed glioblastoma, was a weak antagonist of pSmad2 phosphorylation. These results validate integrin inhibition as a promising strategy not only to inhibit  angiogenesis, but also to block transforming growth factor-beta-controlled features of malignancy including invasiveness, stemness and immunosuppression in  human glioblastoma.

 

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[145]

TÍTULO / TITLE:  - MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar 4. doi: 10.3892/ijo.2013.1844.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1844

AUTORES / AUTHORS:  - Niu CS; Yang Y; Cheng CD

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230001, P.R. China.

RESUMEN / SUMMARY:  - MiR-134 is a brain-enriched miRNA that plays an essential role in the development of the embryonic stem cell-orientated differentiation to central nervous system by suppression of Nanog and neural development (including neurons, cylindraxile and dendrites) and has been shown to be downregulated in oligodendrogliomas (ODG) and glioblastomas (GBM), suggesting its possible involvement in brain tumor progression. In this study, we defined the expression and function of miR-134, which we found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR (real-time PCR). Early reports have characterized Nanog as a direct target of miR-134 by a dual-luciferase reporter assay in 293T cells. In our study, overexpression of miR-134 in U87 glioblastoma cells resulted in significant downregulation of Nanog mRNA levels as well as protein levels. miR-134 overexpression reduced the proliferation, invasiveness and migration capability of U87 cells while promoted apoptosis of these cells in vitro and suppressed the  growth of tumor xenografts in vivo. These findings demonstrated that miR-134 deregulation is common in human gliomas. Restoration of its function inhibits cell proliferation, invasion and migration capability and promotes apoptosis, which could be partly due to its inhibitory effect on Nanog protein expression in glioblastoma cells. MiR-134 could play an important role as a tumor suppressor relying on its direct translational attenuation of Nanog.

 

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[146]

TÍTULO / TITLE:  - A comprehensive analysis of 41 patients with rosette-forming glioneuronal tumors  of the fourth ventricle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar;20(3):335-41. doi: 10.1016/j.jocn.2012.09.003. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.09.003

AUTORES / AUTHORS:  - Zhang J; Babu R; McLendon RE; Friedman AH; Adamson C

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Department of Surgery, Duke University Medical Center,  DUMC 2624, Durham, NC 27710, USA.

RESUMEN / SUMMARY:  - The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described, rare, and distinct tumor of the glioneuronal family. The presentation, natural history, and treatment response of these tumors has been unclear as there are no significant series of a sizeable population with long-term follow-up. We report a comprehensive analysis of 41 patients with RGNT  to provide the most current understanding of this rare tumor. Treatment of these  patients has consisted of resection via the transvermian and telovelar approaches, with one patient requiring radiotherapy due to tumor recurrence. Various unique imaging characteristics may allow for the preoperative identification of these tumors. Resection via the telovelar approach should be considered for symptomatic tumors and those that pose a risk of obstructive hydrocephalus. Due to their benign nature and low propensity for recurrence, subtotal resection may be appropriate for those that are adherent to the brainstem. Radiotherapy may be considered for patients with tumor recurrence.

 

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[147]

TÍTULO / TITLE:  - Poly(amido amine) is an ideal carrier of miR-7 for enhancing gene silencing effects on the EGFR pathway in U251 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Apr;29(4):1387-94. doi: 10.3892/or.2013.2283. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2283

AUTORES / AUTHORS:  - Liu X; Li G; Su Z; Jiang Z; Chen L; Wang J; Yu S; Liu Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, PR China.

RESUMEN / SUMMARY:  - microRNAs are regarded as promising drugs for glioma gene therapy. However, conventional administration routes, such as oral administration and intravenous infusion, present low efficiency due to the blood-brain barrier and intercellular retention, thereby limiting their application. Recent studies showed poly(amido amine) (PAMAM) was a candidate carrier due to its high solubilization, delayed release and low toxicity. In the present study, U251 human brain glioma cells were transfected with the miR-7 gene using PAMAM as the vector to determine the transfection efficiency and therapeutic effects in vivo and in vitro. We found that PAMAM exhibited higher transfection efficiency and longer duration of action compared with liposome delivery, and miR-7 efficiently silenced some genes involved in the epidermal growth factor receptor (EGFR) pathway and achieved favorable effects in treating glioma in vivo and in vitro. These investigations provide a basis for developing high-efficiency micromolecular drug delivery.

 

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[148]

TÍTULO / TITLE:  - Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice  With Intracranial Gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Feb 22. pii: S0360-3016(13)00004-7. doi: 10.1016/j.ijrobp.2012.12.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.025

AUTORES / AUTHORS:  - Zeng J; See AP; Phallen J; Jackson CM; Belcaid Z; Ruzevick J; Durham N; Meyer C; Harris TJ; Albesiano E; Pradilla G; Ford E; Wong J; Hammers HJ; Mathios D; Tyler B; Brem H; Tran PT; Pardoll D; Drake CG; Lim M

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins  Medical Institutes, Baltimore, Maryland.

RESUMEN / SUMMARY:  - PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor in  adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to  increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery  in a mouse orthotopic GBM model. METHODS AND MATERIALS: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph  nodes, and spleen. RESULTS: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-gamma+/tumor necrosis factor-alpha+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. CONCLUSIONS: The combination of PD-1 blockade and localized radiation therapy results in long-term survival in mice with orthotopic brain tumors. These studies provide strong preclinical evidence to support combination trials in patients with GBM.

 

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[149]

TÍTULO / TITLE:  - Detection of remote neuronal reactions in the Thalamus and Hippocampus induced by rat glioma using the PET tracer cis-4-[(18)F]fluoro-D-proline.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cereb Blood Flow Metab. 2013 Feb 6. doi: 10.1038/jcbfm.2013.8.

            ●● Enlace al texto completo (gratuito o de pago) 1038/jcbfm.2013.8

AUTORES / AUTHORS:  - Geisler S; Willuweit A; Schroeter M; Zilles K; Hamacher K; Galldiks N; Shah NJ; Coenen HH; Langen KJ

INSTITUCIÓN / INSTITUTION:  - Institute of Neuroscience and Medicine, INM-4-Medical Imaging Physics, Research Centre Julich, Julich, Germany.

RESUMEN / SUMMARY:  - After cerebral ischemia or trauma, secondary neurodegeneration may occur in brain regions remote from the lesion. Little is known about the capacity of cerebral gliomas to induce secondary neurodegeneration. A previous study showed that cis-4-[(18)F]fluoro-D-proline (D-cis-[(18)F]FPro) detects secondary reactions of  thalamic nuclei after cortical infarction with high sensitivity. Here we investigated the potential of D-cis-[(18)F]FPro to detect neuronal reactions in remote brain areas in the F98 rat glioma model using ex vivo autoradiography. Although the tumor tissue of F98 gliomas showed no significant D-cis-[(18)F]FPro  uptake, we observed prominent tracer uptake in 7 of 10 animals in the nuclei of the ipsilateral thalamus, which varied with the specific connectivity with the cortical areas affected by the tumor. In addition, strong D-cis-[(18)F]FPro accumulation was noted in the hippocampal area CA1 in two animals with ipsilateral F98 gliomas involving hippocampal subarea CA3 rostral to that area. Furthermore, focal D-cis-[(18)F]FPro uptake was present in the necrotic center of the tumors. Cis-4-[(18)F]fluoro-D-proline uptake was accompanied by microglial activation in the thalamus, in the hippocampus, and in the necrotic center of the tumors. The data suggest that brain tumors induce secondary neuronal reactions in remote brain areas, which may be detected by positron emission tomography (PET) using D-cis-[(18)F]FPro.Journal of Cerebral Blood Flow & Metabolism advance online publication, 6 February 2013; doi:10.1038/jcbfm.2013.8.

 

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[150]

TÍTULO / TITLE:  - Postoperative ischemic changes following resection of newly diagnosed and recurrent gliomas and their clinical relevance.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):801-8. doi: 10.3171/2012.12.JNS12125. Epub 2013 Feb  1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS12125

AUTORES / AUTHORS:  - Gempt J; Forschler A; Buchmann N; Pape H; Ryang YM; Krieg SM; Zimmer C; Meyer B; Ringel F

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and.

RESUMEN / SUMMARY:  - Object The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve  the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of  newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function. Methods Patients who underwent glioma resection for newly  diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded. Results New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than  in patients with newly diagnosed tumors. Patients with neurological deficits had  a significantly higher rate of ischemic lesions. Conclusions Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

 

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[151]

TÍTULO / TITLE:  - Folate receptor-mediated drug targeting: a possible strategy for nonfunctioning pituitary adenomas?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinology. 2013 Apr;154(4):1387-9. doi: 10.1210/en.2013-1182.

            ●● Enlace al texto completo (gratuito o de pago) 1210/en.2013-1182

AUTORES / AUTHORS:  - Lee M; Pellegata NS

INSTITUCIÓN / INSTITUTION:  - PhD, Helmholtz Zentrum Munchen-German Research Center, for Environmental Health,  Institute of Pathology, Ingolstadter Landstrasse 1, Neuherberg, D-85764, Germany. natalia.pellegata@helmholtz-muenchen.de.

 

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[152]

TÍTULO / TITLE:  - GOLPH3 regulates the migration and invasion of glioma cells though RhoA.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Mar 13. pii: S0006-291X(13)00394-X. doi: 10.1016/j.bbrc.2013.03.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.03.003

AUTORES / AUTHORS:  - Zhou X; Zhan W; Bian W; Hua L; Shi Q; Xie S; Yang D; Li Y; Zhang X; Liu G; Yu R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Lab of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu, China; Key Laboratory of Brain Disease Biology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China. Electronic address: xpzhou@xzmc.edu.cn.

RESUMEN / SUMMARY:  - Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, the biological significance of GOLPH3 in glioma progression remains largely unknown. In this study, we report, for the first time, that downregulation of GOLPH3 led to clear reductions in glioma cell migration and invasion. In addition, downregulation of GOLPH3 inhibited the expression of the small GTPase RhoA as well as cytoskeletal reorganization, which are both required for glioma cell migration. Furthermore, we found that the observed reductions in glioma cell migration and RhoA level could be rescued by RhoA overexpression. Taken together, these results show that  GOLPH3 contributes to the motility of glioma cells by regulating the expression of RhoA.

 

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[153]

TÍTULO / TITLE:  - Cell surface Nestin is a biomarker for glioma stem cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Mar 21. pii: S0006-291X(13)00434-8. doi: 10.1016/j.bbrc.2013.03.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.03.021

AUTORES / AUTHORS:  - Jin X; Jin X; Jung JE; Beck S; Kim H

INSTITUCIÓN / INSTITUTION:  - School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.

RESUMEN / SUMMARY:  - Cancer stem cells (CSCs) are the most aggressive cell type in many malignancies.  Cell surface proteins are generally used to isolate and characterize CSCs. Therefore, the identification of CSC-specific cell surface markers is very important for the diagnosis and treatment of malignancies. We found that Nestin (a type VI intermediate filament protein), like the glioma stem cell (GSC) markers CD133 and CD15, exhibited different levels of expression in primary human glioblastoma specimens. Similar to our previous finding that cytoplasmic Nestin is expressed as a cell surface form in mouse GSCs, the cell surface form of Nestin was also expressed at different levels in human GSCs. We isolated cell surface Nestin-positive cell populations from human GSCs by fluorescence-activated cell sorting FACS analysis, and observed that these populations exhibited robust CSC properties, such as increased tumorsphere-forming ability and tumorsphere size. Mechanistically, we found that  DAPT, a gamma-secretase (a multi-subunit protease complex) inhibitor, reduced the proportion of cell surface Nestin-positive cells in human GSCs in a time- and dose-dependent manner, without significant changes in total Nestin expression, implying that a post-translational modification was involved in the generation of cell surface Nestin. Taken together, our data provides the first evidence that cell surface Nestin may serve as a promising GSC marker for the isolation and characterization of heterogeneous GSCs in glioblastomas.

 

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[154]

TÍTULO / TITLE:  - Advanced Intimal Hyperplasia Without Luminal Narrowing of Leptomeningeal Arteries in CADASIL.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stroke. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1161/STROKEAHA.111.000721

AUTORES / AUTHORS:  - Dong H; Ding H; Young K; Blaivas M; Christensen PJ; Wang MM

INSTITUCIÓN / INSTITUTION:  - From the Departments of Neurology, Pathology, Medicine, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI; Departments of Neurology and Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; and Departments of Medicine and Neurology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: Leptomeningeal artery abnormalities in Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) have not been extensively characterized. We quantified substructure and diameter of leptomeningeal arteries in CADASIL compared with age-matched controls and the very old; in addition, we characterized intimal thickening in CADASIL using immunohistochemistry. METHODS: Frontal and temporal cortex of 6 genetically proven CADASIL brains (average age, 66 years), 6 controls without symptoms of cerebrovascular disease, and 6 very old brains (average age, 89 years) were examined for leptomeningeal artery intimal, medial, and adventitial thickness; inner diameter; and sclerotic index and for smooth muscle markers. RESULTS: The intima of CADASIL arteries was thickened 5-fold compared with controls and the very aged (P<0.0001). Medial thickness was lower in CADASIL compared with controls and the very old (P<0.01). The adventitia was not significantly increased in CADASIL compared with age-matched controls. Arterial diameters were  not smaller in CADASIL compared with controls. Sclerotic index was significantly  increased in CADASIL compared with other groups (P<0.00001). Intimal cells in CADASIL expressed smooth muscle actin, S100A4, and vimentin but not desmin. CONCLUSIONS: Principle changes of leptomeningeal arteries in CADASIL include intimal thickening and medial thinning, but not luminal narrowing. Smooth muscle-like cells participate in neointimal thickening of CADASIL arteries.

 

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[155]

TÍTULO / TITLE:  - Effect of lomeguatrib-temozolomide combination on MGMT promoter methylation and expression in primary glioblastoma tumor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0738-7

AUTORES / AUTHORS:  - Taspinar M; Ilgaz S; Ozdemir M; Ozkan T; Oztuna D; Canpinar H; Rey JA; Sunguroglu A; Castresana JS; Ugur HC

INSTITUCIÓN / INSTITUTION:  - Department of Medical Biology, Ankara University School of Medicine, Ankara, Turkey, mtaspinartr@gmail.com.

RESUMEN / SUMMARY:  - Temozolomide (TMZ) is commonly used in the treatment of glioblastoma (GBM). The MGMT repair enzyme (O 6-methylguanine-DNA methyltransferase) is an important factor causing chemotherapeutic resistance. MGMT prevents the formation of toxic  effects of alkyl adducts by removing them from the DNA. Therefore, MGMT inhibition is an interesting therapeutic approach to circumvent TMZ resistance. The aim of the study was to investigate the effect of the combination of lomeguatrib (an MGMT inactivator) with TMZ, on MGMT expression and methylation. Primary cell cultures were obtained from GBM tumor tissues. The sensitivity of primary GBM cell cultures and GBM cell lines to TMZ, and to the combination of TMZ and lomeguatrib, was determined by a cytotoxicity assay (MTT). MGMT and p53 expression, and MGMT methylation were investigated after drug application. In addition, the proportion of apoptotic cells and DNA fragmentation was analyzed. The combination of TMZ and lomeguatrib in primary GBM cell cultures and glioma cell lines decreased MGMT expression, increased p53 expression, and did not change MGMT methylation. Moreover, apoptosis was induced and DNA fragmentation was increased in cells. In addition, we also showed that lomeguatrib-TMZ combination did not have any effect on the cell cycle. Finally, we determined that the sensitivity of each primary GBM cells and glioma cell lines to the lomeguatrib-TMZ combination was different and significantly associated with the structure of MGMT methylation. Our study suggests that lomeguatrib can be used with TMZ for GBM treatment, although further clinical studies will be needed so as to determine the feasibility of this therapeutic approach.

 

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[156]

TÍTULO / TITLE:  - Adenovirus-mediated expression of BmK CT suppresses growth and invasion of rat C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biotechnol Lett. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10529-013-1167-9

AUTORES / AUTHORS:  - Du J; Fu Y; Wang J; Liang A

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, People’s Republic of China.

RESUMEN / SUMMARY:  - BmK CT, one of the key toxins in the venom of the scorpion, Buthus martensii Karsch, can interact specifically with glioma cells as a chloride channel blocker and inhibit the invasion and migration of those cells via MMP-2. A recombinant adenovirus, Ad-BmK CT, was constructed and characterized by in vitro and in vivo  studies, using MTT cytotoxicity assay and the glioma C6/RFP (red fluorescence protein)/BALB/c allogeneic athymic nude mice model, respectively. The adenovirus-mediated expression of BmK CT displayed a high activity in suppressing rat C6 glioma cells growth and invasion thereby suggesting that this recombinant  adenovirus may be a powerful method for treating glioblastoma.

 

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[157]

TÍTULO / TITLE:  - Dental diagnostic X-ray exposure and risk of benign and malignant brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt016

AUTORES / AUTHORS:  - Lin MC; Lee CF; Lin CL; Wu YC; Wang HE; Chen CL; Sung FC; Kao CH

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, E-DA Hospital, I-Shou University, Kaohsiung.

RESUMEN / SUMMARY:  - BackgroundThis study evaluates the risk of benign brain tumors (BBTs) and malignant brain tumors (MBTs) associated with dental diagnostic X-ray, using a large population-based case-control study.Materials and methodsWe identified 4123 BBT cases and 16 492 controls without BBT (study 1) and 197 MBT cases and 788 controls without MBT (study 2) from Taiwan National Health Insurance claim data.  The risks of both types of tumor were estimated in association with the frequency of received dental diagnostic X-ray.ResultsThe mean ages were approximately 44.2  years in study 1 and 40.6 years in study 2. Multivariable unconditional logistic  regression analysis showed that the risk of BBT increases as the frequency of received dental diagnostic X-ray increases. The BBT odds ratio increased from 1.33 [95% confidence interval (CI) 1.22-1.44] for those with annual mean X-ray examination of less than one to 1.65 (95% CI 1.37-1.98) for those with three or more X-ray examinations, after controlling for comorbidities. No significant association was found between MBTs and dental diagnostic X-ray exposure.ConclusionsExposure to dental diagnostic X-rays in oral and maxillofacial care increases the risk of BBTs, but not MBTs.

 

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[158]

TÍTULO / TITLE:  - Histological Predictors of Outcome in Ependymoma are Dependent on Anatomic Site Within the Central Nervous System.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Mar 4. doi: 10.1111/bpa.12050.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12050

AUTORES / AUTHORS:  - Raghunathan A; Wani K; Armstrong TS; Vera-Bolanos E; Fouladi M; Gilbertson R; Gajjar A; Goldman S; Lehman NL; Metellus P; Mikkelsen T; Necesito-Reyes MJ; Omuro A; Packer RJ; Partap S; Pollack IF; Prados MD; Robins HI; Soffietti R; Wu J; Miller CR; Gilbert MR; Aldape KD

INSTITUCIÓN / INSTITUTION:  - The University of Texas MD Anderson Cancer Center, Houston, TX.

RESUMEN / SUMMARY:  - Ependymomas originate in posterior fossa (PF), supratentorial (ST) or spinal cord (SC) compartments. At present, grading schemes are applied independent of anatomic site. We performed detailed histological examination on 238 World Health Organization grade II and III ependymomas. Among PF ependymomas, the presence of  hypercellular areas, necrosis, microvascular proliferation and elevated mitotic rate (all P < 0.01) were significantly associated with worse progression-free survival (PFS), while extensive ependymal canal formation was not (P = 0.89). Similar to the PF tumors, microvascular proliferation (P = 0.01) and elevated mitotic rate (P = 0.03) were significantly associated with worse PFS in the ST tumors. However, in contrast to PF tumors, extensive ependymal canals (P = 0.03)  were associated with worse clinical outcome in ST ependymomas, but hypercellularity (P = 0.57) and necrosis (P = 0.47) were not. On multivariate Cox regression, after adjusting for relevant clinical variables, individual histological factors and a composite histological score remained significant among ST and PF ependymoma. In contrast to both PF and ST ependymoma, histological features were not found to be associated with PFS in SC tumors. Taken together, the clinical relevance of specific histological features in ependymoma appears to be related to the anatomic site of origin and suggests that site-specific grading criteria be considered in future classification systems.

 

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[159]

TÍTULO / TITLE:  - Inhibition of PI3K/AKT/mTOR pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinology. 2013 Mar;154(3):1247-59. doi: 10.1210/en.2012-1908. Epub 2013 Feb  5.

            ●● Enlace al texto completo (gratuito o de pago) 1210/en.2012-1908

AUTORES / AUTHORS:  - Dai C; Zhang B; Liu X; Ma S; Yang Y; Yao Y; Feng M; Bao X; Li G; Wang J; Guo K; Ma W; Xing B; Lian W; Xiao J; Cai F; Zhang H; Wang R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Peking Union Medical College Hospital, Beijing 100730, China.

RESUMEN / SUMMARY:  - Invasive pituitary adenomas (PAs) are often refractory to standard therapy and salvage treatment with temozolomide (TMZ). Hyperactivation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway contributes to chemotherapy resistance in many cancers. XL765, a novel dual-PI3K/mTOR inhibitor, has recently shown its efficacy as a monotherapy and in combination with conventional therapeutics in many cancers. The hyperactive PI3K/AKT/mTOR pathway frequently occurs in invasive PAs. In this study, we investigated whether XL765 sensitizes PA cells to TMZ in vitro and in vivo. Experiments were carried out to evaluate the effect of XL765 and TMZ alone or in  combination on cell proliferation and apoptosis of PA cell lines (alphaT3-1, GH3, and MMQ) in vitro as well as the tumor growth and serum GH and prolactin secretions in a GH3 xenograft tumor model of female nude mice. XL765 and TMZ synergistically inhibited the growth of PA cell lines and induced apoptosis. Combination of XL765 and TMZ synergistically inhibited tumor growth, decreased serum GH and prolactin levels, and reduced the sacrifice rate of GH3 xenograft tumor models without increased systemic side effects. In addition, XL765 in combination with TMZ dramatically decreased phosphorylation of AKT and mTOR as well as the expression of Bcl-2. The increased expression of cleaved poly (ADP-ribose) polymerase and Bcl-2-associated X protein along with elevated caspase-3/7 activity were also observed in the combination group. Therefore, dual inhibitors of PI3K and mTOR may enhance alkylating agent-mediated cytotoxicity and provide a novel regimen in the treatment of invasive PAs.

 

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[160]

TÍTULO / TITLE:  - Cellular Plasticity Confers Migratory and Invasive Advantages to a Population of  Glioblastoma-initiating Cells that Infiltrate Peritumoral Tissue.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. 2013 Feb 8. doi: 10.1002/stem.1349.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1349

AUTORES / AUTHORS:  - Ruiz-Ontanon P; Orgaz JL; Aldaz B; Elosegui-Artola A; Martino J; Berciano MT; Montero JA; Grande L; Nogueira L; Diaz-Moralli S; Esparis-Ogando A; Vazquez-Barquero A; Lafarga M; Pandiella A; Cascante M; Segura V; Martinez-Climent JA; Sanz-Moreno V; Fernandez-Luna JL

INSTITUCIÓN / INSTITUTION:  - Molecular Genetics Unit, Hospital Universitario Marques de Valdecilla and Instituto de Formacion e Investigacion Marques de Valdecilla (IFIMAV), Av. Cardenal Herrera Oria s/n, 39011 Santander, España.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is associated with infiltration of peritumoral parenchyma by isolated tumor cells that leads to tumor regrowth. Recently, GBM stem-like or initiating cells (GICs) have been identified in the peritumoral (PT) area, but whether these GICs have enhanced migratory and invasive capabilities compared with GICs from the tumor mass ™ is presently unknown. We isolated GICs from the infiltrated PT tissue and the TM of three patients and found that PT cells have an advantage over TM cells in 2D and 3D migration and invasion assays. Interestingly, PT cells display a high plasticity in protrusion formation and cell shape and their migration is insensitive to substrate stiffness, which represent advantages to infiltrate microenvironments of different rigidity. Furthermore, mouse and chicken embryo xenografts revealed that only PT cells showed a dispersed distribution pattern, closely associated to blood vessels. Consistent with cellular plasticity, simultaneous Rac and RhoA activation is required for the enhanced invasive capacity of PT cells. Moreover, Rho GTPase signaling modulators alphaVbeta3 and p27 play key roles in GIC invasiveness. Of note, p27 is upregulated in TM cells and inhibits RhoA activity. Gene silencing of p27 increased the invasive capacity of TM GICs. Additionally, beta3 integrin is upregulated in PT cells. Blockade of dimeric integrin alphaVbeta3, a Rac activator, reduced the invasive capacity of PT GICs in vitro and abrogated the spreading of PT cells into chicken embryos. Thus, our results describe the invasive features acquired by a unique subpopulation of GICs that infiltrate neighbouring tissue.

 

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[161]

TÍTULO / TITLE:  - Mass spectrometric peptide analysis of 2DE-separated mouse spinal cord and rat hippocampus proteins suggests an NGxG motif of importance for in-vivo deamidation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Electrophoresis. 2013 Mar 20. doi: 10.1002/elps.201200682.

            ●● Enlace al texto completo (gratuito o de pago) 1002/elps.201200682

AUTORES / AUTHORS:  - Mikkat S; Kischstein T; Kreutzer M; Glocker MO

INSTITUCIÓN / INSTITUTION:  - Core Facility Proteome Analysis, University Medicine Rostock, Rostock, Germany; Proteome Center Rostock, University Medicine Rostock, Rostock, Germany.

RESUMEN / SUMMARY:  - Asparagine deamidation is a common nonenzymatic posttranslational modification comprising the conversion of asparaginyl residues to aspartyl and isoaspartyl residues, respectively. As a result an additional negative charge is introduced that can affect the tertiary structure as well as the biological activity of a protein. Since deamidation reduces the protein’s pI value, differentially deamidated forms of a protein can be separated in 2D gels. We have analyzed a dataset of 430 protein spots from 2D gels that contained mouse spinal cord proteins and estimated that roughly 10% of the spots in a Coomassie-stained gel derive from in-vivo deamidation at particular asparaginyl residues. Several of the deamidated protein forms, e.g. tropomodulin-2, V-type proton ATPase subunit B, and protein disulfide-isomerase A3 were also found in 2D gels of proteins extracted from rat hippocampus. All identified deamidation sites contained a glycine residue on the carboxyl side of the asparaginyl residue. Strikingly, a second glycine residue at the +3 position was found in the majority of the deamidated peptides. We propose that the NGxG motif confers exceptional susceptibility to in-vivo asparagine deamidation.

 

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[162]

TÍTULO / TITLE:  - NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Drugs. 2013 Apr;24(4):344-54. doi: 10.1097/CAD.0b013e32835ef440.

            ●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835ef440

AUTORES / AUTHORS:  - Lewis KM; Harford-Wright E; Vink R; Ghabriel MN

INSTITUCIÓN / INSTITUTION:  - Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.

RESUMEN / SUMMARY:  - Emend, an NK1 antagonist, and dexamethasone are used to treat complications associated with metastatic brain tumours and their treatment. It has been suggested that these agents exert anticancer effects apart from their current use. The effects of the NK1 antagonists, Emend and N-acetyl-L-tryptophan, and dexamethasone on tumour growth were investigated in vitro and in vivo at clinically relevant doses. For animal experiments, a stereotaxic injection model  of Walker 256 rat breast carcinoma cells into the striatum of Wistar rats was used. Emend treatment led to a decrease in tumour cell viability in vitro, although this effect was not replicated by N-acetyl-L-tryptophan. Dexamethasone did not decrease tumour cell viability in vitro but decreased tumour volume in vivo, likely to be through a reduction in tumour oedema, as indicated by the increase in tumour cell density. None of the agents investigated altered tumour cell replication or apoptosis in vivo. Inoculated animals showed increased glial  fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity indicative of astrocytes and microglia in the peritumoral area,  whereas treatment with Emend and dexamethasone reduced the labelling for both glial cells. These results do not support the hypothesis that NK1 antagonists or  dexamethasone exert a cytotoxic action on tumour cells, although these conclusions may be specific to this model and cell line.

 

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[163]

TÍTULO / TITLE:  - Teaching NeuroImages: Pseudo-abnormal DaTscan findings in meningioma-induced parkinsonism.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurology. 2013 Mar 26;80(13):e147. doi: 10.1212/WNL.0b013e318289709d.

            ●● Enlace al texto completo (gratuito o de pago) 1212/WNL.0b013e318289709d

AUTORES / AUTHORS:  - Erro R; Pappata S; Picillo M; Rocco M; Santangelo G; Barone P; Vitale C

INSTITUCIÓN / INSTITUTION:  - From the University of Naples (R.E., M.P., M.R.), Federico II, Naples; Institute  of Biostructure and Bioimaging (S.P.), CNR, Naples; Istituto di Diagnosi e Cura Hermitage Capodimonte (G.S., P.B., C.V.), Naples; Department of Psychology (G.S.), Second University of Naples, Caserta; University of Salerno (P.B.), Center for Neurodegenerative Diseases, Salerno; and University Parthenope (C.V.), Naples, Italy.

RESUMEN / SUMMARY:  - A 71-year-old man presented with a 6-month history of rest tremor and slowness in his left hand. Apart from mild left parkinsonism, neurologic examination was unremarkable. Because response to l-dopa, up to 600 mg/d, was lacking, [(123)I]FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-[4-iodophenyl]nortropane) SPECT was prescribed with unexpected results: transverse and coronal slices showed the right striatum to be moved upward and medially, suggesting a structural compression rather than degenerative damage (figure). Brain MRI revealed the presence of a frontal meningioma. Caution is required when interpreting DaTscan findings,(1,2) and morphologic imaging should always be performed first.

 

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[164]

TÍTULO / TITLE:  - Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 16. pii: S0304-3835(13)00131-6. doi: 10.1016/j.canlet.2013.02.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.019

AUTORES / AUTHORS:  - Katakowski M; Buller B; Zheng X; Lu Y; Rogers T; Osobamiro O; Shu W; Jiang F; Chopp M

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.

RESUMEN / SUMMARY:  - Exosomes are 30-150nm vesicles secreted by a wide range of mammalian cells that can contain microRNA (miRNA). To test if marrow stromal cell (MSC) exosomes could be used as a vehicle for delivery of anti-tumor miRNAs, we transfected MSCs with  a miR-146b expression plasmid, and harvested exosomes released by the MSCs. Intra-tumor injection of exosomes derived from miR-146-expressing MSCs significantly reduced glioma xenograft growth in a rat model of primary brain tumor.

 

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[165]

TÍTULO / TITLE:  - mTORC1 Inhibitors Suppress Meningioma Growth in Mouse Models.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Mar 1;19(5):1180-9. doi: 10.1158/1078-0432.CCR-12-1904. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-1904

AUTORES / AUTHORS:  - Pachow D; Andrae N; Kliese N; Angenstein F; Stork O; Wilisch-Neumann A; Kirches E; Mawrin C

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Neuropathology and Genetics & Molecular Neurobiology, Institute of Biology, Otto-von-Guericke University; and Laboratory  for Non-Invasive Imaging, Leibniz Institute for Neurobiology, Magdeburg, Germany.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the mTORC1 (mammalian target of rapamycin complex 1) pathway in meningiomas and to explore mTORC1 as a therapeutic target in meningioma cell lines and mouse models. EXPERIMENTAL DESIGN: Tissue microarrays (53 meningiomas of all WHO grades) were stained for phosphorylated polypeptides of mTOR, Akt, and the mTORC1 targets 4EBP1 and p70S6K, the latter being the consensus marker for mTORC1 activity. Expression of proteins and mRNAs was assessed by Western blotting and real-time PCR in 25 tumors. Cell lines Ben-Men-1 (benign), IOMM-Lee  and KT21 (malignant), and pairs of merlin-positive or -negative meningioma cells  were used to assess sensitivity toward mTORC1 inhibitors in methyl-tetrazolium and bromodeoxyuridine (BrdUrd) assays. The effect of temsirolimus (20 mg/kg daily) on tumor weight or MRI-estimated tumor volume was tested by treatment of eight nude mice (vs. 7 controls) carrying subcutaneous IOMM-Lee xenografts, or of eight (5) mice xenotransplanted intracranially with IOMM-Lee (KT21) cells in comparison to eight (5) untreated controls. RESULTS: All components of the mTORC1 pathway were expressed and activated in meningiomas, independent of their WHO grade. A significant dosage-dependent growth inhibition by temsirolimus and everolimus was observed in all cell lines. It was slightly diminished by merlin loss. In the orthotopic and subcutaneous xenograft models, temsirolimus treatment resulted in about 70% growth reduction of tumors (P < 0.01), which was paralleled by reduction of Ki67 mitotic index (P < 0.05) and reduction of mTORC1 activity (p70S6K phosphorylation) within the tumors. CONCLUSION: mTORC1 inhibitors suppress meningioma growth in mouse models, although the present study did not measure survival. Clin Cancer Res; 19(5); 1180-9. ©2012 AACR.

 

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[166]

TÍTULO / TITLE:  - Gene expression changes associated with erlotinib response in glioma cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Jan 29. pii: S0959-8049(13)00006-3. doi: 10.1016/j.ejca.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.002

AUTORES / AUTHORS:  - Garcia-Claver A; Lorente M; Mur P; Campos-Martin Y; Mollejo M; Velasco G; Melendez B

INSTITUCIÓN / INSTITUTION:  - Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, España.

RESUMEN / SUMMARY:  - Erlotinib (ERL), a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR), is used as a second line treatment for glioma therapy, with controversial findings regarding its response. Here, we analysed the gene expression profiles of a series of human glioma cell lines with differing sensitivities to ERL to identify the gene expression changes associated with ERL  response. The varying responses to ERL were associated with different expression  levels of specific genes (HRAS, CTFG, ERCC5 and HDAC3) and genes associated with  specific pathways (apoptosis and cell death). PI3K pathway genes were primarily affected by ERL, as we found that PIK3R3 was repressed by ERL treatment in sensitive glioma cell lines. The cell cycle and ubiquitin pathways were also affected by EGFR inhibition, as GAS5, PLK1 and BIRC5 were the most significantly  affected genes. In this study we have identified several genes such as PIK3R3 and GAS5, that can be targeted in order to enhance the response to ERL therapy.

 

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[167]

TÍTULO / TITLE:  - Pituitary tumor-transforming gene 1 as a proliferation marker lacking prognostic  value in cutaneous squamous cell carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Dermatol. 2013 Feb 15. doi: 10.1111/exd.12118.

            ●● Enlace al texto completo (gratuito o de pago) 1111/exd.12118

AUTORES / AUTHORS:  - Ishitsuka Y; Kawachi Y; Taguchi S; Maruyama H; Nakamura Y; Fujisawa Y; Furuta JI; Nakamura Y; Ishii Y; Otsuka F

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.

RESUMEN / SUMMARY:  - Non-melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto-oncogenes and tumor suppressor genes. The proto-oncogene pituitary tumor-transforming gene 1 (PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas (SCC), actinic keratoses (AK) and Bowen’s disease (BD). Expression levels of PTTG1 were  compared among these disease groups to test for correlations with proliferation,  differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC.

 

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[168]

TÍTULO / TITLE:  - Mechanisms of intracerebral lymphoma growth delineated in a syngeneic mouse model of central nervous system lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Apr;72(4):325-36. doi: 10.1097/NEN.0b013e31828b7a98.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e31828b7a98

AUTORES / AUTHORS:  - Montesinos-Rongen M; Sanchez-Ruiz M; Brunn A; Hong K; Bens S; Perales SR; Cigudosa JC; Siebert R; Deckert M

INSTITUCIÓN / INSTITUTION:  - From the Institute for Neuropathology, University Hospital of Cologne, Cologne (MM-R, MS-R, AB, KH, MD); and Institute for Human Genetics, Christian-Albrechts-University Kiel (SB, RS); and University Hospital Schleswig Holstein, Campus Kiel, Kiel (SB, RS), Germany; and Molecular Cytogenetics Group,  Centro Nacional de Investigaciones Oncologicas, Madrid, España (SRP, JCC).

RESUMEN / SUMMARY:  - Primary lymphoma of the central nervous system (PCNSL) is defined as lymphoma of  the diffuse large B-cell type confined to the CNS. To understand the effects of the CNS microenvironment on the malignant B cells and their interactions with the cells of the target organ, we analyzed a syngeneic mouse model. Transplantation of BAL17 cells into the frontal white matter of syngeneic BALB/c mice induced lymphomas with major clinical and neuropathologic features that parallel those of human PCNSL, including an angiocentric growth pattern in the brain parenchyma and tropism for the inner and outer ventricular system. Seven cycles of repeated isolation of lymphoma cells from the CNS and their intracerebral reimplantation induced genotypic and phenotypic alterations in resulting BAL17VII cells; the affected genes regulate apoptosis and are of the JAK/STAT pathway. Because lymphoma growth of BAL17VII cells was significantly accelerated, that is, shortening the time to death of the mice, these data indicate that prolonged stay of the lymphoma cells in the CNS was associated with worse outcome. These findings suggest that the CNS microenvironment fosters aggressiveness of lymphoma cells, thereby accelerating the lethal course of PCNSL.

 

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[169]

TÍTULO / TITLE:  - Pleomorphic xanthoastrocytoma: Long-term results of surgical treatment and analysis of prognostic factors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.776666

AUTORES / AUTHORS:  - Gallo P; Cecchi PC; Locatelli F; Rizzo P; Ghimenton C; Gerosa M; Pinna G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital , Verona , Italy.

RESUMEN / SUMMARY:  - Background. Pleomorphic Xanthoastrocytoma (PXA) is a rare brain tumour, most commonly affecting children and young adults. To date, only few data regarding the long-term follow-up of these patients after surgery are available. The aim of this study is to describe our single-institution experience in the surgical management of this particular glioma over a period of over 18 years. Methods. We  performed a retrospective review of all cases of PXA (40 patients) operated upon  at the Department of Neurosurgery of Verona, Italy, between 1990 and 2008. The impact of clinical, radiological, surgical and histological factors on overall survival (OS) and progression-free survival (PFS) was analysed by means of univariate and multivariate models. Findings. We achieved a gross total resection (GTR) in 65% of patients. Histological diagnosis was of grade II in 80%; anaplastic features were present in the remaining 20%. Adjuvant treatment, radiotherapy or chemo-radiotherapy, was administered in 40% of the cases. Median  follow-up was 74 months. OS at 5- and 10 years was 76.32% and 68.24%, respectively. PFS at 5- and 10 years was 71% and 58%, respectively. In the multivariate model, histological grade, extent of resection and age at diagnosis  (</= 30 years vs > 30 years) were the only independent prognostic factors for both OS and PFS. Conclusions. Our retrospective long-term study confirms the relatively favourable prognosis associated with PXA. Young patients with a low-grade tumour (WHO grade II) who underwent GTR carry the longest OS and PFS.

 

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[170]

TÍTULO / TITLE:  - Histone 3 Lysine 9 Trimethylation Is Differentially Associated With Isocitrate Dehydrogenase Mutations in Oligodendrogliomas and High-Grade Astrocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Apr;72(4):298-306.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e3182898113

AUTORES / AUTHORS:  - Venneti S; Felicella MM; Coyne T; Phillips JJ; Gorovets D; Huse JT; Kofler J; Lu C; Tihan T; Sullivan LM; Santi M; Judkins AR; Perry A; Thompson CB

INSTITUCIÓN / INSTITUTION:  - From the Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York (SV, DG, JTH, CL, CBT); Department of Pathology, University of California, San Francisco, California (MMF, JJP, TT, AP); Departments of Pathology and Laboratory Medicine (TC), and Cancer Biology (CL), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology,  University of Pittsburgh, Pittsburgh, Pennsylvania (JK); Department of Pathology, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania (LMS, MS); Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern  California, Los Angeles, California (ARJ).

RESUMEN / SUMMARY:  - Trimethylation of histone 3 lysine 9 (H3K9me3) is a marker of repressed transcription. Cells transfected with mutant isocitrate dehydrogenase (IDH) show  increased methylation of histone lysine residues, including H3K9me3, because of inhibition of histone demethylases by 2-hydroxyglutarate. Here, we evaluated H3K9me3 and its association with IDH mutations in 284 gliomas. Trimethylation of  H3K9 was significantly associated with IDH mutations in oligodendrogliomas. Moreover, 72% of World Health Organization grade II and 65% of grade III oligodendrogliomas showed combined H3K9me3 positivity and 1p19q codeletion. In astrocytic tumors, H3K9me3 positivity was found in all grades of tumors; it showed a significant relationship with IDH mutational status in grade II astrocytomas but not in grade III astrocytomas or glioblastomas. Finally, H3K9me3-positive grade II oligodendrogliomas, but not other tumor subtypes, showed improved overall survival compared with H3K9me3-negative cases. These results suggest that repressive trimethylation of H3K9 in gliomas may occur in a  context-dependent manner and is associated with IDH mutations in oligodendrogliomas but may be differently regulated in high-grade astrocytic tumors. Furthermore, H3K9me3 may define a subset of grade II oligodendrogliomas with better overall survival. Our results suggest variable roles for IDH mutations in the pathogenesis of oligodendrogliomas versus astrocytic tumors.

 

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[171]

TÍTULO / TITLE:  - Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Virol. 2013 May;57(1):36-42. doi: 10.1016/j.jcv.2012.12.018. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcv.2012.12.018

AUTORES / AUTHORS:  - Rahbar A; Orrego A; Peredo I; Dzabic M; Wolmer-Solberg N; Straat K; Stragliotto G; Soderberg-Naucler C

INSTITUCIÓN / INSTITUTION:  - Department of Medicine Solna, Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.

RESUMEN / SUMMARY:  - BACKGROUND: Patients with glioblastoma multiforme (GBM) generally live 12-15 months after diagnosis, despite maximal surgical resection, adjuvant radiotherapy, and chemotherapy. HCMV has been detected in 90-100% of GBMs. We recently found that low grade HCMV infection in GBM tumours was highly associated with survival over 18 months (case-control study). Here, we sought to determine whether low-grade HCMV infection in GBMs is associated with prolonged survival in a consecutive patient cohort, analysed retrospectively. STUDY DESIGN: Tumour samples from 75 consecutive GBM patients treated surgically at Karolinska University Hospital in 2004-2005 were examined by immunohistochemistry (IHC) and  in situ hybridization for HCMV proteins and DNA, respectively. Tumours were graded 1-4, depending on the percentage of positive cells by IHC. Low-grade HCMV  was defined as grade 1 (<25% of HCMV infected tumour cells). Time to tumour progression (TTP) and survival data were analysed with Cox regression and Kaplan-Meier models. RESULTS: HCMV infection was detected in 74 of 75 tumours (99%). In patients with low-grade HCMV infection, median survival was 20 months longer than in patients with high-grade infections (P=0.036, HR: 2.2), and TTP was 8 months longer (P=0.1, HR: 1.8). Two-year survival was much higher in patients with low-grade HCMV infection (63.6% vs. 17.2%, P=0.003). CONCLUSION: The longer survival in patients whose tumours had low-grade HCMV infection suggests that the level of HCMV infection in GBMs has a prognostic value and that HCMV may contribute to the pathogenesis of GBM.

 

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[172]

TÍTULO / TITLE:  - Interstitial brachytherapy with iodine-125 seeds for low grade brain stem gliomas in adults: Diagnostic and therapeutic intervention in a one-step procedure.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb 25. pii: S0303-8467(13)00039-5. doi: 10.1016/j.clineuro.2013.01.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.01.012

AUTORES / AUTHORS:  - Lopez WO; Trippel M; Doostkam S; Reithmeier T

INSTITUCIÓN / INSTITUTION:  - Division of Stereotactic Neurosurgery, Department of General Neurosurgery, University Medical Center Freiburg, Freiburg, Germany. Electronic address: william.contreras@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - PURPOSE: To report on iodine-125 (I125) interstitial irradiation in the treatment of low grade brain stem gliomas in adults. PATIENTS AND METHODS: Ten patients with well-circumscribed lesions of the brainstem and histological confirmation of low grade glioma treated with stereotactically implanted I-125 seed in our department between 1995 and 2012 were retrospectively analyzed. RESULTS: In 9 patients the lesion was treated with one I-125 seed and in one patient, 2 spatial separated lesions were implanted, therefore a total of 11 I-125 seeds were implanted. The mean volume of the 11 lesions was 2.76ml (range: 0.5-7.2ml), mean  activity of the seeds was 6.23mCi (range: 1.5-11.1mCi), mean duration of irradiation was 28.5 days (range: 21-41 days) and mean effective dose rate was 9.16cGy/h (range: 6.2-12cGy/h). The 30 days perioperative morbidity and mortality rate was 0%. Median follow up was 72.5 month (range 5-168 months). Six of ten patients were free of progression until last follow up. CONCLUSION: In our experience at the University Clinic in Freiburg Germany, interstitial radiosurgery based on MRI is a safe and effective method to diagnose and treat low grade gliomas of the brain stem. Furthermore randomized studies are needed to confirm the therapeutic impact of this method in comparison to external beam radiation of brain stem gliomas.

 

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[173]

TÍTULO / TITLE:  - Combined temozolomide and sunitinib treatment leads to better tumour control but  increased vascular resistance in O-methylguanine methyltransferase-methylated gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Mar 14. pii: S0959-8049(13)00149-4. doi: 10.1016/j.ejca.2013.02.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.019

AUTORES / AUTHORS:  - Czabanka M; Bruenner J; Parmaksiz G; Broggini T; Topalovic M; Bayerl SH; Auf G; Kremenetskaia I; Nieminen M; Jabouille A; Mueller S; Harms U; Harms C; Koch A; Heppner FL; Vajkoczy P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Universitatsmedizin Charite, Berlin, Germany.

RESUMEN / SUMMARY:  - INTRODUCTION: Combined antiangiogenic and cytotoxic treatment represents an appealing treatment approach for malignant glioma. In this study we characterised the antitumoural and microvascular consequences of sunitinib (Su) and temozolomide (TMZ) therapy and verified the ideal treatment protocol, with special focus on a potential therapeutic window for combined scheduling. MATERIALS AND METHODS: O6-Methylguanine methyltransferase (MGMT) status was analysed by pyrosequencing. Tumour growth of subcutaneous xenografts was assessed under different treatment protocols (TMZ, SU, SU followed by TMZ, TMZ followed by SU, combined TMZ/SU). Intravital microscopy (dorsal skinfold chamber model) assessed microvascular consequences. Immunohistochemistry included tumour and endothelial cell proliferation, apoptosis and vascular pericyte coverage. Real-time polymerase chain reaction (RT-PCR) analysed the expression of angiogenesis-related pathways in response to therapy. RESULTS: Combined TMZ/SU resulted in significantly reduced tumour growth compared to either monotreatment  (TMZ: 106+/-13mm3; SU: 114+/-53mm3; TMZ/SU: 34+/-7mm3) by additional antiangiogenic effects and synergistic induction of apoptosis versus TMZ monotreatment. Sequential treatment protocols did not show additive antitumour responses. TMZ/SU aggravated vascular resistance mechanisms characterised by significantly higher blood flow rate (TMZ: 74+/-34mul/s; SU: 164+/-36mul/s; TMZ/SU: 254+/-95mul/s), reduced permeability (TMZ: 1.05+/-0.02; SU: 0.99+/-0.07;  TMZ/SU: 0.89+/-0.05) and recovery of pericyte-endothelial interactions (TMZ: 89+/-7%; SU: 67+/-9%, TMZ/SU:80+/-10%) versus either monotreatment. Vascular resistance was paralleled by an increase in Ang-1 and Tie-2 and by the downregulation of Dll4. CONCLUSION: Sequential application of TMZ and SU in the angiogenic window does not add antitumour efficacy to monotherapy. Simultaneous application yields beneficial tumour control due to additive antiangiogenic and proapoptotic effects. Combined treatment may aggravate pericyte-mediated vascular resistance mechanisms by altering Ang-1-Tie-2 and Dll4/Notch pathways.

 

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[174]

TÍTULO / TITLE:  - Bcl-2 proapoptotic proteins distribution in U-87 MG glioma cells before and after hypericin photodynamic action.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Gen Physiol Biophys. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 4149/gpb_2013021

AUTORES / AUTHORS:  - Balogova L; Maslanakova M; Dzurova L; Miskovsky P; Stroffekova K

INSTITUCIÓN / INSTITUTION:  - Department of Biophysic, Institute of Physical Sciences, P. J. Safarik University, Kosice, Slovak Republic.

RESUMEN / SUMMARY:  - Apoptosis is a key process in the development and maintenance of tissue homeostasis. This process of controlled cell death is tightly regulated by a balance between cell survival and damage signals. We focused our attention towards one apoptotic pathway, the intrinsic mitochondrial one where Bcl-2 family of proteins plays the major role. We are particularly interested in two pro-apoptotic players Bak and Bax from this family. Here we investigated their role in apoptosis triggered by photodynamic action. Targeted photodynamic therapy (PDT) is a promising approach to diagnose and treat different types of cancer. We show the localization of Bax and Bak in U-87 MG human glioma cells incubated with photosensitizer hypericin (Hyp) before and after photodynamic action. Apoptotic stimulus by Hyp photodynamic action causes Bax translocation into mitochondria. However our results suggest that under these conditions there are two populations of mitochondria: one which contains Bax and Bak simultaneously, and is almost exclusively localized near the plasma membrane; the other which contains Bax only and is distributed throughout the cell. The different protein content and spatial distribution of these two populations suggest that they can play different roles  in response to apoptotic stimuli.

 

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[175]

TÍTULO / TITLE:  - Retrospective analysis of treatment outcome of pediatric ependymomas in Korea: analysis of Korean multi-institutional data.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1087-5

AUTORES / AUTHORS:  - Kim YJ; Kim JY; Lim DH; Park HJ; Joo J; Sung KW; Shin HJ; Kim SK; Phi JH; Kim IH; Park KD; Ahn SD; Jung J; Rha YS; Kim DS; Suh CO

INSTITUCIÓN / INSTITUTION:  - Research Institute and Hospital, National Cancer Center, Goyang, South Korea.

RESUMEN / SUMMARY:  - We analyzed the treatment outcomes of intracranial ependymomas in Korean children aged <18 years. Data for 96 patients were collected from five hospitals. Survival rates were calculated using the Kaplan-Meier method. Log-rank tests for univariate analyses and Cox regression model for multivariate analysis were conducted to identify prognostic factors for survival. The median age of the patients was 4 years (range, 0.3-17.9 years). The median follow-up was 55 months  (range, 2-343 months). Age <3 years was an important factor for selecting adjuvant therapy after surgery. Among children aged <3 and >/=3 years, adjuvant radiotherapy (RT) was applied to 55 and 84 %, respectively, and adjuvant chemotherapy to 52 and 10 %, respectively. The 5 year local progression-free survival (LPFS), disease-free survival (DFS), and overall survival (OS) rates were 54, 52, and 79 %, respectively. Gross total resection was the most significant prognostic factor for all survival endpoints. Age >/=3 years and RT were significant prognostic factors for superior LPFS and DFS. However, the significance of age was lost in multivariate analysis for DFS. LPFS, DFS, and OS  were superior in patients who started RT within 44 days after surgery (the median time) than in patients who started RT later in the patients aged >/=3 years. Postoperative RT was a strong prognostic factor for intracranial ependymomas. Our results suggest that early use of RT is an essential component of treatment, and  should be considered in young children.

 

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[176]

TÍTULO / TITLE:  - Evaluation of Histone 3 Lysine 27 Trimethylation (H3K27me3) and Enhancer of Zest  2 (EZH2) in Pediatric Glial and Glioneuronal Tumors Shows Decreased H3K27me3 in H3F3A K27M Mutant Glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Feb 18. doi: 10.1111/bpa.12042.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12042

AUTORES / AUTHORS:  - Venneti S; Garimella MT; Sullivan LM; Martinez D; Huse JT; Heguy A; Santi M; Thompson CB; Judkins AR

INSTITUCIÓN / INSTITUTION:  - Cancer biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New  York, NY.

RESUMEN / SUMMARY:  - H3F3A mutations are seen in approximately 30% of pediatric glioblastoma (GBMs) and involve either the lysine residue at position 27 (K27M) or glycine at position 34 (G34R/V). Sixteen genes encode histone H3, each variant differing in  only a few amino acids. Therefore, how mutations in a single H3 gene contribute to carcinogenesis is unknown. H3F3A K27M mutations are predicted to alter methylation of H3K27. H3K27me3 is a repressive mark critical to stem cell maintenance and is mediated by EZH2, a member of the polycomb-group (PcG) family. We evaluated H3K27me3 and EZH2 expression using immunohistochemistry in 76 pediatric brain tumors. H3K27me3 was lowered/absent in tumor cells but preserved  in endothelial cells and infiltrating lymphocytes in six out of 20 GBMs. H3K27me3 showed strong immunoreactivity in all other tumor subtypes. Sequencing of GBMs showed H3F3A K27M mutations in all six cases with lowered/absent H3K27me3. EZH2 expression was high in GBMs, but absent/focal in other tumors. However, no significant differences in EZH2 expression were observed between H3F3A K27M mutant and wild type GBMs, suggesting that EZH2 mediated trimethylation of H3K27  is inhibited in GBM harboring K27M mutations. Our results indicate that H3F3A K27M mutant GBMs show decreased H3K27me3 that may be of both diagnostic and biological relevance.

 

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[177]

TÍTULO / TITLE:  - Bereaved Parents’ Intentions and Suggestions about Research Autopsies in Children with Lethal Brain Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr. 2013 Feb 19. pii: S0022-3476(13)00039-5. doi: 10.1016/j.jpeds.2013.01.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpeds.2013.01.015

AUTORES / AUTHORS:  - Baker JN; Windham JA; Hinds PS; Gattuso JS; Mandrell B; Gajjar P; West NK; Hammarback T; Broniscer A

INSTITUCIÓN / INSTITUTION:  - Division of Quality of Life and Palliative Care, Departments of Pediatric Medicine and Oncology, St. Jude Children’s Research Hospital, Memphis, TN. Electronic address: justin.baker@stjude.org.

RESUMEN / SUMMARY:  - OBJECTIVE: To determine bereaved parents’ perceptions about participating in autopsy-related research and to elucidate their suggestions about how to improve  the process. STUDY DESIGN: A prospective multicenter study was conducted to collect tumor tissue by autopsy of children with diffuse intrinsic pontine glioma. In the study, parents completed a questionnaire after their child’s death to describe the purpose for, hopes (ie, desired outcomes of), and regrets about their participation in autopsy-related research. Parents also suggested ways to improve autopsy-related discussions. A semantic content analytic method was used  to analyze responses and identify themes within and across parent responses. RESULTS: Responses from 33 parents indicated that the main reasons for participating in this study were to advance medical knowledge or find a cure, a desire to help others, and choosing as their child would want. Parents hoped that participation would help others or help find a cure as well as provide closure. Providing education/anticipatory guidance and having a trusted professional sensitively broach the topic of autopsy were suggestions to improve autopsy discussions. All parents felt that study participation was the right decision, and none regretted it; 91% agreed that they would make the choice again. CONCLUSION: Because autopsy can help advance scientific understanding of the disease itself and because parents reported having no regret and even cited benefits, researchers should be encouraged to continue autopsy-related research.  Parental perceptions about such studies should be evaluated in other types of pediatric diseases.

 

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[178]

TÍTULO / TITLE:  - Modern surgical outcomes following surgery for sphenoid wing meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS11539

AUTORES / AUTHORS:  - Sughrue ME; Rutkowski MJ; Chen CJ; Shangari G; Kane AJ; Parsa AT; Berger MS; McDermott MW

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California.

RESUMEN / SUMMARY:  - Object Cushing and Eisenhardt were the first to describe sphenoid wing meningiomas in detail, categorizing globoid tumors into 3 groups: 1) medial; 2) middle; and 3) lateral. The authors review their experience with resection of sphenoid wing meningiomas at a single center, to examine whether this classification predicts clinical presentation and postsurgical outcome. Methods All patients undergoing resection of sphenoid wing meningioma at the authors’ institution over a 9-year period were identified. Clinical data were compared from patients with tumors arising at different points along the sphenoid wing to  determine if these tumors behaved differently in terms of symptoms, radiographic  characteristics, and postsurgical outcome. Results A total of 56 patients underwent microsurgical resection for sphenoid wing meningioma during this period. The rates of optic canal invasion (medial 50% vs middle 5% vs lateral 0%; p < 0.0001, chi-square test), supraclinoid internal carotid artery encasement (medial 32% vs middle 5% vs lateral 0%; p < 0.01, chi-square test), and middle cerebral artery encasement (medial 45% vs middle 24% vs lateral 0%; p < 0.01, chi-square test) were all highest with medial-third tumors. New or worsened neurological deficits occurred in 10 (19%) of 56 patients. Of all the imaging characteristics studied, only location of the tumor along the medial third of the sphenoid wing significantly predicted an increased rate of new or worsened neurological deficit (OR 2.7, p < 0.05). Conclusions The authors report outcomes  in a large series of sphenoid wing meningiomas that were treated using modern surgical techniques.

 

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[179]

TÍTULO / TITLE:  - HER2-positive breast cancer metastatic to intracranial meningioma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Pathol. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2013-201455

AUTORES / AUTHORS:  - McCormack M; Salinas-La Rosa C; Murphy M; Fox SB

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.

 

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[180]

TÍTULO / TITLE:  - Ultrasound-sensitive siRNA-loaded nanobubbles formed by hetero-assembly of polymeric micelles and liposomes and their therapeutic effect in gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomaterials. 2013 Jun;34(18):4532-43. doi: 10.1016/j.biomaterials.2013.02.067. Epub 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.02.067

AUTORES / AUTHORS:  - Yin T; Wang P; Li J; Zheng R; Zheng B; Cheng D; Li R; Lai J; Shuai X

INSTITUCIÓN / INSTITUTION:  - Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.

RESUMEN / SUMMARY:  - Ultrasound (US)-sensitive nanobubble (NB) which may utilize the physical power of US exposure to improve delivery efficiency to target cells is emerging as one of  the most promising nanocarriers for drug delivery. On the basis of successfully fabricating NBs with the ability of passively accumulating in tumor tissue, in this study we synthesized a US-sensitive NB bearing siRNA (siRNA-NB) for tumor therapy via a hetero-assembling strategy using the siRNA-complexed polymeric micelles and gas-cored liposomes. The US exposure-aided siRNA transfection effectively enhanced the gene silencing effect of siRNA-NBs both in vitro and in  vivo, which resulted in much elevated level of cancer cell apoptosis. Consequently, significantly improved therapeutic effect was achieved in a nude mouse glioma model, using siRNA-NBs bearing siRNA to target the anti-apoptosis gene sirtuin 2 (SIRT2). These results show that, with the aid of US exposure, the US-sensitive siRNA-NB may be an ideal delivery vector to mediate highly effective RNA interference for tumor treatment.

 

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[181]

TÍTULO / TITLE:  - Resolution of Mass Effect and Compression Symptoms following Endoluminal Flow Diversion for the Treatment of Intracranial Aneurysms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3547

AUTORES / AUTHORS:  - Szikora I; Marosfoi M; Salomvary B; Berentei Z; Gubucz I

INSTITUCIÓN / INSTITUTION:  - Departments of Neurointerventions and Neuroophthalmology, National Institute of Clinical Neurosciences, Budapest, Hungary.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Alleviation of aneurysm induced mass effect has been difficult with both conventional endovascular and surgical techniques. Our aim was to study the efficacy of endovascular flow modification on aneurysm-induced mass effect and compression syndrome, as demonstrated by cross-sectional imaging  studies and clinical follow-up.MATERIALS AND METHODS:Thirty aneurysms larger than 10 mm were treated by flow diversion alone and previously had undergone pre- and  posttreatment cross-sectional imaging. Pretreatment MR imaging or contrast CT, follow-up angiography at 6 months, and follow-up MR imaging studies between 6 and 18 months were retrospectively analyzed. The neurologic and neuro-ophthalmologic  statuses of all patients were recorded before treatment and at the time of follow-up cross-sectional imaging.RESULTS:At 6 months, 28 aneurysms were completely occluded, 1 had a neck remnant, and 1 had residual filling on angiography. Between 6 and 18 months, 3 aneurysms decreased in size and 27 completely collapsed as demonstrated on MR imaging. Before treatment, 6 patients  had vision loss, 10 had double vision due to a third or sixth nerve palsy or both, and 1 had hemiparesis due to brain stem compression. On MR imaging follow-up, vision loss had either improved or resolved in all except 1 patient, double vision had resolved completely (7/10) or partially (3/10), and the patient with brain stem compression became asymptomatic. There was no bleeding observed in this series. One parent artery thrombosis resulted in a major infarct.CONCLUSIONS:Endovascular flow diversion is a highly effective technique for resolving radiologic mass effect and clinical compression syndromes.

 

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[182]

TÍTULO / TITLE:  - Snail depletes the tumorigenic potential of glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncogene. 2013 Mar 25. doi: 10.1038/onc.2013.67.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.67

AUTORES / AUTHORS:  - Savary K; Caglayan D; Caja L; Tzavlaki K; Bin Nayeem S; Bergstrom T; Jiang Y; Uhrbom L; Forsberg-Nilsson K; Westermark B; Heldin CH; Ferletta M; Moustakas A

INSTITUCIÓN / INSTITUTION:  - Ludwig Institute for Cancer Research, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is an aggressive brain malignancy characterized by  high heterogeneity and invasiveness. It is increasingly accepted that the refractory feature of GBM to current therapies stems from the existence of few tumorigenic cells that sustain tumor growth and spreading, the so-called glioma-initiating cells (GICs). Previous studies showed that cytokines of the bone morphogenetic protein (BMP) family induce differentiation of the GICs, and thus act as tumor suppressors. Molecular pathways that explain this behavior of BMP cytokines remain largely elusive. Here, we show that BMP signaling induces Smad-dependent expression of the transcriptional regulator Snail in a rapid and sustained manner. Consistent with its already established promigratory function in other cell types, we report that Snail silencing decreases GBM cell migration. Consequently, overexpression of Snail increases GBM invasiveness in a mouse xenograft model. Surprisingly, we found that Snail depletes the GBM capacity to form gliomaspheres in vitro and to grow tumors in vivo, both of which are important features shared by GICs. Thus Snail, acting downstream of BMP signaling, dissociates the invasive capacity of GBM cells from their tumorigenic  potential.Oncogene advance online publication, 25 March 2013; doi:10.1038/onc.2013.67.

 

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[183]

TÍTULO / TITLE:  - Hepatocyte Growth Factor Sensitizes Brain Tumors to c-MET Kinase Inhibition.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Mar 15;19(6):1433-44. doi: 10.1158/1078-0432.CCR-12-2832. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2832

AUTORES / AUTHORS:  - Zhang Y; Farenholtz KE; Yang Y; Guessous F; Dipierro CG; Calvert VS; Deng J; Schiff D; Xin W; Lee JK; Purow B; Christensen J; Petricoin E; Abounader R

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Microbiology, Immunology and Cancer Biology, Neurology, and Pathology, and Cancer Center, University of Virginia, Charlottesville; Public Health Sciences; George Mason University, Fairfax; and Pfizer Global Research and Development, Richmond, Virginia.

RESUMEN / SUMMARY:  - PURPOSE: The receptor tyrosine kinase (RTK) c-MET and its ligand hepatocyte growth factor (HGF) are deregulated and promote malignancy in cancer and brain tumors. Consequently, clinically applicable c-MET inhibitors have been developed. The purpose of this study was to investigate the not-well-known molecular determinants that predict responsiveness to c-MET inhibitors and to explore new strategies for improving inhibitor efficacy in brain tumors. EXPERIMENTAL DESIGN: We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells, and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done. We also explored new approaches for improving the efficacy of the inhibitors in vitro and in vivo. RESULTS: We found that HGF coexpression is a key predictor of response to c-MET inhibition among the examined factors and identified an ERK/JAK/p53 pathway activation signature that differentiates c-MET  inhibition in responsive and nonresponsive cells. Surprisingly, we also found that short pretreatment of cells and tumors with exogenous HGF moderately but statistically significantly enhanced the antitumor effects of c-MET inhibition. We observed a similar ligand-induced sensitization effect to an EGF receptor small-molecule kinase inhibitor. CONCLUSIONS: These findings allow the identification of a subset of patients that will be responsive to c-MET inhibition and propose ligand pretreatment as a potential new strategy for improving the anticancer efficacy of RTK inhibitors. Clin Cancer Res; 19(6); 1433-44. ©2013 AACR.

 

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[184]

TÍTULO / TITLE:  - Depressive-like behaviour induced by an intracerebroventricular injection of streptozotocin in mice: the protective effect of fluoxetine, antitumour necrosis  factor-alpha and thalidomide therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Behav Pharmacol. 2013 Apr;24(2):79-86. doi: 10.1097/FBP.0b013e32835efc2f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/FBP.0b013e32835efc2f

AUTORES / AUTHORS:  - Souza LC; Filho CB; Fabbro LD; de Gomes MG; Goes AT; Jesse CR

INSTITUCIÓN / INSTITUTION:  - Laboratory of Pharmacological and Toxicological Reviews Applied to Bioactive Molecules - LaftamBio Pampa - Federal University of Pampa, Itaqui, RS, Brazil.

RESUMEN / SUMMARY:  - Information on the effect of an intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) on noncognitive behaviour in rodents such as depression states is scarce. Thus, the aim of this study was to examine the depressive-like  effect of STZ injected by the i.c.v. route in mice and the potential protective effect of fluoxetine, antitumour necrosis factor-alpha (anti-TNF-alpha) and thalidomide. Our results indicated that a single injection of STZ (0.1 mg/site) promoted depressive-like behaviour in the tail suspension and sucrose preference  tests without altering either locomotor activity or plasma glucose levels. We also showed that STZ increased TNF-alpha levels in the hippocampus of mice. Fluoxetine (32 mg/kg, intraperitoneally. 30 min before STZ injection), and the anti-TNF-alpha antibody (0.1 pg/site, i.c.v.) and thalidomide (3 mg/kg, subcutaneously), coadministered with STZ, prevented these effects. This is the first study to report depressive-like effects of STZ using the i.c.v. route in mice. We concluded that fluoxetine, anti-TNF-alpha antibody and thalidomide were  effective in preventing depressive-like behaviour and the increase in TNF-alpha levels in the hippocampus of mice induced by an i.c.v. injection of STZ, reinforcing the involvement of TNF-alpha in the pathophysiology of depression. This model and the mechanisms studied may contribute towards the development of new antidepressant drugs and enhance the options for studying depression.

 

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[185]

TÍTULO / TITLE:  - MRI assessment of relapsed glioblastoma during treatment with bevacizumab: Volumetric measurement of enhanced and FLAIR lesions for evaluation of response and progression-A pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Radiol. 2013 May;82(5):e240-5. doi: 10.1016/j.ejrad.2012.12.018. Epub 2013  Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.12.018

AUTORES / AUTHORS:  - Pichler J; Pachinger C; Pelz M; Kleiser R

INSTITUCIÓN / INSTITUTION:  - Wagner Jauregg Weg 15, 4020 Linz, Landesnervenklinik Linz, Austria. Electronic address: josef.pichler@gespag.at.

RESUMEN / SUMMARY:  - PURPOSE: To develop a magnetic resonance imaging (MRI) metric that is useful for  therapy monitoring in patients with relapsed glioblastoma (GBM) during treatment  with the antiangiogenic monoclonal antibody bevacizumab (Bev). We evaluated the feasibility of tumour volume measurement with our software tool in clinical routine and tried to establish reproducible and quantitative parameters for surveillance of patients on treatment with antiangiogenic drugs. MATERIALS AND METHODS: In this retrospective institutional pilot study, 18 patients (11 men, 7  women; mean age 53.5) with recurrent GBM received bevacizumab and irinotecan every two weeks as second line therapy. Follow up scans were assessed every two to four months. Data were collected on a 1.5T MR System (Siemens, Symphony) with  the standard head coil using our standardized tumour protocol. Volumetric measurement was performed with a commercial available software stroketool in FLAIR and T1-c imaging with following procedure: Pre-processing involved cutting  noise and electing a Gaussian of 3x3 to smooth images, selecting a ROI (region of interest) in healthy brain area of the contra lateral side with quantifying the intensity value, adding 20% to this value to define the threshold level. Only values above this threshold are left corresponding to the tumour lesion. For the  volumetric measurement the detected tumour area was circuited in all slices and finally summing up all values and multiplied by slice thickness to get the whole  volume. RESULTS: With McDonalds criteria progression was indicated in 14 out of 18 patients. In contrast, volumetric measurement showed an increase of contrast enhancement of >25%, defined as threshold for progression, in 11 patients (78%) and in 12 patients (85%) in FLAIR volume, respectively. 6 patients revealed that  volumes in MRI increased earlier than the last scan, which was primarily defined  as the date of progression with McDonald criteria, changing PFS after re-evaluation of the tumour volumes from 6.8 to 5.6 months. CONCLUSION: In this pilot study the applied imaging estimates objectively tumour response and progression compared to the bi-dimensional measurement. The quantitative parameters are reproducible and also applicable for the diffuse infiltrating lesions.

 

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[186]

TÍTULO / TITLE:  - Tumor blood flow from arterial spin labeling perfusion MRI: A key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24026.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24026

AUTORES / AUTHORS:  - Yoo RE; Choi SH; Cho HR; Kim TM; Lee SH; Park CK; Park SH; Kim IH; Yun TJ; Kim JH; Sohn CH; Han MH; Chang KH

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the usefulness of pseudo-continuous arterial spin labeling (pCASL) imaging in differentiating high-grade gliomas from lymphomas and in noninvasively predicting genetic biomarkers in high-grade gliomas. MATERIALS AND  METHODS: Twelve glioblastoma multiforme (GBM), 3 anaplastic astrocytoma (AA), 5 recurred GBM, and 9 lymphoma patients underwent conventional MR and pCASL imaging. On pCASL perfusion map, mean absolute tumor blood flow (mTBF) was calculated from five regions of interest (ROIs) within the enhancing portion of the tumor. Relative TBF (rTBF = mTBF/mBF(gm) x 100) was also calculated. mTBF and rTBF of high-grade gliomas and lymphomas were compared using unpaired Student’s t-test and receiver operating characteristic (ROC) analysis. Additionally, the association of TBF and six immunohistochemically confirmed genetic biomarkers was analyzed by Pearson correlation analysis in the group of high-grade gliomas. RESULTS: Both mTBF and rTBF of the high-grade gliomas were significantly higher than those of the lymphomas: 92.1 +/- 34.7 versus 53.6 +/- 30.5 mL/min/100 mg (P  = 0.008) and 182.3 +/- 69.5 versus 92.5 +/- 44.9 (P = 0.002), respectively. Only  epidermal growth factor receptor (EGFR) expression status showed a significant positive correlation with mTBF(P = 0.015) and rTBF(P = 0.007). CONCLUSION: pCASL  imaging may facilitate differentiation of high-grade gliomas from lymphomas and prediction of EGFR expression status in high-grade gliomas. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.

 

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[187]

TÍTULO / TITLE:  - Whole-Exome Sequencing Studies of Nonfunctioning Pituitary Adenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4028

AUTORES / AUTHORS:  - Newey PJ; Nesbit MA; Rimmer AJ; Head RA; Gorvin CM; Attar M; Gregory L; Wass JA; Buck D; Karavitaki N; Grossman AB; McVean G; Ansorge O; Thakker RV

INSTITUCIÓN / INSTITUTION:  - Academic Endocrine Unit (P.J.N., M.A.N., R.A.H., C.M.G., R.V.T.), Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom; Bioinformatics and Statistical Genetics Group (A.J.R., G.M.) and High-Throughput Genomics Group (M.A., L.G., D.B.), Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Department  of Endocrinology (J.A.H.W., N.K., A.B.G.), Oxford Centre for Diabetes, Endocrinology, and Metabolism, Oxford University Hospitals Trust, Oxford OX3 7LJ, United Kingdom; and Department of Neuropathology (O.A.), John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford OX3 9DU, United Kingdom.

RESUMEN / SUMMARY:  - Context:The tumorigenic role of genetic abnormalities in sporadic pituitary nonfunctioning adenomas (NFAs), which usually originate from gonadotroph cells, is unknown.Objective:The objective of the study was to identify somatic genetic abnormalities in sporadic pituitary NFAs.Design:Whole-exome sequencing was performed using DNA from 7 pituitary NFAs and leukocyte samples obtained from the same patients. Somatic variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 24 pituitary NFAs.Results:Whole-exome sequencing achieved a high degree of coverage such that  approximately 97% of targeted bases were represented by more than 10 base reads;  24 somatic variants were identified and confirmed in the discovery set of 7 pituitary NFAs (mean 3.5 variants/tumor; range 1-7). Approximately 80% of variants occurred as missense single nucleotide variants and the remainder were synonymous changes or small frameshift deletions. Each of the 24 mutations occurred in independent genes with no recurrent mutations. Mutations were not observed in genes previously associated with pituitary tumorigenesis, although somatic variants in putative driver genes including platelet-derived growth factor D (PDGFD), N-myc down-regulated gene family member 4 (NDRG4), and Zipper sterile-alpha-motif kinase (ZAK) were identified; however, DNA sequence analysis  of these in the validation set of 24 pituitary NFAs did not reveal any mutations  indicating that these genes are unlikely to contribute significantly in the etiology of sporadic pituitary NFAs.Conclusions:Pituitary NFAs harbor few somatic mutations consistent with their low proliferation rates and benign nature, but mechanisms other than somatic mutation are likely involved in the etiology of sporadic pituitary NFAs.

 

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[188]

TÍTULO / TITLE:  - Recurrences of ACTH-Secreting Adenomas After Pituitary Adenomectomy Can Be Accurately Predicted by Perioperative Measurements of Plasma ACTH Levels.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3910

AUTORES / AUTHORS:  - Abdelmannan D; Chaiban J; Selman WR; Arafah BM

INSTITUCIÓN / INSTITUTION:  - Division of Clinical and Molecular Endocrinology, Department of Neurological Surgery, University Hospitals Case Medical Center, Louis Stokes Cleveland Veterans Medical Center And Case Western Reserve University, Cleveland, Ohio 44106.

RESUMEN / SUMMARY:  - Background:Adenomectomy is the treatment of choice for ACTH-secreting adenomas. Although the development of ACTH deficiency immediately after adenomectomy suggests surgical success, disease recurrence was reported in patients who developed hypocortisolism postoperatively. In the current study, we examined the  value of measuring perioperative plasma ACTH and cortisol levels in predicting disease recurrence of patients with ACTH-secreting adenomas.Methods:Consecutive patients (n = 55; 41 females, 14 males) with clinical, biochemical, and histological documentation of ACTH-secreting adenomas were investigated after pituitary adenomectomy. All patients were followed with clinical monitoring and frequent measurements of plasma ACTH and serum cortisol levels, and none received glucocorticoids unless or until they developed symptoms of adrenal insufficiency  or when their serum cortisol levels were </=3 mug/dL.Results:Postoperative serum  cortisol levels reached </=3 mug/dL in 46 of 55 and were >/=4 mug/dL in the remaining 9. Simultaneously measured plasma ACTH levels in the latter 9 patients  were >40 ng/L when the serum cortisol reached its nadir. In contrast, among the 46 patients who had serum cortisol levels of </=3 mug/dL, plasma ACTH levels measured simultaneously were </=20 ng/L in 38 of 46 and >20 ng/L in the remaining 8. During a mean follow-up period of nearly 7 years, patients who had a nadir plasma ACTH of >20 ng/L developed recurrences even though their postoperative serum cortisol levels were </=3 mug/dL.Conclusions:Despite profound hypocortisolemia after adenomectomy, a simultaneously measured plasma ACTH level  of >20 ng/L in the perioperative period is highly predictive of future recurrence of ACTH-secreting adenomas.

 

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[189]

TÍTULO / TITLE:  - Management of pediatric spinal cord astrocytomas: outcomes with adjuvant radiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1307-11. doi: 10.1016/j.ijrobp.2012.11.022. Epub 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.022

AUTORES / AUTHORS:  - Guss ZD; Moningi S; Jallo GI; Cohen KJ; Wharam MD; Terezakis SA

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins  Hospital, Baltimore, Maryland.

RESUMEN / SUMMARY:  - PURPOSE: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. METHODS AND MATERIALS: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. RESULTS: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy  (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with  a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. CONCLUSION: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease  control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy may enhance tumor control with an acceptably low risk of long-term sequelae in this sensitive patient population.

 

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[190]

TÍTULO / TITLE:  - Diagnosis and surgical treatment of sporadic meningioangiomatosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb 25. pii: S0303-8467(13)00048-6. doi: 10.1016/j.clineuro.2013.01.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.01.021

AUTORES / AUTHORS:  - Feng R; Hu J; Che X; Pan L; Wang Z; Zhang M; Huang F; Xu B; Mao R; Sun A; Bao W; Zhong P; Wang Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040,  China.

RESUMEN / SUMMARY:  - OBJECTIVE: To discuss the clinical characteristics, radiological features, surgical treatment and prognosis of sporadic meningioangiomatosis (MA). METHODS:  We retrospectively analyzed the medical records of ten histopathologically confirmed MA patients who were treated in the Department of Neurosurgery of Huashan hospital from 2002 to 2011. All of the patients presented with symptomatic seizure attacks before craniotomy surgeries. Magnetic resonance imaging (MRI) and/or computed tomography (CT) were the main radiological examination for preoperative diagnosis of all cases. RESULTS: All patients underwent craniotomy surgeries with gross total resections (GTRs) of the MA lesions. Postoperative follow-ups range from 8 to 108 months, in average 42.7 months, median 40.5 months. No radiological recurrence can be found in any case.  Eight patients (80.0%) have achieved total symptomatic remission after surgeries  (one of them underwent delayed remission), while two (20.0%) are still suffering  from seizure attacks infrequently under several antiepileptic drugs (AEDs). CONCLUSION: Although MA cases are quite rare and usually misdiagnosed presurgically, a correct preoperative diagnosis, at least a differential diagnosis, can be rationally achieved via a triad of patients’ ages, symptomatic  seizure attacks and radiological features (both CT and MR). MA is curable and the prognosis is excellent since most patients became free of seizure and recurrence  after surgical treatments.

 

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[191]

TÍTULO / TITLE:  - Striatal TH-immunopositive fibers recover after an intrastriatal injection of 6-hydroxydopamine in golden hamsters treated with prednisolone: Roles of tumor necrosis factor-alpha and inducible nitric oxide synthase in neurodegeneration.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosci Res. 2013 Mar 5. pii: S0168-0102(13)00038-2. doi: 10.1016/j.neures.2013.02.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neures.2013.02.004

AUTORES / AUTHORS:  - Rodriguez S; Uchida K; Nakayama H

INSTITUCIÓN / INSTITUTION:  - Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan. Electronic address: sebastian.rodriguez1978@hotmail.com.

RESUMEN / SUMMARY:  - Neuroinflammation has been implicated in the pathology of neurodegenerative processes such as Parkinson’s disease (PD). Using the golden hamster (GH) 6-hydroxydopamine (6-OHDA) model, we investigated whether the attenuation of neuroinflammation influences the onset and progression of dopamine cell degeneration. 6-OHDA-injected GH received a treatment of minocycline (MINO), prednisolone (Pred) or a combination of minocycline and prednisolone (MINO+Pred). Immunohistochemistry for tyrosine hydroxylase (TH), Iba-1 and glial fibrillary acidic protein (GFAP) was used to evaluate lesions in the nigrostriatal axis and  the amount of activated microglia and astroglia, respectively. RT-PCR was used to measure mRNA levels of cytokines and trophic neuroprotective factors. The three anti-inflammatory treatments dramatically reduced activated microglia in the nigrostriatal axis. In addition, TH-immunostaining showed that the positive areas in the ipsilateral striatum of either MINO or Pred groups were higher than that of control. However, only in Pred group this recovery was significant. mRNA measurements demonstrated lower levels of TNF-alpha, iNOS, BDNF and GDNF in Pred  group when compared with controls. The results suggest that TH-immunopositive fibers have the ability to recover after 6-OHDA-induced toxicity of dopaminergic  neurons, and this recovery may be due to a decrease in the microglial production  of TNF-alpha and iNOS.

 

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[192]

TÍTULO / TITLE:  - Regulation of Epidermal Growth Factor Receptor Signaling by plasmid-based MicroRNA-7 inhibits human malignant gliomas growth and metastasis in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasma. 2013;60(3):274-83. doi: 10.4149/neo_2013_036.

            ●● Enlace al texto completo (gratuito o de pago) 4149/neo_2013_036

AUTORES / AUTHORS:  - Wang W; Dai LX; Zhang S; Yang Y; Yan N; Fan P; Dai L; Tian HW; Cheng L; Zhang XM; Li C; Zhang JF; Xu F; Shi G; Chen XL; DU T; Li YM; Wei YQ; Deng HX

RESUMEN / SUMMARY:  - MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate genes expression by binding to the 3’ untranslated region (UTR) of targets mRNAs and play critical roles in cancer pathways. Malignant glioma is the most common and highly lethal central nervous system tumor for which little effective treatment is available over several decades. The purpose of this study  was to explore the therapeutic potential of plasmid-based microRNA-7 (miR-7) for  gliomas in vivo. Enhancing miR-7 levels in vitro could significantly induce cell  apoptosis, and inhibit cell proliferation, cell migration and invasion. Western blotting analysis was performed, which indicated that miR-7 directly inhibited epidermal growth factor receptor (EGFR) and further antagonized the downstream protein kinases including ERK, Akt and Stat3. Furthermore, systemic administration of miR-7 encapsulated in cationic liposome resulted in glioma xenografts growth arrest and the metastatic nodules decrease effectively in asequence-specific manner. In this study, miR-7 was applied in glioma treatment for the first time in vivo. Our findings suggested that the plasmid-mediated gene therapy with miR-7 appeared to be apromising candidate for the development of new antitumor and anti-metastasis treatment for human glioma. Keywords: miR-7, glioma, metastasis, apoptosis, gene therapy.

 

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[193]

TÍTULO / TITLE:  - MELK-dependent FOXM1 Phosphorylation is Essential for Proliferation of Glioma Stem Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. 2013 Feb 13. doi: 10.1002/stem.1358.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1358

AUTORES / AUTHORS:  - Joshi K; Banasavadi-Siddegowda Y; Mo X; Kim SH; Mao P; Kig C; Nardini D; Sobol RW; Chow LM; Kornblum HI; Waclaw R; Beullens M; Nakano I

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator of mitotic progression of cancer cells in various organs. Here, we demonstrate that FOXM1 forms a protein complex with the mitotic  kinase MELK in GSCs, leading to phosphorylation and activation of FOXM1 in a MELK kinase-dependent manner. This MELK-dependent activation of FOXM1 results in a subsequent increase in mitotic regulatory genes in GSCs. MELK-driven FOXM1 activation is regulated by the binding and subsequent trans-phosphorylation of FOXM1 by another kinase PLK1. Using mouse neural progenitors (NPCs), we found that transgenic expression of FOXM1 enhances, while siRNA-mediated gene silencing diminishes neurosphere formation, suggesting that FOXM1 is required for NPC growth. During tumorigenesis, FOXM1 expression sequentially increases as cells progress from NPCs, to pre-tumorigenic progenitors and GSCs. The antibiotic Siomycin A disrupts MELK-mediated FOXM1 signaling with a greater sensitivity in GSC compared to NSC. Treatment with the first-line chemotherapy agent for GBM, Temozolomide, paradoxically enriches for both FOXM1 (+) and MELK (+) cells in GBM cells, and addition of Siomycin A to Temozolomide treatment in mice harboring GSC-derived intracranial tumors enhances the effects of the latter. Collectively, our data indicate that FOXM1 signaling through its direct interaction with MELK regulates key mitotic genes in GSCs in a PLK1-dependent manner and thus, this protein complex is a potential therapeutic target for GBM.

 

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[194]

TÍTULO / TITLE:  - Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. 2013 Mar 26. doi: 10.1002/stem.1373.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1373

AUTORES / AUTHORS:  - Turchi L; Debruyne DN; Almairac F; Virolle V; Fareh M; Neirijnck Y; Burel-Vandenbos F; Paquis P; Junier MP; Van Obberghen-Schilling E; Chneiweiss H; Virolle T

INSTITUCIÓN / INSTITUTION:  - Universite de Nice-Sophia Antipolis; institut de Biologie Valrose, CNRS UMR7277 - INSERM UMR1091, Nice, France.

RESUMEN / SUMMARY:  - Stem cell-like properties of Glioma initiating Cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise the tumor.  It is therefore likely that the molecular circuitries that regulate their decision to self-renew or commit to a more differentiated state may offer targets for future innovative therapies. In previous micro-RNA profiling studies to search for regulators of stem cell plasticity we identified miR-18a* as a potential candidate and its expression correlated with the stemness state. Here,  using human GiCs we found that miR-18a* expression promotes clonal proliferation  in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of  miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH,  thus enhancing the level of activated NOTCH-1. Activated NOTCH-1 in turn is required for sustained ERK activation. This feedforward loop, driven by miR-18a*, is required to turn on the SHH-GLI-NANOG network, essential for GiC self-renewal. Hence, by tightly regulating expression of DLL3, miR-18a* constitutes an important signaling mediator for fine tuning the level of GiC self-renewal.

 

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[195]

TÍTULO / TITLE:  - Modulation of the Wnt/beta-catenin pathway in human oligodendroglioma cells by Sox17 regulates proliferation and differentiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 6. pii: S0304-3835(13)00221-8. doi: 10.1016/j.canlet.2013.02.058.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.058

AUTORES / AUTHORS:  - Chen HL; Chew LJ; Packer RJ; Gallo V

INSTITUCIÓN / INSTITUTION:  - Center for Neuroscience Research, Children’s National Medical Center, Washington, DC 20010, USA; Daniel and Jennifer Gilbert Neurofibromatosis Institute, Children’s National Medical Center, Washington, DC 20010, USA.

RESUMEN / SUMMARY:  - Oligodendrogliomas originate from oligodendrocyte progenitor cells (OPCs), whose  development is regulated by the Sonic hedgehog and Wnt/beta-catenin pathways. We  investigated the contribution of these pathways in the proliferation and differentiation of human oligodendroglioma cells (HOG). Inhibition of Hedgehog signaling with cyclopamine decreased cell survival and increased phosphorylated beta-catenin without altering myelin protein levels. Conversely, treatment of HOG with the Wnt antagonist secreted frizzled related protein (SFRP1), led to increased myelin protein levels and reduced cell proliferation, suggesting cell cycle arrest and differentiation. Unlike normal primary human OPCs, beta-catenin  in HOG cells is not associated with endogenous Sox17 protein despite high levels  of both proteins. Retroviral overexpression of recombinant Sox17 increased HOG cell cycle exit and apoptosis, and raised myelin protein levels and the percentage of O4+ cells, indicating increased differentiation. Recombinant Sox17  also increased beta-catenin-TCF4-Sox17 complex formation and decreased total cellular levels of beta-catenin. These changes were associated with increased SFRP1, and reduced expression of Wnt-1 and Frizzled-1, -3 and -7 RNA, indicating  that Sox17 induced a Hedgehog target, and regulated Wnt signaling at multiple levels. Our studies indicate that Wnt signaling regulates HOG cell cycle arrest and differentiation, and that recombinant Sox17 mediates modulation of the Wnt pathway through changes in beta-catenin, SFRP1 and Wnt/Frizzled expression. Our results thus identify Sox17 as a potential molecular target to include in HOG therapeutic strategies.

 

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[196]

TÍTULO / TITLE:  - Metabolic modulation of epigenetics in gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Mar;23(2):217-21. doi: 10.1111/bpa.12022.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12022

AUTORES / AUTHORS:  - Venneti S; Thompson CB

INSTITUCIÓN / INSTITUTION:  - Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New  York, NY 10065, USA.

RESUMEN / SUMMARY:  - Cancer metabolism and epigenetics are two relatively new areas of cancer research. Recent years have seen an explosion of studies implicating either altered tumor metabolism or epigenetic mechanisms in the pathogenesis or maintenance of brain tumors. A new paradigm is emerging in cancer biology that represents a convergence of these themes, the metabolic regulation of epigenetics. We discuss this interrelationship in the context of two metabolic enzymes that can influence the pathogenesis of gliomas by altering the epigenetic state. The first of these enzymes is isocitrate dehydrogenase 1 (IDH1), which is  mutated in secondary glioblastomas and ~70% of grade II/III astrocytomas and oligodendrogliomas. Mutant IDH1 results in the production of a metabolite 2-hydroxyglutarate (2-HG) that can inhibit DNA and histone demethylating enzymes  resulting in the glioma-CpG island phenotype (G-CIMP) and increased histone methylation marks. Pyruvate kinase M2 (PKM2), an enzyme that plays a critical role in the glycolytic pathway, is a second example of a metabolic enzyme that can affect histone modifications. In epidermal growth factor receptor (EGFR)-driven glioblastoma, PKM2 translocates to the nucleus and phosphorylates histone 3 at threonine 11 (H3-T11). This causes dissociation of HDAC3 from the CCND1 (Cyclin D1) and c-MYC promoters and subsequent histone acetylation, leading to transcription of Cyclin-D1 and c-MYC, and subsequent cell proliferation. Modification of the epigenetic state by alterations in metabolic enzymes is a novel phenomenon that contributes to the pathogenesis of gliomas and may help in  the identification of new therapeutic targets.

 

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[197]

TÍTULO / TITLE:  - Genistein alleviates the mitochondria-targeted DNA damage induced by beta-amyloid peptides 25-35 in C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurochem Res. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11064-013-1019-y

AUTORES / AUTHORS:  - Ma WW; Hou CC; Zhou X; Yu HL; Xi YD; Ding J; Zhao X; Xiao R

INSTITUCIÓN / INSTITUTION:  - School of Public Health and Family Medicine, Capital Medical University, No.10 Xitoutiao, No.10 Xitoutiao, You An Men, Beijing, 100069, People’s Republic of China.

RESUMEN / SUMMARY:  - Reactive oxygen species (ROS) are mainly produced by mitochondria which can cause oxidative stress. It has been considered that mitochondrial damage induced by oxidative stress is related to Alzheimer’s disease (AD). Besides, mitochondrial DNA (mtDNA) is more vulnerable to oxidative damage than other biomacromolecules,  causing serious dysfunction to mitochondria. beta-amyloid peptides (Abeta) is a main factor responsible for the occurence and development of AD. Astrocytes is an important target cell for Abeta’ toxicity and can be activated to neglect their normal fountain in the central nervous system. Genistein (Gen), a main active ingredient of soybean isoflavone, has been shown to have neuroprotective effects  by antagonizing oxidative damage induced by Abeta. Thus, in the present study, we evaluated Abeta25-35 induced mitochondrial DNA (mtDNA) damage and the protective  effect of Gen in C6 glioma cells (C6 cells). The study design was consisted of four groups: control group (vehicle), Abeta group treated with Abeta25-35, Gen +  Abeta group treated with Gen + Abeta25-35 and Gen group treated with Gen only. C6 cells were pre-incubated with or without Gen (50 muM) for 2 h followed by the incubation with Abeta25-35 (25 muM) for another 24 h. Then the cells were harvested and processed to perform the analysis according to protocols. The mitochondrial ROS in C6 cells were measured by fluorescence spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to detect the mitochondrial reduced glutathione (GSH) and oxidized glutathione (GSSG) in C6 cells, then the ratio of GSH and GSSG was calculated. The levels of 8-hydroxydeoxyguanosine (8-OHdG) in C6 cells was also detected by ELISA. In addition, mtDNA deletion was  detected by polymerase chain reaction (PCR). The mRNA and protein expression of 8-oxoguanine DNA glycosylase (OGG1) in both C6 cells and its mitochondria, and manganese superoxide dismutase (MnSOD) in mitochondria were detected by using reverse transcription-PCR and Western blot. The results showed that the increased mitochondrial ROS accumulation in C6 cells induced by Abeta was profoundly reversed by pre-treaded with Gen (p < 0.05). The ratio of GSH and GSSG in mitochondria was significantly increased in both Gen + Abeta group and Gen group  compared with Abeta group (p < 0.05). The levels of 8-OHdG in C6 cells and mtDNA  deletion were decreased after pre-treated with Gen (p < 0.05). Gen could also up-regulate the mRNA and protein expression of OGG1 in both C6 cells and its mitochondria and mitochondrial MnSOD compared with the Abeta group (p < 0.05). These results confirmed that Gen could alleviate the mitochondria-targeted oxidative damage induced by beta-amyloid 25-35 in C6 cells which might be useful  for the treatment of neurodegenerative diseases.

 

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[198]

TÍTULO / TITLE:  - PEG2000-DPSE-coated quercetin nanoparticles remarkably enhanced anticancer effects through induced programed cell death on C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Biomed Mater Res A. 2013 Mar 25. doi: 10.1002/jbm.a.34607.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jbm.a.34607

AUTORES / AUTHORS:  - Wang G; Wang J; Luo J; Wang L; Chen X; Zhang L; Jiang S

INSTITUCIÓN / INSTITUTION:  - Department of Hospital Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China. 13972481839@163.com, wangan139@163.com.

RESUMEN / SUMMARY:  - In this study, PEGylated nanoparticles quercetin drug delivery vehicles were investigated as carriers for anticancer drugs induced programed cell death (PCD). PEG2000-DPSE-coated quercetin nanoparticles were prepared and tumor cell killing  efficacy was studied on glioma C6 cells and assayed for cell survival, apoptosis, or necrosis. The levels of ROS production and mitochondrial membrane potential (DeltaPsim) were determined. Western blot assayed p53, p-p53, cytochrome C, and caspase proteins expression were also studied. Results indicate that PEG2000-DPSE-QUE-NPS showed dose-dependent cytotoxicity to C6 glioma cells and enhanced ROS accumulation induced upregulation of p53 protein, which was accompanied with an increase in cytochrome c and caspase-3 protein levels. These  results support the hypothesis that quercetin nanoparticles-coated PEG2000-DPSE remarkably enhanced anticancer effect of induced programed cell death on C6 glioma cells. Overall, PEG2000-DPSE-coated quercetin nanoparticles showed promising potential as a drug carrier for cancer therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

 

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[199]

TÍTULO / TITLE:  - The effect of functionalizing lipid nanocapsules with NFL-TBS.40-63 peptide on their uptake by glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomaterials. 2013 Apr;34(13):3381-9. doi: 10.1016/j.biomaterials.2013.01.068. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.068

AUTORES / AUTHORS:  - Balzeau J; Pinier M; Berges R; Saulnier P; Benoit JP; Eyer J

INSTITUCIÓN / INSTITUTION:  - Laboratoire Neurobiologie & Transgenese, UPRES-EA3143, Batiment IBS, Centre Hospitalier Universitaire, LUNAM, 49033 Angers, France.

RESUMEN / SUMMARY:  - We previously described a neurofilament derived cell-penetrating peptide, NFL-TBS.40-63, that specifically enters in glioblastoma cells where it disturbs the microtubule network both in vitro and in vivo. The aim of this study is to test whether this peptide can increase the targeted uptake by glioblastoma cells  of lipid nanocapsules filled with Paclitaxel, and thus can increase their anti-proliferation in vitro and in vivo. Here, using the drop tensiometry we show that approximately 60 NFL-TBS.40-63 peptides can bind to one 50 nm lipid nanocapsule. When nanocapsules are filled with a far-red fluorochrome (DiD) and Paclitaxel, the presence of the NFL-TBS.40-63 peptide increases their uptake by glioblastoma cells in culture as evaluated by FACS analysis, and thus reduces their proliferation. Finally, when such nanocapsules were injected in mice bearing a glioma tumour, they are preferentially targeted to the tumour and reduce its progression. These results show that nanocapsules functionalized with  the NFL-TBS.40-63 peptide represent a powerful drug-carrier system for glioma targeted treatment.

 

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[200]

TÍTULO / TITLE:  - The value of temozolomide in combination with radiotherapy during standard treatment for newly diagnosed glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):277-83. doi: 10.1007/s11060-013-1060-3. Epub 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1060-3

AUTORES / AUTHORS:  - Park CK; Lee SH; Kim TM; Choi SH; Park SH; Heo DS; Kim IH; Jung HW

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul National University College of Medicine, Seoul  National University Hospital, Seoul, South Korea.

RESUMEN / SUMMARY:  - The current best standard care for glioblastoma still has limitations and unsatisfactory outcomes in patients with an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Whether the effects of temozolomide are primarily due to its concomitant use with radiotherapy or are also mediated by their independent use in the adjuvant phase remain unclear. To validate the concomitant use of temozolomide in the standard protocol, we compared the overall survival of two prospective patient groups: one treated with radiotherapy alone followed by adjuvant temozolomide (RT --> TMZ group) and the other treated with concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (CCRT-TMZ group). Each patient in the RT --> TMZ group (n = 25) was matched with  two patients in the CCRT-TMZ group (n = 50) with respect to age, extent of resection, MGMT promoter methylation status, and postsurgical performance status  to minimize the influence of confounding factors. In patients with MGMT promoter  methylation, the CCRT-TMZ group showed superior overall survival (OS; median, 41.0 months) and progression-free survival (PFS; median, 24.0 months) compared with the RT --> TMZ group. However, the OS and PFS did not differ between the CCRT-TMZ and the RT --> TMZ groups in the patients without MGMT promoter methylation. Although this data is from a retrospective analysis using small number of patients, the study might indicate that concomitant use of temozolomide with radiotherapy is a crucial step in the standard treatment for glioblastoma patients with MGMT promoter methylation. And the use of temozolomide, either concurrently or by adjuvant after radiotherapy, remains a questionable value for  those with an unmethylated MGMT promoter.

 

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[201]

TÍTULO / TITLE:  - Stromal protein periostin identified as a progression associated and prognostic biomarker in glioma via inducing an invasive and proliferative phenotype.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar 5. doi: 10.3892/ijo.2013.1847.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1847

AUTORES / AUTHORS:  - Wang H; Wang Y; Jiang C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

RESUMEN / SUMMARY:  - To explore the expression pattern, prognostic value and functional role of stromal periostin (POSTN) in glioma patients, POSTN expression was measured using the Agilent Whole Human Genome Oligo Microarray in 220 frozen glioma tissues. We  analyzed POSTN expression in 71 independent validated glioma samples using immuno-histochemistry. The expression levels of POSTN were relative to glioma grade progression and inversely correlated with overall survival in high-grade glioma patients (anaplastic gliomas and glioblastomas). Gene ontology (GO) analysis performed using DAVID showed that the gene sets related to cell migration and proliferation were significantly enriched in the cases with POSTN overexpression. Functional analyses in LN229 and U87 cells revealed that POSTN was involved in cell invasion and proliferation. MMP-9 was an effector of POSTN signaling in glioma cells. The expression of stromal protein POSTN is relative to glioma grade progression and confers a poor prognosis via promoting cellular invasion and proliferation in high-grade glioma patients.

 

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[202]

TÍTULO / TITLE:  - Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Radiol. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2823-0

AUTORES / AUTHORS:  - Fatima Z; Motosugi U; Waqar AB; Hori M; Ishigame K; Oishi N; Onodera T; Yagi K; Katoh R; Araki T

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi, 409-3898, Japan.

RESUMEN / SUMMARY:  - OBJECTIVES: The purposes of this MR-based study were to calculate q-space imaging (QSI)-derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI). METHODS: MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI  in 17 patients who underwent subsequent surgery. RESULTS: ADC and MDP values were found to have a strong correlation: r = 0.78 (P = <0.0001). Both ADC and MDP values had a significant negative association with TCC: r = -0.53 (p = 0.02) and  -0.48 (P = 0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters. CONCLUSION: In meningiomas, both ADC and MDP may be representative of cell density. KEY POINTS:  * Diffusion-weighted MRI offers possibilities to assess the aggressiveness of meningiomas. * The q-space imaging-derived mean displacement correlates strongly  with apparent diffusion coefficients. * Both diffusion parameters showed a strong negative association with tumour cell counts. * Derived mean displacement may help assess the aggressiveness of meningiomas preoperatively.

 

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[203]

TÍTULO / TITLE:  - A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1098-2

AUTORES / AUTHORS:  - Hargrave D; Geoerger B; Frappaz D; Pietsch T; Gesner L; Cisar L; Breazna A; Dorman A; Cruz-Martinez O; Fuster JL; Rialland X; Icher C; Leblond P; Ashley D; Perilongo G; Elliott M; English M; Clausen N; Grill J

INSTITUCIÓN / INSTITUTION:  - Paediatric Oncology Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, darren.hargrave@nhs.net.

RESUMEN / SUMMARY:  - A multicenter, two stage phase II study, investigated irinotecan plus temozolomide in children with newly diagnosed high grade glioma. The primary endpoint was tumor response during a two-cycle treatment window, confirmed by external review committee. Patients received oral temozolomide 100 mg/(m2 day) (days 1-5) and intravenous irinotecan 10 mg/(m2 day) (days 1-5 and 8-12) for two  21-day cycles (three cycles for patients exhibiting objective tumor response). Standard treatment was then administered according to local investigator choice.  In total 17 patients were enrolled and treated by local investigators. However, central pathology review found three patients did not have a diagnosis of high grade glioma and another four patients did not have evaluable disease according to independent central radiological review. The primary endpoint was based on the first ten evaluable patients as determined by the external review committee. Recruitment was stopped for futility after there were no complete or partial responses during the two-cycle treatment window in the first ten evaluable patients. Five patients had stable disease, and five progressed. Data for secondary endpoints including; time to tumor progression, time to treatment failure, and overall survival is reported. The safety profile of the treatment showed the combination was tolerable with two patients (11.8 %) having grade three nausea, and one (5.9 %) experiencing a grade four neutropenia, leading to permanent discontinuation from adjuvant treatment. Irinotecan plus temozolomide,  although well tolerated did not improve outcome over historical controls in this  setting.

 

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[204]

TÍTULO / TITLE:  - Silencing of mitochondrial NADP(+)-dependent isocitrate dehydrogenase gene enhances glioma radiosensitivity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Apr 5;433(2):260-5. doi: 10.1016/j.bbrc.2013.02.093. Epub 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.093

AUTORES / AUTHORS:  - Kim SY; Yoo YH; Park JW

INSTITUCIÓN / INSTITUTION:  - School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, Republic of Korea.

RESUMEN / SUMMARY:  - Reactive oxygen species (ROS) levels are elevated in organisms that have been exposed to ionizing radiation and are protagonists in the induction of cell death. Recently, we demonstrated that the control of mitochondrial redox balance  and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) via the supply of NADPH for antioxidant systems. In the present study, we report an autophagic response to ionizing radiation in A172 glioma cells transfected with small interfering RNA (siRNA) targeting the IDPm gene. Autophagy in A172 transfectant cells was associated with enhanced autophagolysosome formation and GFP-LC3 punctuation/aggregation. Furthermore, we found that the inhibition of autophagy by chloroquine augmented apoptotic cell death of irradiated A172 cells transfected with IDPm siRNA. Taken together, our data suggest that autophagy functions as a survival mechanism in A172 cells against ionizing radiation-induced apoptosis and the sensitizing effect of IDPm siRNA and autophagy inhibitor on the ionizing radiation-induced apoptotic cell death of glioma cells offers a novel redox-active therapeutic strategy for the treatment of cancer.

 

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[205]

TÍTULO / TITLE:  - Suppression of CLIC4/mtCLIC enhances hydrogen peroxide-induced apoptosis in C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Apr;29(4):1483-91. doi: 10.3892/or.2013.2265. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2265

AUTORES / AUTHORS:  - Xu Y; Kang J; Yuan Z; Li H; Su J; Li Y; Kong X; Zhang H; Wang W; Sun L

INSTITUCIÓN / INSTITUTION:  - Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.

RESUMEN / SUMMARY:  - CLIC4/mtCLIC (referred to here as CLIC4) is one of the seven-member family of chloride intracellular channels (CLIC). CLIC4 localizes to the mitochondria, nucleus, cytoplasm and other organellular compartments and participates in the apoptotic response to stress. However, the role of CLIC4 in oxidative stress and  apoptosis is not well understood. In this study, we showed the important role of  CLIC4 in apoptosis of C6 glioma cells induced by hydrogen peroxide (H2O2). Our results showed that CLIC4 protein expression was upregulated following H2O2-induced C6 cell apoptosis. The upregulation of CLIC4 protein expression was  paralleled with an increased Bax/Bcl-2 ratio, cytochrome c and cleaved caspase-3  protein expression upon H2O2-induced C6 cell apoptosis. Suppression of CLIC4 expression by RNA interference enhanced cell apoptosis, but the ratio of Bax/Bcl-2 was not involved in this process. Dissipation of mitochondrial membrane potential and nuclear translocation of CLIC4 were involved in the activation of apoptosis induced by H2O2. Our data indicate that CLIC4 protein may be a key element in the apoptotic response to oxidative stress.

 

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[206]

TÍTULO / TITLE:  - Paraganglioma of the Carotid Body: Treatment Strategy and SDH-gene Mutations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Vasc Endovasc Surg. 2013 Feb 19. pii: S1078-5884(13)00058-0. doi: 10.1016/j.ejvs.2013.01.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejvs.2013.01.018

AUTORES / AUTHORS:  - Fruhmann J; Geigl JB; Konstantiniuk P; Cohnert TU

INSTITUCIÓN / INSTITUTION:  - Department of Vascular Surgery, Medical University of Graz, Auenbruggerplatz 29,  8036 Graz, Austria. Electronic address: johanna.fruhmann@medunigraz.at.

RESUMEN / SUMMARY:  - OBJECTIVES: The aim of the present study was to review treatment results in patients with paraganglioma (PGL) of the neck presenting as carotid body tumour,  long-term follow-up and relevance of genetic testing for succinate dehydrogenase  (SDH)-gene mutations. DESIGN: Retrospective analysis of prospectively collected data and prospective genetic analysis. MATERIALS AND METHODS: Over a 25-year period (1987-2011) 50 patients were operated for 63 PGLs of the neck. Pre-, intra- and postoperative findings were analysed. Sanger sequencing was performed  for genetic testing of SDH-gene mutations (SDH B, SDHC and SDHD). RESULTS: Fifty  patients underwent resection of 63 PGLs (62 benign, one malignant) without mortality. Eight patients underwent preoperative embolisation. Vascular surgical  procedures were required in 15 operations (15/63 = 23.8%). Nerve lesions occurred after 13 operations (13/63 = 20.6%) and were associated with large tumours. A total of 44 patients are alive after a mean follow-up of 9.8 years. In 40 patients 17 SDH-gene mutations were detected (17/40 = 42.5%): 14 SDHD mutations,  two SDHB mutations and one rare SDHC mutation. CONCLUSION: Surgery for PGL is recommended. All PGL patients should be screened for SDH mutations because it impacts the individual follow-up strategy. Whereas all PGL patients require annual ultrasound control, mutation carriers and family members with proven mutations should in addition be regularly examined by magnetic resonance imaging  (MRI) of head, neck, thorax, abdomen and pelvis.

 

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[207]

TÍTULO / TITLE:  - Emerging insights into the ependymoma epigenome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Mar;23(2):206-9. doi: 10.1111/bpa.12020.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12020

AUTORES / AUTHORS:  - Mack SC; Witt H; Wang X; Milde T; Yao Y; Bertrand KC; Korshunov A; Pfister SM; Taylor MD

INSTITUCIÓN / INSTITUTION:  - Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada. stephen.mack@mail.utoronto.ca

RESUMEN / SUMMARY:  - Ependymoma is the third most common pediatric brain tumor, yet because of the paucity of effective therapeutic interventions, 45% of patients remain incurable. Recent transcriptional and copy number profiling of the disease has identified few driver genes and in fact points to a balanced genomic profile. Candidate gene approaches looking at hypermethylated promoters and genome-wide epigenetic arrays suggest that DNA methylation may be critical to ependymoma pathogenesis. This review attempts to highlight existing and emerging evidence implicating the ependymoma epigenome as a key player and that epigenetic modifiers may offer new  targeted therapeutic avenues for patients.

 

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[208]

TÍTULO / TITLE:  - The role of chromatin remodeling in medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Pathol. 2013 Mar;23(2):193-9. doi: 10.1111/bpa.12019.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12019

AUTORES / AUTHORS:  - Jones DT; Northcott PA; Kool M; Pfister SM

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

RESUMEN / SUMMARY:  - The unexpectedly high frequency and universality of alterations to the chromatin  machinery is one of the most striking themes emerging from the current deluge of  cancer genomics data. Medulloblastoma (MB), a malignant pediatric brain tumor, is no exception to this trend, with a wealth of recent studies indicating multiple alterations at all levels of chromatin processing. MB is typically now regarded as being composed of four major molecular entities (WNT, SHH, Group 3 and Group 4), which vary in their clinical and biological characteristics. Similarities and differences across these subgroups are also reflected in the specific chromatin modifiers that are found to be altered in each group, and each new cancer genome  sequence or microarray profile is adding to this important knowledge base. These  data are fundamentally changing our understanding of tumor developmental pathways, not just for MB but also for cancer as a whole. They also provide a new class of targets for the development of rational, personalized therapeutic approaches. The mechanisms by which these chromatin remodelers are dysregulated in MB, and the consequences both for future basic research and for translation to the clinic, will be examined here.

 

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[209]

TÍTULO / TITLE:  - Erratum to: Early response evaluation for recurrent high grade gliomas treated with bevacizumab: a volumetric analysis using diffusion-weighted imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1105-7

AUTORES / AUTHORS:  - Hwang EJ; Cha Y; Lee AL; Yun TJ; Kim TM; Park CK; Kim JH; Sohn CH; Park SH; Kim IH; Heo DS; Lee SH; Choi SH

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea.

 

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[210]

TÍTULO / TITLE:  - Early response evaluation for recurrent high grade gliomas treated with bevacizumab: a volumetric analysis using diffusion-weighted imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1072-z

AUTORES / AUTHORS:  - Hwang EJ; Cha Y; Lee AL; Yun TJ; Kim TM; Park CK; Kim JH; Sohn CH; Park SH; Kim IH; Heo DS; Lee SH; Choi SH

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea.

RESUMEN / SUMMARY:  - Bevacizumab is a novel treatment for the recurrent high-grade gliomas (rHGG). However, only a subset of the patients shows response to the bevacizumab treatment and the response evaluation using conventional criteria is difficult. The purpose of our study was to evaluate the early response for rHGG treated with bevacizumab using volumetric analysis of diffusion-weighted imaging (DWI). Twenty-nine patients who received bevacizumab therapy for rHGG were included in our study. All patients received a conventional MRI scan with DWI before and after the initial bevacizumab dose. For each MRI, we measured the total volume of the T2 hyperintense lesion (HT2) of the rHGG, the volume of foci with a lower ADC value than that of the normal cortex (LADC), and the proportion of LADC to HT2 (LADC/HT2). The Changes in the HT2, LADC and LADC/HT2 after bevacizumab treatment were also determined. Thereafter, those volumetric data were compared to the progression free survival (PFS). After the analyses, we found a significant negative correlation between the PFS and the LADC for the post-bevacizumab ADC maps (r = -0.413, P = 0.026). The patients with an LADC of <2.5 cm3 showed a longer PFS than those with an LADC of >/=2.5 cm3 (median = 135 vs. 91 days, P = 0.002) on the post-bevacizumab ADC maps. A multiple linear regression analysis revealed that only the post-bevacizumab LADC was a significant predictor of the PFS (P = 0.026). In conclusion, the post-bevacizumab LADC can be used for an early response evaluation and can predict the PFS for rHGG patients treated with  bevacizumab.

 

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[211]

TÍTULO / TITLE:  - The role of DNA methylation and histone acetylation in the regulation of progesterone receptor isoforms expression in human astrocytoma cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Steroids. 2013 Mar 5;78(5):500-507. doi: 10.1016/j.steroids.2013.02.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.steroids.2013.02.010

AUTORES / AUTHORS:  - Hansberg-Pastor V; Gonzalez-Arenas A; Pena-Ortiz MA; Garcia-Gomez E; Rodriguez-Dorantes M; Camacho-Arroyo I

INSTITUCIÓN / INSTITUTION:  - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, Av. Universidad 3000, Ciudad Universitaria, Coyoacan 04510, Mexico, D.F., Mexico.

RESUMEN / SUMMARY:  - Many progesterone (P4) effects are mediated by its intracellular receptor (PR), which has two isoforms, PR-A and PR-B, each of them with different function and regulation. Differential PR expression in cancer cells has been associated to a PR isoform-specific promoter methylation. In astrocytomas, the most frequent and  aggressive brain tumors, PR isoforms expression is directly correlated to the tumor’s evolution grade. However, there is no evidence of the role of epigenetic  regulation of PR expression in astrocytomas. We evaluated the effect of the demethylating agent 5-aza-2’-deoxycytidine (5AzadC) and the histone deacetylase inhibitor trichostatin A (TSA) on PR expression in human astrocytoma cell lines U373 (grade III) and D54 (grade IV) by RT-PCR and Western blot. Total PR expression increased with 5muM 5AzadC treatment, whereas PR-B expression increased with 5 and 10muM 5AzadC treatment in U373 cells, but not in D54 cells.  In U373 cells, PR-A protein content augmented with 10muM 5AzadC treatment, while  PR-B content increased with 5 and 10muM 5AzadC. PR-B expression was not modified  by the TSA concentrations that were used, and the combination with 5AzadC did not change the effects of the latter. The study of 5AzadC effects on the number of astrocytoma cells showed that P4 treatment increased the number of U373 cells, whereas 5AzadC and the combined treatment with P4 reduced it. Our results suggest that PR-B expression is regulated by methylation and not by histone acetylation in U373 cells, and that DNA demethylation reduced the number of U373 cells.

 

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[212]

TÍTULO / TITLE:  - The influence of regional health system characteristics on the surgical management and receipt of post operative radiation therapy for glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1068-8

AUTORES / AUTHORS:  - Aneja S; Khullar D; Yu JB

INSTITUCIÓN / INSTITUTION:  - Yale School of Medicine, New Haven, CT, USA.

RESUMEN / SUMMARY:  - Despite a known optimal treatment protocol for the management of glioblastoma multiforme (GBM), many patients fail to receive complete surgical resection or post-operative radiation therapy (PORT). The underlying reasons behind this disparity are unclear. Our study investigates the influence of regional health system resources on the surgical management and PORT receipt in patients with GBM. Surgical intervention, PORT receipt and patient data for patients diagnosed  with GBM were obtained from the years 2004 to 2008 from the NCI Surveillance, Epidemiology, and End Results database and combined with the health system data from the Area Resource File. Four logistic models were constructed to test the effect of health system characteristics on surgical treatment choice and PORT receipt among health service areas (HSAs). We found that younger, married patients in HSAs with higher median incomes were significantly more likely to receive both gross total resection (p < 0.001, p < 0.001, p = 0.002) and PORT (p  < 0.001, p < 0.001, p = 0.008). The density of radiation oncology equipped hospitals was also a significant predictor of PORT receipt (p = 0.002). Our findings suggest regional variations in of neuro-oncology services and income may have impact on GBM management. Policies aimed at narrowing disparities in treatment may need to focus on addressing regional variations in oncology resources.

 

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[213]

TÍTULO / TITLE:  - Differentiation between Oligodendroglioma Genotypes Using Dynamic Susceptibility  Contrast Perfusion-Weighted Imaging and Proton MR Spectroscopy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3384

AUTORES / AUTHORS:  - Chawla S; Krejza J; Vossough A; Zhang Y; Kapoor GS; Wang S; O’Rourke DM; Melhem ER; Poptani H

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology and Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Oligodendrogliomas with 1p/19q chromosome LOH are more sensitive to chemoradiation therapy than those with intact alleles. The usefulness of dynamic susceptibility contrast-PWI-guided (1)H-MRS in differentiating these 2 genotypes was tested in this study.MATERIALS AND METHODS:Forty patients with oligodendrogliomas, 1p/19q LOH (n = 23) and intact alleles (n = 17), underwent MR imaging and 2D-(1)H-MRS. (1)H-MRS VOI was overlaid on FLAIR images to encompass the hyperintense abnormality on the largest cross-section of the neoplasm and then overlaid on CBV maps to coregister CBV maps with (1)H-MRS VOI. rCBV(max) values were obtained by measuring the CBV from  each of the selected (1)H-MRS voxels in the neoplasm and were normalized with respect to contralateral white matter. Metabolite ratios with respect to ipsilateral Cr were computed from the voxel corresponding to the rCBV(max) value. Logistic regression and receiver operating characteristic analyses were performed to ascertain the best model to discriminate the 2 genotypes of oligodendrogliomas. Qualitative evaluation of conventional MR imaging characteristics (patterns of tumor border, signal intensity, contrast enhancement, and paramagnetic susceptibility effect) was also performed to distinguish the 2 groups of oligodendrogliomas.RESULTS:The incorporation of rCBV(max) value and metabolite ratios (NAA/Cr, Cho/Cr, Glx/Cr, myo-inositol/Cr, and lipid + lactate/Cr) into the multivariate logistic regression model provided  the best discriminatory classification with sensitivity (82.6%), specificity (64.7%), and accuracy (72%) in distinguishing 2 oligodendroglioma genotypes. Oligodendrogliomas with 1p/19q LOH were also more associated with paramagnetic susceptibility effect (P < .05).CONCLUSIONS:Our preliminary results indicate the  potential of combing PWI and (1)H-MRS to distinguish oligodendroglial genotypes.

 

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[214]

TÍTULO / TITLE:  - RNA Interference with EAG1 Enhances Interferon Gamma Injury to Glioma Cells In Vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Mar;33(3):865-70.

AUTORES / AUTHORS:  - Cunha LC; Del Bel E; Pardo L; Stuhmer W; Titze-DE-Almeida R

INSTITUCIÓN / INSTITUTION:  - Technology for Gene Therapy Laboratory, University of Brasilia - UnB/FAV, Darcy Ribeiro campus, ICC - ASS 128, Brasilia, DF, Brazil. ricardo.titze@hotmail.com.

RESUMEN / SUMMARY:  - Aim: The aim of this study was to silence Ether a go-go 1 (EAG1) in glioma cells  by RNAi in order to further analyze whether silencing this channel would improve  injury caused by interferon gamma (IFN-gamma). MATERIALS AND METHODS: EAG1 silencing by the siRNAs EAG1hum_287 and EAG1hum_1727 (sequence targets 5’-GGCCTATTGTGTACAGCAATT-3’ and 5’-GGGACTTCCTGAAGCTCTATT-3’, respectively) was determined by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability was measured by the 3-(4,5)-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay. U-138MG glioma cells were injured by IFN-gamma (25 ng/ml, 24 h) with or without the RNAi for EAG1 by a non-viral vector (pKV10.1-3, 0.2 mug). RESULTS: EAG1hum_287 and EAG1hum_1727 caused 0.46- and 0.52-fold decrease in EAG1 mRNA content, respectively. RNAi for EAG1 by pKv10.1-3 strengthened the reduction in cell viability caused by IFN-gamma (11.4% versus 40.4%, p<0.05). CONCLUSION: The  present study reinforces the notion that EAG1 has a role in glioma biology, suggesting that this channel is a relevant player preserving the cell viability during IFN-gamma injury.

 

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[215]

TÍTULO / TITLE:  - T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial  cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1095-5

AUTORES / AUTHORS:  - Bhattacharya D; Singh MK; Chaudhuri S; Acharya S; Basu AK; Chaudhuri S

INSTITUCIÓN / INSTITUTION:  - Immunology Research Laboratory, Department of Laboratory Medicine, School of Tropical Medicine, 108 C. R. Avenue, Kolkata, 700073, India.

RESUMEN / SUMMARY:  - The crucial role of angiogenesis in malignant glioma progression makes it a potential target of therapeutic intervention in glioma. Previous studies from our lab showed that sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) has potent anti-neoplastic and immune stimulatory effects in rodent glioma model. In the present study we investigated the anti-angiogenic potential  of T11TS and deciphered the underlying molecular mechanism of its anti-angiogenic action in malignant glioma. Vascular endothelial growth factor (VEGF) signaling is crucial for initiating tumor angiogenic responses. The present preclinical study was designed to evaluate the effect of T11TS therapy on VEGF and VEGFR-2 expression in glioma associated brain endothelial cells and to determine the effects of in vivo T11TS administration on expression of PTEN and downstream pro-survival PI3K/Akt/eNOS pathway proteins in glioma associated brain endothelial cells. T11TS therapy in rodent glioma model significantly downregulated expression of VEGF along with its receptor VEGFR-2 and inhibited the expression of pro-survival PI3K/Akt/eNOS proteins in glioma associated brain  endothelial cells. Furthermore, T11TS therapy in glioma induced rats significantly upregulated brain endothelial cell PTEN expression, inhibited eNOS  phosphorylation and production of nitric oxide in glioma associated brain endothelial cells. Taken together our findings suggest that T11TS can be introduced as an effective angiogenesis inhibitor in human glioma as T11TS targets multiple levels of angiogenic signaling cascade impeding glioma neovascularisation.

 

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[216]

TÍTULO / TITLE:  - Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Feb 20. pii: S0360-3016(13)00077-1. doi: 10.1016/j.ijrobp.2013.01.014.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.01.014

AUTORES / AUTHORS:  - Brown AP; Barney CL; Grosshans DR; McAleer MF; de Groot JF; Puduvalli VK; Tucker SL; Crawford CN; Khan M; Khatua S; Gilbert MR; Brown PD; Mahajan A

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - PURPOSE: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. METHODS AND MATERIALS: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson  Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. RESULTS:  p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI  patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. CONCLUSIONS: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

 

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[217]

TÍTULO / TITLE:  - Expression of pituitary tumor transforming gene (PTTG) in human pituitary macroadenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumour Biol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0686-2

AUTORES / AUTHORS:  - Jia W; Lu R; Jia G; Ni M; Xu Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Beijing, 100050, Dongcheng District, China, jiawbj@yeah.net.

RESUMEN / SUMMARY:  - The purpose of this study was to elucidate the relationship between pituitary tumor transforming gene (PTTG) and invasiveness in pituitary macroadenomas and to determine the association between PTTG and both the tumor proliferative activity  marker proliferation cell nuclear antigen (PCNA) and the angiogenic factor basic  fibroblast growth factor. A total of 70 patients with pituitary adenomas who underwent transsphenoidal or craniotomy surgical resection were enrolled. The average age were 42.5 +/- 13.7 years (17-64 years) for the invasive group and 46.8 +/- 12.1 years (16-71 years) for the non-invasive group, with no significant difference (P = 0.179) between the two groups. RT-PCR analysis of a group of pituitary macroadenomas demonstrated that the expression levels of PTTG and PCNA  in invasive pituitary adenomas were significantly higher than in non-invasive pituitary adenomas. Both factors are both closely related to the invasive growth  of pituitary adenomas and may possibly serve as important markers of this growth. In conclusion, PTTG may promote invasive tumor growth by stimulating pituitary adenomas proliferation. The mechanisms of tumor growth promotion and invasion of  the surrounding structures by PTTG need to be further explored.

 

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[218]

TÍTULO / TITLE:  - Anthropometric factors in relation to risk of glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Causes Control. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10552-013-0178-0

AUTORES / AUTHORS:  - Little RB; Madden MH; Thompson RC; Olson JJ; Larocca RV; Pan E; Browning JE; Egan KM; Nabors LB

INSTITUCIÓN / INSTITUTION:  - Neuro-oncology Program, University of Alabama at Birmingham, FOT 1020, 510 20th St. South, Birmingham, AL, 35294, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Increased height and greater adiposity have been linked to an increased risk of many cancer types, though few large studies have examined these associations in glioma. We examined body weight and height as potential risk factors for glioma in a large US-based case-control study. METHODS: The analysis  included 1,111 glioma cases and 1,096 community controls. In a structured interview, participants reported their height and weight at 21 years of age, lowest and highest weight in adulthood, and weight 1-5 years in the past. RESULTS: Being underweight at age 21 (BMI < 18.5 kg/m2) was inversely associated  with the risk of glioma development. This protective association was observed in  both men and women, but reached statistical significance in women only (multivariate OR 0.68; 95 % CI 0.48, 0.96). When BMI at age 21 was assessed as a  continuous variate, a small but significant increase in risk was observed per unit increase in kg/m2 (OR 1.04; 95 % CI 1.02, 1.07). Adult height, recent body weight, and weight change in adulthood were not associated with glioma risk. All  results were similar among never smokers and were consistent after stratifying by glioma subtype. CONCLUSION: The present data suggest that a low body weight in early adulthood is associated with a reduced risk of glioma later in life. Results are consistent with previous studies in showing no material association of glioma risk with usual adult body weight. The present study does not support any association of adult stature with glioma risk.

 

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[219]

TÍTULO / TITLE:  - miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 29. pii: S0304-3835(13)00085-2. doi: 10.1016/j.canlet.2013.01.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.039

AUTORES / AUTHORS:  - Zhao S; Liu H; Liu Y; Wu J; Wang C; Hou X; Chen X; Yang G; Zhao L; Che H; Bi Y; Wang H; Peng F; Ai J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150001, People’s Republic of China. Electronic address: guangsz@hotmail.com.

RESUMEN / SUMMARY:  - Glioblastomas rely mainly on aerobic glycolysis to sustain proliferation and growth; however, little is known about the regulatory mechanisms of metabolism in glioblastoma stem cells. We show that miR-143 is significantly down-regulated in  glioma tissues and glioblastoma stem-like cells (GSLCs), while miR-143 over-expression inhibits glycolysis by directly targeting hexokinase 2, and promotes differentiation of GSLCs. Moreover, miR-143 inhibits proliferation of GSLCs under hypoxic conditions and decreases tumor formation capacity of GSLCs in vivo. We also show that a combination of miR-143 and 2-DG, a widely used glycolysis inhibitor, has synergistic effects against GSLCs. miR-143 is a potential therapeutic target for glioblastoma treatment.

 

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[220]

TÍTULO / TITLE:  - Genetic changes with prognostic value in histologically benign meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300580

AUTORES / AUTHORS:  - Barbera S; San Miguel T; Gil-Benso R; Munoz-Hidalgo L; Roldan P; Gonzalez-Darder J; Cerda-Nicolas M; Lopez-Gines C

RESUMEN / SUMMARY:  - Meningiomas add up to 25% of intracranial tumors. Although the majority is considered histologically benign, the prediction of their potential aggressiveness is still unclear. We studied the histopathology and aberrations of chromosomes 1p, 14, and 22 by FISH (fluorescence in situ hybridization) in histologically benign meningiomas of 70 patientsfor the purpose of defining the prognostic value of these alterations in tumoral progression and the risk of recurrence. According to the WHO histopathological criteria, the study set comprised 53 benign, 11 atypical, and 6 anaplastic meningiomas. In benign meningiomas, 25% of the cases displayed a normal karyotype, isolated monosomy 22  (36%), monosomy 22 + 1p deletion (14%), 1p deletion (10%), monosomy 22 + 14q deletion (5%), monosomy 22 + 1p deletion + 14q deletion (5%), or other alterations (5%). Grade II meningiomas presented losses in chromosome 14 in most  of the cases (67%), and Grade III meningiomas showed alterations in chromosome 14 in all patients. We observed an overall relapse rate of 31%: recurrence was observed in 19% of Grade I meningiomas, 64% of Grade II, and 83% of Grade III. 9  out of 10 recurrent cases revealed abnormalities in chromosomes 1 and 14, which was a notably higher incidence compared to the series of tumors without relapse.  Thus, benign meningiomas with cytogenetic alterations in chromosomes 1p and 14 may be more closely related to atypical meningiomas than benign meningiomas without these alterations, especially in terms of recurrence risk.

 

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[221]

TÍTULO / TITLE:  - Cavernous hemangioma of the cavernous sinus misdiagnosed as a meningioma: a case  report and MR imaging findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Imaging. 2013 Feb 28. pii: S0899-7071(13)00023-5. doi: 10.1016/j.clinimag.2013.01.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2013.01.018

AUTORES / AUTHORS:  - Hasiloglu ZI; Asik M; Kizilkilic O; Albayram S; Islak C

INSTITUCIÓN / INSTITUTION:  - Division of Neuroradiology, Department of Radiology, Istanbul University Cerrahpasa Medical School, 34303, Istanbul, Turkey. Electronic address: zhasiloglu@gmail.com.

RESUMEN / SUMMARY:  - Cavernous hemangioma (CH) is a benign vascular malformation. Intracranial CH is generally localized as an intracranial-intraaxial and responsible for 5-13% of all intracranial vascular malformations. Intracranial-extraaxial CHs are rare rather than intracranial-intraaxial CHs. Clinical findings, imaging characteristics, and surgical approach of extraaxial CHs are rather different than intraaxial CHs. Diagnosing cavernous sinus CH preoperatively is very important, but its radiological differential diagnosis is quite difficult. In this study, we present magnetic resonance imaging findings of a 48-year-old male  who was considered preoperatively to have meningioma but was diagnosed with cavernous sinus CH during surgery by pathological examination.

 

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[222]

TÍTULO / TITLE:  - Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar;112(1):39-48. doi: 10.1007/s11060-012-1034-x. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1034-x

AUTORES / AUTHORS:  - Liu H; Han D; Liu Y; Hou X; Wu J; Li H; Yang J; Shen C; Yang G; Fu C; Li X; Che H; Ai J; Zhao S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, People’s Republic of China.

RESUMEN / SUMMARY:  - Harmine hydrochloride (Har-hc), a derivative from Harmine which is a natural extractive from plants, has been considered for treatment of kinds of cancers and cerebral diseases. In this study, we found that Har-hc clearly decreased cell viability, induced apoptosis and inhibited Akt phosphorylation in glioblastoma cell lines. Moreover, Har-hc had the ability to inhibit self-renewal and promote  differentiation of glioblastoma stem like cells (GSLCs) accompanied by inhibition of Akt phosphorylation. Especially, we demonstrated that Har-hc inhibited neurosphere formation of human primary GSLCs. In vivo test also confirmed Har-hc  decreased the tumorigenicity of GSLCs. Thus we conclude that Har-hc has potent anti-cancer effects in glioblastoma cells, which is at least partially via inhibition of Akt phosphorylation. Administration of Har-hc may act as a new approach to glioblastoma treatment.

 

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[223]

TÍTULO / TITLE:  - Radiation Optic Neuropathy After Proton Beam Therapy for Optic Nerve Sheath Meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuroophthalmol. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WNO.0b013e31828292b8

AUTORES / AUTHORS:  - Siddiqui JD; Loeffler JS; Murphy MA

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology (JDS), Rhode Island Hospital, Providence, Rhode Island; Department of Radiation Oncology (JSL), Massachusetts General Hospital, Boston, Massachusetts; and Department of Ophthalmology (MAM), Providence Veterans Affairs Medical Center, Providence, Rhode Island.

RESUMEN / SUMMARY:  - ABSTRACT:: A 63-year-old woman with a 1-month history of blurred vision in the right eye was found to have a right optic nerve sheath meningioma. She was treated with fractionated proton beam therapy using a total dose of 50.4 cobalt gray equivalent (CGE) in 1.8 CGE fractions, with subsequent improvement in vision. Twenty-seven months later, the patient reported a 6-week history of progressive blurred vision in her right eye. Magnetic resonance imaging revealed  enhancement of the right optic nerve consistent with radiation optic neuropathy (RON). We are unaware of any previous reports of RON when radiotherapy doses fall within the current recommended guidelines of <55 CGE fractionated into daily doses <2 CGE.

 

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[224]

TÍTULO / TITLE:  - Copper induces cellular senescence in human glioblastoma multiforme cells through downregulation of Bmi-1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar 6. doi: 10.3892/or.2013.2333.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2333

AUTORES / AUTHORS:  - Li Y; Hu J; Guan F; Song L; Fan R; Zhu H; Hu X; Shen E; Yang B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

RESUMEN / SUMMARY:  - Most human tumor cells, including glioblastoma multiforme (GBM) cells, have aberrant control of cell aging and apoptosis. Subcytotoxic concentrations of oxidative or stresscausing agents, such as hydrogen peroxide, may induce human cell senescence. Thus, induction of tumor cells into premature senescence may provide a useful in vitro model for developing novel therapeutic strategy to combat tumors. In the present study, we assessed the molecular mechanism(s) underlying senescence in GBM cells induced by copper sulfate. Following pretreatment with subcytotoxic concentrations of copper sulfate, U87-MG tumor cells showed typical aging characteristics, including reduced cell proliferation, cell enlargement, increased level of senescence-associated beta-galactosidase (SA beta-gal) activity, and overexpression of several senescence-associated genes, p16, p21, transforming growth factor beta-1 (TGF-beta1), insulin growth factor binding protein 3 (IGFBP3) and apolipoprotein J (ApoJ). We further demonstrated that the Bmi-1 pathway was downregulated in GBM cells in parallel with the induced senescence. The present study for the first time demonstrates the ability of copper to induce GBM cell senescence by downregulating Bmi-1.

 

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[225]

TÍTULO / TITLE:  - Differential language trajectories following treatment for pediatric posterior fossa tumor: an investigation of four cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - NeuroRehabilitation. 2013;32(1):165-83. doi: 10.3233/NRE-130834.

            ●● Enlace al texto completo (gratuito o de pago) 3233/NRE-130834

AUTORES / AUTHORS:  - Lewis FM; Murdoch BE

INSTITUCIÓN / INSTITUTION:  - Centre for Neurogenic Communication Disorders Research, School of Health and Rehabilitation Sciences, University of QLD, Brisbane, Australia. f.lewis@uq.edu.au

RESUMEN / SUMMARY:  - Up to 85% of children treated for brain tumor survive beyond five years; hence optimizing quality of life in survivorship has become a priority. As multiple factors contribute to the heterogeneity of neurocognitive and language outcomes for individual children following treatment, a means of monitoring subsequent development is needed for the individual child, particularly when pre-morbid performance indices are not available. The current study investigated the use of  developmental language trajectories as a means of monitoring language development subsequent to treatment for tumors located within the posterior fossa. The language skills of four children treated for posterior fossa tumor (PFT) were monitored over time (range of monitoring: 2-6 years) and the resultant trajectories were plotted against the trajectories based on tests’ normative data as well as the trajectories of control children drawn from each child’s local community. Each child’s trajectory was considered in terms of age-appropriate developmental gains and discussed regarding the need for ongoing clinical monitoring of emerging, developing or established language skills. The study’s findings highlight the heterogeneity of language outcomes following PFT. The utility of the application of developmental trajectories for the provision of individualized post-treatment support is discussed.

 

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[226]

TÍTULO / TITLE:  - Impact of carbon ion irradiation on epidermal growth factor receptor signaling and glioma cell migration in comparison to conventional photon irradiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Radiat Biol. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 3109/09553002.2013.766769

AUTORES / AUTHORS:  - Stahler C; Roth J; Cordes N; Taucher-Scholz G; Mueller-Klieser W

INSTITUCIÓN / INSTITUTION:  - Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz , Mainz.

RESUMEN / SUMMARY:  - Purpose: Radiotherapy of malignant gliomas may be limited by an interference of radiation with the migratory potential of tumor cells. Therefore, the influence of conventional photon and modern carbon ion ((12)C) irradiation on glioblastoma  cell migration and on epidermal growth factor receptor-related (EGFR) signaling was investigated in vitro. Materials and methods: EGFR overexpressing glioblastoma cell lines U87 EGFR++ and LN229 EGFR++ were irradiated with 0, 2 or  6 Gy photons or (12)C heavy ions. Migration was analyzed 24 h after treatment in  a standardized Boyden Chamber assay. At different time points EGFR, protein kinase B (PKB/AKT) and extracellular signal-related kinases (ERK1/2) were analyzed by Western blotting. Results: 2 Gy photon irradiation increased U87 EGFR++ migration and decreased motility of LN229 EGFR++ cells. Heavy ions decreased migration of both cell lines as a function of dose. There was a time-dependent increase of phosphorylation of EGFR, AKT and ERK1/2 in U87 EGFR++  after 2 Gy photon irradiation. After heavy ion irradiation EGFR, AKT or ERK1/2 remained unchanged. Conclusions: Results suggest that the impact of irradiation on tumor cell migration depends on radiation type and cell line. Photons, but not heavy ions, potentially contribute to treatment failure by increasing EGFR-related tumor cell migration.

 

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[227]

TÍTULO / TITLE:  - Intracranial hemangiopericytoma: MR imaging findings and diagnostic usefulness of minimum ADC values.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Mar 5. doi: 10.1002/jmri.24075.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24075

AUTORES / AUTHORS:  - Liu G; Chen ZY; Ma L; Lou X; Li SJ; Wang YL

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, People’s Liberation Army General Hospital, China.

RESUMEN / SUMMARY:  - PURPOSE: To describe the clinical and magnetic resonance (MR) imaging features of primary intracranial hemangiopericytoma (HPC), and to assess the usefulness of minimum apparent diffusion coefficient (MinADC) value of HPC in the differential  diagnosis from meningioma. MATERIALS AND METHODS: From 2004 to 2010, fifteen patients with primary intracranial HPC were included. The clinical data, conventional MR findings (n = 15), and diffusion weighted image (DWI) features (n = 10) were retrospectively analyzed. MinADC value of the HPCs (n = 10) was measured on ADC map and was compared with that of meningiomas (n = 37). RESULTS:  In 15 cases of HPC, isointense signal was detected on both T1-weighted images (T1WI) and T2-weighted images (T2WI) in 11 cases, and heterogeneous signal was demonstrated in 4 cases. Isointensity (n = 9) and iso- and slight hyperintensity  (n = 1) were shown on DWI. The mean MinADC value of HPC [(1.116 +/- 0.127) x 10-3 mm2 /s] was significantly higher than that of meningioma [(0.875 +/- 0.104) x 10-3 mm2 /s] (P < 0.01). For the differentiation between HPC and meningioma, the  critical cutoff MinADC value was 0.991 x 10-3 mm2 /s, which provided the best combination of sensitivity (88.9%) and specificity (82.4%). CONCLUSION: MinADC value may be an useful tool for the differentiation between HPC and meningioma. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.

 

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[228]

TÍTULO / TITLE:  - Sunitinib for the Treatment of Metastatic Paraganglioma and Vasoactive Intestinal Polypeptide-Producing Tumor (VIPoma).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pancreas. 2013 Mar;42(2):348-52. doi: 10.1097/MPA.0b013e31825c53fa.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825c53fa

AUTORES / AUTHORS:  - Bourcier ME; Vinik AI

INSTITUCIÓN / INSTITUTION:  - From the Strelitz Diabetes Center and Neuroendocrine Unit, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.

RESUMEN / SUMMARY:  - OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare tumors of the endocrine and nervous systems. Whereas early surgical resection can significantly reduce tumor mass, there are few data available concerning the control of hormonal secretion and associated symptoms. Studies have shown that the tyrosine kinase inhibitor sunitinib significantly prolongs progression-free survival in patients with pancreatic NETs. Here, we present 2 case reports of sunitinib in patients with different types of NETs. METHODS: The patients were a  12-year-old boy with metastatic vasoactive intestinal polypeptide-producing tumor (VIPoma) and a 70-year-old woman with metastatic paraganglioma/NET. Both were treated in an outpatient clinical setting. Sunitinib was titrated to 37.5 mg on a continuous daily dosing schedule in the patient with VIPoma, and the dose was 50  mg/d (4 weeks on, 2 weeks off) in the patient with the paraganglioma/NET. RESULTS: The patient with the paraganglioma/NET had a confirmed complete radiographic response and the patient with VIPoma had a confirmed partial response (Response Evaluation Criteria in Solid Tumors). In both patients, improvements were observed in biochemical tumor markers, clinical responses, and  quality of life. CONCLUSIONS: In these patients, sunitinib reduced biochemical markers and stabilized or reduced tumor bulk and may therefore be a potential therapeutic option for these tumor types.

 

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[229]

TÍTULO / TITLE:  - Embolized meningiomas: risk of overgrading and neo-angiogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1117-3

AUTORES / AUTHORS:  - Barresi V; Branca G; Granata F; Alafaci C; Caffo M; Tuccari G

INSTITUCIÓN / INSTITUTION:  - Department of Human Pathology, University of Messina, Messina, Italy, vbarresi@unime.it.

RESUMEN / SUMMARY:  - Pre-operative embolization (POE) of meningiomas may induce histological changes which simulate malignancy, possibly resulting in overgrading. Aims of the present study were to identify clues to distinguish malignancy-related features from POE-related changes and to test for overgrading the grading scheme currently in use, in embolized meningiomas. In addition, we aimed to analyze whether the POE procedure may stimulate neo-angiogenesis in meningiomas. The histological features of a series of embolized meningiomas were evaluated and considered for grading assessment. In the same cases neo-angiogenesis was quantified by the evaluation of microvessel density (MVD) and correlated with the interval between  POE and surgery. Necrosis and macronucleoli represented common findings in embolized meningiomas. Nonetheless, in most of the cases, necrosis showed an abrupt line of demarcation from the viable tumour tissue, and macronucleoli were  restricted to peri-necrotic areas. Suggesting that these were POE-associated changes, exclusion of necrotic areas with an abrupt line of transition and focal  macronucleoli from grading assessment resulted in increased specificity and positive predictive value in the identification of recurring meningiomas. In our  cohort, MVD significantly increased with the time between POE and surgery, suggesting that POE procedure may induce neo-angiogenesis in meningiomas. In conclusion, a risk of overgrading there exists in embolized meningiomas, as a consequence of the frequent evidence of necrosis and prominent nucleoli in these  tumours. In order to avoid overgrading, we suggest that necrosis showing an abrupt line of demarcation and focal peri-necrotic macronucleoli are not included in grading assessment. Also, caution should be used in the interpretation of MVD  as a prognostic factor in embolized meningioma, as it may also result from POE procedure.

 

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[230]

TÍTULO / TITLE:  - Down-regulation of miR-106b suppresses the growth of human glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):179-89. doi: 10.1007/s11060-013-1061-2. Epub 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1061-2

AUTORES / AUTHORS:  - Zhang A; Hao J; Wang K; Huang Q; Yu K; Kang C; Wang G; Jia Z; Han L; Pu P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery; Tianjin Medical University General Hospital; Tianjin  Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration of the Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China.

RESUMEN / SUMMARY:  - Recently, many studies have found that the miR-106b ~25 cluster plays an oncogenic role in tumor progression. However, the precise role of each microRNAs  (miRNAs) in the cluster is not yet clear. In the present study, we examined the expression of miR-106b in glioma samples and a tissue microarray by real-time PCR and in situ hybridization (ISH), respectively, finding that miR-106b is overexpressed in the majority of gliomas. Meanwhile, the expression of miR-106b was positively correlated with tumor grade (p < 0.05). The transfection of a miR-106b anti-sense oligonucleotide (ASON) into three human glioma cell lines (U251, LN229 and TJ905) suppressed the proliferation of these cells. Moreover, the growth of xenograft tumors in nude mice treated with miR-106b ASON was significantly impaired. A bioinformatics analysis predicted that RBL2 may be the  target of miR-106b, and dual-luciferase reporter assays identified RBL2, but not  RB1 or RBL1, as a target of miR-106b. These results suggest that miR-106b facilitates glioma cell growth by promoting cell cycle progression through the negative regulation of RBL2.

 

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[231]

TÍTULO / TITLE:  - A “drug cocktail” delivered by microspheres for the local treatment of rat glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Microencapsul. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02652048.2013.774446

AUTORES / AUTHORS:  - Allhenn D; Neumann D; Beduneau A; Pellequer Y; Lamprecht A

INSTITUCIÓN / INSTITUTION:  - Laboratory of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, University of Bonn , Germany.

RESUMEN / SUMMARY:  - For the treatment of glioblastoma multiforme, an “anticancer drug cocktail” delivered by biodegradable poly-lactide-co-glycolide (PLGA)-microspheres is proposed. Celecoxib, etoposide, and elacridar were encapsulated by an oil/water emulsification solvent evaporation method. Drug-loaded microspheres were analyzed for their physicochemical properties and evaluated in a rat glioblastoma model. Microspheres had a mean diameter 10-20 microm, and encapsulation rates varied upon lipophilicity of the drug (celecoxib: 97.4 +/- 0.4%; elacridar: 98.1 +/- 0.3%; and etoposide: 38.7 +/- 8.3%). Drug release of celecoxib and elacridar resulted in a burst (t50: 3.1 h and 1.0 h, respectively) while etoposide release  was slower (t50: 45.3 h). The comparison of celecoxib (p = 0.021) and etoposide microspheres (p = 0.002) as well as their combination (p = 0.011) led to a significant increase in the probability of survival compared to blank microspheres. Local delivery of celecoxib and etoposide microspheres was found to be suitable for the treatment of glioblastoma in rats although simultaneous drug  administration did not improve the therapeutic outcome.

 

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[232]

TÍTULO / TITLE:  - H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Pathol. 2013 Mar;139(3):345-9. doi: 10.1309/AJCPABOHBC33FVMO.

            ●● Enlace al texto completo (gratuito o de pago) 1309/AJCPABOHBC33FVMO

AUTORES / AUTHORS:  - Gielen GH; Gessi M; Hammes J; Kramm CM; Waha A; Pietsch T

INSTITUCIÓN / INSTITUTION:  - Institute of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Gerrit.Gielen@ukb.uni-bonn.de

RESUMEN / SUMMARY:  - Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation occurred in 35 of 129 glioblastomas (27.1%) and in 5 of 28 (17.9%) anaplastic astrocytomas. None of the other tumor entities showed H3F3A K27M mutation. Because H3F3A K27M mutations occur exclusively in pediatric diffuse high-grade astrocytomas, analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms.

 

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[233]

TÍTULO / TITLE:  - An unbalanced translocation involving loss of 10q26.2 and gain of 11q25 in a pedigree with autism spectrum disorder and cerebellar juvenile pilocytic astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Med Genet A. 2013 Apr;161(4):787-91. doi: 10.1002/ajmg.a.35841. Epub 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ajmg.a.35841

AUTORES / AUTHORS:  - Minhas HM; Pescosolido MF; Schwede M; Piasecka J; Gaitanis J; Tantravahi U; Morrow EM

INSTITUCIÓN / INSTITUTION:  - Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Psychiatry and Human Behavior, Butler Hospital, The Warren  Alpert Medical School of Brown University, Providence, Rhode Island; Rhode Island Consortium for Autism Research and Treatment (RI-CART), The Warren Alpert Medical School of Brown University, Providence, Rhode Island.

RESUMEN / SUMMARY:  - We report on a pedigree with a pair of brothers each with minor anomalies, developmental delay, and autistic-symptoms who share an unbalanced translocation  (not detectable by karyotype). The unbalanced translocation involves a 7.1 Mb loss of the terminal portion of 10q, and a 4.2 Mb gain of 11q. One of the brothers also developed a cerebellar juvenile pilocytic astrocytoma. The father was found to be a balanced carrier and the couple had a previous miscarriage. We  demonstrate that the breakpoint for the triplicated region from chromosome 11 is  adjacent to two IgLON genes, namely Neurotrimin (NTM) and Opioid Binding Protein/Cell Adhesion Molecule-like (OPCML). These genes are highly similar neural cell adhesion molecules that have been implicated in synaptogenesis and oncogenesis, respectively. The children also have a 10q deletion and are compared to other children with the 10q deletion syndrome which generally does not involve autism spectrum disorders (ASDs) or cancer. Together these data support a role for NTM and OPCML in developmental delay and potentially in cancer susceptibility. © 2013 Wiley Periodicals, Inc.

 

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[234]

TÍTULO / TITLE:  - Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Res. 2013 Feb;33(2):609-13.

AUTORES / AUTHORS:  - El Hindy N; Bankfalvi A; Herring A; Adamzik M; Lambertz N; Zhu Y; Siffert W; Sure U; Sandalcioglu IE

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital Essen, Hufelandstrasse 55, 45122  Essen, Germany. nicolai.elhindy@uk-essen.de

RESUMEN / SUMMARY:  - Aquaporin-1 (AQP1) is a water channel protein, widely expressed in epithelial and endothelial cells, known to be associated with invasion, angiogenesis, cell migration and formation of tumour oedema in several malignancies. We investigated the pattern of immunohistochemical expression of AQP1 in human astrocytomas and its role in tumour angiogenesis and infiltration. Immunohistochemical staining of AQP1 was performed in astrocytomas of grade II, III and IV. Intensity and pattern of expression were analysed. Non-neoplastic brain tissues served as control. There was a significant increase in the intensity of AQP1 expression from low-grade to high-grade astrocytomas (p<0.0001). Despite intense expression of AQP1 in astrocytoma grade IV, we observed strong regional differences. AQP1 up-regulation was predominantly located perivascularly, in areas of tumour infiltration, distant from the necrotic tumour core. AQP1 expression correlates with the grade of malignancy and is associated with angiogenesis, as well as with invasion of grade IV tumour in areas of tumour infiltration. Suppression of AQP1  expression could be a potential means of reducing invasion of glioma cells.

 

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[235]

TÍTULO / TITLE:  - Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Radiol. 2013 Feb;86(1022):20120414. doi: 10.1259/bjr.20120414.

            ●● Enlace al texto completo (gratuito o de pago) 1259/bjr.20120414

AUTORES / AUTHORS:  - Sherriff J; Tamangani J; Senthil L; Cruickshank G; Spooner D; Jones B; Brookes C; Sanghera P

INSTITUCIÓN / INSTITUTION:  - Hall-Edwards Radiotherapy Research Group, Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK. Jennifer.Sherriff@nhs.net

RESUMEN / SUMMARY:  - OBJECTIVE: Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this  evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ). METHODS: A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm. RESULTS: 105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere. CONCLUSION: Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients. ADVANCES IN KNOWLEDGE: Central relapse remains the predominant pattern  of failure following chemoradiotherapy for glioblastomas.

 

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[236]

TÍTULO / TITLE:  - Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Gerontol. 2013 Feb 21. pii: S0531-5565(13)00047-8. doi: 10.1016/j.exger.2013.02.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.exger.2013.02.016

AUTORES / AUTHORS:  - Brandhorst S; Wei M; Hwang S; Morgan TE; Longo VD

INSTITUCIÓN / INSTITUTION:  - Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.

RESUMEN / SUMMARY:  - Short-term starvation (STS) protects normal cells while simultaneously sensitizing malignant cells to high-dose chemotherapeutic drugs in mice and possibly patients. The fasting-dependent protection of normal cells and sensitization of malignant cells depends, in part, on reduced levels of insulin-like growth factor-1 (IGF-1) and glucose. Calorie restricted diets with defined macronutrient (carbohydrate, protein, fat) ratios were evaluated for the  effects on stress sensitization markers and protection in mice treated with high-dose chemotherapy. We show that short-term CR significantly reduced both glucose and IGF-1 levels, but when specific macronutrient deficiencies were tested, only the complete lack of proteins reduced IGF-1 levels. Short-term 50% CR combined with either severe protein-deficiency or ketogenic diets improved chemotoxicity resistance similarly to the standard 50% CR, but did not result in  the high protection caused by STS. Notably, a high protein diet reversed the beneficial effects of short-term CR. In a subcutaneous mouse model of glioma, feeding a low protein (4% calories from protein) diet for more than 20days did not delay tumor progression once the tumor became palpable. Also, cycles of short-term (3days) 50% CR did not augment the chemotherapy efficacy of cisplatin  in a murine breast cancer model. These results indicate that the protection from  chemotoxicity and retardation of the progression of certain tumors achieved with  fasting is not obtained with short-term calorie and/or macronutrient restriction.

 

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[237]

TÍTULO / TITLE:  - Expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR1  and VEGFR2 in primary and recurrent WHO grade III meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Mar 11.

AUTORES / AUTHORS:  - Baumgarten P; Brokinkel B; Zinke J; Zachskorn C; Ebel H; Albert FK; Stummer W; Plate KH; Harter PN; Hasselblatt M; Mittelbronn M

INSTITUCIÓN / INSTITUTION:  - Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany.

RESUMEN / SUMMARY:  - Aims: WHO grade III meningiomas are malignant neoplasms for which new and more targeted treatment strategies are urgently needed. Although clinical trials investigating anti-angiogenic vascular endothelial growth factor (VEGF) targeted  therapies are currently recruiting, knowledge about the expression of VEGF and VEGF receptors remains to be determined. Methods: We investigated the expression  of VEGF and its receptors VEGFR1 and VEGFR2 in 32 WHO grade III meningioma samples by immunohistochemistry. Furthermore, we performed in-situ hybridisation  for VEGF. Results: We found low VEGF expression in tumor and endothelial cells. Highest VEGF expression levels were seen in peri-necrotic tumor cells potentially suffering from hypoxia. VEGFR1 and 2 were virtually absent on tumor cells, although endothelial cells displayed significantly higher levels reaching stronger expression for VEGFR2 than VEGFR1. Conclusions: Our findings showing constant expression levels of VEGFR2 in endothelial cells serve as a first indication that the use of small tyrosine kinase inhibitors such as Sunitinib directly targeting the VEGF-receptors might be worth testing, also in the clincial context in cases of therapy-refractory meningiomas. Further investigations are needed to study the response to drugs targeting the VEGF pathway in relation to the expression profile of VEGF and its receptors in high grade meningiomas.

 

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[238]

TÍTULO / TITLE:  - Clinical neuropathology practice news 2-2013: immunohistochemistry pins IDH in glioma - molecular testing procedures under scrutiny.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Mar-Apr;32(2):82-3.

AUTORES / AUTHORS:  - Preusser M; Bent Mv

INSTITUCIÓN / INSTITUTION:  - Department of Medicine I and Comprehensive Cancer Center CNS Unit, Medical University of Vienna, Austria. matthias.preusser@meduniwien.ac.at

RESUMEN / SUMMARY:  - Isocitrate dehydrogenase 1 (IDH1) gene mutations occur in ~ 60 - 90% of diffuse and anaplastic gliomas and secondary glioblastomas. IDH status is strongly associated with patient survival times and IDH testing is relevant for clinical patient management and for stratification in clinical trials. A recent interlaboratory ring trial shows that immunohistochemistry is a highly reliable method to detect the most common IDH mutation (R132H), while IDH gene sequencing  is less robust. These results support initial immunohistochemistry and subsequent gene sequencing in cases with negative or inconclusive immunostaining result as valid algorithm for IDH testing. Furthermore, they highlight the need for strict  quality control of DNA-based biomarker analyses on formalinfixed and paraffin-embedded tumor samples.

 

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[239]

TÍTULO / TITLE:  - Aggressive Silent GH Pituitary Tumor Resistant to Multiple Treatments, Including  Temozolomide.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Invest. 2013 Mar;31(3):190-6. doi: 10.3109/07357907.2013.775293.

            ●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2013.775293

AUTORES / AUTHORS:  - Batisse M; Raverot G; Maqdasy S; Durando X; Sturm N; Montoriol PF; Kemeny JL; Chazal J; Trouillas J; Tauveron I

INSTITUCIÓN / INSTITUTION:  - Department Endocrinologie, CHU Clermont-Ferrand , Clermont-Ferrand , France,1.

RESUMEN / SUMMARY:  - Temozolomide (TMZ) has been proposed as a therapeutic option in aggressive pituitary tumors. Among the published cases, GH expressing tumors were rare. We describe a patient with initially benign silent GH adenoma that transformed into  an aggressive GH secreting tumor resistant to usual therapy. MGMT expression was  high and the MGMT promoter was unmethylated. Before this aggressive course, patient received three cycles of TMZ; no response was observed. Four cases of GH  aggressive tumor treated by TMZ have been reported. Response to TMZ was observed  in one of these four patients. Predictive factors of failure of TMZ remain unclear.

 

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[240]

TÍTULO / TITLE:  - Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Ethnopharmacol. 2013 Mar 27;146(2):440-8. doi: 10.1016/j.jep.2012.12.015. Epub  2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jep.2012.12.015

AUTORES / AUTHORS:  - Ishola IO; Chaturvedi JP; Rai S; Rajasekar N; Adeyemi OO; Shukla R; Narender T

INSTITUCIÓN / INSTITUTION:  - Pharmacology Division, Central Drug Research Institute, Lucknow-226 001, Uttar Pradesh, India; Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria.

RESUMEN / SUMMARY:  - ETHNOPHARMACOLOGICAL RELEVANCE: Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. AIM OF THE STUDY: This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-alpha production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. MATERIALS AND METHODS: Rat astrocytoma cells (C6) were stimulated with LPS (10mug/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3mug/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-alpha level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test.  RESULTS: LPS (10mug/ml) significantly (P<0.05) stimulated C6 cells to release nitrite, ROS, MDA, and TNF-alpha generation while GSH was down regulated in comparison to control. However, amentoflavone significantly (P<0.05) attenuated nitrite, ROS, MDA and TNF-alpha generation and also up regulated the level of GSH. Amentoflavone per se did not have any significant effect on C6 and THP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (P<0.05) reduced number of writhes and also increase pain threshold in hot plate test. It produced time course significant (P<0.05) decrease in oedema formation in rodents. DISCUSSION AND CONCLUSION: Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in  neuroinflammation associated disorders.

 

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[241]

TÍTULO / TITLE:  - Recurrent exophytic meningioma in pregnancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):475-8. doi: 10.1097/AOG.0b013e31827e6251.

AUTORES / AUTHORS:  - Chow MS; Mercier PA; Omahen DA; Wood SL; Johnson JA

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics & Gynecology, Foothills Hospital, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - BACKGROUND: Meningiomas are slow-growing tumors that may present in pregnancy because of accelerated growth. We present the case of a recurrent meningioma in two separate pregnancies in the same woman. CASE: A 35-year-old woman presented at 30 weeks of gestation with limb weakness, vomiting, and a progressive decreased level of consciousness with an enlarging forehead mass. Imaging revealed a massive extra-axial exophytic tumor. An emergency craniotomy was performed, complicated by massive blood loss. Final pathology showed a grade I meningioma positive for progesterone receptors. Maternal-fetal outcome was good,  with return of normal neurologic status and elective delivery at 38 weeks of gestation. CONCLUSION: Pregnancy is associated with accelerated meningioma growth and recurrence. Treatment during pregnancy is possible and requires a multidisciplinary approach.

 

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[242]

TÍTULO / TITLE:  - Kif3a is necessary for initiation and maintenance of medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt041

AUTORES / AUTHORS:  - Barakat MT; Humke EW; Scott MP

INSTITUCIÓN / INSTITUTION:  - Departments of Developmental Biology, Genetics, and Bioengineering.

RESUMEN / SUMMARY:  - Medulloblastoma (MB) cells arise from granule neuron precursors (GNPs) that have  lost growth control. During normal development, GNPs divide in response to Sonic  hedgehog (SHH), a ligand that binds to the patched (PTCH) receptor on GNPs. If one copy of the Ptch gene is lost, as in human Gorlin’s syndrome and in Ptch+/- mice, MBs may form. Proper transduction of the SHH signal critically depends on primary cilia. Loss of primary cilia results in improper signal reception and failure to properly activate SHH target genes. KIF3a, part of a kinesin motor, is required for formation of primary cilia. Here, we use tamoxifen-induced ablation  of Kif3a in GNPs of postnatal Ptch+/- mouse cerebella to show that KIF3a is necessary for MB formation. To investigate the importance of primary cilia in established tumors, we deleted Kif3a from cultured cells and from tumor cell grafts. The loss of Kif3a from established tumors led to their growth arrest and  regression. MBs behave as if they are addicted to the presence of primary cilia.  These results underscore the potential utility of agents that disrupt cilia for the treatment of Hh pathway-related MBs.

 

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[243]

TÍTULO / TITLE:  - Expression of Indoleamine 2,3-dioxygenase and Correlation with Pathological Malignancy in Gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31828cf945

AUTORES / AUTHORS:  - Mitsuka K; Kawataki T; Satoh E; Asahara T; Horikoshi T; Kinouchi H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.

RESUMEN / SUMMARY:  - BACKGROUND:: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme involved in immune tolerance and tumor immune escape processes. Recently, IDO expression has been found to correlate with the prognosis of malignant tumors, but the implication of IDO in glioma progression remains unknown. OBJECTIVE:: To  investigate the relationship between IDO expression and histological malignancy in gliomas. METHODS:: IDO expression was examined in a total of 75 surgical specimens obtained from 68 patients with glioma using immunohistochemical staining. The 75 specimens included 15 diffuse astrocytomas, 21 anaplastic astrocytomas, and 39 glioblastomas. Six of 39 glioblastomas were secondary glioblastomas, transforming from grade II or III glioma, which had been determined at the first surgery. IDO expression rate was compared in each histological grade, and patient’s survival was analyzed. RESULTS:: Expression of  IDO was found in 72 of 75 gliomas at varying intensities. Stronger expression of  IDO was more likely to be observed in malignant gliomas compared to low-grade gliomas. IDO expression in the 6 cases of secondary glioblastoma was stronger than in the initial low-grade glioma. Survival analysis using the Kaplan-Meier method revealed that grade IV patients with strong IDO expression had significantly worse OS rates (p=.037) than patients with weak IDO expression. CONCLUSION:: IDO expressed more strongly in both primary and secondary glioblastoma tissue than low-grade glioma and may affect clinical outcome. If IDO promotes glioma cells to escape from the immune system, IDO may be a crucial therapeutic target for malignant gliomas.

 

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[244]

TÍTULO / TITLE:  - Diazepam Inhibits Proliferation of Human Glioblastoma Cells Through Triggering a  G0/G1 Cell Cycle Arrest.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Anesthesiol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1097/ANA.0b013e31828bac6a

AUTORES / AUTHORS:  - Chen J; Ouyang Y; Cao L; Zhu W; Zhou Y; Zhou Y; Zhang H; Yang X; Mao L; Lin S; Lin J; Hu J; Yan G

INSTITUCIÓN / INSTITUTION:  - Departments of daggerNeonatology double daggerAnesthesiology, Sun Yat-sen Memorial Hospital Departments of *Pharmacology parallelGuangzhou Cellproteck Pharmaceutical Co. Ltd paragraph signMicrobiology, Zhongshan School of Medicine,  Sun Yat-sen University, Guangzhou, P.R. China section signDepartment of Anesthesiology, State University of New York-Downstate Medical Center, Brooklyn,  NY.

RESUMEN / SUMMARY:  - BACKGROUND:: Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive malignancy in humans. Its rapid proliferation is a major obstacle to successful treatment. Patients with GBM often suffer from psychological disturbances associated with poor prognosis and physical discomfort. Diazepam is  one of the most frequently used benzodiazepines (BZs) in cancer patients for its  desirable psychotropic effects. The central effects of BZs are mediated by the activation of central BZ receptors. This study investigates whether diazepam has  inhibitory effect on proliferation of GBM cell line T98G and explores its possible mechanism. METHODS:: Cell viability and proliferation were respectively  determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and 5-bromo-2’-deoxyuridine (BrdU) incorporation assay. Cell cycle distribution was examined by flow cytometry. Western blot with specific protein antibodies was used to detect regulatory proteins involved in cell cycle regulation. RESULTS:: Diazepam significantly decreased the proliferation of T98G  cells in a dose-dependent and time-dependent manner. This effect was not reversed by the central BZ receptor antagonist flumazenil or the peripheral BZ receptor antagonist PK11195, indicating that it was not mediated by BZ receptors. Flow cytometry indicated that diazepam caused a cell accumulation in G0/G1 phase, thereby contributing to cell proliferation inhibition. Furthermore, our findings  showed that lessened phosphorylation of Rb accounted for diazepam-induced G0/G1 phase arrest. CONCLUSION:: Diazepam inhibits the proliferation of human GBM T98G  cells by inducing G0/G1 phase arrest. Diazepam has potential to be a lead for new drugs in GBM therapy because of its antitumor activity.

 

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[245]

TÍTULO / TITLE:  - Tetramethylpyrazine (TMP) protects cerebral neurocytes and inhibits glioma by down regulating chemokine receptor CXCR4 expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 21. pii: S0304-3835(13)00243-7. doi: 10.1016/j.canlet.2013.03.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.015

AUTORES / AUTHORS:  - Chen Z; Pan X; Georgakilas AG; Chen P; Hu H; Yang Y; Tian S; Xia L; Zhang J; Cai X; Ge J; Yu K; Zhuang J

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 S. Xianlie Road, Guangzhou 510060, China.

RESUMEN / SUMMARY:  - The survival in patients with malignant gliomas still remains limited and novel treatment strategies are urgently needed. Tetramethylpyrazine (TMP) extracted from the Chinese herb Chuanxiong, has been suggested to have a therapeutic potential towards glioma primarily through its neural protection activity. However, the exact mechanisms correlating TMP’s antitumor function and neural protection have not been yet elucidated. Thus, this study aimed to investigate TMP’s molecular target in tumor inhibition and neural protection. The primary cultured cerebral neurocytes were treated with 100muM TMP for 14days in vitro. We found TMP can effectively promote neurons survival, compared to controls. TMP effectively inhibits H2O2-induced rise of [Ca2+]i and glutamate releasing in cerebral neurocytes, compared to controls. In addition, we verify previous results that TMP significantly decreases the migration and proliferation of C6 glioma cells. Using glioma-neuronal co-culturing system, we further confirm TMP bioactivity in inhibition of glioma cells and protection of cerebral neurocytes.  More importantly, our study demonstrates that the expression of chemokine receptor, CXCR4, which plays a key role in tumor development and various neurodegenerative diseases, is significantly decreased in both cerebral neurocytes and C6 glioma cells with TMP treatment, cultured alone or co-cultured. Compared with CXCR4 antagonist, AMD3100, TMP is more effective on glioma inhibition and neural protection. Glutamate concentration in medium of co-culturing system was lower after treatment with 100muM TMP. Therefore, our findings suggest that TMP-mediated suppression of C6 gliomas and neural protection involves inhibition of CXCR4 expression. Thus, this study provides new insights into TMP’s therapeutic potential in the treatment of malignant gliomas.

 

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[246]

TÍTULO / TITLE:  - The role of intraoperative magnetic resonance imaging in complex meningioma surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Magn Reson Imaging. 2013 Feb 28. pii: S0730-725X(13)00042-8. doi: 10.1016/j.mri.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mri.2012.12.005

AUTORES / AUTHORS:  - Soleman J; Fathi AR; Marbacher S; Fandino J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kantonsspital Aarau, 5001 Aarau, Switzerland.

RESUMEN / SUMMARY:  - Intraoperative magnetic resonance imaging (iMRI) has gained importance in the treatment of gliomas and sellar tumors. In intracranial meningiomas, the extent of surgical tumor removal is one of the most important factors in the prevention  of tumor recurrence and patient survival. Complex meningiomas located at the skull base or near eloquent brain regions show higher recurrence rates, morbidity and mortality. The aim of this study was to evaluate whether iMRI contributes to  more extensive surgical resection in these tumors. Patients undergoing complex meningioma resection using iMRI from January 2007 to January 2011 were included in this study. The indication for iMRI-guided tumor resection included patients presenting with meningiomas located in the skull base or compressing eloquent brain areas in whom a radical resection was considered to be difficult. Intraoperative 0.15-T MRI scan (PoleStar; Medtronic Navigation, Louisville, CO, USA) was performed before and after maximal possible resection using standard microsurgical and neuronavigation techniques. All patients underwent fluorescence-guided resection. The following data were analyzed: tumor localization, histological grade, Simpson resection grade, duration of the procedure, iMRI scan time, iMRI findings, resection extent based on postresection iMRI, hospitalization time, surgical complications and outcome, and MRI follow-up 2-27months postoperation. Twenty-seven consecutive patients undergoing complex meningioma resection using iMRI were included. In this series, only one patient (3.4%) underwent resection of tumor remnant after iMRI, although without improvement of the Simpson resection grade. Temporary neurologic deficits were found in 8 patients (27.6%) postoperatively, whereas 11 patients (37.9%) had permanent postoperative neurologic deficits. In one case (3.4%), fatal postoperative bleeding occurred which was not detected by iMRI. Our results show  that iMRI has no influence on intraoperative strategy in terms of resection grade or detection of early postoperative complications. The benefits of iMRI in complex meningioma surgery are therefore doubtful; however, it may still prove to be effective in certain subsets of complex meningiomas.

 

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[247]

TÍTULO / TITLE:  - Assessment of the utility of the 2-micro thulium laser in surgical removal of intracranial meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Lasers Surg Med. 2013 Mar;45(3):148-54. doi: 10.1002/lsm.22123. Epub 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lsm.22123

AUTORES / AUTHORS:  - Passacantilli E; Anichini G; Lapadula G; Salvati M; Lenzi J; Santoro A

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Sciences, Neurosurgery, University of Rome “Sapienza”, Rome 00161, Italy. e.passacantilli@gmail.com.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE: Since the 1960s, lasers have been used in neurosurgery  for surgical removal of intracranial tumors. Because of its limited penetration (2 mm) through tissues and its wavelength, which is useful in water medium, the 2-micro thulium laser has been applied primarily in urology. Its features are attractive for application under microscope magnification during neurosurgical procedures. The aim of this study was to evaluate the usefulness of the 2-micro thulium laser during microsurgical removal of intracranial meningiomas. MATERIALS AND METHODS: Twenty patients with a diagnosis of intracranial meningiomas were treated with surgical intervention using a 2-micro thulium laser together with bipolar forceps, cavitron ultrasonic surgical aspirator (CUSA) and traditional microdissection instruments. Surgical removal was divided in four phases: (1) dissection from the external structures; (2) coagulation and debulking; (3) dissection from the deep structures; and (4) coagulation and removal of the basal implant. During all these steps, we evaluated the percentage of usage of the 2-micro thulium laser comparing them with bipolar forceps and ultrasonic aspirator and blunt dissection. RESULTS: Thulium laser was used mainly during phases 2 and 4 for 43% and 48.7% of the total removal, respectively. Although also useful during phases 1 and 3, it was only used for 2.2% and 31.3%, respectively: traditional dissection with scissors and forceps was preferred. CONCLUSIONS: Thulium laser seems to be a useful aid in the surgery of intracranial meningiomas, especially to debulk, shrink, and coagulate the mass and the basal implant. Lasers Surg. Med. 45: 148-154, 2013. © 2013 Wiley Periodicals, Inc.

 

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[248]

TÍTULO / TITLE:  - Distinct roles of CSF family cytokines in macrophage infiltration and activation  in glioma progression and injury response.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pathol. 2013 Mar 20. doi: 10.1002/path.4192.

            ●● Enlace al texto completo (gratuito o de pago) 1002/path.4192

AUTORES / AUTHORS:  - Sielska M; Przanowski P; Wylot B; Gabrusiewicz K; Maleszewska M; Kijewska M; Zawadzka M; Kucharska J; Vinnakota K; Kettenmann H; Kotulska K; Grajkowska W; Kaminska B

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland.

RESUMEN / SUMMARY:  - Gliomas attract brain resident (microglia) and peripheral macrophages and re-program these cells into immunosuppressive, pro-invasive cells. M-CSF (macrophage colony stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM-CSF (granulocyte-macrophage colony stimulating factor encoded by the CSF2 gene) but not M-CSF when compared to normal astrocytes. Knockdown of GM-CSF in GL261 glioma cells strongly reduced microglia-dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1+ cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM-CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro-invasive activation in GM-CSF-depleted gliomas. Deficiency of M-CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1+ cells, but impaired accumulation of  Iba1+ cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and  in response to injury. The expression of CSF2 (but not CSF1) was highly up-regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM-CSF triggers and drives the alternative activation of tumour-infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas.

 

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[249]

TÍTULO / TITLE:  - Dual effect of serum amyloid a on the invasiveness of glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mediators Inflamm. 2013;2013:509089. doi: 10.1155/2013/509089. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/509089

AUTORES / AUTHORS:  - Knebel FH; Albuquerque RC; Massaro RR; Maria-Engler SS; Campa A

INSTITUCIÓN / INSTITUTION:  - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Avenida Prof. Lineu Prestes, 580 Cidade Universitaria, 05508-000 Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - Evidence sustains a role for the acute-phase protein serum amyloid A (SAA) in carcinogenesis and metastasis, and the protein has been suggested as a marker for tumor progression. Nevertheless, the demonstration of a direct activity of SAA on tumor cells is still incipient. We have investigated the effect of human recombinant SAA (rSAA) on two human glioma cell lines, A172 and T98G. rSAA stimulated the [(3)H]-thymidine incorporation of both lines, but had dual effects on migration and invasiveness which varied according to the cell line. In T98G, the rSAA increased migration and invasion behaviors whereas in A172 it decreased  these behaviors. These findings agree with the effect triggered by rSAA on matrix metalloproteinases (MMPs) activities measured in a gelatinolytic assay. rSAA inhibited activity of both MMPs in A172 cells while increasing them in T98G cells. rSAA also affected the production of compounds present in the tumor microenvironment that orchestrate tumor progression, such as IL-8, the production of reactive oxygen species (ROS) and nitric oxide (NO). We also observed that both lines expressed all three of the isoforms of SAA: SAA1, SAA2, and SAA4. These data suggest that some tumor cells are responsive to SAA and, in these cases, SAA may have a role in cancer progression that varies according to the cell type.

 

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[250]

TÍTULO / TITLE:  - MicroRNA-153 is tumor suppressive in glioblastoma stem cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Biol Rep. 2013 Apr;40(4):2789-98. doi: 10.1007/s11033-012-2278-4. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11033-012-2278-4

AUTORES / AUTHORS:  - Zhao S; Deng Y; Liu Y; Chen X; Yang G; Mu Y; Zhang D; Kang J; Wu Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People’s Republic of China, guangsz@hotmail.com.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is lethal brain tumor thought to arise from GBM stem cells (GBM-SCs). MicroRNAs carry out post-transcriptional regulation of various cellular processes that modulate the stemness properties of GBM-SCs. Here, we investigated the critical role of miR-153 in GBM-SCs. First, GBM-SCs were isolated from six GBM specimens. These GBM-SCs formed GBM spheres, expressed markers associated with neural stem cells, and possessed the capacity for self-renewal and multilineage differentiation. Then qRT-PCR analysis showed that  miR-153 expression was down-regulated in GBM tissues relative to normal brain tissues, and in CD133 positive cells relative to CD133 negative cells. This project demonstrates for the first time that transient transfection of miR-153 into GBM-SCs can inhibit their stemness properties, such as impairing self-renewal ability and inducing differentiation. Meanwhile, miR-153 can also repress GBM-SCs growth and induce apoptosis. Altogether, these results indicate that reactivation of miR-153 expression suggests novel therapeutic strategies for GBM-SCs.

 

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[251]

TÍTULO / TITLE:  - Murine cell line model of proneural glioma for evaluation of anti-tumor therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1082-x

AUTORES / AUTHORS:  - Sonabend AM; Yun J; Lei L; Leung R; Soderquist C; Crisman C; Gill BJ; Carminucci A; Sisti J; Castelli M; Sims PA; Bruce JN; Canoll P

INSTITUCIÓN / INSTITUTION:  - Gabriele Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University Medical Center, 1130 St. Nicholas Ave Rm. 1001, New York, NY, 10032, USA.

RESUMEN / SUMMARY:  - Molecular subtypes of glioblastoma (GBM) with distinct alterations have been identified. There is need for reproducible, versatile preclinical models that resemble specific GBM phenotypes to facilitate preclinical testing of novel therapies. We present a cell line-based murine proneural GBM model and characterize its response to radiation therapy. Proneural gliomas were generated  by injecting PDGF-IRES-Cre retrovirus into the subcortical white matter of adult  mice that harbor floxed tumor suppressors (Pten and p53) and stop-floxed reporters. Primary cell cultures were generated from the retrovirus induced tumors and maintained in vitro for multiple passages. RNA sequencing-based expression profiling of the resulting cell lines was performed. The tumorigenic potential of the cells was assessed by intracranial injection into adult naive mice from different strains. Tumor growth was assessed by bioluminescence imaging (BLI). BLI for tumor cells and brain slices were obtained and compared to in vivo BLI. Response to whole-brain radiation was assessed in glioma-bearing animals. Intracranial injection of Pdgf+Pten-/-p53-/-luciferase+ glioma cells led to formation of GBM-like tumors with 100 % efficiency (n = 48) and tumorigenesis was retained for more than 3 generations. The cell lines specifically resembled proneural GBM based on expression profiling by RNA-Seq. Pdgf+Pten-/-p53-/-luciferase+ cell number correlated with BLI signal. Serial BLI  measured tumor growth and correlated with size and location by ex vivo imaging. Moreover, BLI predicted tumor-related mortality with a 93 % risk of death within  5 days following a BLI signal between 1 x 108 and 5 x 108 photons/s cm2. BLI signal had transient but significant response following radiotherapy, which corresponded to a modest survival benefit for radiated mice (p < 0.05). Intracranial injection of Pdgf+Pten-/-p53-/-luciferase+ cells constitutes a novel and highly reproducible model, recapitulating key features of human proneural GBM, and can be used to evaluate tumor-growth and response to therapy.

 

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[252]

TÍTULO / TITLE:  - Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nitric Oxide. 2013 Apr 1;30:17-25. doi: 10.1016/j.niox.2013.01.003. Epub 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.niox.2013.01.003

AUTORES / AUTHORS:  - Weidensteiner C; Reichardt W; Shami PJ; Saavedra JE; Keefer LK; Baumer B; Werres A; Jasinski R; Osterberg N; Weyerbrock A

INSTITUCIÓN / INSTITUTION:  - Dept. of Radiology/Medical Physics, University Medical Center Freiburg, Breisacher Strasse 60a, 79106 Freiburg, Germany. Electronic address: claudia.weidensteiner@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - Nitric oxide (NO) released from NO donors can be cytotoxic in tumor cells and can enhance the transport of drugs into brain tumors by altering blood-tumor barrier  permeability. The NO donor JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] releases NO upon enzymatic activation selectively in cells overexpressing glutathione-S-transferases (GSTs) such as gliomas. Thus, JS-K-dependent NO effects - especially on cell viability and vascular permeability - were investigated in U87 glioma cells in vitro and in an orthotopic U87 xenograft model in vivo by magnetic resonance imaging (MRI). In vitro experiments showed dose-dependent antiproliferative and cytotoxic effects in U87 cells. In addition, treatment of U87 cells with JS-K resulted in a dose-dependent activation of soluble guanylate cyclase and intracellular accumulation of cyclic guanosine monophosphate (cGMP) which was irreversibly inhibited by the selective inhibitor  of soluble guanylate cyclase ODQ (1H-[1,2,4]oxadiazolo(4,3a)quinoxaline-1-one). Using dynamic contrast enhanced MRI (DCE-MRI) as a minimally invasive technique,  we demonstrated for the first time a significant increase in the DCE-MRI read-out initial area under the concentration curve (iAUC60) indicating an acute increase  in blood-tumor barrier permeability after i.v. treatment with JS-K. Repeated MR imaging of animals with intracranial U87 gliomas under treatment with JS-K (3.5mumol/kg JS-K 3x/week) and of untreated controls on day 12 and 19 after tumor inoculation revealed no significant changes in tumor growth, edema formation or tumor perfusion. Immunohistochemical workup of the brains showed a significant antiproliferative effect of JS-K in the gliomas. Taken together, in vitro and in  vivo data suggest that JS-K has antiproliferative effects in U87 gliomas and opens the blood-tumor barrier by activation of the NO/cGMP signaling pathway. This might be a novel approach to facilitate entry of therapeutic drugs into brain tumors. DCE-MRI is a non-invasive, repeatable imaging modality to monitor biological effects of NO donors and other experimental therapeutics in intracranial tumor models.

 

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[253]

TÍTULO / TITLE:  - Surgical outcomes in recurrent glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.2.JNS121731

AUTORES / AUTHORS:  - Hoover JM; Nwojo M; Puffer R; Mandrekar J; Meyer FB; Parney IF

INSTITUCIÓN / INSTITUTION:  - Departments of Neurologic Surgery and.

RESUMEN / SUMMARY:  - Object The object of this study was to assess outcomes after surgery for recurrent intracranial glioma. Methods The authors retrospectively reviewed cases involving adult patients with intracranial glioma patients undergoing initial surgery (biopsy or resection) and one or more additional surgeries at their institution. Results A total of 323 operations were performed in 131 patients. The median survival was 76 months after first surgery, 36 months after second, 24 months after third, and 26.5 months after 4 or more surgeries. The overall complication rate was 12.8% after first surgery, 27.0% after second (OR 2.52, p = 0.0068), 22.0% after third (OR 1.92, not statistically significant [NS]), and 22.2% after 4 or more (OR 1.95, NS). Neurological complications occurred in 4.8%  of patients at first surgery, 12.1% at second (OR 2.7, p = 0.0437), 8.2% at third (OR 1.75, NS), and 11.1% at 4 or more surgeries (OR 2.4583, NS). Regional complications occurred in 6.2% after first surgery, 9.9% after second surgery (OR 2.30, p = 0.095), 13.7% after third surgery (OR 3.31, p = 0.015), and 22.2% after 4 or more surgeries (OR 5.95, p = 0.056). Systemic complications occurred in 3.2% after first surgery, in 7.3% after second surgery (OR 2.3, p = 0.NS), in 4.1% after third surgery (OR 1.3, NS), and 0% after 4 or more surgeries. Reduction in  Karnofsky Performance Status score occurred in 0% after first surgery, 8.1% after second surgery (OR 3.13, p = 0.0018), 10.2% after third surgery (OR 5.52, p < 0.0001), and 11.1% after 4 or more surgeries (OR 1.037, NS). Conclusions Postoperative survival is relatively prolonged but complication risk increases in patients with glioma who undergo multiple cranial surgeries. The largest increase in neurological risk occurs between the first and second surgery. In contrast, regional complication risk increases consistently with each surgery. The risk of  systemic complications is not significantly altered with increasing surgeries. However, these complications only result in a modestly increased risk of functional decline after 2 or more surgeries. These findings may help counsel patients considering multiple glioma surgeries.

 

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[254]

TÍTULO / TITLE:  - Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cell Endocrinol. 2013 Apr 30;369(1-2):107-18. doi: 10.1016/j.mce.2013.01.010. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mce.2013.01.010

AUTORES / AUTHORS:  - Sviridonov L; Dobkin-Bekman M; Shterntal B; Przedecki F; Formishell L; Kravchook S; Rahamim-Ben Navi L; Bar-Lev TH; Kazanietz MG; Yao Z; Seger R; Naor Z

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.

RESUMEN / SUMMARY:  - The GnRH receptor (GnRHR) mediates the pituitary functions of GnRH, as well as its anti-proliferative effects in sex hormone-dependent cancer cells. Here we compare the signaling of GnRHR in pituitary gonadotrope cell lines vs. prostate cancer cell lines. We first noticed that the expression level of PKCalpha, PKCbetaII and PKCepsilon is much higher in alphaT3-1 and LbetaT2 gonadotrope cell lines vs. LNCaP and DU-145 cell lines, while the opposite is seen for PKCdelta. Activation of PKCalpha, PKCbetaII and PKCepsilon by GnRH is relatively transient  in alphaT3-1 and LbetaT2 gonadotrope cell lines and more prolonged in LNCaP and DU-145 cell lines. On the otherhand, the activation and re-distribution of the above PKCs by PMA was similar for both gonadotrope cell lines and prostate cancer cell lines. Activation of ERK1/2 by GnRH and PMA was robust in the gonadotrope cell lines, with a smaller effect observed in the prostate cancer cell lines. The Ca(2+) ionophore A23187 stimulated ERK1/2 in gonadotrope cell lines but not in prostate cancer cell lines. GnRH, PMA and A23187 stimulated JNK activity in gonadotrope cell lines, with a more sustained effect in prostate cancer cell lines. Sustained activation of p38 was observed for PMA and A23187 in Du-145 cells, while p38 activation by GnRH, PMA and A23187 in LbetaT2 cells was transient. Thus, differential expression and re-distribution of PKCs by GnRH and  the transient vs. the more sustained nature of the activation of the PKC-MAPK cascade by GnRH in gonadotrope cell lines vs. prostate cancer cell lines respectively, may provide the mechanistic basis for the cell context-dependent differential biological responses observed in GnRH interaction with pituitary gonadotropes vs. prostate cancer cells.

 

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[255]

TÍTULO / TITLE:  - Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mod Pathol. 2013 Feb 22. doi: 10.1038/modpathol.2012.166.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.166

AUTORES / AUTHORS:  - Boots-Sprenger SH; Sijben A; Rijntjes J; Tops BB; Idema AJ; Rivera AL; Bleeker FE; Gijtenbeek AM; Diefes K; Heathcock L; Aldape KD; Jeuken JW; Wesseling P

INSTITUCIÓN / INSTITUTION:  - 1] Department of Pathology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands [2] Department of Neurology, RUNMC, Nijmegen, The Netherlands.

RESUMEN / SUMMARY:  - The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n=110, anaplastic n=118 and glioblastoma n=333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse  glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients >50 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular  diagnostics is a powerful tool to obtain prognostically relevant information for  glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such  as age and histopathological diagnosis.Modern Pathology advance online publication, 22 February 2013; doi:10.1038/modpathol.2012.166.

 

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[256]

TÍTULO / TITLE:  - Paradoxical Role of 3-Methyladenine in Pyocyanin-Induced Toxicity in 1321N1 Astrocytoma and SH-SY5Y Neuroblastoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Toxicol. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1091581813482146

AUTORES / AUTHORS:  - McFarland AJ; Grant GD; Perkins AV; Flegg C; Davey AK; Allsopp TJ; Renshaw G; Kavanagh J; McDermott CM; Anoopkumar-Dukie S

INSTITUCIÓN / INSTITUTION:  - Griffith University, Queensland, Australia.

RESUMEN / SUMMARY:  - The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous  system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 mumol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 mumol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2  (PGE2), and leukotriene B4 (LTB4) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE2, and LTB4 in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma  cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE2, and LTB4 production.

 

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[257]

TÍTULO / TITLE:  - Risks of presurgical embolization of feeding arteries in 137 intracranial meningeal tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):707-14. doi: 10.1007/s00701-013-1632-1. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1632-1

AUTORES / AUTHORS:  - Law-Ye B; Clarencon F; Sourour NA; Di Maria F; Jean B; Bonneville F; Biondi A; Iosif C; Navarro S; Cornu P; Chiras J

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, Pitie-Salpetriere Hospital, APHP, Paris VI University, 47, Bd de l’Hopital, 75013, Paris, France.

RESUMEN / SUMMARY:  - BACKGROUND: Embolization of extra-axial tumors has shown its effectiveness in reducing perisurgical blood loss. However, the complication rate of this procedure is poorly reported. We aimed to evaluate the rate of procedure-related  complications and their risk factors. METHODS: From 1998 to 2011, 193 consecutive patients (141 females, 52 males; mean age = 52.9 years) were referred to our institution for presurgical embolization of an extra-axial tumor (meningiomas: n  = 178; solitary fibrous tumors: n = 3; other: n = 12). Of 193 patients, 137 (71 %) underwent 141 embolizations (by microparticles: n = 133; by glue: n = 8). The  remaining 56 patients (29 %) were not embolized due to unstable catheterization or dangerous anastomosis. Occurrence of neurological deficit was systematically assessed during and after embolization. The risk factors of procedure-related neurological complications were evaluated. RESULTS: Neither intratumoral hemorrhage nor procedure-related death was reported. Two of the 137 patients (1.5 %) had ischemic events with permanent neurological deficit after microparticles embolization. One patient had cortical blindness and one had hemiparesis. Both complications involved the vertebrobasilar system. The first patient had direct intratumoral anastomosis between the middle and the posterior meningeal arteries  (PMA); the second one had reflux in the vertebral artery during particles injection in the PMA. Occurrence of ischemic complication was not related to the  size of the microparticles. CONCLUSIONS: Though embolization of meningeal tumors  is considered as a safe technique, serious neurological complications may occur.  Opening of dangerous anastomosis or uncontrolled reflux caused two neurological complications (1.5 %). The size of the microparticles was not associated with the occurrence of neurological event.

 

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[258]

TÍTULO / TITLE:  - A hypoxia-inducible factor (HIF)-3alpha splicing variant, HIF-3alpha4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced  HIF-3alpha4.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Mar 29;433(1):139-44. doi: 10.1016/j.bbrc.2013.02.044. Epub 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.044

AUTORES / AUTHORS:  - Ando H; Natsume A; Iwami K; Ohka F; Kuchimaru T; Kizaka-Kondoh S; Ito K; Saito K; Sugita S; Hoshino T; Wakabayashi T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan;  Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima, Japan.

RESUMEN / SUMMARY:  - Hypoxia inducible factor is a dominant regulator of adaptive cellular responses to hypoxia and controls the expression of a large number of genes regulating angiogenesis as well as metabolism, cell survival, apoptosis, and other cellular  functions in an oxygen level-dependent manner. When a neoplasm is able to induce  angiogenesis, tumor progression occurs more rapidly because of the nutrients provided by the neovasculature. Meningioma is one of the most hypervascular brain tumors, making anti-angiogenic therapy an attractive novel therapy for these tumors. HIF-3alpha has been conventionally regarded as a dominant-negative regulator of HIF-1alpha, and although alternative HIF-3alpha splicing variants are extensively reported, their specific functions have not yet been determined.  In this study, we found that the transcription of HIF-3alpha4 was silenced by the promoter DNA methylation in meningiomas, and inducible HIF-3alpha4 impaired angiogenesis, proliferation, and metabolism/oxidation in hypervascular meningiomas. Thus, HIF-3alpha4 could be a potential molecular target in meningiomas.

 

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[259]

TÍTULO / TITLE:  - Involvement of estrogen receptor beta5 in the progression of glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Res. 2013 Mar 29;1503:97-107. doi: 10.1016/j.brainres.2013.02.004. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.brainres.2013.02.004

AUTORES / AUTHORS:  - Li W; Winters A; Poteet E; Ryou MG; Lin S; Hao S; Wu Z; Yuan F; Hatanpaa KJ; Simpkins JW; Yang SH

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and Neuroscience, Institute for Alzheimer’s Disease and Aging Research, University of North Texas Health Science Center, Fort Worth,  TX 76107, USA.

RESUMEN / SUMMARY:  - Emerging evidence suggests a decline of ERbeta expression in various peripheral cancers. ERbeta has been proposed as a cancer brake that inhibits tumor proliferation. In the current study, we have identified ERbeta5 as the predominant isoform of ERbeta in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERbeta transcription in U87 cells, suggesting elevated ERbeta expression in glioma might be induced by the hypoxic stress in the tumor. Over-expression of either ERbeta1  or ERbeta5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway. In addition, ERbeta5 inhibited the MAPK/ERK pathway. In U87 cells, ERbeta1 and ERbeta5 inhibit cell proliferation and reduced cells in the S+G2/M phase. Our findings suggest hypoxia induced ERbeta5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERbeta5 might serve as a therapeutic target for the treatment of glioma.

 

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[260]

TÍTULO / TITLE:  - Spinal cord ependymoma in children - Results of postoperative radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiother Oncol. 2013 Mar 11. pii: S0167-8140(13)00059-5. doi: 10.1016/j.radonc.2013.02.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2013.02.007

AUTORES / AUTHORS:  - Katarzyna P; Anna SG; Marzanna C

INSTITUCIÓN / INSTITUTION:  - Department of Radiotherapy, M. Sklodowska-Curie Memorial Cancer Center - Institute, Warsaw, Poland. Electronic address: 3kasia@wp.pl.

RESUMEN / SUMMARY:  - PURPOSE: A retrospective study was performed to evaluate the results of postoperative radiation therapy of spinal cord ependymoma in children. METHODS AND MATERIALS: Between 1984 and 2005, 28 children with spinal cord ependymoma were treated with radiotherapy, after surgery and in three cases after chemotherapy as well. Median age at diagnosis was 13.3years (range from 4.7 to 16.2years). Ependymoma myxopapillare was identified in 13, ependymoma in 12 and anaplastic ependymoma in 3 cases. RESULTS: With a median follow-up of 8.7years (range from 3 to 25years) 22 patients were alive. The overall survival rate of 2, 5 and 10years was 93%, 85% and 77% respectively, whereas progression free survival rate was 82%, 74% and 74% respectively. Patients with myxopapillary ependymoma had significantly better 5-year overall survival rate 100% than those  with other histopathological types 60% (p=0.016). There were 2 relapse incidences observed among 13 patients with myxopapillary ependymoma, both underwent repeated surgery and reirradiation. In the group of 20 patients with gross total resection the overall 5-year survival rate was 100% in comparison with 62.5% with partial surgery, but it did not achieve statistical significance. CONCLUSIONS: The histological type of ependymoma myxopapillary was a statistical significant favourable prognostic factor. The gross total resection with adjuvant radiotherapy allows obtaining a high total survival rate.

 

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[261]

TÍTULO / TITLE:  - Glioblastoma with oligodendroglial component represents a subgroup of glioblastoma with high prevalence of IDH1 mutation and association with younger age.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1073-y

AUTORES / AUTHORS:  - Ha SY; Kang SY; Do IG; Suh YL

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.

RESUMEN / SUMMARY:  - Glioblastoma with an oligodendroglial component (GBMO) is recognized as a subgroup of glioblastoma (GBM); however, the molecular and clinicopathological characteristics of GBMO are obscure. We evaluated the methylation status of MGMT, IDH1/2 mutation, deletions of 1p and 19q and expression of IDH1, p53, p16, CD151, and galectin3 proteins in 42 GBMOs (32 primary and 10 secondary tumors). Our aims were to correlate our molecular findings with clinicopathologic features, and to  compare molecular-to-clinical correlations in the 42 GBMOs with the corresponding correlations in 45 GBMs. GBMO was subdivided into two subgroups according to the  predominant cell component comprising >50 % of tumors: the astrocytic predominant type (GBMO-A) and oligodendroglioma predominant type (GBMO-O). Methylation of MGMT, IDH1/2 mutation, and co-deletion of 1p and 19q were found in 31.0, 26.2, and 17.9 % of patients with GBMO, respectively. Clinicopathological and molecular characteristics did not differ significantly between GBMO-A and GBMO-O. However,  patients with GBMO-O experienced better outcomes than patients with GBMO-A (p = 0.007). On multivariate analysis the predominant cell type was an independent prognostic factor in overall survival [hazard ratio 4.2 (95 % confidence interval 1.4-12.8), p = 0.011]. When compared to patients with classic GBM, those with GBMO were younger (49.21 vs. 57.47, p = 0.003) and more frequently had tumors with IDH1 mutation (23.8 vs. 4.4 %, p = 0.009). Survival was similar in patients  with GBMO and with classic GBM. Based on these results, GBMO may represent a subgroup of GBM that is associated with IDH1 mutation and younger age, although similar to classic GBM in prognosis.

 

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[262]

TÍTULO / TITLE:  - The impact of adjuvant stereotactic radiosurgery on atypical meningioma recurrence following aggressive microsurgical resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS12414

AUTORES / AUTHORS:  - Hardesty DA; Wolf AB; Brachman DG; McBride HL; Youssef E; Nakaji P; Porter RW; Smith KA; Spetzler RF; Sanai N

INSTITUCIÓN / INSTITUTION:  - Division of Neurological Surgery, Barrow Neurological Institute, and.

RESUMEN / SUMMARY:  - Object Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define  the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome. Methods The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical  meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively. Results Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%-20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32  patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p < 0.0001), but postoperative SRS was not associated with improved PFS in all patients or in  only those with subtotal resections. Conclusions Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up  may reveal a therapeutic benefit in the future.

 

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[263]

TÍTULO / TITLE:  - Three-dimensional amide proton transfer MR imaging of gliomas: Initial experience and comparison with gadolinium enhancement.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Feb 25. doi: 10.1002/jmri.24067.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24067

AUTORES / AUTHORS:  - Zhou J; Zhu H; Lim M; Blair L; Quinones-Hinojosa A; Messina SA; Eberhart CG; Pomper MG; Laterra J; Barker PB; van Zijl PC; Blakeley JO

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA. jzhou@mri.jhu.edu.

RESUMEN / SUMMARY:  - PURPOSE: To investigate the feasibility of a three-dimensional amide-proton-transfer (APT) imaging sequence with gradient- and spin-echo readouts at 3 Tesla in patients with high- or low-grade gliomas. MATERIALS AND METHODS: Fourteen patients with newly diagnosed gliomas were recruited. After B(0) inhomogeneity correction on a voxel-by-voxel basis, APT-weighted images were reconstructed using a magnetization-transfer-ratio asymmetry at offsets of +/-3.5 ppm with respect to the water resonance. Analysis of variance post hoc tests were used for statistical evaluations, and results were validated with pathology. RESULTS: In six patients with gadolinium-enhancing high-grade gliomas, enhancing  tumors on the postcontrast T(1) -weighted images were consistently hyperintense on the APT-weighted images. Increased APT-weighted signal intensity was also clearly visible in two pathologically proven, high-grade gliomas without gadolinium enhancement. The average APT-weighted signal was significantly higher  in the lesions than in the contralateral normal-appearing brain tissue (P < 0.001). In six low-grade gliomas, including two with gadolinium enhancement, APT-weighted imaging showed iso-intensity or mild punctate hyperintensity within  all the lesions, which was significantly lower than that seen in the high-grade gliomas (P < 0.001). CONCLUSION: The proposed three-dimensional APT imaging sequence can be incorporated into standard brain MRI protocols for patients with  malignant gliomas. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.

 

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[264]

TÍTULO / TITLE:  - Primary CNS germ cell tumors: current epidemiology and update on treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Jun;30(2):496. doi: 10.1007/s12032-013-0496-9. Epub 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0496-9

AUTORES / AUTHORS:  - Thakkar JP; Chew L; Villano JL

INSTITUCIÓN / INSTITUTION:  - Department of Medicine and Neurology, University of Kentucky, 800 Rose St., CC447, Lexington, KY 40536-0093, USA.

RESUMEN / SUMMARY:  - Primary central nervous system (CNS) germ cell tumors (GCTs) are a heterogeneous  group of lesions that account for 0.5 % of all primary brain and CNS tumors, occurring at an incidence rate of 0.10 per 100,000 person-years in the United States with approximately 90 % of the cases before the age of 20 years. Primary CNS GCTs demonstrate a remarkable difference in incidence based on gender and location within the brain with males having a 15:1 incidence in the pineal region while the gender incidence is nearly 1:1 in the rest of the brain. Also, historically the incidence was noted to be significantly higher in Japan and East Asia, but recent studies in Japan demonstrate similar incidence as in the United  States. They are broadly classified as germinomas and non-germinomatous germ cell tumors (NGGCTs) based on clinicopathologic features. Germinomas are sensitive to  treatment with radiotherapy and chemotherapy with high cure rates and carry an excellent prognosis, while NGGCTs display various forms of differentiation, have  a poorer prognosis and are refractory to therapy. Standard management of CNS GTCs remains unsettled and ongoing research aims to achieve best possible survival rates and post-treatment quality of life by reduction in treatment intensity.

 

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[265]

TÍTULO / TITLE:  - Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Apr;72(4):N17-8. doi: 10.1227/01.neu.0000428422.82081.62.

            ●● Enlace al texto completo (gratuito o de pago) 1227/01.neu.0000428422.82081.62

AUTORES / AUTHORS:  - Parry PV; Engh JA

 

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[266]

TÍTULO / TITLE:  - Distinctive MRI features of pediatric medulloblastoma subtypes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Apr;200(4):895-903. doi: 10.2214/AJR.12.9249.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.9249

AUTORES / AUTHORS:  - Yeom KW; Mobley BC; Lober RM; Andre JB; Partap S; Vogel H; Barnes PD

INSTITUCIÓN / INSTITUTION:  - 1 Department of Radiology, Lucile Packard Children’s Hospital, Stanford University, 725 Welch Rd, Pediatric MRI & CT, Rm 0511, Palo Alto, CA 94304.

RESUMEN / SUMMARY:  - OBJECTIVE. We hypothesized that the apparent diffusion coefficient (ADC) and other MRI features can be used to predict medulloblastoma histologic subtypes, as defined by the World Health Organization (WHO) in WHO Classification of Tumours of the Central Nervous System. MATERIALS AND METHODS. A retrospective review of pediatric patients with medulloblastoma between 1989 and 2011 identified 38 patients with both pretreatment MRI and original pathology slides. The mean and minimum tumor ADC values and conventional MRI features were compared among medulloblastoma histologic subtypes. RESULTS. The cohort of 38 patients included  the following histologic subtypes: 24 classic medulloblastomas, nine large cell (LC) or anaplastic medulloblastomas, four desmoplastic medulloblastomas, and one  medulloblastoma with extensive nodularity. The median age at diagnosis was 8 years (range, 1-21 years) and the median follow-up time was 33 months (range, 0-150 months). The mean ADC (x 10(-3) mm(2)/s) was lower in classic medulloblastoma (0.733 +/- 0.046 [SD]) than in LC or anaplastic medulloblastoma (0.935 +/- 0.127) (Mann-Whitney test, p = 0.004). Similarly, the minimum ADC was  lower in classic medulloblastoma (average +/- SD, 0.464 +/- 0.056) than in LC or  anaplastic medulloblastoma (0.630 +/- 0.053) (p = 0.004). The MRI finding of focal cysts correlated with the classic and desmoplastic subtypes (Fisher exact test, p = 0.026). Leptomeningeal enhancement positively correlated with the LC or anaplastic medulloblastoma subtype and inversely correlated with the classic medulloblastoma and desmoplastic medulloblastoma subtypes (p = 0.04). Ring enhancement correlated with tumor necrosis (p = 0.022) and with the LC or anaplastic medulloblastoma histologic subtype (p < 0.001). CONCLUSION. The LC or  anaplastic medulloblastoma subtype was associated with increased ADC and with ring enhancement, the latter of which correlated with tumor necrosis. These features could be considered in the evaluation of high-risk medulloblastoma subtypes.

 

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[267]

TÍTULO / TITLE:  - Assessment of the Changes in 9L and C6 Glioma pO2 by EPR Oximetry as a Prognostic Indicator of Differential Response to Radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Res. 2013 Mar;179(3):343-51. doi: 10.1667/RR2811.1. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1667/RR2811.1

AUTORES / AUTHORS:  - Hou H; Mupparaju SP; Lariviere JP; Hodge S; Gui J; Swartz HM; Khan N

INSTITUCIÓN / INSTITUTION:  - a EPR Center for Viable Systems, Department of Radiology, and.

RESUMEN / SUMMARY:  - Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO such as EPR oximetry may enhance the efficacy of  radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor pO may also identify responders, and thereby facilitate the design of better treatment plans for nonresponding tumors. We have investigated the temporal changes in the ectopic 9L and C6 glioma pO irradiated with single radiation doses less than 10 Gy by EPR oximetry. The 9L and C6 tumors were hypoxic with pO of approximately 5-9 mmHg. The pO of C6 tumors increased significantly with irradiation of 4.8-9.3 Gy. However, no change in the 9L tumor  pO was observed. The irradiation of the oxygenated C6 tumors with a second dose of 4.8 Gy resulted in a significant delay in growth compared to hypoxic and 2 Gy  x 5 treatment groups. The C6 tumors with an increase in pO of greater than 50% from the baseline of irradiation with 4.8 Gy (responders) had a significant tumor growth delay compared to nonresponders. These results indicate that the ectopic 9L and C6 tumors responded differently to radiotherapy. We propose that the repeated measurement of the oxygen levels in the tumors during radiotherapy can be used to identify responders and to design tumor oxygen guided treatment plans  to improve the outcome.

 

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[268]

TÍTULO / TITLE:  - Intraoperative magnetic resonance spectroscopy for identification of residual tumor during low-grade glioma surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS111561

AUTORES / AUTHORS:  - Pamir MN; Ozduman K; Yildiz E; Sav A; Dincer A

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery.

RESUMEN / SUMMARY:  - Object The authors had previously shown that 3-T intraoperative MRI (ioMRI) detects residual tumor tissue during low-grade glioma and that it helps to increase the extent of resection. In a proportion of their cases, however, the ioMRI disclosed T2-hyperintense areas at the tumor resection border after the initial resection attempt and prompted a differential diagnosis between residual  tumor and nontumoral changes. To guide this differential diagnosis the authors used intraoperative long-TE single-voxel proton MR spectroscopy (ioMRS) and tested the correlation of these findings with findings from pathological examination of resected tissue. Methods Patients who were undergoing surgery for  hemispheric or insular WHO Grade II gliomas and were found to have T2 changes around the resection cavity at the initial ioMRI were prospectively examined with ioMRS and biopsies were taken from corresponding localizations. In 14 consecutive patients, the ioMRS diagnosis in 20 voxels of interest was tested against the histopathological diagnosis. Intraoperative diffusion-weighted imaging (ioDWI) was also performed, as a part of the routine imaging, to rule out surgically induced changes, which could also appear as T2 hyperintensity. Results Presence of tumor was documented in 14 (70%) of the 20 T2-hyperintense areas by histopathological examination. The sensitivity of ioMRS for identifying residual  tumor was 85.7%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 75%. The specificity of ioDWI for surgically induced changes was high (100%), but the sensitivity was only 60%. Conclusions This is the first clinical series to indicate that ioMRS can be used  to differentiate residual tumor from nontumoral changes around the resection cavity, with high sensitivity and specificity.

 

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[269]

TÍTULO / TITLE:  - Letter to the Editor: Atypical meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):912-3. doi: 10.3171/2012.11.JNS121838. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121838

AUTORES / AUTHORS:  - Chiu SH; Wang ID; Sytwu HK; Hueng DY

INSTITUCIÓN / INSTITUTION:  - Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

 

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[270]

TÍTULO / TITLE:  - Editorial: Stereotactic radiosurgery and atypical meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.8.JNS121566

AUTORES / AUTHORS:  - Dunn IF; Chiocca EA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachusetts.

 

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[271]

TÍTULO / TITLE:  - Editorial: Sphenoid wing meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.6.JNS112303

AUTORES / AUTHORS:  - Morcos JJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Miami, Florida.

 

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[272]

TÍTULO / TITLE:  - Suppression of MMQ cells by fulvestrant: possible mechanism of action and potential application for bromocriptine-resistant prolactinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 22. pii: S0967-5868(12)00527-9. doi: 10.1016/j.jocn.2012.07.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.07.008

AUTORES / AUTHORS:  - Bai J; Gui S; Zhang Y

INSTITUCIÓN / INSTITUTION:  - Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing 100050, China.

RESUMEN / SUMMARY:  - Bromocriptine is an effective treatment for most prolactinomas. Estrogen receptor (ER) antagonists are an alternative for treating patients with bromocriptine-resistant prolactinomas (BCRP). Previously, we reported that fulvestrant, a selective ER antagonist, significantly inhibited the proliferation of, and prolactin secretion by, MMQ cells, a prolactin-secreting rat pituitary cell line, an exemplary model for prolactinoma. In this study, we used fulvestrant to block ERalpha expression by MMQ cells and analyzed the expression  of beta-catenin and Wnt inhibitory factor-1 (WIF1) to investigate the effects of  fulvestrant on the Wnt signaling pathway. In addition, we examined the gene expression of ERalpha, beta-catenin and WIF1 in clinical BCRP specimens to explore the correlation between gender and clinical features. There was no significant difference in beta-catenin expression between fulvestrant-treated cells and untreated cells, whereas WIF1 expression was higher in the treated cells. In clinical BCRP specimens, ERalpha expression was higher (especially in male patients), whereas beta-catenin expression was similar to normal pituitaries. In addition, WIF1 expression was significantly lower in BCRP specimens than in normal pituitaries. The tumor volume was larger in male patients than in female patients. Prolactin concentration was positively correlated with tumor volume, and a positive linear correlation was observed between ERalpha expression and tumor volume. In conclusion, the anti-tumor activity of fulvestrant on MMQ cells seems to be associated with ERalpha and the  non-canonical Wnt pathway, and higher ERalpha levels in male patients with BCRP may contribute to the larger tumor volumes observed. Fulvestrant holds promise as a therapeutic agent for BCRP.

 

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[273]

TÍTULO / TITLE:  - Anaplastic ependymoma with holocordal and intracranial meningeal carcinomatosis and holospinal bone metastases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Mar;72(3):E497-503; discussion E503-4. doi: 10.1227/NEU.0b013e31827d102e.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31827d102e

AUTORES / AUTHORS:  - Perez-Bovet J; Rimbau-Munoz J; Martin-Ferrer S

INSTITUCIÓN / INSTITUTION:  - Neurosurgery Department, University Hospital Dr. Josep Trueta, Girona (Girona), España. sgf_39@hotmail.com

RESUMEN / SUMMARY:  - BACKGROUND AND IMPORTANCE: Ependymomas are the most frequent intramedullary neoplasms in adult patients. Anaplastic histology, extramedullary location, meningeal dissemination at initial diagnosis, and extraneural metastases are rare findings. We describe a case of extramedullary anaplastic ependymoma that presented with holocordal and intracranial leptomeningeal carcinomatosis and bone metastases in all the vertebral bodies and the sternum. Such an aggressive dissemination at initial diagnosis has not been previously reported. CLINICAL PRESENTATION: A 36-year-old woman presented with headache, multiple cranial nerve palsies, visual hallucinations, confusion, hemiparesis, hemihipoestesia, episodes of disconnection, and toxic syndrome. Magnetic resonance imaging and positron emission tomography scan revealed leptomeningeal carcinomatosis in the brainstem, the cerebellum, and along the whole spinal cord. Various nodular, intradural extramedullary lesions were present at multiple dorsal and lumbar levels. Metastatic bone disease affected all the vertebral bodies and various extraspinal bones. An intradural and bone biopsy was performed at L4, providing the diagnosis of anaplastic ependymoma (World Health Organization grade III) with focal neuronal differentiation. Despite chemotherapy, the patient’s symptoms quickly progressed, and she died 7 weeks after diagnosis. CONCLUSION: To our knowledge, there are no previous descriptions of ependymomas with this extensive leptomeningeal, spinal, intracranial, and extraneural dissemination at clinical onset. Bone metastases in spinal ependymoma have not been previously reported.

 

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[274]

TÍTULO / TITLE:  - SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomaterials. 2013 May;34(14):3706-15. doi: 10.1016/j.biomaterials.2013.01.099. Epub 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.099

AUTORES / AUTHORS:  - Fan CH; Ting CY; Lin HJ; Wang CH; Liu HL; Yen TC; Yeh CK

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan, ROC.

RESUMEN / SUMMARY:  - The blood-brain barrier (BBB) can be temporarily and locally opened by focused ultrasound (FUS) in the presence of circulating microbubbles (MBs). Currently, contrast-enhanced magnetic resonance imaging (CE-MRI) is used to monitor contrast agent leakage to verify BBB-opening and infer drug deposition. However, despite being administered concurrently, MBs, therapeutic agent, and contrast agent have  distinct pharmacodynamic behaviors, thus complicating the quantification and optimization of BBB-opening and drug delivery. Here we propose multifunctional MBs loaded with therapeutic agent (doxorubicin; DOX) and conjugated with superparamagnetic iron oxide (SPIO) nanoparticles. These DOX-SPIO-MBs were designed to concurrently open the BBB and perform drug delivery upon FUS exposure, act as dual MRI and ultrasound contrast agent, and allow magnetic targeting (MT) to achieve enhanced drug delivery. We performed burst-tone FUS after injection of DOX-SPIO-MBs, followed by MT with an external magnet attached  to the scalp in a rat glioma model. Animals were monitored by T2-weighted MRI and susceptibility weighted imaging and the concentration of SPIO particles was determined by spin-spin relaxivity. We found that DOX-SPIO-MBs were stable and provided significant superparamagnetic/acoustic properties for imaging. BBB-opening and drug delivery were achieved concurrently during the FUS exposure. In addition, MT increased local SPIO deposition in tumor regions by 22.4%. Our findings suggest that DOX-SPIO-MBs with FUS could be an excellent theranostic tool for future image-guided drug delivery to brain tumors.

 

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[275]

TÍTULO / TITLE:  - Endoscopic treatment of interhemispheric arachnoid cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Neurosurg. 2012;48(3):157-62. doi: 10.1159/000346263. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000346263

AUTORES / AUTHORS:  - Giannetti AV; Ferreira Fraga SM; Silva MC; Gurgel-Giannetti J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

RESUMEN / SUMMARY:  - Background: To describe the neuroendoscopic treatment of interhemispheric arachnoid cysts. Methods: Five children (aged 1-9 months) harboring interhemispheric arachnoid cysts underwent the procedure. The neuroendoscopic technique included cystoventriculostomy and cystocisternostomy. Imaging exams were compared before and after surgery, and the differences in cyst diameters were calculated. Head circumference and neurological development were also evaluated. Results: The cystoventriculostomy was performed through the lateral ventricle in 4 cases and through the third ventricle in 4 cases. An added cystocisternostomy was performed in 1 case. Cyst diameters were reduced in the anterior-posterior, lateral-medial and superior-inferior planes in 22, 31 and 31% of the cases, respectively. The rate of increasing head circumference slowed; however, all the children continued to show slight macrocrania. There were complications in 2 cases: cerebrospinal fluid fistula was managed by lumbar puncture in 1 case and subdural collection was treated with a shunt in another single case. Conclusion: The neuroendoscopic approach to interhemispheric arachnoid cysts was effective with few complications.

 

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[276]

TÍTULO / TITLE:  - How molecular testing can help (and hurt) in the workup of gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Pathol. 2013 Mar;139(3):275-88. doi: 10.1309/AJCPFO8IIDNBIJ8Y.

            ●● Enlace al texto completo (gratuito o de pago) 1309/AJCPFO8IIDNBIJ8Y

AUTORES / AUTHORS:  - Clark K; Voronovich Z; Horbinski C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

RESUMEN / SUMMARY:  - Advances in genetics research have greatly expanded our ability to accurately diagnose gliomas and provide more useful prognostic information. Herein specific  examples are used to show how high-yield targets such as EGFR, 1p/19q, IDH1/2, MGMT, and BRAF can expand the power of the surgical neuropathologist. To avoid errors, however, the significance and controversies associated with each test must be thoroughly understood.

 

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[277]

TÍTULO / TITLE:  - Breast metastasis of anaplastic oligodendroglioma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Tumori. 2012 Nov;98(6):162e-4e. doi: 10.1700/1217.13513.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1217.13513

AUTORES / AUTHORS:  - Alacacioglu A; Unal S; Canpolat S; Yurt A; Oztekin O; Coskun A; Karatas A; Postaci H; Sop G

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Department of Internal Medicine, Bozyaka Research and Training Hospital, Bozyaka, Izmir, Turkey. dralacacioglu@hotmail.com

RESUMEN / SUMMARY:  - Extracranial metastasis of primary brain tumors is rarely observed. Of all brain  malignancies, glioblastomas, medulloblastomas and astrocytomas metastasize most frequently. Metastasis of oligondendroglioma is rare. We present a case of breast metastasis in a 58-year-old man with an anaplastic oligodendroglioma.

 

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[278]

TÍTULO / TITLE:  - Imaging integrin alpha(v)beta(3) positive glioma with a novel RGD dimer probe and the impact of antiangiogenic agent (Endostar) on its tumor uptake.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 8. pii: S0304-3835(13)00111-0. doi: 10.1016/j.canlet.2013.01.053.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.053

AUTORES / AUTHORS:  - Wu H; Chen H; Sun Y; Wan Y; Wang F; Jia B; Su X

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: wuhua1025@163.com.

RESUMEN / SUMMARY:  - Integrin alpha(v)beta(3) has been recognized to play an important role in angiogenesis, tumor growth and metastasis. It will be of interest to apply this promising target for tumor imaging and visualization of tumor angiogenesis in vivo. In this study, a novel integrin alpha(v)beta(3) targetting imaging probe, (99m)Tc-HYNIC-E[c(RGDfK)](2), was used to investigate the glioma uptake in vitro  and in vivo before and after treatment with an antiangiogenic agent, endostar. The results indicated that U87MG glioma cells have high expression of integrin alpha(v)beta(3) and special uptake of (99m)Tc-HYNIC-E[c(RGDfK)](2) both in cell line and in tumor xenograft. The endostatin analogue endostar can inhibit the expression of integrin alpha(v)beta(3) receptors in both U87MG cells in vitro and glioma tissues, which suggested that integrin pathway may play a role in antiangiogenic effect of Endostar. (99m)Tc-HYNIC-E[c(RGDfK)](2) may be a promising molecular imaging probe for integrin alpha(v)beta(3) positive tumor imaging and open up the possibility to establish an molecular imaging modality for assessment of tomor antiangiogenic therapy.

 

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[279]

TÍTULO / TITLE:  - Rathke’s cleft cysts with significant squamous metaplasia-high risk of postoperative deterioration and close origins to craniopharyngioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1593-9

AUTORES / AUTHORS:  - Ogawa Y; Watanabe M; Tominaga T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kohnan Hospital, 4-20-1 Nagamachiminami, Taihaku-ku,  Sendai, Miyagi, 982-8523, Japan, yogawa@kohnan-sendai.or.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Rathke’s cleft cyst (RCC) with significant squamous and/or stratified epithelium including smooth transition from single cuboidal to squamous epithelium (tRCC) is rare and possibly represents an intermediate form to craniopharyngioma. METHODS: Twelve patients with histologically confirmed tRCC were retrospectively investigated from a series of 167 cases of RCC and 96 cases  of craniopharyngiomas. Clinical data were reviewed, and immunohistochemistry findings for cytokeratins and beta-catenin were examined. RESULTS: All lesions were located in the sella turcica with marked extension to suprasellar cistern. Six of the 12 patients had suffered postoperative re-enlargement, and three of these six patients required more than two additional operations and irradiation.  CAM5.2 was positive in the glandular epithelium in all tRCCs and focally positive in the squamous epithelium of all these tRCCs. 34betaE12 was positive in the squamous epithelium in all tRCCs and focally positive in the glandular epithelium in all but one tRCC. The findings of cytokeratin expression of tRCCs were very similar to those of craniopharyngioma. beta-Catenin showed nuclear translocation  in five cases. All patients with nuclear translocation of beta-catenin suffered postoperative re-enlargement. CONCLUSIONS: tRCC carries an extremely high risk of re-enlargement. Cytokeratin expression resembles that in craniopharyngioma, which might indicate a very close origin of these pathologies. Nuclear translocation of beta-catenin may be related to the aggressive clinical course.

 

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[280]

TÍTULO / TITLE:  - Clinical and imaging features of central neurocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 19. pii: S0967-5868(12)00524-3. doi: 10.1016/j.jocn.2012.05.053.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.05.053

AUTORES / AUTHORS:  - Wang M; Jia D; Shen J; Zhang J; Li G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Qilu Hospital of Shandong University, 107 Wenhua Western Road, Jinan 250012, Shandong Province, China.

RESUMEN / SUMMARY:  - To describe the clinical and imaging characteristics of patients with central neurocytoma (CN), we reviewed data on 27 patients who had histologically confirmed CN and were treated in our institution between 1999 and 2010. Neuro-imaging findings on CT scan (n=18) and MRI (n=25) were retrospectively evaluated. There were 15 males and 12 females with a mean age of 29years (range,  11-46years). The most frequent presentations included headache (n=21) and vomiting (n=6). Tumor sites included bilateral lateral ventricles (n=10), right lateral ventricle (n=7), left lateral ventricle (n=7) and fourth ventricle (n=3). On MRI, the T1-weighted signal was hypointense in 12 patients and isointense in 13, and the T2-weighted signal was isointense in 8 patients and hyperintense in 15. CT scans/MRI revealed a cystic component in 18 patients. Tumors showed a mild to marked enhancement in 26 patients. Flow voids from tumor vessels on MRI were present in 14 patients, and calcification was noted in six of 18 patients with CT scans. All lateral ventricle tumors were resected through a transcortical or transcallosal approach. Gross total resection was achieved in 19 patients, near total in two and subtotal in six. One patient died of cerebral infarction in the  perioperative period. At the last follow up, there were three known clinical recurrences in this series. However, no recurrence was noted in 17 patients who underwent gross total resection with no adjuvant therapy.

 

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[281]

TÍTULO / TITLE:  - IFNgamma in combination with IL-7 enhances immunotherapy in two rat glioma models.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuroimmunol. 2013 Mar 22. pii: S0165-5728(13)00055-6. doi: 10.1016/j.jneuroim.2013.02.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jneuroim.2013.02.017

AUTORES / AUTHORS:  - Fritzell S; Eberstal S; Sanden E; Visse E; Darabi A; Siesjo P

INSTITUCIÓN / INSTITUTION:  - Glioma Immunotherapy group, Division of Neurosurgery, Department of Clinical Sciences, BMC D14, Lund University, SE-221 84 Lund, Sweden. Electronic address: sara.fritzell@med.lu.se.

RESUMEN / SUMMARY:  - Peripheral immunization, using a combination of interferon-gamma (IFNgamma)- and  interleukin-7 (IL-7)-producing tumor cells, eradicated 75% of pre-established intracerebral N32 rat glioma tumors, and prolonged survival in the more aggressive RG2 model. Rats immunized with IFNgamma- and IL7-transduced N32 cells  displayed increases in IFNgamma plasma levels and proliferating circulating T cells when compared with rats immunized with N32-wild type cells. Following irradiation, the expression of MHC I and II was high on N32-IFNgamma cells, but low on RG2-IFNgamma cells. In conclusion, IFNgamma and IL-7 immunizations prolong survival in two rat glioma models.

 

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[282]

TÍTULO / TITLE:  - A decision analysis tool for the assessment of posterior fossa tumour surgery outcomes in children-the “Liverpool Neurosurgical Complication Causality Assessment Tool”

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2065-0

AUTORES / AUTHORS:  - Zakaria R; Ellenbogen J; Graham C; Pizer B; Mallucci C; Kumar R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK, rzakaria@nhs.net.

RESUMEN / SUMMARY:  - INTRODUCTION: Complications may occur following posterior fossa tumour surgery in children. Such complications are subjectively and inconsistently reported even though they may have significant long-term behavioural and cognitive consequences for the child. This makes comparison of surgeons, programmes and treatments problematic. MATERIALS AND METHODS: We have devised a causality tool for assessing if an adverse event after surgery can be classified as a surgical complication using a series of simple questions, based on a tool used in assessing adverse drug reactions. This tool, which we have called the “Liverpool  Neurosurgical Complication Causality Assessment Tool”, was developed by reviewing a series of ten posterior fossa tumour cases with a panel of neurosurgery, neurology, oncology and neuropsychology specialists working in a multidisciplinary paediatric tumour treatment programme. DISCUSSION AND CONCLUSION: We have demonstrated its use and hope that it may improve reliability between different assessors both in evaluating the outcomes of existing programmes and treatments as well as aiding in trials which may directly compare  the effects of surgical and medical treatments.

 

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[283]

TÍTULO / TITLE:  - Multiple intracranial tumors in Philadelphia chromosome-positive acute lymphoblastic leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Hematol. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12185-013-1285-0

AUTORES / AUTHORS:  - Hatakeyama N; Hori T; Yamamoto M; Inazawa N; Igarashi K; Tsutsumi H; Suzuki N

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16 Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan, nhatake@sapmed.ac.jp.

 

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[284]

TÍTULO / TITLE:  - Cytoprotective effect of methanolic extract of Nardostachys jatamansi against hydrogen peroxide induced oxidative damage in C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Biochim Pol. 2013;60(1):21-31. Epub 2013 Mar 20.

AUTORES / AUTHORS:  - Dhuna K; Dhuna V; Bhatia G; Singh J; Kamboj SS

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar- Punjab, India.

RESUMEN / SUMMARY:  - Oxidative stress has been implicated as an important factor in the process of neurodegeneration and hydrogen peroxide (H2O2) is one of the most important precursors of reactive oxygen species (ROS), responsible for many neurodegenerative diseases. This study used extracts from Nardostachys jatamansi  rhizomes, known for nerve relaxing properties in Ayurvedic medicine, to ascertain their protective role in H2O2-induced oxidative stress in C6 glioma cells. The protective effect of methanolic, ethanolic and water extracts of N. jatamansi (NJ-MEx, NJ-EEx and NJ-WEx respectively) was determined by MTT assay. NJ-MEx significantly protected against H2O2 cytotoxicity when cells were pretreated for  24 h. The level of antioxidant enzymes, catalase, superoxide dismutase (Cu-ZnSOD), glutathione peroxidase (GPx), and a direct scavenger of free radicals, glutathione (GSH), significantly increased following pre-treatment with NJ-MEx. Lipid peroxidation (LPx) significantly decreased in NJ-MEx-pretreated cultures. The expression of a C6 differentiation marker, GFAP (glial fibrillary acidic protein), stress markers HSP70 (heat shock protein) and mortalin (also called glucose regulated protein 75, Grp75) significantly decreased when cells were pre-treated with NJ-MEx before being subjected to H2O2 treatment as shown by immunofluorescence, western blotting and RT-PCR results. The present study suggests that NJ-MEx could serve as a potential treatment and/or preventive measure against neurodegenerative diseases.

 

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[285]

TÍTULO / TITLE:  - Very late isolated CNS relapse of acute myeloid leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Mar;35(2):e57-9. doi: 10.1097/MPH.0b013e318281e63b.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318281e63b

AUTORES / AUTHORS:  - Molina B; Lassaletta A; Gonzalez-Vicent M; Andion M; Diaz MA; Madero L

INSTITUCIÓN / INSTITUTION:  - Pediatric Hematology Oncology Department, Hospital Nino Jesus, Madrid, España.

RESUMEN / SUMMARY:  - Isolated central nervous system (CNS) relapse in acute myeloid leukemia (AML) rarely occurs later than 2 years after remission. We present a child diagnosed with AML (FAB M5) without CNS involvement at diagnosis who was treated with chemotherapy and consolidated with autologous hematopoietic stem cell transplantation. He was in complete remission for >6 years until he had an isolated CNS relapse. He was treated with only intrathecal chemotherapy and achieved a second complete remission, but relapsed in the bone marrow 5 months after the CNS relapse. Treatment of late isolated CNS relapse of AML is discussed.

 

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[286]

TÍTULO / TITLE:  - Suprasellar granular cell tumor of the neurohypophysis in a child: unusual presentation in pediatric age of a rare tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2062-3

AUTORES / AUTHORS:  - Gagliardi F; Losa M; Boari N; Franzin A; Pozzobon G; Weber G; Mortini P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy, gagliardi.filippo@hsr.it.

RESUMEN / SUMMARY:  - PURPOSE: Granular cell tumors (GCT) of the neurohypophysis are rare, solitary, nodular-shaped lesions, mostly presenting in the adult age with a female predilection. They rarely grow to a sufficient size to cause mass effect related  symptoms and they may be found in most cases incidentally at autopsy of older patients. Few cases of symptomatic GCT of the neurohypophysis have been reported  in the literature and only one of these in a pediatric patient in the first decade of life, who presented with central precocious puberty. METHODS: We report the case of a 11-year-old boy with a large suprasellar GCT of the neurohypophysis, complaining severe headache and pituitary insufficiency. Before  our referral, the child was operated at another insitution through a pterional approach for tumor biopsy and underwent chemotherapy because of the misleading diagnosis of glioma. RESULTS: The patient was operated on by a fronto-orbito-zygomatic approach with subtotal tumor resection. At last follow-up examination, a partial hypopituitarism was detected. The quality of life with replacement therapy was excellent. Fractionated radiotherapy on tumor remnant was advised. CONCLUSIONS: The reported case is exceptional because the tumor developed in a male pediatric patient, causing clinical symptoms related to intracranial hypertension and unusual endocrinological features. GCT has to be considered in the differential diagnosis of suprasellar masses, to avoid misleading interpretation and consequent wrong therapeutic management.

 

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[287]

TÍTULO / TITLE:  - Risk of subsequent cancer following a primary CNS tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):285-95. doi: 10.1007/s11060-013-1063-0. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1063-0

AUTORES / AUTHORS:  - Strodtbeck K; Sloan A; Rogers L; Fisher PG; Stearns D; Campbell L; Barnholtz-Sloan J

INSTITUCIÓN / INSTITUTION:  - Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA, Kxs213@case.edu.

RESUMEN / SUMMARY:  - Improvements in survival among central nervous system (CNS) tumor patients has made the risk of developing a subsequent cancer an important survivorship issue.  Such a risk is likely influenced by histological and treatment differences between CNS tumors. De-identified data for 41,159 patients with a primary CNS tumor diagnosis from 9 Surveillance, Epidemiology and End Results (SEER) registries were used to calculate potential risk for subsequent cancer development. Relative risk (RR) and 95 % confidence interval (CI) of subsequent cancer was calculated using SEER*Stat 7.0.9, comparing observed number of subsequent cancers versus expected in the general United States population. For all CNS tumors studied, there were 830 subsequent cancers with a RR of 1.26 (95 % CI, 1.18-1.35). Subsequent cancers were observed in the CNS, digestive system, bones/joints, soft tissue, thyroid and leukemia. Radiotherapy was associated with an elevated risk, particularly in patients diagnosed with a medulloblastoma/primitive neuroectodermal tumor (MPNET). MPNET patients who received radiotherapy were at a significant risk for development of cancers of the digestive system, leukemia, bone/joint and cranial nerves. Glioblastoma multiforme patients who received radiotherapy were at lower risks for female breast and prostate cancers, though at an elevated risk for cancers of the thyroid and brain. Radiotherapy is associated with subsequent cancer development, particularly for sites within the field of radiation, though host susceptibility  and post-treatment status underlie this risk. Variation in subsequent cancer risk among different CNS tumor histological subtypes indicate a complex interplay between risk factors in subsequent cancer development.

 

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[288]

TÍTULO / TITLE:  - Arginine modified PAMAM dendrimer for interferon beta gene delivery to malignant  glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Pharm. 2013 Mar 10;445(1-2):79-87. doi: 10.1016/j.ijpharm.2013.01.057. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijpharm.2013.01.057

AUTORES / AUTHORS:  - Bai CZ; Choi S; Nam K; An S; Park JS

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry, Seoul National University, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-beta). We used 4’,6-diamidino-2-phenylindole staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and the caspase-3 activity assay to determine the induction of apoptosis upon transfection with the PAMAM-R/IFN-beta gene polyplex  in vitro. The polyplex was injected into xenograft brain tumors. Mice treated with PAMAM-R/pORF-IFN-beta exhibited a significantly smaller tumor size than control mice and PAMAM-R/pORF treated mice. Hematoxylin/eosin staining and immunohistochemistry with the endothelial growth factor receptor antibody also revealed inhibition of tumor growth. Furthermore, reverse transcription polymerase chain reaction and the TUNEL assay also verified the expression of IFN-beta and induction of apoptosis in vivo. These results indicate that the PAMAM-R/pORF-IFN-beta polyplex is an effective therapeutic candidate for glioblastoma multiforme due to its selective induction of apoptosis in tumor cells.

 

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[289]

TÍTULO / TITLE:  - Pediatric glioblastoma with oligodendroglioma component: Aggressive clinical phenotype with distinct molecular characteristics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Mar 27. doi: 10.1111/neup.12029.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12029

AUTORES / AUTHORS:  - Mizoguchi M; Hata N; Suzuki SO; Fujioka Y; Murata H; Amano T; Nakamizo A; Yoshimoto K; Iwaki T; Sasaki T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kyushu University, Fukuoka, Japan.

RESUMEN / SUMMARY:  - The 2007 World Health Organization classification defined a new variant of glioblastoma (GBM) containing oligodendroglioma foci as GBM with an oligodendroglioma component (GBMO), which shows a favorable clinical outcome compared with “classic” GBM. However, all of the reported cases of GBMO have been adult cases, with no previous reports of pediatric cases. In this report, we demonstrated molecular characteristics of a pediatric GBMO case, showing aggressive clinical behavior with 8-month overall survival. The case showed neither isocitrate dehydrogenase ½ genes (IDH1/2) mutation nor 1p/19q co-deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite  instability, leading to the putative mechanism of temozolomide (TMZ) resistance,  was frequently detected. Molecular genetic analysis may provide critical prognostic and therapeutic insights, especially for the pediatric glioma containing oligodendroglioma components.

 

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[290]

TÍTULO / TITLE:  - Cytoplasmic iron deposition is associated with the expression of oxidative DNA damage marker in meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Feb 13. doi: 10.1111/neup.12023.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12023

AUTORES / AUTHORS:  - Nagaishi M; Yokoo H; Osawa T; Nobusawa S; Tanaka Y; Ikota H; Yoshimoto Y; Nakazato Y

INSTITUCIÓN / INSTITUTION:  - Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

RESUMEN / SUMMARY:  - Angiomatous meningiomas are rare meningioma subtypes, which are characterized by  abundant, well-formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron. In an attempt to understand its pathological significance, we assessed this unusual finding in representatives for each grade  of meningiomas and immunoexpression of transferrin receptor (CD71) and the oxidative DNA damage marker, 8-hydroxy-2’-deoxyguanosine (8-OHdG). Iron deposition in the tumor cells was observed in 8/15 (53%) angiomatous meningioma cases, 2/6 (33%) microcystic meningiomas and 2/20 (10%) meningothelial meningiomas, which included clustered microvessels, but not in fibrous, atypical  or anaplastic meningiomas (P = 0.001). Cytoplasmic CD71 expression was largely negative in angiomatous meningioma cases, but positive in meningothelial and high-grade meningiomas, suggesting that the transferrin-dependent iron transporter was involved in iron uptake in meningiomas. Nuclear expression of 8-OHdG was observed in >/=50% of the tumor cells in all 15 cases of angiomatous meningioma and was associated with the presence of regressive histopathological findings, such as hyalinized vessels and cystic changes. In addition, the fraction of iron-containing tumor cells was correlated to those expressing 8-OHdG (P = 0.005). Our finding indicates that cytoplasmic iron deposition in tumor cells is characteristic of highly vascularized benign meningiomas and related to  increased oxidative DNA damage markers.

 

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[291]

TÍTULO / TITLE:  - P2XR suppression promotes glioma growth through epidermal growth factor receptor  signal pathway.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Biochem Cell Biol. 2013 Mar 19. pii: S1357-2725(13)00073-3. doi: 10.1016/j.biocel.2013.03.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biocel.2013.03.005

AUTORES / AUTHORS:  - Fang J; Chen X; Zhang L; Chen J; Liang Y; Li X; Xiang J; Wang L; Guo G; Zhang B; Zhang W

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

RESUMEN / SUMMARY:  - P2X7 receptor (P2X7R) has been shown to mediate an anticancer effect via apoptosis in different types of cancer. However, whether P2X7R exerts a promoting or suppressive effect on brain glioma is still a controversial issue and its underlying mechanism remains unknown. We showed here that P2X7R suppression exerted a pro-growth effect on glioma through directly promoting cells proliferation and pro-angiogenesis, which was associated with epidermal growth factor receptor (EGFR) signaling. The P2X7R was markedly downregulated by cells exposure to the P2X7R antagonist, brilliant blue G (BBG), moreover, the cells proliferation was enhanced in a dose-dependent manner and the expression of EGFR  or p-EGFR protein was significantly upregulated. By constructing C6 cells with reduced expression of P2X7R using shRNA, we also demonstrated strong upregulation in cells proliferation and EGFR/p-EGFR expression. However, this effect of BBG was reversed in the presence of gefitinib or suramin. Magnetic resonance imaging  and computed tomography perfusion showed that the BBG or P2X7R shRNA promoted the tumor growth by about 40% and 50%, respectively, and significantly increased angiogenesis. Nissl and Ki-67 staining also confirmed that BBG or P2X7R shRNA notably increased the tumor growth. More importantly, either BBG or P2X7R shRNA could markedly upregulated the expression of EGFR, p-EGFR, HIF-1a and VEGF in glioma cells. In conclusion, P2X7R suppression exerts a promoting effect on glioma growth, which is likely to be related to upregulated EGFR, HIF-1a and VEGF expression. These findings provide important clues to the molecular basis of anticancer effect of targeting purinergic receptors.

 

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[292]

TÍTULO / TITLE:  - Protective Effect of Taurine on Triorthocresyl Phosphate (TOCP)-Induced Cytotoxicity in C6 Glioma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Adv Exp Med Biol. 2013;776:231-40. doi: 10.1007/978-1-4614-6093-0_22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6093-0_22

AUTORES / AUTHORS:  - Li Y; Piao F; Liu X

INSTITUCIÓN / INSTITUTION:  - Department of Occupational and Environmental Health, Dalian Medical University, Dalian, Liaoning, 116044, China.

RESUMEN / SUMMARY:  - Triorthocresyl phosphate (TOCP) an organophosphorus ester can cause neurotoxicity via oxidative stress pathway. Taurine is an antioxidant. The objective of this study was to investigate the protective effect of taurine on TOCP-induced cytotoxicity in C6 glioma cell. The C6 glioma cells were pretreated with 0, 1, 3, and 9 mM of taurine for 30 min prior to 1 mM TOCP treatment. After 48 h, cell survival was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. The content of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were also analyzed by kits. Our results showed that survival of the glioma cells decreased  in the group treated with TOCP alone and increased significantly in the groups pretreated with taurine in a concentration-dependent manner. TOCP induced decrease in the activity of GPx and the content of GSH. However, taurine prevented these decreases. Our results suggested that taurine has protective effect on TOCP-induced toxicity to glioma cells via elevating antioxidant capacity.

 

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[293]

TÍTULO / TITLE:  - Expression of c-Jun and Sox-2 in human schwannomas and traumatic neuromas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histopathology. 2013 Mar;62(4):651-6. doi: 10.1111/his.12062. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1111/his.12062

AUTORES / AUTHORS:  - Shivane A; Parkinson DB; Ammoun S; Hanemann CO

INSTITUCIÓN / INSTITUTION:  - Department of Cellular and Anatomical Pathology, Derriford Hospital, Plymouth, UK. aditya.shivane@nhs.net

RESUMEN / SUMMARY:  - AIMS: Schwann cells myelinate axons of the peripheral nervous system. This process of myelination is regulated by various transcription factors. c-Jun and Sox-2 are negative regulators of myelination and control Schwann cell differentiation and plasticity. Schwannoma cells within tumours no longer express myelin markers, and show increased proliferation and decreased apoptosis. We have shown previously that several signalling pathways are activated in schwannoma cells in situ, in particular the c-Jun N-terminal kinase (JNK) pathway. Both in vitro and in vivo we have demonstrated that c-Jun and Sox-2 are co-regulated in Schwann cells and evidence shows that both these proteins regulate myelination negatively. In this study, we aimed to characterize the expression of c-Jun and Sox-2 in schwannoma and traumatic neuroma. METHODS AND RESULTS: Immunohistochemistry using antibodies to c-Jun and Sox-2 was applied to six schwannomas, and the results were compared with those seen in traumatic neuroma and normal nerve. Increased expression of c-Jun and Sox-2 was seen in schwannoma. CONCLUSIONS: We have demonstrated increased expression of c-Jun and Sox-2 in schwannoma compared to traumatic neuroma. There was no expression of c-Jun and Sox-2 in a histologically normal peripheral nerve.

 

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[294]

TÍTULO / TITLE:  - Primary pulmonary malignant meningioma with lymph node and liver metastasis in a  centenary woman, an autopsy case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virchows Arch. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00428-013-1383-7

AUTORES / AUTHORS:  - Weber C; Pautex S; Zulian GB; Pusztaszeri M; Lobrinus JA

INSTITUCIÓN / INSTITUTION:  - Division of Primary Care, University Hospital Geneva, Geneva, Switzerland.

RESUMEN / SUMMARY:  - Primary meningiomas arising outside the central nervous system are very rare. They have been reported in the head and neck region, in the thorax, the retroperitoneum, and the pelvis. Usually, they behave as slow-growing tumors with a good prognosis. Herein, we report an autopsy case of a 108-year-old woman, known for a right-sided slowly growing lung nodule for 39 years. Death was attributed to cachexia. At post-mortem, a 15-cm mass was present in the right inferior lobe of the lung, associated with an ipsilateral hilar lymphadenopathy,  and another 10-cm mass in the liver. Histology revealed a WHO grade III meningioma. No tumor was observed in the cranial cavity. This case illustrates a  rare location of meningioma and highlights its biological behavior, with a very slow progression from a most probably benign tumor to a malignant lesion with metastasis over four decades.

 

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[295]

TÍTULO / TITLE:  - Editorial: Intraoperative magnetic resonance spectroscopy and gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.8.JNS121409

AUTORES / AUTHORS:  - Shaikhouni A; Chiocca EA

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, James Cancer Center and Wexner Medical Center at The Ohio State University, Columbus, Ohio; and.

 

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[296]

TÍTULO / TITLE:  - Lessons we Learned from High-Throughput and Top-Down Systems Biology Analyses about Glioma Stem Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Pharm Des. 2013 Mar 19.

AUTORES / AUTHORS:  - Mock A; Chiblak S; Herold-Mende C

INSTITUCIÓN / INSTITUTION:  - Experimentelle Neurochirurgie Neurochirurgische Universitatsklinik INF 400 69120  Heidelberg, Germany. H.Mende@med.uni-heidelberg.de.

RESUMEN / SUMMARY:  - A growing body of evidence suggests that glioma stem cells (GSCs) account for tumor initiation, therapy resistance, and the subsequent regrowth of gliomas. Thus, continuous efforts have been undertaken to further characterize this subpopulation of less differentiated tumor cells. Although we are able to enrich  GSCs, we still lack a comprehensive understanding of GSC phenotypes and behavior. The advent of high-throughput technologies raised hope that incorporation of these newly developed platforms would help to tackle such questions. Since then a couple of comparative genome-, transcriptome- and proteome-wide studies on GSCs have been conducted giving new insights in GSC biology. However, lessons had to be learned in designing high-throughput experiments and some of the resulting conclusions fell short of expectations because they were performed on only a few  GSC lines or at one molecular level instead of an integrative poly-omics approach. Despite these shortcomings, our knowledge of GSC biology has markedly expanded due to a number of survival-associated biomarkers as well as glioma-relevant signaling pathways and therapeutic targets being identified. In this article we review recent findings obtained by comparative high-throughput analyses of GSCs. We further summarize fundamental concepts of systems biology as well as its applications for glioma stem cell research.

 

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[297]

TÍTULO / TITLE:  - Development of therapeutics for high grade gliomas using orthotopic rodent models.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Med Chem. 2013 Mar 15.

AUTORES / AUTHORS:  - Frosina G

INSTITUCIÓN / INSTITUTION:  - Molecular Mutagenesis & DNA Repair Unit, IRCCS Azienda Ospedaliera Universitaria  San Martino - IST Istituto Nazionale Ricerca Cancro, Largo Rosanna Benzi n. 10, 16132 Genova, Italy. guido.frosina@istge.it.

RESUMEN / SUMMARY:  - To study novel treatments for high grade gliomas (WHO grade III and IV) we need animal models of those disorders. Orthotopic tumours in mouse or rats seem at present the most reliable in vivo glioma model in order to develop specific therapies. The orthotopic tumour characteristics should yet closely mimic the human glioma features (in particular infiltrating growth and neovascularization). In this regard, glioma cell lines with stem properties (glioma stem cells - GSC)  may fulfil at best those needs. Orthotopic gliomas developed from some widely used, established non-stem cell lines showing poor infiltrating capacity are not  suitable. Therapeutic and diagnostic procedures recently developed using orthotopic rodent glioma tumours along their potentialities and pitfalls are analyzed.

 

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[298]

TÍTULO / TITLE:  - Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1121-7

AUTORES / AUTHORS:  - Ke HL; Ke RH; Li ST; Li B; Lu HT; Wang XQ

INSTITUCIÓN / INSTITUTION:  - Department of Emergency Medicine, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - Recently, Rac GTPase-activating protein 1 (RACGAP1) has been shown to have a critical role in various tumors. The aim of the present study was to investigate  the expression of RACGAP1 in human meningiomas and to compare these results with  the clinicopathological parameters. Thirty-two cases, classified as 13 World Health Organization grade I (40.6 %), 10 grade II (31.3 %) and 9 grade III (28.1  %) primary meningiomas, were selected from our pathological files. Clinico-pathological data, including survival data, were also available. RACGAP1  expression in the meningiomas was measured by real-time quantitative PCR and western blot. Our results showed the level of RACGAP1 expression in grade III meningioma is higher than that of grade I. Higher levels of RACGAP1 mRNA were significantly correlated with tumor size, higher Simpson grade, histological type and clinical course (P < 0.05). Furthermore, the level of RACGAP1 expression mRNA was positively correlated with MIB-1 labeling index in different meningiomas tissue (r 2 = 0.3237, P = 0.0007). Additionally, Kaplan-Meier curves demonstrated a significantly worse survival in patients with high levels of RACGAP1 mRNA (P =  0.008). In conclusion, these findings suggest that RACGAP1 may be used as a potential predictor for tumor proliferative and patient prognosis in meningiomas.

 

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[299]

TÍTULO / TITLE:  - Anesthetic management for resection of hepatic paraganglioma metastatic from the  donor organ in an orthotopic liver transplant recipient: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Transplant Proc. 2013 Mar;45(2):817-9. doi: 10.1016/j.transproceed.2012.10.043.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.transproceed.2012.10.043

AUTORES / AUTHORS:  - Sharma S; Wray C; Nourmand H

INSTITUCIÓN / INSTITUTION:  - University of California-Los Angeles, Los Angeles, California, USA. Electronic address: shasharma@mednet.ucla.edu.

RESUMEN / SUMMARY:  - This is a case report of the anesthetic management for the hepatic resection of a metastatic paraganglioma in a patient with a history of prior orthotopic liver transplantation. Of interest, the metastatic paraganglioma originated from the donor organ. The patient is an 80-year-old woman with multiple medical problems including a history of cryptogenic cirrhosis who underwent successful orthotopic  liver transplantation 9 years prior. She later presented with signs and symptoms  of catecholamine excess suggestive of a catecholamine-producing tumor (paraganglioma or pheochromocytoma). Elevated urine catecholamine levels and radiographic evidence of a paraganglioma in the transplanted liver metastatic from the donor organ confirmed the diagnosis. Radiofrequency ablation of the tumor and surgical resection was previously attempted without success. We describe the anesthetic management for the successful resection of the metastatic hepatic paraganglioma, which was complicated by profound intraoperative hypertension and hypotension that necessitated the use of multiple vasoactive infusions, extensive surgical blood loss requiring blood transfusion, and difficult glycemic control in an insulin-dependent diabetic patient. The postoperative course is also described. This unique case presented the anesthesia team with challenges specific to both surgery for hepatic resection as well as for catecholamine-secreting tumors. We are not aware of any reports of paragangliomas of either donor or recipient origin involving a transplanted liver, making this the first such report to the best of our knowledge.

 

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[300]

TÍTULO / TITLE:  - A case of more than 20 years survival with glioblastoma, and development of cavernous angioma as a delayed complication of radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Feb 13. doi: 10.1111/neup.12022.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12022

AUTORES / AUTHORS:  - Fukushima S; Narita Y; Miyakita Y; Ohno M; Takizawa T; Takusagawa Y; Mori M; Ichimura K; Tsuda H; Shibui S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan; Division of Brain Tumor Translational Research, National  Cancer Center Research Institute, Tokyo, Japan.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is the most common malignant CNS neoplasm, the prognosis of which remains poor even after multidisciplinary treatment. The 5-year overall survival rate of GBM is less than 10% and has remained unchanged for more than 50 years. Because GBM patients rarely survive over a decade, only very few cases of  delayed complications caused by therapy have been reported. Here, we report the case of a 24-year-old man who is still alive 21 years after surgical resection and chemoradiotherapy for GBM. This patient developed a cavernous angioma 19 years after the initial surgery as a delayed complication of radiotherapy. The diagnosis of the initial tumor was confirmed by histopathological review, which indicated that the tumor had immunohistochemical and genetic profiles consistent  with GBM. Long-term survival in the case of this GBM patient likely resulted from a combination of factors, including hypermethylation of the MGMT (O(6) -methyl guanine methyl transferase) CpG island, young age at diagnosis, good performance  status, and complete surgical resection of the tumor. To the best of our knowledge, this case report describes one of the longest-surviving GBM patients and is the first on radiation-induced cavernous angioma in a GBM patient.

 

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[301]

TÍTULO / TITLE:  - Central nervous system tumors in the first year of life: a clinical and pathologic experience from a single cancer center.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2081-0

AUTORES / AUTHORS:  - Al-Hussaini M; Swaidan M; Al-Jumaily U; Musharbash A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, King Hussein Cancer Center, Queen Rania Al Abdullah Street, P.O. Box 1269, Al-Jubeiha, Amman, 11941, Jordan, mhussaini@khcc.jo.

RESUMEN / SUMMARY:  - PURPOSE: This study aims to review our experience with central nervous system (CNS) tumors occurring during the first year of life and to report differing features found in our series. METHODS: This is a retrospective study of infants with CNS tumors diagnosed at our institution from 2006 to 2011. RESULTS: A total  of 19 cases were identified, with a median age of 232 days and predominance of male gender. Males were younger than females at the time of diagnosis (p value =  0.039). There were 13 low-grade tumors, glial tumors being the most common (11/13, p value = 0.003) and six high-grade tumors, atypical teratoid rhabdoid tumor being the most common (4/6). Low-grade tumors predominated in the supratentorial region, while high-grade tumors were seen in the infratentorial area (p value = 0.035). Males had a predilection to have more supratentorial tumors (p value = 0.058). Four patients underwent gross total resection, and eight received chemotherapy; none received radiotherapy. Two patients had spinal  cord tumors; both were of pilomyxoid astrocytoma histology. Rare tumors included  hemangiopericytoma (n = 1) and atypical choroid plexus tumor (n = 1), both occurring in the supratentorial area and affecting the youngest patients in this  group; they were diagnosed prenatally and at 107 days, respectively. The median progression-free and overall survivals were 269 and 667 days, respectively. Among all tested parameters, only the grade of the tumor affected the outcome. CONCLUSIONS: Diagnosis and management of infant’s CNS tumors remain challenging.  Pathologists should be aware of the diversity of histological types. Assigning appropriate tumor grade is fundamental in predicting the outcome.

 

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[302]

TÍTULO / TITLE:  - Telomerase Activity in Human Brain Tumors: Astrocytoma and Meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Mol Neurobiol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10571-013-9923-x

AUTORES / AUTHORS:  - Kheirollahi M; Mehrazin M; Kamalian N; Mohammadi-Asl J; Mehdipour P

INSTITUCIÓN / INSTITUTION:  - Pediatric Inherited Diseases Research Center, Genetics and Molecular Biology Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan,  Iran, mkheirollahi@med.mui.ac.ir.

RESUMEN / SUMMARY:  - Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the  standard protocols. In the brain tissues, telomerase activity was positive in 39  (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

 

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[303]

TÍTULO / TITLE:  - Pituitary adenomas: Surgery and radiotherapy in the age of molecular diagnostics  and pathology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Probl Cancer. 2013 Jan-Feb;37(1):6-37. doi: 10.1016/j.currproblcancer.2012.10.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.currproblcancer.2012.10.001

AUTORES / AUTHORS:  - McCutcheon IE

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

 

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[304]

TÍTULO / TITLE:  - Quality of life after stereotactic radiotherapy for meningioma: a prospective non-randomized study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1099-1

AUTORES / AUTHORS:  - Henzel M; Fokas E; Sitter H; Wittig A; Engenhart-Cabillic R

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Philipps University, Marburg, Germany.

RESUMEN / SUMMARY:  - Stereotactic radiotherapy (SRT) is well-established in the treatment of meningiomas offering high local control with low toxicity. However, the impact of SRT on quality of life (QoL) of patients remains largely unknown. This work aimed to prospectively evaluate QoL (longitudinal analysis) during and after SRT of meningiomas. We performed a single center, one-armed, prospective non-randomized  study to assess QoL before and at the end of SRT (median fraction dose: 1.8 Gy; median cumulative dose: 54.0 Gy) and furthermore biannually until 24 months after SRT with the “medical outcome study short form 36”. This questionnaire evaluates  8 health parameters summarized in “physical component scale” (PCS) and “mental component scale” (MCS). Between 2005 and 2007, 67 patients were enrolled and treated with SRT. 42/52 patients underwent previous operations and 10/52 primary  SRT. Complete follow-up data were available from 44 patients. Compared to the german normal population (GNP) a general decrease in the mean values of all parameters was observed. After SRT mean values still declined and 12 months after SRT all parameters normalized towards their initial values. The cohort (previous  operations) had better values for MCS (p = 0.004). The cohort (primary SRT) had worse values for PCS that increased asymptotically 6 months after SRT to values of cohort (previous operations) (p = 0.054). Gender, age and tumor related symptoms did not affect QoL according to MCS and PCS (p > 0.05). Local control was 98 %. Treatment was well tolerated and no severe side effects were observed.  Patients with meningiomas have an impaired QoL compared to GNP. The QoL assessment after SRT revealed three phases: “depressive phase”, “recovery phase”  and “normalization phase”. Patients treated with primary SRT developed a stable increase of the mean values for PCS. Gender, age, applied dose, symptomatology did not affect QoL.

 

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[305]

TÍTULO / TITLE:  - Computerized assessment of cognitive late effects among adolescent brain tumor survivors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1123-5

AUTORES / AUTHORS:  - Conklin HM; Ashford JM; Di Pinto M; Vaughan CG; Gioia GA; Merchant TE; Ogg RJ; Santana V; Wu S

INSTITUCIÓN / INSTITUTION:  - Department of Psychology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105-2794, USA, heather.conklin@stjude.org.

RESUMEN / SUMMARY:  - Advantages of computerized assessment of neuropsychological functions include improved standardization and increased reliability of response time variables. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a computerized battery developed for monitoring recovery following mild brain injuries that assesses attention, memory and processing speed. Despite evidence that core areas of deficit among cancer survivors are those assessed by ImPACT, it has not previously been used with this population. Twenty four childhood brain tumor (BT) survivors treated with conformal radiation therapy (mean age = 15.7 +/- 1.6; mean age at irradiation = 9.8 +/- 2.5), twenty solid tumor (ST) survivors treated without CNS-directed therapy (mean age = 16.2 +/- 1.8) and twenty healthy siblings (mean age = 15.1 +/- 1.6 years) were administered an age  modified version of ImPACT. Additional computerized measures of working memory and recognition memory were administered. Univariate ANOVAs revealed group differences (p < 0.05) on measures of recognition memory, spatial working memory, processing speed and reaction time, with BT survivors performing significantly worse than ST survivors and siblings. Pearson correlation coefficients revealed significant associations between ImPACT memory tasks and computerized forced choice recognition tasks (rs = 0.30-0.33, p < 0.05). Multiple surgical resections, hydrocephalus and CSF shunt placement most consistently predicted worse ImPACT performance using linear mixed models (p < 0.05). The ImPACT test battery demonstrated sensitivity to cognitive late effects experienced by some BT survivors with clinical predictors of performance consistent with the pediatric oncology literature. Correlations with measures of similar constructs provide evidence for convergent validity. Findings offer initial support for the utility  of ImPACT for monitoring of cognitive late effects.

 

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[306]

TÍTULO / TITLE:  - Subcompartmentalization of extracellular extravascular space (EES) into permeability and leaky space with local arterial input function (AIF) results in  improved discrimination between high- and low-grade glioma using dynamic contrast-enhanced (DCE) MRI.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24021.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24021

AUTORES / AUTHORS:  - Sahoo P; Rathore RK; Awasthi R; Roy B; Verma S; Rathore D; Behari S; Husain M; Husain N; Pandey CM; Mohakud S; Gupta RK

INSTITUCIÓN / INSTITUTION:  - Department of Mathematics & Statistics, Indian Institute of Technology Kanpur, India.

RESUMEN / SUMMARY:  - PURPOSE: To modify the generalized tracer kinetic model (GTKM) by introducing an  additional tissue uptake leakage compartment in extracellular extravascular space (LTKM). In addition, an implicit determination of voxel-wise local arterial input function (AIF) C(p) (t) was performed to see whether these changes help in better discrimination between low- and high-grade glioma using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). MATERIALS AND METHODS: The modified model (LTKM) was explored and fitted to the concentration-time curve C(t) of each voxel, in which the local AIF C(p) (t) could be estimated by a time invariant convolution approximation based on a separately measured global AIF C(a) (t). A comparative study of tracer kinetic analysis was performed on 184 glioma patients using DCE-MRI data on 1.5T and 3T MRI systems. RESULTS: The LTKM analysis provided more accurate pharmacokinetic parameters as evidenced by their relative  constancy with respect to the length of concentration-time curve used. In addition, LTKM with local AIF resulted in improved discrimination between low-grade and high-grade gliomas. CONCLUSION: LTKM with local AIF provides more accurate estimation of physiological parameters and improves discrimination between low-grade and high-grade gliomas as compared with GTKM. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. (c) 2013 Wiley Periodicals, Inc.

 

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[307]

TÍTULO / TITLE:  - Expression level of human miR-34a correlates with glioma grade and prognosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1119-1

AUTORES / AUTHORS:  - Gao H; Zhao H; Xiang W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, Hubei, People’s Republic of China.

RESUMEN / SUMMARY:  - The aim of this study is to investigate the expression level of microRNA-34a (miR-34a) in glioma patients and its significance for predicting the prognosis of glioma. In this study, we examined the expression of miR-34a in glioma tissues of various World Health Organization (WHO) grades and explored the association between miR-34a expression and clinical and pathological parameters of glioma patients. We found that the tissues from high-grade gliomas (grade III and IV) had much lower miR-34a expression compared to normal brain tissues. The results of a 72-month follow-up in 146 glioma patients further demonstrated that miR-34a  expression levels positively correlated with tumor WHO grades. Additionally, in the patients with grade III and IV gliomas, lower miR-34a expression correlated with worse progression-free survival and overall survival. Univariate and multivariate analysis revealed that miR-34a was an independent prognostic indicator for glioma. Additionally, we explored the correlation between miR-34a expression and p53 status and Bcl-2 expression in grade III and IV glioma tissues. Wild-type p53 tumors displayed significantly higher miR-34a expression level than mutant p53 tumors. In addition, glioma tissues with high miR-34a expression had dramatically lower Bcl-2 expression levels than tissues with low miR-34a expression. These findings indicate the role of miR-34a in tumor progression may be closely associated with p53 mutation and inversely correlated  to Bcl-2 expression. In conclusion, our work presents comprehensive evidence for  miR-34a expression as a novel and potentially useful signature for predicting prognosis of glioma.

 

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[308]

TÍTULO / TITLE:  - Outcome prediction in intracranial tumor surgery: the National Surgical Quality Improvement Program 2005-2010.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1089-3

AUTORES / AUTHORS:  - Bekelis K; Bakhoum SF; Desai A; Mackenzie TA; Roberts DW

INSTITUCIÓN / INSTITUTION:  - Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH, 03756, USA, kbekelis@gmail.com.

RESUMEN / SUMMARY:  - Accurate knowledge of individualized risks is crucial for decision-making in the  surgical management of patients with brain tumors. Precise delineation of those risks remains a topic of debate. We attempted to create a predictive model of outcomes in patients undergoing craniotomies for tumor resection (CTR). We performed a retrospective cohort study involving patients who underwent CTR from  2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database. A model for outcome prediction based on individual patient characteristics was developed. Of the 1,834 patients, 457 had  meningiomas (24.9 %) and 1377 had non-meningioma tumors (75.1 %). The respective  30-day postoperative risks were 2.1 % for stroke, 1.3 % for MI, 2.7 % for death,  2.4 % for deep surgical site infection, and 6.6 % for return to the OR. Multivariate analysis demonstrated that pre-operative tumor-related neurologic deficit, stroke, altered mental status, and weight loss, were independently associated with most outcomes, including post-operative MI, death, and deep surgical site infection. An additive effect of the variables on the risk of all outcomes was observed. A validated model for outcome prediction based on individual patient characteristics was developed. The accuracy of the model was estimated by the area under the receiver operating characteristic curve, which was 0.687, 0.929, 0.749, 0.746, and 0.679 for postoperative risk of stroke, MI, death, infection, and return to the OR, respectively. Our model can provide individualized estimates of the risks of post-operative complications based on pre-operative conditions, and can potentially be utilized as an adjunct in the decision-making for surgical intervention in brain tumor patients.

 

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[309]

TÍTULO / TITLE:  - Glioblastomas with oligodendroglial component have the same clinical phenotype as classical glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Feb 18.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.767315

AUTORES / AUTHORS:  - Elmahdi A; Frary AJ; Scotton WJ; O’Donovan DG; Price SJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Addenbrooke’s Hospital, Cambridge University Hospitals Foundation Trust , Cambridge , UK.

RESUMEN / SUMMARY:  - Introduction. Glioblastomas are the commonest primary brain tumour and are considered one of the most heterogeneous tumour types. The introduction of a glioblastoma with oligodendroglial component (GBM + O) in the latest WHO Classification of Tumours of the Central Nervous System (1) was to help with this. There has been conflicting evidence as to whether this tumour conferred a better prognosis than classical glioblastoma (GBM). The aim of this study was to  study the clinical phenotype of these GBM + O tumours and compare it to the classical GBM. Materials and methods. All patients with histological evidence of  a glioblastoma between 1st January 2007 and 31st January 2011 were identified from the Neuropathology Database. Clinical and radiological details were obtained for all patients. The overall survival of patients who were treated with chemoradiotherapy was obtained and the GBM + O cohort compared to the classical GBM cohort. Results. Three hundred and ninety-six patients with newly diagnosed glioblastomas were identified: 294 (74.2%) had classical GBM and 102 (25.6%) had  GBM + O. The two cohorts presented at a similar age (61.1 years GBM + O vs. 63.2  years GBM; P = 0.09) and were matched for sex and side of the tumour. GBM + O were more likely to be located in the frontal lobes (38.2% for GBM + O vs. 27.2%  for GBM: P = 0.04). In the group that was treated with chemoradiotherapy the overall survival was similar (median survival GBM + O 361 days vs. 379 days GBM;  Log Rank 0.61, P = 0.43). Conclusion. The presence of an oligodendroglial component does not confer any improvement in survival and has a similar clinical  phenotype to classical GBMs.

 

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[310]

TÍTULO / TITLE:  - MRI assessment of experimental gliomas using 17.6 T.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuroradiology. 2013 Mar 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00234-013-1149-6

AUTORES / AUTHORS:  - Schwarz MA; Pham M; Helluy X; Doerfler A; Engelhorn T

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany, marc.schwarz@uk-erlangen.de.

RESUMEN / SUMMARY:  - INTRODUCTION: Using ultra-high-field contrast-enhanced magnetic resonance imaging (MRI), an increase of field strength is associated with a decrease of T 1 relaxivity. Yet, the impact of this effect on signal characteristics and contrast-enhanced pathology remains unclear. Hence, we evaluated the potential of a 17.6-T MRI to assess contrast-enhancing parts of experimentally induced rat gliomas compared to 3 T. METHODS: A total of eight tumor-bearing rats were used for MRI assessments either at 17.6 T (four rats) or at 3 T (four rats) at 11 days after stereotactic implantation of F98 glioma cells into the right frontal lobe.  T 1-weighted sequences were used to investigate signal-to-noise-ratios, contrast-to-noise-ratios, and relative contrast enhancement up to 16 min after double-dose contrast application. In addition, tumor volumes were calculated and  compared to histology. RESULTS: The 17.6-T-derived contrast-enhancing volumes were 31.5 +/- 15.4 mm3 at 4 min, 38.8 +/- 12.7 mm3 at 8 min, 51.1 +/- 12.6 mm3 at 12 min, and 61.5 +/- 10.8 mm3 at 16 min after gadobutrol injection. Corresponding histology-derived volumes were clearly higher (138.8 +/- 8.4 mm3; P < 0.01). At 3 T, contrast-enhancing volumes were 85.2 +/- 11.7 mm3 at 4 min, 107.3 +/- 11.0 mm3 at 8 min, 117.0 +/- 10.5 mm3 at 12 min, and 129.1 +/- 10.0 mm3 at 16 min after contrast agent application. Averaged histology-derived volumes (139.1 +/- 13.4 mm3) in this group were comparable to the 16-min volume (P <-->16 min = 0.38). Compared to ultra-high-field MRI, all 3-T-derived volumes were significantly higher (P < 0.02). CONCLUSION: Compared to 3-T-derived images and histology, tumor volumes were underestimated by approximately 50 % at 17.6 T. Hence, contrast-enhanced 17.6-T MRI provided no further benefits in tumor measurement compared to 3 T.

 

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[311]

TÍTULO / TITLE:  - Anti-tissue factor (TF9-10H10) treatment reduces tumor cell invasiveness in a novel migratory glioma model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Feb 5. doi: 10.1111/neup.12018.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12018

AUTORES / AUTHORS:  - Harter PN; Dutzmann S; Drott U; Zachskorn C; Hattingen E; Capper D; Gessler F; Senft C; Seifert V; Plate KH; Kogel D; Mittelbronn M

INSTITUCIÓN / INSTITUTION:  - Edinger Institute, Institute of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany.

RESUMEN / SUMMARY:  - In vitro and descriptive studies of human tissue samples revealed the pro-coagulant glycoprotein tissue factor (TF) as a potent player in glioma cell infiltration that is activated by hypoxia and has also been shown to be upregulated by mutations of TP53 or PTEN. Here we present the morphological and genetic characterization of a novel glioblastoma in vivo model and provide evidence that treatment with an antibody targeting TF leads to reduced glioma cell invasiveness. Therefore, we established a murine xenograft treatment model by transplanting the angiogenic and diffusely infiltrating human glioma cell line MZ-18 with endogenous TF expression into nude mice brains and treating these mice with an intracranial osmotic pump system continuously infusing a monoclonal antibody against TF (mAb TF9-10H10). The human MZ-18 cell line harbors two TP53 mutations resulting in a strong nuclear accumulation of p53, thereby facilitating the unambiguous identification of tumor cells in the xenograft model. Intracranial application of TF9-10H10 significantly reduced invasion of MZ-18 cells compared to mock-treated control animals. The extent of activated blood vessels was also reduced upon anti-TF treatment. Thus, targeting the TF pathway might be a promising treatment strategy for future glioblastoma therapies, by affecting both invading tumor cells and tumor vasculature.

 

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[312]

TÍTULO / TITLE:  - Distinguishing Pseudoprogression From Progression in High-Grade Gliomas: A Brief  Review of Current Clinical Practice and Demonstration of the Potential Value of 18F-FDG PET.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318286c148

AUTORES / AUTHORS:  - Oborski MJ; Laymon CM; Lieberman FS; Mountz JM

INSTITUCIÓN / INSTITUTION:  - From the *Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; and daggerDepartment of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

RESUMEN / SUMMARY:  - We report a case in which F-FDG PET was able to discriminate pseudoprogression from progression observed on contrast-enhanced (CE) MRI (CE-MRI). A 56-year-old male patient with anaplastic oligodendroglioma demonstrated markedly increased tumor enhancement on CE-MRI 1 month after completing radiation therapy (RT), suggesting radiological progression. However, the patient was clinically improved and therefore received an early-therapy response assessment PET to assess for pseudoprogression. PET showed low tumor uptake indicating stable disease. Follow-up CE-MRI at 3 and 4 months post-RT confirmed stable disease. This case emphasizes the value of F-FDG PET when pseudoprogression is clinically suspected.

 

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[313]

TÍTULO / TITLE:  - Good outcome following emergency decompressive craniectomy in a case of malignant middle cerebral artery infarction in a 14-month-old infant.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.776668

AUTORES / AUTHORS:  - Grigoratos DN; Mazarakis NK; Lumsden DE; Kariyawasam S; Bhangoo R; Gordon A; Lin JP; Dlamini N

INSTITUCIÓN / INSTITUTION:  - Department of Paediatric Neurosciences, Evelina Children’s Hospital , London , UK.

RESUMEN / SUMMARY:  - We report the case of a 14-month-old infant presenting with unresponsiveness and  seizure following thoracic surgery. Imaging showed full territory left middle cerebral artery infarct and signs of raised intracranial pressure (ICP) that required emergency decompressive craniectomy (DC). The child made a good functional recovery. We discuss the case.

 

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[314]

TÍTULO / TITLE:  - Targeting the Cytosolic Innate Immune Receptors RIG-I and MDA5 Effectively Counteracts Cancer Cell Heterogeneity in Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. 2013 Feb 6. doi: 10.1002/stem.1350.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1350

AUTORES / AUTHORS:  - Glas M; Coch C; Trageser D; Dassler J; Simon M; Koch P; Mertens J; Quandel T; Gorris R; Reinartz R; Wieland A; von Lehe M; Pusch A; Roy K; Schlee M; Neumann H; Fimmers R; Herrlinger U; Brustle O; Hartmann G; Besch R; Scheffler B

INSTITUCIÓN / INSTITUTION:  - Stem Cell Pathologies, Bonn, Germany; Institute of Reconstructive Neurobiology, Bonn, Germany; Division of Clinical Neurooncology, Deptartment of Neurology, Bonn, Germany; Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik and University of Bonn Medical Center, 53105 Bonn, Germany. martin.glas@ukb.uni-bonn.de.

RESUMEN / SUMMARY:  - Cellular heterogeneity, e.g. the intratumoral coexistence of cancer cells with and without stem cell characteristics, represents a potential root of therapeutic resistance and a significant challenge for modern drug development in glioblastoma (GBM). We propose here that activation of the innate immune system by stimulation of innate immune receptors involved in antiviral and antitumor responses can similarly target different malignant populations of glioma cells. We used short-term expanded patient-specific primary human GBM cells to study the stimulation of the cytosolic nucleic acid receptors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). Specifically, we analyzed cells from the tumor core vs. ‘residual GBM cells’ derived from the tumor resection margin as well as stem cell-enriched primary cultures vs. specimens without stem cell properties. A portfolio of human, non-tumor neural cells was used as a control for these studies. The expression of RIG-I and MDA5 could be induced in all of these cells. Receptor stimulation with their respective ligands, p(I:C) and 3pRNA, led to in vitro evidence for an effective activation of the innate immune system. Most intriguingly, all investigated cancer cell populations additionally responded with a pronounced induction of apoptotic signaling cascades revealing a second, direct mechanism of antitumor activity. By contrast, p(I:C) and 3pRNA induced only little toxicity in human non-malignant neural cells. Granted that the challenge of effective CNS delivery can be overcome, targeting of RIG-I and MDA5  could thus become a quintessential strategy to encounter heterogeneous cancers in the sophisticated environments of the brain.

 

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[315]

TÍTULO / TITLE:  - Super-Resolution Track Density Imaging of Glioblastoma: Histopathologic Correlation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3400

AUTORES / AUTHORS:  - Barajas RF Jr; Hess CP; Phillips JJ; Von Morze CJ; Yu JP; Chang SM; Nelson SJ; McDermott MW; Berger MS; Cha S

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology and Biomedical Imaging, Pathology, and Neurological Surgery, University of California, San Francisco, California.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Super-resolution track density imaging generates anatomic  images with submillimeter voxel resolution by using high-angular-resolution diffusion imaging and fiber-tractography. TDI within the diseased human brain has not been previously described. The purpose of this study was to correlate TDI with histopathologic features of GBM.MATERIALS AND METHODS:A total of 43 tumor specimens (24 contrast-enhancing, 12 NE, and 7 centrally necrotic regions) were collected from 18 patients with treatment-naive GBM by use of MR imaging-guided neurosurgical techniques. Immunohistochemical stains were used to evaluate the following histopathologic features: hypoxia, architectural disruption, microvascular hyperplasia, and cellular proliferation. We reconstructed track density maps at a 0.25-mm isotropic spatial resolution by using probabilistic streamline tractography combined with constrained spheric deconvolution (model order, 8; 0.1-mm step size; 1 million seed points). Track density values were obtained from each tissue site. A P value of .05 was considered significant and was adjusted for multiple comparisons by use of the false discovery rate method.RESULTS:Track density was not significantly different between contrast-enhancing and NE regions but was more likely to be elevated within regions demonstrating aggressive histopathologic features (P < .05). Significant  correlation between relative track density and hypoxia (odds ratio, 3.52; P = .01), architectural disruption (odds ratio, 3.49; P = .03), and cellular proliferation (odds ratio, 1.70; P = .05) was observed irrespective of the presence or absence of contrast enhancement.CONCLUSIONS:Numeric values of track density correlate with GBM biologic features and may be clinically useful for identification of regions of tumor infiltration within both enhancing and NE components of GBM.

 

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[316]

TÍTULO / TITLE:  - Superior sagittal sinus reconstruction using a femoral venous graft after total removal of a meningioma. Case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurochirurgie. 2013 Feb;59(1):43-6. doi: 10.1016/j.neuchi.2012.10.141. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neuchi.2012.10.141

AUTORES / AUTHORS:  - Desse N; Malikov S; Fuentes S; Pech-Gourg G; Graillon T; Dufour H

INSTITUCIÓN / INSTITUTION:  - Service de neurochirurgie, centre hospitalier universitaire Timone, 264, rue Saint-Pierre, 13385 Marseille, France. Electronic address: ndesse.neurochir@gmail.com.

RESUMEN / SUMMARY:  - OBJECTIVE: Resection of a parasagittal meningioma invading the superior sagittal  sinus (SSS) needs the reconstruction of the sinus by a patch or a venous graft depending of sinus invasion degree. METHOD: We present here a case of a 21-year-old man who underwent radical removal of a radio-induced parasagittal meningioma totally invading the posterior third of the sinus. For its reconstruction, we used the patient’s left superficial femoral vein without valves as an autograft, by realizing two end-to-end anastomoses between the sinus and the graft after an en-bloc removal of the meningioma and the invaded sinus. RESULTS: Two years after surgery, clinical examination of the patient was strictly normal and the femoral venous graft was still patent on CT angiograms. CONCLUSION: The superficial femoral vein without valves seems to be convenient for SSS reconstruction.

 

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[317]

TÍTULO / TITLE:  - Heterogeneous cellular origins for glioma in murine model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Apr;72(4):N20. doi: 10.1227/01.neu.0000428425.83867.ce.

            ●● Enlace al texto completo (gratuito o de pago) 1227/01.neu.0000428425.83867.ce

AUTORES / AUTHORS:  - Jandial R; Chen MY

 

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[318]

TÍTULO / TITLE:  - LETTER TO THE EDITOR: Central nervous system relapse in acute promyelocytic leukemia: a single institution experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Leuk Lymphoma. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.782609

AUTORES / AUTHORS:  - Gupta V; Gonsalves W; Patnaik M; Gangat N

 

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[319]

TÍTULO / TITLE:  - Posterior fossa calcifying pseudoneoplasm of the central nervous system.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):896-902. doi: 10.3171/2013.1.JNS121755. Epub 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121755

AUTORES / AUTHORS:  - Kerr EE; Borys E; Bobinski M; Shahlaie K

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery.

RESUMEN / SUMMARY:  - Calcifying pseudoneoplasms of the neuraxis are rare, poorly understood masses that may arise throughout the CNS. Although these lesions are generally considered benign and noninfiltrative, reports exist that document growth of these masses on serial plain radiographs. The authors report a case of a posterior fossa calcifying pseudoneoplasm of the neuraxis demonstrating interval  development of peritumoral edema on serial MRI. Their findings suggest that these lesions may sometimes behave in a more aggressive manner than commonly thought.

 

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[320]

TÍTULO / TITLE:  - Brainstem gangliogliomas: a retrospective series.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Apr;118(4):884-8. doi: 10.3171/2013.1.JNS121323. Epub 2013 Feb  1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121323

AUTORES / AUTHORS:  - Zhang S; Wang X; Liu X; Ju Y; Hui X

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China.

RESUMEN / SUMMARY:  - Object The authors retrospectively analyzed data on brainstem gangliogliomas treated in their department and reviewed the pertinent literature to foster understanding of the preoperative characteristics, management, and clinical outcomes of this disease. Methods In 2006, the authors established a database of  treated lesions of the posterior fossa. The epidemiology findings, clinical presentations, radiological investigations, pathological diagnoses, management, and prognosis for brainstem gangliogliomas were retrospectively analyzed. Results Between 2006 and 2012, 7 patients suffering from brainstem ganglioglioma were treated at the West China Hospital of Sichuan University. The mean age of the patients, mean duration of symptoms prior to diagnosis, and mean duration of follow-up were 28.6 years, 19.4 months, and 38.1 months, respectively. The main presentations were progressive cranial nerve deficits and cerebellar signs. Subtotal resection was achieved in 2 patients, and partial resection in 5. All tumors were pathologically diagnosed as WHO Grade I or II ganglioglioma. Radiotherapy and adjuvant chemotherapy were not administered. After 21-69 months  of follow-up, patient symptoms were resolved or stable without aggravation, and MRI showed that the size of residual lesions was unchanged without progression or recurrence. Conclusions The diagnosis of brainstem ganglioglioma is of great importance given its favorable prognosis. The authors recommend the maximal safe  resection followed by close observation without adjuvant therapy as the optimal treatment for this disease.

 

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[321]

TÍTULO / TITLE:  - Intraoperative flow cytometry analysis of glioma tissue for rapid determination of tumor presence and its histopathological grade.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS12681

AUTORES / AUTHORS:  - Shioyama T; Muragaki Y; Maruyama T; Komori T; Iseki H

INSTITUCIÓN / INSTITUTION:  - Institute of Advanced Biomedical Engineering and Science;

RESUMEN / SUMMARY:  - Object Intraoperative histopathological investigation plays an important role during surgery for gliomas. To facilitate the rapid characterization of resected  tissue, an original technique of intraoperative flow cytometry (iFC) was established. The objective in this study was evaluation of this technique’s efficacy for rapidly determining tumor presence in the surgical biopsy sample and WHO histopathological grade of the neoplasm. Methods In total, 328 separate biopsy specimens obtained during the resection of 81 intracranial gliomas were analyzed with iFC. The evaluated malignancy index (MI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. The duration of iFC in all cases was approximately 10 minutes. Each sample was additionally investigated histopathologically on frozen and permanent  formalin-fixed paraffin-embedded tissue sections. The latter process was used as  a “gold standard” control for evaluation of the diagnostic efficacy of iFC analysis. Results The MI differed significantly between neoplastic and perilesional brain tissue (25.3% +/- 22.0% vs 4.6% +/- 2.6%, p < 0.01). Receiver  operating characteristic curve analysis revealed a corresponding area under the curve value of 0.941. The optimal cutoff level of the MI for identification of tumor in the biopsy specimen was 6.8%, which provided 0.88 sensitivity, 0.88 specificity, 0.97 positive predictive value, 0.60 negative predictive value, and  0.88 diagnostic accuracy. Additionally, the MI showed a significant association with WHO histopathological grades of glioma (p < 0.01), but its values in Grade II, III, and IV tumors overlapped prominently and were on average 13.3% +/- 11.0%, 35.0% +/- 21.8%, and 46.6% +/- 23.1%, respectively. Conclusions Results of this study demonstrate that iFC with the determination of the MI may be feasible  for rapidly determining glioma presence in a surgical biopsy sample.

 

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[322]

TÍTULO / TITLE:  - Letter to the Editor: Glioma grade.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS122115

AUTORES / AUTHORS:  - Kapoor S

INSTITUCIÓN / INSTITUTION:  - Mechanicsville, Virginia.

 

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[323]

TÍTULO / TITLE:  - Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.JNS121537

AUTORES / AUTHORS:  - Cage TA; Pekmezci M; Prados M; Berger MS

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Recurrent glioblastoma (GBM) can occur locally or at distant sites within the brain. Though MRI is the standard imaging modality for primary and recurrent GBM, the full extent of diffuse lesions may not be appreciated on MRI alone. Glioblastomas with ependymal and/or subependymal spread are examples of diffuse infiltrative tumors that are incompletely seen on MRI. Some other adjuvant visualization technique such as intraoperative fluorescence-assisted 5-aminolevulinic acid (5-ALA) could be used to assist the surgeon in localizing the infiltrating tumor. The authors report on a 56-year-old man who presented 7 years after initial resection of an occipital lobe GBM with imaging consistent with distant discrete foci of tumor recurrence. Because these foci were distant from the original resection cavity, there was concern for diffuse, infiltrative tumor elsewhere throughout the brain versus a distant multicentric recurrence. Therefore, the patient was given 5-ALA prior to surgery to aid in tumor detection intraoperatively. Using fluorescent visualization of the resection cavity, it was confirmed that there was subependymal and ependymal spread of the recurrent tumor along the lateral ventricle connecting the recurrence to the previous tumor site. Magnetic resonance imaging may not completely detect the presence of diffuse tumor infiltrating the ependymal or subependymal spaces. Therefore, adjunct intraoperative use of fluorescence-assisted visualization with 5-ALA may be helpful in highlighting and detecting infiltrative tumor to accurately detect tumor burden and distinguish it from a separate multicentric recurrence.

 

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[324]

TÍTULO / TITLE:  - Editorial: Low-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.7.JNS121358

AUTORES / AUTHORS:  - Berger MS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of California, San Francisco, California.

 

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[325]

TÍTULO / TITLE:  - Effects of slice thickness and head rotation when measuring glioma sizes on MRI:  in support of volume segmentation versus two largest diameters methods.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):165-72. doi: 10.1007/s11060-013-1051-4. Epub 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1051-4

AUTORES / AUTHORS:  - Schmitt P; Mandonnet E; Perdreau A; Angelini ED

INSTITUCIÓN / INSTITUTION:  - Institut Mines-Telecom, Telecom ParisTech, CNRS LTCI, 46 Rue Barrault, 75013, Paris, France, pierre.schmitt@telecom-paristech.fr.

RESUMEN / SUMMARY:  - This paper presents a study of the effects of scanning parameters variability when assessing glioma sizes on MRI. A database of lesions of various shapes and sizes, segmented on 3D-SPGR MRI images, was acquired on 65 patients with low-grade glioma. Simulations of large slice thickness and patient’s head rotation were performed, allowing us to study their influence on two size indices: the bi-dimensional diameter product index (computed with the two largest diameters method) and the equivalent diameter index (computed with the volume segmentation method). Results show that thick slices and axial plane rotation can induce average (maximal) uncertainties on the bi-dimensional diameter product index between 32 and 6 % (150 %) for small and large tumors (size range 0.5-286 ml). The uncertainty on the equivalent diameter index, for the same categories of tumors, drops below 8 and 0.1 % (23 %). This study shows that the volume segmentation method is subject to less variability inherent to scanning conditions compared to the two largest diameters method. It also emphasizes the need for strict clinical guidelines on the replication of scanning conditions when performing MRI follow-ups on patients harboring small tumors. These implications await confirmation on a series of real patients being re-scanned with FLAIR MRI.

 

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[326]

TÍTULO / TITLE:  - Effects of Glial Cell Line-derived Neurotrophic Factor on the Cultured Adult Full-thickness Porcine Retina.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Eye Res. 2013 Apr;38(4):503-15. doi: 10.3109/02713683.2013.763989. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02713683.2013.763989

AUTORES / AUTHORS:  - Taylor L; Arner K; Engelsberg K; Ghosh F

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Lund University Hospital , Lund , Sweden.

RESUMEN / SUMMARY:  - Abstract Background: The tissue culture system offers a possibility to study factors involved in neuronal survival which may be important in a transplantation paradigm. The use of adult tissue in this setting poses specific challenges since traditionally mature neurons survive poorly in vitro. In the current paper, we have explored effects of glial cell line-derived neurotrophic factor (GDNF) on cultures of adult porcine retina. Methods: Full-thickness retinal sheets were isolated from adult porcine eyes and were cultured for 5 or 10 days under standard culture conditions with or without GDNF added to the culture medium. The grafts were analyzed morphologically using hematoxylin and eosin staining, immunohistochemistry and transferase dUTP nick end labeling (TUNEL) labeling. Retinas derived from normal adult porcine eyes were used as controls. Results: After 5 d in vitro (DIV), cultures without GDNF showed dissolving retinal lamination while specimens cultured with GDNF displayed the normal laminated morphology. At 10 DIV, the untreated cultures had been reduced to a degenerated cell mass, while the GDNF-cultured specimens retained thin but distinguishable retinal layers. TUNEL labeling confirmed these results. Immunohistochemical labelings and outer nuclear layer thickness measurements showed an increased preservation of photoreceptors and horizontal cells in the GDNF-treated group. Conclusions: The procedure of culturing retina involves several steps causing severe traumatic effects on the tissue, such as ganglion cell axotomy, interruption of the blood flow as well as separation from the retinal pigment epithelium (RPE). In this paper, we have shown that addition of GDNF in the culture medium attenuates the effect of these steps, resulting in enhanced preservation of several retinal neuronal subtypes. The results may be of importance for research in retinal transplantation where storage time of the donor tissue prior to transplantation is a critical issue.

 

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[327]

TÍTULO / TITLE:  - Transventricular endoscopic fenestration of intrasellar arachnoid cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurgery. 2013 Apr;72(4):520-8. doi: 10.1227/NEU.0b013e318282a6e3.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e318282a6e3

AUTORES / AUTHORS:  - Shim KW; Park EK; Lee YH; Kim SH; Kim DS

INSTITUCIÓN / INSTITUTION:  - *Pediatric Neurosurgery, Severance Children’s Hospital, Department of Neurosurgery, Brain Korea 21 project for medical science, Yonsei University College of Medicine, Seoul, South Korea double daggerNeuro-oncology, Department of Neurosurgery, Brain Korea 21 project for medical science, Yonsei University College of Medicine, Seoul, South Korea section signNational Health Insurance Corporation, Ilsan Hospital, Gayang, South Korea.

RESUMEN / SUMMARY:  - BACKGROUND: : To manage arachnoid cysts, incorporation with the normal circulation is the single most important determinant of success. Although the postoperative cerebrospinal fluid leakage rate is 3.9% for all cases of transsphenoidal surgery, it is 21.4% for intrasellar arachnoid cysts. OBJECTIVE:  : To present a safe, relatively easy, and effective treatment option for very rare intrasellar arachnoid cysts. METHODS: : We performed a prospective study of  intrasellar cystic lesions without a solid portion. Endoscopic exploration and fenestration were performed for all lesions under neuronavigational guidance. We  analyzed presenting symptoms, endocrinological status, and magnetic resonance images. RESULTS: : There were 2 male and 4 female patients with a mean age of 45  years (range, 27-67 years). All patients presented with the visual disturbance of bitemporal hemianopsia. Four patients had endocrinological symptoms including galactorrhea, dysmenorrhea, and diabetes insipidus. Endoscopic fenestration of the cyst was successfully performed in all patients. All patients were confirmed  to have a pure cystic lesion, namely an arachnoid cyst. The follow-up period was  10 months on average (range, 6-12 months). Visual disturbance improved in 5 patients. Endocrinological problems persisted in all patients for 3 months and then normalized, with the exception of the patient with diabetes insipidus. There was no evidence of recurrence in any of the 6 patients in the 12-month postoperative imaging studies (median follow-up of 10 months). Two patients showed syndrome of inappropriate antidiuretic hormone at 2 and 4 weeks after the  operation, but antidiuretic hormones recovered to normal levels after this time point. CONCLUSION: : Endoscopic fenestration of an intrasellar arachnoid cyst is  a safe and simple procedure without serious complications. ABBREVIATIONS: : IAC,  intrasellar arachnoid cystSPAC, suprasellar-prepontine arachnoid cyst.

 

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[328]

TÍTULO / TITLE:  - Tumors in the cerebellopontine angle in children: warning of a high probability of malignancy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1067-9

AUTORES / AUTHORS:  - Phi JH; Wang KC; Kim IO; Cheon JE; Choi JW; Cho BK; Kim SK

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - Cerebellopontine angle (CPA) tumors are uncommon in children, and the pathological spectrum is different from that of adults. In this study, we reviewed the pathological diagnosis of pediatric patients with a CPA tumor to determine the pattern in this age group. In a cohort of 267 patients with posterior fossa tumor, tumor locations were determined with preoperative magnetic resonance imaging (MRI). The pathological diagnosis, imaging characteristic, and  treatment outcomes of patients with CPA tumors was reviewed and analyzed. Twenty-six patients (9.7 %) had a tumor in the CPA. The pathological spectrum was wide, from malignant intrinsic brain tumors to benign extra-axial tumors and sarcomatous lesions. Eighteen patients (69 %) had malignant tumors. The pathological nature was strongly linked to patient age. The mean age of malignant tumor group was significantly younger than that of benign tumor group. MRI findings that favored malignant histology included a plastic feature of the tumor, multiple signal voids, encasement of major arteries, widening of lateral recess, focal cerebellar edema, and hydrocephalus. The presence of seeding in the neuraxis also indicated malignant pathology. Especially, increased density on precontrast computed tomography was a strong predictor of malignant pathology. Malignant CPA tumors showed high surgical morbidity rate and grim long-term prognosis. Patient age and tumor location are the two most important clues for the diagnosis of any brain tumor. Unlike in adult patients, clinicians should expect a high probability of malignant histology for pediatric CPA tumors, especially in infants and young children.

 

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[329]

TÍTULO / TITLE:  - Correlative Imaging With 18F-FDG PET/CT and MRI in Paraneoplastic Limbic Encephalitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318286bda5

AUTORES / AUTHORS:  - Maffione AM; Chondrogiannis S; Ferretti A; Al-Nahhas A; Rubello D

INSTITUCIÓN / INSTITUTION:  - From the *Department of Nuclear Medicine, PET/CT Centre, Santa Maria della Misericordia Hospital Rovigo, Rovigo, Italy; and daggerDepartment of Nuclear Medicine, Hammersmith Hospital, London, UK.

RESUMEN / SUMMARY:  - Limbic encephalitis is one of the most common paraneoplastic neurological syndromes, which is mostly associated with small cell lung cancer, testicular tumors, and breast cancer. F-FDG PET/CT can have an important role both in the identification of limbic encephalitis itself and in the detection of the unknown  malignancy that might have caused it. We report a case of a 57-year-old female patient with paraneoplastic limbic encephalitis, confirmed both by MRI and F-FDG  PET/CT, and the concurrent identification of an unknown lung malignancy by whole-body PET/CT.

 

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[330]

TÍTULO / TITLE:  - Paclitaxel Poliglumex, Temozolomide, and Radiation for Newly Diagnosed High-grade Glioma: A Brown University Oncology Group Study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827de92b

AUTORES / AUTHORS:  - Jeyapalan S; Boxerman J; Donahue J; Goldman M; Kinsella T; Dipetrillo T; Evans D; Elinzano H; Constantinou M; Stopa E; Puthawala Y; Cielo D; Santaniello A; Oyelese A; Mantripragada K; Rosati K; Isdale D; Safran H

INSTITUCIÓN / INSTITUTION:  - *The Brown University Oncology Group, Providence, RI daggerMaine Medical Center,  Portland, ME.

RESUMEN / SUMMARY:  - OBJECTIVES:: Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel  to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas. METHODS:: Eligible patients were required to have WHO grade 3 or 4 gliomas. Patients received weekly PPX (50 mg/m/wk) combined with standard daily temozolomide (75 mg/m) for 6 weeks with concomitant radiation (2.0 Gy, 5 d/wk for a total dose of 60 Gy). RESULTS:: Twenty-five patients were enrolled, 17 with glioblastoma and 8 with grade 3 gliomas. Seven of 25 patients had grade 4 myelosuppression. Hematologic toxicity  lasted up to 5 months suggesting a drug interaction between PPX and temozolomide. For patients with glioblastoma, the median progression-free survival was 11.5 months and the median overall survival was 18 months. CONCLUSIONS:: PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.

 

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[331]

TÍTULO / TITLE:  - Supra- and infratentorial pediatric ependymomas differ significantly in NeuN, p75 and GFAP expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Apr;112(2):191-7. doi: 10.1007/s11060-013-1062-1. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1062-1

AUTORES / AUTHORS:  - Hagel C; Treszl A; Fehlert J; Harder J; von Haxthausen F; Kern M; von Bueren AO; Kordes U

INSTITUCIÓN / INSTITUTION:  - Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany, hagel@uke.de.

RESUMEN / SUMMARY:  - Ependymomas comprise 8 % of all intracranial tumors in children <15 years. Recent studies revealed that some supratentorial ependymomas express neuronal antigens and that high expression of neurofilament protein light polypeptide (NEFL) correlates with better clinical outcome. We retrospectively analyzed an expanded  panel of proteins in 6 supratentorial, 15 posterior fossa and 4 spinal pediatric  ependymomas by immunohistochemistry. Expression of high and low affinity neurotrophin receptors TrkA (NTRK1) and p75 (NGFR), pan-neuronal markers NeuN (RBFOX3) and synaptophysin, radial glial marker SOX9, adhesion molecules CD56 (NCAM) and CD44, junctional protein connexin 43 (GJA1), glial fibrillary acidic protein (GFAP), epithelial membrane antigen and proliferation associated antigen  Ki-67 were evaluated in a semi-quantitative or quantitative (Ki-67 and NeuN-index) fashion. We found p75 and NeuN to be expressed at significantly higher levels in supratentorial versus infratentorial tumors and GFAP to be expressed at significantly higher levels in infratentorial lesions. In conclusion, immunohistochemical expression of p75, NeuN and GFAP differed in ependymomas depending on tumor topography supporting the view of divergent cells  of origin. However, because of the small sample size the results are of preliminary nature and replication in a larger cohort would be desirable.

 

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[332]

TÍTULO / TITLE:  - The role of the CXCR4 cell surface chemokine receptor in glioma biology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1108-4

AUTORES / AUTHORS:  - Ehtesham M; Min E; Issar NM; Kasl RA; Khan IS; Thompson RC

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224, Medical Center North, Nashville, TN, 37232, USA, moneeb.ehtesham@vanderbilt.edu.

RESUMEN / SUMMARY:  - CXCR4, a cell surface chemokine receptor, mediates cellular dissemination, invasion, and proliferation in a wide range of cancers including gliomas. It is over-expressed in glioma progenitor cells, and its protein ligand, CXCL12, has been shown to mediate a specific proliferative response in these cells thereby implicating a role for CXCR4 in glioma initiation and renewal. Given the failure  of currently employed therapies to meaningfully impact prognosis in patients with high-grade gliomas, the CXCR4-CXCL12 axis represents a novel biologically relevant mechanism that could be specifically targeted for therapy. From this perspective, this review summarizes the biological effects of CXCR4 activity and  its implications for glioma pathogenesis. Ultimately, the development of effective treatment approaches for malignant glioma must be based on a rational mechanistic understanding of tumor cell biology. As such, this article presents such a framework with regard to the CXCR4 pathway in glioma thereby supporting the further investigation of CXCR4 as a therapeutic target in patients with this  disease.

 

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[333]

TÍTULO / TITLE:  - Evaluation of the antitumor effects of rilotumumab by PET imaging in a U-87 MG mouse xenograft model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nucl Med Biol. 2013 Feb 27. pii: S0969-8051(13)00007-3. doi: 10.1016/j.nucmedbio.2013.01.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.nucmedbio.2013.01.004

AUTORES / AUTHORS:  - Rex K; Lewis XZ; Gobalakrishnan S; Glaus C; Silva MD; Radinsky R; Burgess TL; Gambhir SS; Coxon A

INSTITUCIÓN / INSTITUTION:  - Oncology Research, Amgen Inc., Thousand Oaks, CA, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway has been implicated in various cancers. Rilotumumab is an investigational, fully human monoclonal antibody that binds and neutralizes HGF. The purpose of this study was to evaluate the efficacy of rilotumumab in a U-87 MG mouse xenograft tumor model using 18F-FDG and 18F-FLT PET. METHODS: U-87 MG tumor-bearing nude mice received rilotumumab or control IgG2. In the dose response study, increasing doses of rilotumumab (10, 30, 100, 300, or 500mug) were administered, and mice were evaluated with 18F-FDG PET at baseline and 7days post-treatment. In the time course study, 300mug of rilotumumab twice per week was used for the treatment, and mice were evaluated over 7days using 18F-FDG and 18F-FLT PET. RESULTS: In the dose response study, rilotumumab at doses of 300 and 500mug was similarly effective against tumor growth. Treatment with 300 and 500mug rilotumumab inhibited 18F-FDG accumulation with significant decreases of -37% and -40% in the percent injected dose per gram of tissue (%ID/g), respectively. In the time course study, treatment with 300mug rilotumumab inhibited 18F-FDG and 18F-FLT accumulation with a maximum %ID/g of -41% and -64%, respectively. No apparent differences between the use of either tracer to evaluate rilotumumab efficacy were observed. CONCLUSIONS: Rilotumumab inhibited 18F-FDG and 18F-FLT accumulation as early as 2 and 4days after treatment, respectively, in a mouse tumor model. Further studies to evaluate 18F-FDG PET imaging as an early tumor response marker for rilotumumab are warranted. Rilotumumab is currently being tested in patients with MET-positive, advanced gastric and gastroesophageal cancer.

 

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[334]

TÍTULO / TITLE:  - Intraoperative use of diffusion tensor imaging-based tractography for resection of gliomas located near the pyramidal tract: comparison with subcortical stimulation mapping and contribution to surgical outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.771730

AUTORES / AUTHORS:  - Vassal F; Schneider F; Nuti C

INSTITUCIÓN / INSTITUTION:  - Service de Neurochirurgie, Hopital Nord, Centre Hospitalier Universitaire de Saint-Etienne , Saint-Etienne , France.

RESUMEN / SUMMARY:  - Introduction. For gliomas, the goal of surgery is maximal tumour removal with the preservation of neurological function. We evaluated the contribution of the combination of diffusion tensor imaging-based fibre tracking (DTI-FT) of the pyramidal tract (PT) integrated to the navigation and subcortical direct electrical stimulations (DESs) to surgical outcomes. Method. Ten patients underwent surgery for gliomas located in close relationship with the subcortical  course of the PT. Preoperative DTI was performed with a three-Tesla magnetic resonance scanner applying an echo-planar sequence with 20 diffusion directions.  DTI-FT data were systematically loaded into the navigation for intraoperative guidance. When the resection closely approached the PT as illustrated on navigation images, subcortical DESs were used to confirm the proximity of the PT  by observing motor responses. The location of all subcortically stimulated points with positive motor response was correlated with the illustrated PT. Motor deficits were evaluated pre- and postoperatively, and compared with the extent of tumour removal. Results. DTI-FT of the PT was successfully performed in all patients. A total of fifteen positive subcortical DESs were obtained in 8 of 10 patients; in these cases, the mean distance from the stimulated point to the PT was 6.2 +/- 3.6 mm. The mean tumoural volumetric resection was 90.8 +/- 10.4%, with a gross total resection in four patients. At one month after surgery, only one patient had a slight impairment of motor function (decreased fine motor hand  skills). Conclusions. DTI-FT is an accurate technique to map the PT in the vicinity of brain tumours. By combining anatomical (DTI-FT) and functional (subcortical DES) studies for intraoperative localization of the PT, the authors  achieved a good volumetric resection of tumours located in eloquent motor areas,  with low morbidity. Careful use of this protocol requires the knowledge of some pitfalls, mainly the occurrence of brain shift during removal of large tumours.

 

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[335]

TÍTULO / TITLE:  - Tracking the source of cerebellar epilepsy: Hemifacial seizures associated with cerebellar cortical dysplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Epilepsy Res. 2013 Jan 31. pii: S0920-1211(13)00012-0. doi: 10.1016/j.eplepsyres.2012.12.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.eplepsyres.2012.12.010

AUTORES / AUTHORS:  - Lascano AM; Lemkaddem A; Granziera C; Korff CM; Boex C; Jenny B; Schmitt-Mechelke T; Thiran JP; Garibotto V; Vargas MI; Schaller K; Seeck M; Vulliemoz S

INSTITUCIÓN / INSTITUTION:  - EEG and Epilepsy Unit, Department of Clinical Neurosciences, University Hospitals and Faculty of Medicine of Geneva, Switzerland.

RESUMEN / SUMMARY:  - Traditionally, subcortical structures such as the cerebellum are supposed to exert a modulatory effect on epileptic seizures, rather than being the primary seizure generator. We report a 14-month old girl presenting, since birth, with seizures symptomatic of a right cerebellar dysplasia, manifested as paroxystic contralateral hemifacial spasm and ipsilateral facial weakness. Multimodal imaging was used to investigate both anatomical landmarks related to the cerebellar lesion and mechanisms underlying seizure generation. Electric source imaging (ESI) supported the hypothesis of a right cerebellar epileptogenic generator in concordance with nuclear imaging findings; subsequently validated by intra-operative intralesional recordings. Diffusion spectrum imaging-related tractography (DSI) showed severe cerebellar structural abnormalities confirmed by histological examination. We suggest that hemispheric cerebellar lesions in cases like this are likely to cause epilepsy via an effect on the facial nuclei through ipsilateral and contralateral aberrant connections.

 

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[336]

TÍTULO / TITLE:  - Prognostic Vascular Imaging Biomarkers in High-Grade Gliomas: Tumor Permeability  as an Adjunct to Blood Volume Estimates.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acad Radiol. 2013 Apr;20(4):478-85. doi: 10.1016/j.acra.2012.11.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.acra.2012.11.011

AUTORES / AUTHORS:  - Jain R; Narang J; Griffith B; Bagher-Ebadian H; Scarpace L; Mikkelsen T; Littenberg B; Schultz LR

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202; Department of Neurosurgery, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202. Electronic address: rajanj@rad.hfh.edu.

RESUMEN / SUMMARY:  - RATIONALE AND OBJECTIVES: Despite recent advances in the treatment of high-grade  gliomas, overall survival (OS) remains poor, which underlines the importance of searching for and determining prognostic imaging biomarkers. The purpose of our retrospective study was to correlate patient survival with relative cerebral blood volume (rCBV) and permeability surface area-product (PS) measured using perfusion computed tomography (PCT) in patients with high-grade gliomas. METHODS: This study was composed of 54 patients with high-grade gliomas (World Health Organization [WHO] grade III, n = 14; WHO grade IV, n = 40) who underwent pretreatment PCT. Kaplan-Meier survival estimates were computed to describe OS for patients with high-versus-low PCT parameters, as well as grade III and IV gliomas. RESULTS: Differences in OS between high and low rCBV, PS, and rCBV + PS  were significant (P < .001) for all high-grade gliomas. After adjustment for WHO  grade, rCBV (P = .041) and rCBV + PS (P = .013) estimates remained significant, whereas PS estimates were not (P = .214). PS estimates showed a statistically significant difference for OS in the grade III glioma group (P = .011), whereas for grade IV gliomas, rCBV estimates were statistically significant (P = .019). rCBV + PS was statistically significant for OS in both grade III (P = .001) and grade IV (P = .004) glioma groups. CONCLUSIONS: Blood volume and permeability estimates measured using PCT can help predict survival in patients with high-grade gliomas. Patients with high PCT parameters showed worse OS compared to the patients with low PCT. Both rCBV and rCBV + PS remained statistically significant even after adjustment for WHO grade, suggesting these may be better predictors of OS than histological grade.

 

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[337]

TÍTULO / TITLE:  - Surgical outcomes of 43 cases with adenoid cystic carcinoma of the external auditory canal.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am J Otolaryngol. 2013 Feb 27. pii: S0196-0709(13)00030-6. doi: 10.1016/j.amjoto.2013.01.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.amjoto.2013.01.018

AUTORES / AUTHORS:  - Gu FM; Chi FL; Dai CF; Chen B; Li HW

INSTITUCIÓN / INSTITUTION:  - Department of Otology and Skull Base Surgery, Eye and ENT Hospital, Fudan University, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate surgical outcomes for adenoid cystic carcinoma (ACC) of the  external auditory canal (EAC). METHODS: Forty-three patients with ACC of the EAC  in Eye and ENT Hospital of Fudan University were analyzed retrospectively for survival. The patients were staged according to the modified Pittsburgh staging system. Thirteen patients with T1 stage underwent local resection (LR), 6 patients with T1 stage underwent lateral temporal bone resection (LTBR), and 8 patients with T1 stage underwent LTBR including superficial parotidectomy (SP). Two patients with T2 stage underwent LTBR, and 1 patient with T2 stage underwent  LTBR+SP. Three patients with T3 stage underwent LTBR. One patient with T4 stage underwent LTBR, two patients with T4 stage underwent subtotal temporal bone resection (STBR), and 7 patients with T4 stage underwent LTBR+SP. RESULTS: Of all patients that underwent surgery, 13 died of their primary cancers during the follow-up time. The 5-year survival rates of patients with T stages 1 through 4 were 85%, 67%, 67%, and 30%, respectively. There was statistically significant difference in 5-year survival rate between T1 and other stages (T2, T3, T4) using the log-rank test (p<0.05). There was significant difference in 5-year survival rate between T4 and other stages using the log-rank test (p<0.05). The 5-year survival rates after LR, LTBR or LTBR plus SP for T1 were 77%, 87% and 100%, respectively. The 5-year survival rates after LTBR, STBR or LTBR plus SP for T4 were 0%, 50% and 29%, respectively. The 5-year survival rates for 19 patients with clear surgical margins and 24 patients with positive margins were 89% and 54%, respectively. The 5-year survival rates of patients with radiotherapy and without radiotherapy were 62% and 86%, respectively. CONCLUSION: An en bloc resection including superficial parotidectomy is favored in an effort to produce  negative surgical margins for ACC of the EAC. Adjunctive radiotherapy is used for patients with positive margins and in advanced lesions.

 

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[338]

TÍTULO / TITLE:  - Unilateral Foot Drop as an Initial Presentation of a Brain Tumor in a Child.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Child Neurol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0883073813479172

AUTORES / AUTHORS:  - Goia E; Hamilton L; Chan J; Wei XC; Mah JK; Rho JM

INSTITUCIÓN / INSTITUTION:  - 1Section of Neurology, Alberta Children’s Hospital, Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - Foot drop is commonly caused by compromise of the peripheral nervous system. Unilateral foot drop as the first sign of a parasagittal brain tumor has been reported in the adult literature but never previously in the pediatric population. We report a child with a right parietal rhabdomyosarcoma in which foot drop was the only abnormal neurologic finding at initial presentation. Localization to the central nervous system should be included in children presenting with foot drop.

 

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[339]

TÍTULO / TITLE:  - Utility of multiparametric 3-T MRI for glioma characterization.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuroradiology. 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00234-013-1145-x

AUTORES / AUTHORS:  - Roy B; Gupta RK; Maudsley AA; Awasthi R; Sheriff S; Gu M; Husain N; Mohakud S; Behari S; Pandey CM; Rathore RK; Spielman DM; Alger JR

INSTITUCIÓN / INSTITUTION:  - Department of Radiology & Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana, India, 122002.

RESUMEN / SUMMARY:  - INTRODUCTION: Accurate grading of cerebral glioma using conventional structural imaging techniques remains challenging due to the relatively poor sensitivity and specificity of these methods. The purpose of this study was to evaluate the relative sensitivity and specificity of structural magnetic resonance imaging and MR measurements of perfusion, diffusion, and whole-brain spectroscopic parameters for glioma grading. METHODS: Fifty-six patients with radiologically suspected untreated glioma were studied with T1- and T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, diffusion tensor imaging, and volumetric whole-brain MR spectroscopic imaging. Receiver-operating characteristic analysis  was performed using the relative cerebral blood volume (rCBV), apparent diffusion coefficient, fractional anisotropy, and multiple spectroscopic parameters to determine optimum thresholds for tumor grading and to obtain the sensitivity, specificity, and positive and negative predictive values for identifying high-grade gliomas. Logistic regression was performed to analyze all the parameters together. RESULTS: The rCBV individually classified glioma as low and  high grade with a sensitivity and specificity of 100 and 88 %, respectively, based on a threshold value of 3.34. On combining all parameters under consideration, the classification was achieved with 2 % error and sensitivity and specificity of 100 and 96 %, respectively. CONCLUSION: Individually, CBV measurement provides the greatest diagnostic performance for predicting glioma grade; however, the most accurate classification can be achieved by combining all of the imaging parameters.

 

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[340]

TÍTULO / TITLE:  - Primary intracranial germ-cell tumors in adults: a practical review.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1114-6

AUTORES / AUTHORS:  - Bromberg JE; Baumert BG; de Vos F; Gijtenbeek JM; Kurt E; Westermann AM; Wesseling P

INSTITUCIÓN / INSTITUTION:  - Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus University Medical Center, P O Box 5201, 3008 AE, Rotterdam, The Netherlands, j.bromberg@erasmusmc.nl.

RESUMEN / SUMMARY:  - Primary intracranial germ-cell tumors are rare tumors primarily of adolescence, and literature on this disease in adults is scarce. The available evidence on intracranial germ-cell tumors is reviewed with a focus on adult patients whenever possible, and used to make suggestions for diagnosis and treatment. Diagnostic and treatment algorithms were developed to provide an evidence-based backbone to  base treatment on in adult patients with a (suspected) primary intracranial germ-cell tumor.

 

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[341]

TÍTULO / TITLE:  - IDH mutation analysis in gliomas as a diagnostic and prognostic biomarker.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.771139

AUTORES / AUTHORS:  - Kurian KM; Haynes HR; Crosby C; Hopkins K; Williams M

INSTITUCIÓN / INSTITUTION:  - Neuropathology and Neurosurgery, Frenchay Hospital , Bristol , UK.

RESUMEN / SUMMARY:  - Introduction. There is a high rate of IDH1/2 mutations in low grade gliomas and in high grade gliomas deriving from them. IDH analysis of gliomas is a novel method of classification and an independent prognostic marker. We compared antibody and sequencing methods for the detection of IDH mutations. Method. 88 samples from 74 patients were identified. For immunohistochemistry: sections were stained with anti-IDH1R132H antibody. For sequencing: DNA was extracted from fresh, frozen tissue. Results. 28% (20/71) of cases were positive for the R132H IDH1 mutation by antibody. An IDH1 mutation was detected by molecular genetics in 37% (21/57) of cases and no IDH2 mutations were detected. 24% (5/21) had rare IDH1 mutations not detected by immunohistochemistry. Where sufficient tissue was  available, immunohistochemistry and DNA analysis were fully concordant for the p.Arg132His mutation. Both Grade II gliomas and anaplastic astrocytomas showed a  statistically different distribution of IDH1 mutation load compared to GBMs (p <  0.0001; p = 0.0021 respectively). Conclusion. A rationalised combined approach involving R132H antibody testing and sequencing of negative cases would be ideal  for the detection of IDH1 mutations - antibody testing is cheaper than sequencing but sequencing demonstrates rare IDH1 mutations not detected by immunohistochemistry.

 

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[342]

TÍTULO / TITLE:  - Plexiform neurofibroma affecting the upper parietal scalp, with cerebellar hamartoma: role of histopathology, colour Doppler imaging and magnetic resonance  imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Dermatol. 2013 Apr;38(3):285-8. doi: 10.1111/ced.12027.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ced.12027

AUTORES / AUTHORS:  - Sehgal VN; Oberai R; Venkatash P; Sharma S; Verma P; Chatterji K

INSTITUCIÓN / INSTITUTION:  - Dermato-Venereology (Skin/VD) Centre, Sehgal Nursing Home, New Delhi, India.

RESUMEN / SUMMARY:  - We report a patient with plexiform neurofibroma, which is pathognomonic for neurofibromatosis type 1 (NF1) affecting the upper parietal region of the scalp.  Cerebellar hamartoma was present, a finding that, to our knowledge, has not been  reported previously. We highlight the role of histopathology, ultrasonography, colour Doppler imaging and magnetic resonance imaging, in addition to the seven existing criteria, for the diagnosis of NF1.

 

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[343]

TÍTULO / TITLE:  - BMP4 reverses multidrug resistance through modulation of BCL-2 and GDNF in glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Res. 2013 Mar 1. pii: S0006-8993(13)00274-6. doi: 10.1016/j.brainres.2013.02.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.brainres.2013.02.039

AUTORES / AUTHORS:  - Liu B; Chen Q; Tian D; Wu L; Dong H; Wang J; Ji B; Zhu X; Cai Q; Wang L; Zhang S

INSTITUCIÓN / INSTITUTION:  - Renmin Hospital, Wuhan University, 238 Jiefang Street, Wuhan 430060, Hubei, China.

RESUMEN / SUMMARY:  - Patients with glioblastoma are commonly treated with chemotherapy. But a significant proportion of patients develop disease progression after an initial response to chemotherapy. Presently, there is no standard of care for such patients. The bone morphogenetic protein 4 (BMP4) has been reported to play a tumor-suppressing role in glioblastoma, but its role in glioblastoma multidrug resistance (MDR) is not clear. We reported that BMP4 can reverse MDR of glioblastoma through the inhibition of B-cell lymphoma 2(BCL-2) and glial cell derived neurotrophic factor (GDNF). We showed that the expression level of BMP4 was lower in glioblastoma compared to normal brain tissue, and also showed that BMP4 expression decreased in multidrug resistance cell line U251/TMZ compared to  U251 cells. Our research demonstrated that over-expression of BMP4 can reverse the multidrug resistance. BCL-2 and GDNF were inhibited when BMP4 was over-expressed, and this data were consistent with the negative relationship in human samples; analysis of 40 patient’s glioblastoma and brain samples revealed a significant negative correlation between BMP4 and BCL-2, GDNF. When BCL-2 and GDNF were knocked down, the effect of BMP4 in regulating MDR was partially lost.  This novel result showed, for the first time, that BMP4 can reverse MDR in glioblastoma, which involved negative inhibition of BCL-2 and GDNF.

 

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[344]

TÍTULO / TITLE:  - ADAM17 promotes U87 glioblastoma stem cell migration and invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Res. 2013 Mar 5. pii: S0006-8993(13)00260-6. doi: 10.1016/j.brainres.2013.02.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.brainres.2013.02.025

AUTORES / AUTHORS:  - Chen X; Chen L; Chen J; Hu W; Gao H; Xie B; Wang X; Yin Z; Li S; Wang X

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China; Department of Neurosurgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, Fujian Province, China.

RESUMEN / SUMMARY:  - Glioblastoma stem cells (GSCs) are thought to contribute to the diffuse invasiveness of malignant gliomas. Emerging evidence supports a role for a disintegrin and metalloproteinase 17 (ADAM17) in proteolytic ectodomain shedding  of several EGFR-binding ligands, which subsequently activate PI3K/AKT and MEK/ERK pathways through EGFR phosphorylation thus mediating glioma invasiveness. However, it is not clear if ADAM17 also plays important roles in promoting GSC invasion. In this study, we isolated CD133+ GSCs from the human glioblastoma cell line U87 using fluorescence-activated cell sorting and demonstrated their increased invasive potential compared with matched non-stem tumor cells. Furthermore, we showed that CD133+ GSCs expressed higher levels of ADAM17. Immunofluorescence staining revealed that high expression levels of ADAM17 at the invasive front were correlated with the presence of CD133+ GSCs in human glioblastoma specimens. Stimulation with the ADAM17 agonist chemokine phorbol myristate acetate increased migration and invasion of GSCs, which was counteracted by ADAM17 knockdown. In addition, ADAM17 also induced CD133+ GSC invasion via activation of the EGFR/PI3K/AKT signaling pathway. These findings suggest that ADAM17 is involved in U87 GSC invasive process and may provide a potential therapeutic target for glioma treatment.

 

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[345]

TÍTULO / TITLE:  - Peritumoral brain edema in angiomatous supratentorial meningiomas: an investigation of the vascular endothelial growth factor A pathway.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - APMIS. 2013 Feb 11. doi: 10.1111/apm.12052.

            ●● Enlace al texto completo (gratuito o de pago) 1111/apm.12052

AUTORES / AUTHORS:  - Nassehi D; Sorensen LP; Dyrbye H; Thomsen C; Juhler M; Laursen H; Broholm H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery; Neuropathology Laboratory.

RESUMEN / SUMMARY:  - The aim of this work was to study the vascular endothelial growth factor A (VEGF-A) pathway and peritumoral brain edema (PTBE) through comparison of non-angiomatous and angiomatous meningiomas. Meningiomas are common intracranial  tumors, which often have PTBE. VEGF-A is an integral part of PTBE formation and angiogenesis, and the capillary-rich angiomatous meningiomas are known for their  PTBE. The VEGF-A receptor VEGFR-2 is responsible for the angiogenic effect of VEGF-A on endothelial cells, which is enhanced by the co-receptor neuropilin-1. Forty non-angiomatous, 22 angiomatous meningiomas, and 10 control tissue samples  were collected for the study. Magnetic resonance images were available for 40 non-angiomatous and 10 angiomatous meningiomas. Tissue sections were immunostained for CD34, MIB-1, estrogen- and progesterone receptors. ELISA, chemiluminescence, and RT-qPCR were used for VEGF-A, VEGFR-2, and neuropilin-1 protein and mRNA quantification. Angiomatous meningiomas had larger PTBE (695 vs  218 cm(3) , p = 0.0045) and longer capillary length (3614 vs 605 mm/mm(3) , p < 0.0001). VEGF-A mRNA, neuropilin-1 mRNA, and VEGFR-2 protein levels were higher in angiomatous meningiomas independently of the capillary length (p < 0.05). Neuropilin-1 protein levels were lower in angiomatous meningiomas (p < 0.0001). The VEGF-A pathway and tumor capillary length may be essential for PTBE-formation in meningiomas. Further investigations of this pathway could lead to earlier therapy and targeted pharmacological treatment options.

 

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[346]

TÍTULO / TITLE:  - Brain tumors in children. Time to diagnosis - a single centre experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Int. 2013 Mar 11. doi: 10.1111/ped.12095.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ped.12095

AUTORES / AUTHORS:  - Molineus A; Boxberger N; Redlich A; Vorwerk P

INSTITUCIÓN / INSTITUTION:  - Otto-von-Guericke-University Children’s Hospital, Pediatric Oncology.

RESUMEN / SUMMARY:  - AIM: The aim of the study was to analyse the pre-diagnostic symptomatic interval  (PSI) of children with brain tumors with regard to the parenteral and doctor’s delay and the clinical symptoms. METHODS: A retrospective review of all children  with brain tumors diagnosed in a single centre over a period of 11 years was performed. RESULTS: 79 patients (35 boys, 44 girls), mean age 9.2 years (0.2 to 23.5 years) were analysed. PSI was 28 weeks with a parenteral delay of 11.1 weeks and a doctor’s delay of 16.9 weeks. Main clinical symptoms were headache (66.7%), vomiting (57.7%), vision (46.2%) and gait (41.6) disorders and fatigue (41.0%) followed by other neurological signs. CONCLUSIONS: Diagnosis of pediatric brain tumors is often delayed in relation to the presenting symptoms. If parents report about a combination of headache with other neurological abnormalities a brain tumor should always be considered.

 

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[347]

TÍTULO / TITLE:  - Allergy and brain tumors in the INTERPHONE study: pooled results from Australia,  Canada, France, Israel, and New Zealand.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Causes Control. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10552-013-0171-7

AUTORES / AUTHORS:  - Turner MC; Krewski D; Armstrong BK; Chetrit A; Giles GG; Hours M; McBride ML; Parent ME; Sadetzki S; Siemiatycki J; Woodward A; Cardis E

INSTITUCIÓN / INSTITUTION:  - McLaughlin Centre for Population Health Risk Assessment, Institute of Population  Health, University of Ottawa, One Stewart Street, Room 313, Ottawa, ON, K1N 6N5,  Canada, mturner@uottawa.ca.

RESUMEN / SUMMARY:  - PURPOSE: A history of allergy has been inversely associated with several types of cancer although the evidence is not entirely consistent. We examined the association between allergy history and risk of glioma, meningioma, acoustic neuroma, and parotid gland tumors using data on a large number of cases and controls from five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand), to better understand potential sources of bias in brain tumor case-control studies and to examine associations between allergy and tumor sites  where few studies exist. METHODS: A total of 793 glioma, 832 meningioma, 394 acoustic neuroma, and 84 parotid gland tumor cases were analyzed with 2,520 controls recruited during 2000-2004. Conditional logistic regression models were  used to obtain odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between self-reported allergy and tumor risk. RESULTS: A significant inverse association was observed between a history of any allergy and glioma (OR  = 0.73, 95 % CI 0.60-0.88), meningioma (OR = 0.77, 95 % CI 0.63-0.93), and acoustic neuroma (OR = 0.64, 95 % CI 0.49-0.83). Inverse associations were also observed with specific allergic conditions. However, inverse associations with asthma and hay fever strengthened with increasing age of allergy onset and weakened with longer time since onset. No overall association was observed for parotid gland tumors (OR = 1.21, 95 % CI 0.73-2.02). CONCLUSIONS: While allergy history might influence glioma, meningioma, and acoustic neuroma risk, the observed associations could be due to information or selection bias or reverse causality.

 

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[348]

TÍTULO / TITLE:  - Management of the optic canal invasion and visual outcome in spheno-orbital meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Mar 7. pii: S0303-8467(13)00065-6. doi: 10.1016/j.clineuro.2013.02.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.02.012

AUTORES / AUTHORS:  - Mariniello G; Bonavolonta G; Tranfa F; Maiuri F

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Sciences, Neurosurgical Clinic, “Federico II” University School of Medicine, Naples, Italy. Electronic address: giumarin@unina.it.

RESUMEN / SUMMARY:  - OBJECTIVE: Spheno-orbital meningiomas often present with visual deficit due to invasion of the optic canal by the tumor. This study discusses the reasons of visual impairment, the choice of the surgical approach according to the type of optic canal involvement, and the factors correlated to the visual outcome in patients harboring a spheno-orbital meningioma. MATERIALS AND METHODS: A surgical series of 60 spheno-orbital meningiomas is reviewed. The preoperative visual symptoms, the involvement of the optic canal in both neuroradiological studies and surgical descriptions, the different surgical approaches are reviewed. These  data are correlated with the postoperative visual outcome. RESULTS: The 60 spheno-orbital meningiomas were classified in 4 types according to the intraorbital tumor localization: type I, supero-lateral (18 cases); type II, inferomedial (8 cases); type III, orbital apex (22 cases); type IV, diffuse (12 cases). Thirty-six of the 60 patients (60%) had variable decrease of the visual acuity on the tumor side. Forty-three patients (71.6%) had tumor extension into the optic canal on imaging studies. On the whole, 36 patients among 43 with invasion of the optic canal (83.7%) had preoperative visual dysfunction; on the other hand, none among 17 patients without tumor invasion of the optic canal had  visual dysfunction. The surgical approaches according to the tumor location were  as follows. A supraorbital-pterional approach was used in the 8 inferomedial tumors, in the 22 orbital apex tumors, and in 9/12 diffuse tumors; these last two types had concentric involvement of the optic canal. Three diffuse tumors with significant extension in the infratemporal fossa were operated on via a frontotemporal-orbitozygomatic approach. A wide decompression of the optic canal  was performed in all cases, excepting in two inferomedial tumors without optic canal invasion. The 18 patients with lateral tumors were approached via a lateral orbitocranial approach, including removal of the sphenoid wing and lateral orbital wall without bone flap; the resection of the lateral aspect of the optic  canal was performed in the 3 cases with canal invasion. Postoperative improvement of the visual function was observed in 18 of 36 cases with visual dysfunction (50%). The rate of visual improvement was significantly higher in cases with lateral involvement (3/3 or 100%) than in those with concentric involvement of the optic canal (11/27 or 40.7%). CONCLUSION: The invasion of the optic canal by  the tumor is the main reason of visual dysfunction in patients with spheno-orbital meningiomas. A wide opening of the optic canal must be performed routinely in patients with orbital apex and diffuse orbital tumors, where there is concentric invasion of the optic canal wall. In these cases the supraorbital-pterional approach is the technique of choice. In selected cases with lateral intraorbital tumors and invasion of the lateral aspect of the optic  canal the complete tumor resection coupled with good decompression of the optic nerve may be achieved via a less invasive lateral orbitocranial approach without  craniotomy.

 

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[349]

TÍTULO / TITLE:  - New Approaches to Understand Cognitive Changes Associated With Chemotherapy for Non-Central Nervous System Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pain Symptom Manage. 2013 Mar 21. pii: S0885-3924(13)00108-5. doi: 10.1016/j.jpainsymman.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpainsymman.2012.11.005

AUTORES / AUTHORS:  - Nelson WL; Suls J

INSTITUCIÓN / INSTITUTION:  - Basic Biobehavioral and Psychological Sciences Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA. Electronic address: nelsonw@mail.nih.gov.

RESUMEN / SUMMARY:  - CONTEXT: Researchers have described a constellation of cognitive deficits (e.g.,  impairments in executive functions, working memory, attention, and information-processing speed) associated with cancer treatment, and specifically  chemotherapy, for non-central nervous system tumors. However, findings have been  inconsistent, largely because of measurement and study design issues. OBJECTIVES: To propose ways for researchers to more clearly delineate and characterize the mild cognitive deficits and related outcomes that appear to affect a subset of cancer patients and suggest methods to make more effective use of the existing data to understand risk factors for impaired neuropsychological functioning. METHODS: We examined the literature on the relationship between chemotherapy and  cognitive impairment, as well as related literature on neuropsychological measurement, structural and functional neuroimaging, alternative measures of health outcomes, and integrative data analysis. RESULTS: A more comprehensive picture of cognitive functioning might be obtained by incorporating nontraditional ecological measures, self-reports, computational modeling, new neuroimaging methods, and markers of occupational functioning. Case-control and integrative data analytic techniques potentially could leverage existing data to  identify risk factors for cognitive dysfunction and test hypotheses about the etiology of these effects. CONCLUSIONS: There is a need to apply new research approaches to understand the real-world functional implications of the cognitive  side effects of chemotherapy to develop and implement strategies to minimize and  remediate these effects before, during, and after cancer treatment.

 

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[350]

TÍTULO / TITLE:  - A novel COLD-PCR/FMCA assay enhances the detection of low-abundance IDH1 mutations in gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Mol Pathol. 2013 Mar;22(1):28-34. doi: 10.1097/PDM.0b013e31826c7ff8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PDM.0b013e31826c7ff8

AUTORES / AUTHORS:  - Pang B; Durso MB; Hamilton RL; Nikiforova MN

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Anatomic Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

RESUMEN / SUMMARY:  - Point mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in many gliomas. The detection of IDH1 mutations becomes challenging on suboptimal glioma biopsies when a limited number of tumor cells is available for analysis. Coamplification at lower denaturing-polymerase chain reaction (COLD-PCR) is a PCR technique that deliberately lowers the denaturing cycle temperature to selectively favor amplification of mutant alleles, allowing for the sensitive detection of low-abundance mutations. We developed a novel COLD-PCR assay on the  LightCycler platform (Roche, Applied Science, Indianapolis, IN), using post-PCR fluorescent melting curve analysis (FMCA) for the detection of mutant IDH1 with a detection limit of 1%. Thirty-five WHO grade I to IV gliomas and 9 non-neoplastic brain and spinal cord biopsies were analyzed with this technique and the results  were compared with the conventional real-time PCR and the Sanger sequencing analysis. COLD-PCR/FMCA was able to detect the most common IDH1 R132H mutation and rare mutation types including R132H, R132C, R132L, R132S, and R132G mutations. Twenty-five glioma cases were positive for IDH1 mutations by COLD-PCR/FMCA, and 23 gliomas were positive by the conventional real-time PCR and Sanger sequencing. A pilocytic astrocytoma (PA I) and a glioblastoma multiforme (GBM IV) showed low-abundance IDH1 mutations detected by COLD-PCR/FMCA. The remaining 10 glioma and 9 non-neoplastic samples were negative by all the 3 methods. In summary, we report a novel COLD-PCR/FMCA method that provides rapid and sensitive detection of IDH1 mutations in formalin-fixed paraffin-embedded tissue and can be used in the clinical setting to assess the small brain biopsies.

 

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[351]

TÍTULO / TITLE:  - Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1078-6

AUTORES / AUTHORS:  - Ilhan-Mutlu A; Wohrer A; Berghoff AS; Widhalm G; Marosi C; Wagner L; Preusser M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine I/Oncology, Medical University of Vienna, Vienna, Austria.

RESUMEN / SUMMARY:  - Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient’s survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important  roles for cancer including proliferation, aggressiveness and metastases development. There exist only few data on the involvement of microRNAs in glioblastoma recurrence. We selected the following 7 microRNAs with potential relevance for glioblastoma pathobiology by means of a comprehensive literature search: microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222. We further selected 15 primary glioblastoma patients, of whom formalin fixed and paraffin embedded tissue (FFPE) of the initial and recurrence surgery were available. All patients had received first line treatment consisting of postoperative combined radiochemotherapy with temozolomide (n = 15). Non-neoplastic brain tissue samples from 3 patients with temporal lobe epilepsy served as control. The expression of the microRNAs were analysed by RT-qPCR. These were correlated with each other and with clinical parameters. All microRNAs showed detectable levels of expressions in glioblastoma group, whereas microRNA-10b was not detectable in epilepsy patients. MicroRNAs except microRNA-21 showed significantly higher levels in epilepsy patients when compared to the levels of first resection of glioblastoma. Comparison of microRNA levels between first and second resections revealed no significant change. Cox regression analyses showed no significant association of microRNA expression levels in the tumor tissue with progression free survival times. Expression levels of microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195,  microRNA-221 and microRNA-222 do not differ significantly between initial and recurrent glioblastoma.

 

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[352]

TÍTULO / TITLE:  - Management of holocord pilocytic astrocytomas in children and adolescents: an update.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Neurosurg. 2012;48(3):133-40. doi: 10.1159/000345593. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345593

AUTORES / AUTHORS:  - Ebner FH; Schittenhelm J; Roser F; Scheel-Walter H; Tatagiba M; Schuhmann MU

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery Children’s Hospital, Tubingen, Germany.

RESUMEN / SUMMARY:  - Holocord intramedullary low-grade astrocytomas in children and adolescents - involving most or all of the cervical and thoracic spinal cord - are a rare finding. Most of the tumors seem to be pilocytic astrocytomas. Surgical management strategies might not be as clear as in small and circumscribed intramedullary tumors. On the basis of 20 previously published cases and 3 own patients, we summarize and discuss possible treatment options and their risks and benefits. Surgery should be performed soon after establishment of the diagnosis,  which per se is often delayed despite a long-standing presence of attributable symptoms or signs in most cases. Following multilevel laminotomy, excellent results can be achieved by electrophysiologically guided microsurgical tumor removal in a single-staged or multistaged approach. The surgical goal is resection as gross total as possible provided intraoperative monitoring indicates preservation of function. Small tumor remnants often remain stable in the due course. In case of unresectable regrowth or recurrence, chemotherapy or radiotherapy are the adjuvant treatment options.

 

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[353]

TÍTULO / TITLE:  - Glutamate and tumor-associated epilepsy: Glial cell dysfunction in the peritumoral environment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurochem Int. 2013 Feb 4. pii: S0197-0186(13)00036-3. doi: 10.1016/j.neuint.2013.01.027.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neuint.2013.01.027

AUTORES / AUTHORS:  - Buckingham SC; Robel S

INSTITUCIÓN / INSTITUTION:  - Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, 1719 6th Avenue South, Birmingham, AL 35294, USA. Electronic address: sbucking@uab.edu.

RESUMEN / SUMMARY:  - Seizures are a serious and debilitating co-morbidity of primary brain tumors that affect most patients, yet their etiology is poorly understood. In many CNS pathologies, including epilepsy and brain injury, high levels of extracellular glutamate have been implicated in seizure generation. It has been shown that gliomas release neurotoxic levels of glutamate through their high expression of system xc-. More recently it was shown that the surrounding peritumoral cortex is spontaneously hyperexcitable. In this review, we discuss how gliomas induce changes in the surrounding environment that may further contribute to elevated extracellular glutamate and tumor-associated seizures. Peritumoral astrocytes become reactive and lose their ability to remove glutamate, while microglia, in response to signals from glioma cells, may release glutamate. In addition, gliomas increase blood brain barrier permeability, allowing seizure-inducing serum components, including glutamate, into the peritumoral region. These factors, working together or alone, may influence the frequency and severity of tumor-associated epilepsy.

 

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[354]

TÍTULO / TITLE:  - Resection of subependymal giant cell astrocytoma guided by intraoperative magnetic resonance imaging and neuronavigation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Feb 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2045-4

AUTORES / AUTHORS:  - Ren H; Chen X; Sun G; Hu S; Zheng G; Li F; Li J; Xu B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.

RESUMEN / SUMMARY:  - PURPOSE: Subependymal giant cell astrocytoma (SEGA) is a rare, benign tumor that  occurs mainly in children; complete resection can achieve cure. Guidance of surgery by combined intraoperative magnetic resonance imaging (iMRI) and functional neuronavigation is reported to achieve more radical resection and reduced complications. However, reports about the resection of SEGA with such guidance are rare. We report here our preliminary experience of the resection of  SEGA guided by iMRI and neuronavigation, focusing on the feasibility, benefits, and pitfalls of this combination of techniques. METHODS: We performed resection of SEGA guided by combined iMRI and functional neuronavigation in seven children. The first iMRI was performed when the surgeon believed that the tumor had been completely resected; the last iMRI was performed immediately after closure. Additional scans were performed as needed. RESULTS: Successful resection was achieved in all seven patients using this combination of techniques. The iMRI scans detected residual tumor in three patients and a large, remote epidural hematoma in one patient. Further resection or other surgery was performed in these four patients. Complete resection was eventually achieved in all patients.  There were no cases of surgery-related neurological dysfunction, except transient memory loss in one patient. No recurrence of tumor or hydrocephalus was observed  in any patients during the follow-up period. CONCLUSIONS: Resection of SEGA in children guided by combined iMRI and neuronavigation is feasible and safe. This combination of techniques enables a higher complete resection rate and reduces brain injury and other unexpected events during surgery.

 

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[355]

TÍTULO / TITLE:  - Cognitive impairment in primary brain tumors outpatients: a prospective cross-sectional survey.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1076-8

AUTORES / AUTHORS:  - Zucchella C; Bartolo M; Di Lorenzo C; Villani V; Pace A

INSTITUCIÓN / INSTITUTION:  - Unit of Neurology, Regina Elena National Cancer Institute, via Elio Chianesi 53,  00144, Rome, Italy, chiara.zucchella@gmail.com.

RESUMEN / SUMMARY:  - Brain tumors and anti-cancer treatments can cause a wide range of cognitive deficits that in turn, being a major cause of disability, significantly affect patients’ independence and quality of life. To evaluate the neurocognitive status of a non selected population of brain tumors outpatients, investigating the correlation with clinical and demographic variables. This prospective cross-sectional survey enrolled consecutive outpatients with a histopathologically confirmed diagnosis of brain tumor. All the patients were evaluated with a battery of standardized neuropsychological tests assessing language, memory, logical-executive functions, attention, visuo-constructional abilities. An univariate regression analysis was performed to assess the impact of socio-demographical and clinical variables on the presence of cognitive impairment. 147 patients (61F/86M, mean age 52.8 +/- 13.3, mean schooling 12.7 +/- 4 were enrolled into the study. Out of the 147 patients evaluated, 80 (54.4 %) showed cognitive impairment: 43 (53.75 %) presented a multidomain impairment,  while 37 (46.25 %) patients revealed cognitive deficits limited respectively to language (n:13, 16.25 %), memory (n:11, 13.75 %), attention (n:7, 8.75 %), logical-executive functions (n:5, 6.25 %), visuo-spatial abilities (n:1, 1.25 %). At the regression analysis the variables significantly related to the development of cognitive impairment were age (p = 0.04), lesion side (p = 0.00), chemotherapy (p = 0.03). As advances in anti-cancer treatment have prolonged life expectancy of neuro-oncological patients, standard clinical endpoints can’t be limited to just survival or progression free survival, but have to consider clinical benefits on both motor and cognitive function and in general quality of life. Hence evaluation of new therapeutic strategies should routinely include longitudinal neuropsychological assessment.

 

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[356]

TÍTULO / TITLE:  - 1p/19q testing has no significance in the workup of glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathol Appl Neurobiol. 2013 Jan 31. doi: 10.1111/nan.12031.

            ●● Enlace al texto completo (gratuito o de pago) 1111/nan.12031

AUTORES / AUTHORS:  - Clark KH; Villano JL; Nikiforova MN; Hamilton RL; Horbinski C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Pittsburgh, Pittsburgh, PA.

RESUMEN / SUMMARY:  - AIMS: To determine whether testing for isolated 1p or 19q losses, or as a codeletion, has any significance in the workup of glioblastomas (GBMs). METHODS:  Upfront 1p/19q testing by fluorescence in situ hybridization (FISH) and/or PCR-based loss of heterozygosity (LOH) was done in 491 gliomas that were histologically diagnosed as GBMs. Outcomes were determined and measured against 1p/19q results. RESULTS: Twenty-eight showed apparent 1p/19q codeletion by either FISH and/or PCR-based LOH, but only 1/26 showed codeletion by both tests. Over 90% of tumours with apparent codeletion by either FISH or LOH also had 10q LOH and/or EGFR amplification, features inversely related to true whole-arm 1p/19q codeletion. Furthermore, only 1/28 tumours demonstrated an R132H IDH1 mutation. Neither 1p/19q codeletion by FISH nor LOH had an impact on GBM survival. Isolated losses of 1p or 19q also had no impact on survival. CONCLUSIONS: These data suggest that 1.) 1p/19q testing is not useful on gliomas that are histologically  GBMs; 2.) codeletion testing should be reserved only for cases with compatible morphology; 3.) EGFR, 10q, and IDH1 testing can help act as safeguards against a  false-positive 1p/19q result.

 

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[357]

TÍTULO / TITLE:  - Radiosynthesis and biological evaluation of alpha-[F-18]fluoromethyl phenylalanine for brain tumor imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nucl Med Biol. 2013 Mar 22. pii: S0969-8051(13)00013-9. doi: 10.1016/j.nucmedbio.2012.12.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.nucmedbio.2012.12.013

AUTORES / AUTHORS:  - Huang C; Yuan L; Rich KM; McConathy J

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Washington University School of Medicine, Campus Box 8223, St. Louis, MO 63110, USA.

RESUMEN / SUMMARY:  - OBJECTIVES: Radiolabeled amino acids have proven utility for imaging brain tumors in humans, particularly those that target system L amino acid transport. We have  prepared the novel phenylalanine analogue, (FMePhe, 9), as part of an effort to develop new system L tracers that can be prepared in high radiochemical yield through nucleophilic [18F]fluorination. The tumor imaging properties of both enantiomers of this new tracer were evaluated through cell uptake, biodistribution and microPET studies in the mouse DBT model of high grade glioma. METHODS: The non-radioactive form of 9 and the cyclic sulfamidate labeling precursor were prepared from commercially available racemic alpha-benzylserine. Racemic [18F]9 was prepared from the labeling precursor in two steps using standard[18F]fluoride nucleophilic reaction conditions followed by acidic deprotection. The individual enantiomers [18F]9a and [18F]9b were isolated using  preparative chiral HPLC. In vitro uptake inhibition assays were performed with each enantiomer using DBT cells. Biodistribution and microPET/CT studies were performed with each enantiomer in male BALB/c mice at approximately 2weeks after  implantation of DBT tumor cells. RESULTS: Radiolabeling of the cyclic sulfamidate precursor 5 provides racemic [18F]9 in high radiochemical yield (60%-70%, n=4) and high radiochemical purity (>96%, n=4). In vitro uptake assays demonstrate that both [18F]9a and [18F]9b undergo tumor cell uptake through system L transport. The biodistribution studies using the single enantiomers [18F]9a and [18F]9b demonstrated good tumor uptake with lower uptake in most normal tissues,  and [18F]9a had higher tumor uptake than [18F]9b. MicroPET imaging demonstrated good tumor visualization within 10min of injection, rapid uptake of radioactivity, and tumor to brain ratios of approximately 6:1 at 60min postinjection. CONCLUSIONS: The novel PET tracer, [18F]FMePhe, is readily synthesized in good yield from a cyclic sulfamidate precursor. Biodistribution and microPET studies in the DBT model demonstrate good tumor to tissue ratios and tumor visualization, with enantiomer [18F]9a having higher tumor uptake. However, the brain availability of both enantiomers was lower than expected for system L substrates, suggesting the [18F]fluorine group in the beta-position affects uptake of these compounds by system L transporters.

 

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[358]

TÍTULO / TITLE:  - Asleep-awake-asleep craniotomy: A comparison with general anesthesia for resection of supratentorial tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Feb 26. pii: S0967-5868(13)00008-8. doi: 10.1016/j.jocn.2012.09.031.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.09.031

AUTORES / AUTHORS:  - Rajan S; Cata JP; Nada E; Weil R; Pal R; Avitsian R

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology, Cleveland Clinic, Cleveland, OH, USA.

RESUMEN / SUMMARY:  - The anesthetic plan for patients undergoing awake craniotomy, when compared to craniotomy under general anesthesia, is different, in that it requires changes in states of consciousness during the procedure. This retrospective review compares  patients undergoing an asleep-awake-asleep technique for craniotomy (group AW: n=101) to patients undergoing craniotomy under general anesthesia (group AS: n=77). Episodes of desaturation (AW=31% versus AS=1%, p<0.0001), although temporary, and hypercarbia (AW=43.75mmHg versus AS=32.75mmHg, p<0.001) were more  common in the AW group. The mean arterial pressure during application of head clamp pins and emergence was significantly lower in AW patients compared to AS patients (pinning 91.47mmHg versus 102.9mmHg, p<0.05 and emergence 84.85mmHg versus 105mmHg, p<0.05). Patients in the AW group required less vasopressors intraoperatively (AW=43% versus AS=69%, p<0.01). Intraoperative fluids were comparable between the two groups. The post anesthesia care unit (PACU) administered significantly fewer intravenous opioids in the AW group. The length  of stay in the PACU and hospital was comparable in both groups. Thus, asleep-awake-asleep craniotomies with propofol-dexmedetomidine infusion had less  hemodynamic response to pinning and emergence, and less overall narcotic use compared to general anesthesia. Despite a higher incidence of temporary episodes  of desaturation and hypoventilation, no adverse clinical consequences were seen.

 

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[359]

TÍTULO / TITLE:  - Transient Optic Perineuritis as the Initial Presentation of Central Nervous System Involvement by Pre-B Cell Lymphocytic Leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuroophthalmol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WNO.0b013e318281b84d

AUTORES / AUTHORS:  - Townsend JH; Dubovy SR; Pasol J; Lam BL

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Emory Eye Center (JHT), Emory University, Atlanta, Georgia; and the Department of Ophthalmology, Bascom Palmer Eye Institute (SRD, JP, BLL), University of Miami Miller School of Medicine, Miami, Florida.

RESUMEN / SUMMARY:  - : A 20-year-old man with a history of pre-B cell acute lymphocytic leukemia (ALL) presented with optic perineuritis of the right eye while undergoing chemotherapy. Evaluation failed to reveal an infectious or neoplastic cause, and the patient improved with oral corticosteroid treatment. He returned 10 weeks later with complete loss of vision in the right eye. Optic nerve biopsy revealed leukemic infiltration of the optic nerve, and the patient was treated for central nervous  system (CNS) relapse of ALL. Transient optic perineuritis may be the initial manifestation of CNS involvement of pre-B cell ALL.

 

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[360]

TÍTULO / TITLE:  - Mathematical modelling of glioma growth: The use of Diffusion Tensor Imaging (DTI) data to predict the anisotropic pathways of cancer invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Theor Biol. 2013 Apr 21;323:25-39. doi: 10.1016/j.jtbi.2013.01.014. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jtbi.2013.01.014

AUTORES / AUTHORS:  - Painter KJ; Hillen T

INSTITUCIÓN / INSTITUTION:  - Department of Mathematics and Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK. Electronic address: K.Painter@hw.ac.uk.

RESUMEN / SUMMARY:  - The nonuniform growth of certain forms of cancer can present significant complications for their treatment, a particularly acute problem in gliomas. A number of experimental results have suggested that invasion is facilitated by the directed movement of cells along the aligned neural fibre tracts that form a large component of the white matter. Diffusion tensor imaging (DTI) provides a window for visualising this anisotropy and gaining insight on the potential invasive pathways. In this paper we develop a mesoscopic model for glioma invasion based on the individual migration pathways of invading cells along the fibre tracts. Via scaling we obtain a macroscopic model that allows us to explore the overall growth of a tumour. To connect DTI data to parameters in the macroscopic model we assume that directional guidance along fibre tracts is described by a bimodal von Mises-Fisher distribution (a normal distribution on a  unit sphere) and parametrised according to the directionality and degree of anisotropy in the diffusion tensors. We demonstrate the results in a simple model for glioma growth, exploiting both synthetic and genuine DTI datasets to reveal the potentially crucial role of anisotropic structure on invasion.

 

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[361]

TÍTULO / TITLE:  - Lipid and macromolecules quantitation in differentiating glioblastoma from solitary metastasis: a short-echo time single-voxel magnetic resonance spectroscopy study at 3 T.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Comput Assist Tomogr. 2013 Mar;37(2):265-71. doi: 10.1097/RCT.0b013e318282d2ba.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RCT.0b013e318282d2ba

AUTORES / AUTHORS:  - Crisi G; Orsingher L; Filice S

INSTITUCIÓN / INSTITUTION:  - From the Department of Neuroradiology, Parma University Hospital Trust, Parma, Italy.

RESUMEN / SUMMARY:  - OBJECTIVE: The differentiation between solitary metastasis (MET) and glioblastoma (GBM) is difficult using only magnetic resonance imaging techniques. Magnetic resonance spectroscopy (MRS) lipid signal indicates cellular necrosis both in GBMs and METs. The purpose of this prospective study was to determine whether a class of lipids and/or macromolecules (MMs), able to efficiently discriminate between these two types of lesions, exists. METHODS: Forty-one patients with solitary brain tumor (23 GBMs and 18 METs) underwent magnetic resonance imaging and single-voxel MRS. Short-echo time point resolved spectroscopy sequence acquisition with water suppression technique was used. Spectra were analyzed using LCModel. Absolute quantification was performed with “water-scaling” procedure. The analysis was focused on sums of lipid and macromolecular (LM) components at 0.9 and 1.3 ppm. RESULTS: The LM13 absolute concentration was statistically different (P < 0.0001) between GBMs and METs. With a cutoff of 81 mM in LM13 absolute concentration, METs and GBMs can be distinguished with a 78%  of specificity and an 81% of sensitivity. The presence of the MM12 peak, related  to the fucose II complex, in tumors harboring a K-ras gene mutation has been investigated. CONCLUSIONS: We exploited the performance of a clinically easily implementable method, such as short-echo time single-voxel MRS, for the differentiation between brain metastasis and primary brain tumors. The study showed that MRS absolute lipid and macromolecular signals could be helpful in differentiating GBM from metastasis. LM13 class was found to be a discriminant parameter with an accuracy of 85%. Detection of the MM12-fucose peak may also have a role in understanding molecular biology of brain metastasis and should be  further investigated to address specific metabolic phenotypes.

 

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[362]

TÍTULO / TITLE:  - Does the choice of antiepileptic drug have an impact on the survival of glioblastoma multiforme?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Apr;27(2):270. doi: 10.3109/02688697.2013.772101. Epub 2013  Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.772101

AUTORES / AUTHORS:  - Guthrie G; Eljamel S

INSTITUCIÓN / INSTITUTION:  - Ninewells Hospital and Medical School , Dundee, Scotland , UK.

 

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[363]

TÍTULO / TITLE:  - Diffusion tensor invasive phenotypes can predict progression-free survival in glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.771136

AUTORES / AUTHORS:  - Mohsen LA; Shi V; Jena R; Gillard JH; Price SJ

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Cambridge , Cambridge , UK.

RESUMEN / SUMMARY:  - Introduction. Glioblastomas multiformes (GBM) remain incurable in most cases. Their invasion into normal brain makes current therapies ineffective. Post-mortem studies suggest about a 25% of GBMs invade less than 1 cm from the tumour bulk and 20% invade more than 3 cm. Aim of study. The study aims to use DTI to assess  tumour extension and determine how previously reported patterns relate to the progression-free survival (PFS). Materials and methods. Twenty-five patients with GBM treated according to the EORTC/NCIC protocol were retrospectively analysed. Patients were imaged post-operatively at 1.5 T. The sequences were composed of standard anatomical and a standard DTI sequence. As described earlier p and q maps were constructed. For each of the p and q maps, regions of interest were drawn around the visible abnormality. Patients were assigned a diffuse, localised or minimally invasive pattern. Progression was defined according to the RANO criteria 4 and PFS determined in days. Kaplan-Meier plots of survival for the three groups were plotted as were the proportion of patients who had not progressed at 24 months. Results. The median PFS for the diffuse group was 278 days, for the localised group 605 days and 820 days for the minimally invasive group. Three-fourth of the minimally invasive group were progression-free at 24 months (LOG RANK 9.25; p = 0.010). Conclusion. It is possible to identify three invasive phenotypes in GBMs using Diffusion tensor imaging , and these three phenotypes have different progression free survival. A minimal phenotype (20% of  patients) predicts a greater delay to progression.

 

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[364]

TÍTULO / TITLE:  - Assessing Occupational Exposure to Chemicals in an International Epidemiological  Study of Brain Tumours.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Occup Hyg. 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annhyg/mes100

AUTORES / AUTHORS:  - van Tongeren M; Kincl L; Richardson L; Benke G; Figuerola J; Kauppinen T; Lakhani R; Lavoue J; McLean D; Plato N; Cardis E

INSTITUCIÓN / INSTITUTION:  - Centre for Human Exposure Science, Institute of Occupational Medicine (IOM), Research Avenue North, Riccarton, Edinburgh EH14 4AP, UK;

RESUMEN / SUMMARY:  - The INTEROCC project is a multi-centre case-control study investigating the risk  of developing brain cancer due to occupational chemical and electromagnetic field exposures. To estimate chemical exposures, the Finnish Job Exposure Matrix (FINJEM) was modified to improve its performance in the INTEROCC study and to address some of its limitations, resulting in the development of the INTEROCC JEM. An international team of occupational hygienists developed a crosswalk between the Finnish occupational codes used in FINJEM and the International Standard Classification of Occupations 1968 (ISCO68). For ISCO68 codes linked to  multiple Finnish codes, weighted means of the exposure estimates were calculated. Similarly, multiple ISCO68 codes linked to a single Finnish code with evidence of heterogeneous exposure were refined. One of the key time periods in FINJEM (1960-1984) was split into two periods (1960-1974 and 1975-1984). Benzene exposure estimates in early periods were modified upwards. The internal consistency of hydrocarbon exposures and exposures to engine exhaust fumes was improved. Finally, exposure to polycyclic aromatic hydrocarbon and benzo(a)pyrene was modified to include the contribution from second-hand smoke. The crosswalk ensured that the FINJEM exposure estimates could be applied to the INTEROCC study subjects. The modifications generally resulted in an increased prevalence of exposure to chemical agents. This increased prevalence of exposure was not restricted to the lowest categories of cumulative exposure, but was seen across all levels for some agents. Although this work has produced a JEM with important  improvements compared to FINJEM, further improvements are possible with the expansion of agents and additional external data.

 

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[365]

TÍTULO / TITLE:  - A new philosophy in surgery for diffuse low-grade glioma (DLGG): Oncological and  functional outcomes.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurochirurgie. 2013 Feb;59(1):2-8. doi: 10.1016/j.neuchi.2012.11.001. Epub 2013  Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neuchi.2012.11.001

AUTORES / AUTHORS:  - Duffau H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Gui-de-Chauliac Hospital, Montpellier University Medical Center, 80, avenue Augustin-Fliche, 34295 Montpellier, France; National Institute for Health and Medical Research (INSERM), U1051 Laboratory, Team “Brain Plasticity, Stem Cells and Glial Tumors”, Institute for Neurosciences of Montpellier, Montpellier University Medical Center, 34091 Montpellier, France. Electronic address: h-duffau@chu-montpellier.fr.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: Surgery for diffuse low-grade glioma (DLGG) was debated for a long time. Discrepancies in the classical literature are mainly due to the  lack of objective radiological assessment of the extent of resection (EOR). Here, the goal is to review the recent data on oncological and functional outcomes. METHODS: Surgical series with calculation of EOR on postoperative MRI were reviewed. RESULTS: In all modern series, a more aggressive resection predicted significant improvement in overall survival (OS) compared with a simple debulking. Especially, an extended removal of a margin beyond the MRI-defined abnormalities (“supra-total” resection) significantly increased OS by delaying malignant transformation. Furthermore, advances in intraoperative brain mapping techniques resulted in a minimization of neurological deficits. DISCUSSION/CONCLUSION: These recent data strongly argue in favor of achieving a maximal resection of DLGG as the first therapeutic option. Biopsy should be considered only in very diffuse lesions (gliomatosis) or when a subtotal resection is not a priori possible. Thus, neurosurgeons should change their mind, by operating the brain involved by a chronic tumoral disease rather than by trying to remove a “tumor mass”. The aim is not to achieve a simple “tumorectomy”, but the most extensive resection of the brain invaded by DLGG, on  the condition that this part of the brain is not crucial for cerebral functions.  This new philosophy suggests to perform early and maximal resection according to  functional (and not purely oncological or anatomical) boundaries in awake patients. This perspective is the best way to build a personalized “functional surgical neuro-oncology”.

 

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[366]

TÍTULO / TITLE:  - Preliminary biological evaluation and mechanism of action studies of selected 2-arylindoles against glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Bioorg Med Chem. 2013 Apr 1;21(7):1918-24. doi: 10.1016/j.bmc.2013.01.032. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bmc.2013.01.032

AUTORES / AUTHORS:  - Prabhu S; Akbar Z; Harris F; Karakoula K; Lea R; Rowther F; Warr T; Snape T

INSTITUCIÓN / INSTITUTION:  - School of Pharmacy and Biomedical Sciences, Maudland Building, University of Central Lancashire, Preston PR1 2HE, UK.

RESUMEN / SUMMARY:  - A series of related 2-arylindoles have been evaluated for their anticancer activity against a range of glioblastoma cell lines using a number of different cell-based assays to determine cell viability after treatment with the compounds. The best indoles, which showed comparable activity to cisplatin against a U87MG cell line in the MTS assay, were taken forward and initial studies suggest that their mechanism of action is consistent with the generation of reactive oxygen species followed by autophagic cell death. Furthermore, activity was also observed in glioblastoma short-term cell cultures for the best lead compound and  in some cases gave low micromolar IC50s.

 

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[367]

TÍTULO / TITLE:  - Cluster-like headache and a cystic hypothalamic tumour as first presentation of sarcoidosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cephalalgia. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0333102412475237

AUTORES / AUTHORS:  - der Vlist SH; Hummelink BJ; Westerga J; Boogerd W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Slotervaartziekenhuis, Netherlands.

RESUMEN / SUMMARY:  - INTRODUCTION: Sarcoidosis is a granulomatous, multisystem inflammatory disease of unknown cause, which presents with a wide variety of symptoms. We describe a rare case of a newly diagnosed sarcoidosis, with cluster-like headache as a presenting symptom. CASE: A 31-year-old man presented with cluster headache with a cystic lesion in the hypothalamus. A non-caseating granuloma consistent with the diagnosis sarcoidosis was found at biopsy. Pulmonary involvement was confirmed on positron electron tomography-computed tomography (PET-CT). Treatment with prednisone led to regression of the hypothalamic lesion. Headache attacks did not recur. DISCUSSION: Cluster-like headache with a cystic hypothalamic lesion as first presentation of sarcoidosis has never been reported. Their possible relationship seems to underline the role of the hypothalamus in the central pain-regulatory areas in the brain, but is not undisputed. This case clearly demonstrates once again the relevance of neuroimaging in new-onset cluster-like headache.

 

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[368]

TÍTULO / TITLE:  - Proximal femoral geometry before and after varus rotational osteotomy in children with cerebral palsy and neuromuscular hip dysplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Orthop. 2013 Mar;33(2):182-9. doi: 10.1097/BPO.0b013e318274541a.

            ●● Enlace al texto completo (gratuito o de pago) 1097/BPO.0b013e318274541a

AUTORES / AUTHORS:  - Davids JR; Gibson TW; Pugh LI; Hardin JW

INSTITUCIÓN / INSTITUTION:  - Shriners Hospitals for Children, Greenville, SC, USA. jdavids@shrinenet.org

RESUMEN / SUMMARY:  - BACKGROUND: Surgical management of hip dysplasia in children with cerebral palsy  (CP) usually includes varus rotational osteotomy (VRO) of the proximal femur. Several techniques of VRO (end-to-end, EE; end-to-side, ES) have been designed to maximize correction and minimize associated deformities. The goals of the current study were to establish the prevalence and contribution of caput valgum to coxa valga deformity in children with CP, compare the geometry of the proximal femur after EE and ES techniques of VRO, and document the response of the proximal femur to subsequent growth after VRO. METHODS: The records of 75 children with CP (Gross Motor Function Classification System, levels IV and V) with 137 surgically treated hips were retrospectively reviewed. Outcomes were limited to the technical domain (eg, radiographic measurements and surgical complications). Measurements made for each hip (preoperative, operative, and follow-up) included  the neck-shaft angle (NSA), head-shaft angle (HSA), and the medialization index.  RESULTS: The mean age at the time of surgery was 7 years. The mean follow-up was  5 years and 6 months. Caput valgum was present in all hips, increasing the actual geometric valgus by a mean of 10%. The ES technique was more effective at medializing the femoral shaft; however, this benefit was lost with growth (P = 0.891). The ES technique was more effective at achieving and maintaining correction of the NSA (P = 0.026). Maintenance of correction of the HSA was comparable for both ES and EE surgical techniques (P = 0.099). Subsequent growth  of the proximal femur resulted in loss of correction of the NSA (mean 29%) and HSA (mean 21%). DISCUSSION: Caput valgum is usually present in children with CP who are undergoing surgical hip reconstruction. The ES technique is a reasonable  alternative for the correction of neuromuscular hip dysplasia associated with extreme coxa valga and long femoral necks. Recurrence of coronal plane deformity  with growth after VRO is common, and further study is required to determine how best to control this phenomena. LEVEL OF EVIDENCE: Level IV-therapeutic.

 

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[369]

TÍTULO / TITLE:  - Distant metastases in meningioma: an underestimated problem.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1074-x

AUTORES / AUTHORS:  - Surov A; Gottschling S; Bolz J; Kornhuber M; Alfieri A; Holzhausen HJ; Abbas J; Kosling S

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Martin-Luther-university Halle-Wittenberg, Ernst-Grube Str. 40, 06097, Halle, Germany, alex.surow@medizin.uni-halle.de.

RESUMEN / SUMMARY:  - Meningioma is a common intracranial neoplasm derived from meningothelial cells. Meningiomas are associated with a benign clinical course. However, malignant behaviour such as metastatic disease has been also described. Our aim was to analyze the metastatic pattern taking tumor grading into consideration, and to determine clinical signs of distant metastases in meningiomas. In this systematic review PubMed database was screened for distant meningioma metastases from 1990 to 2012. 95 articles were identified. Only cases with metastasized meningiomas were included in the analysis. Our analysis comprised 115 cases with 164 metastatic lesions. Primary tumors were in 33.9 % grade 1, 20.9 % grade 2, and 40 % grade 3. In 5.2 % the grade was not reported. In 93 % meningiomas were diagnosed and resected before distant metastases occurred. In 6.1 % metastases were identified simultaneously with primary tumors and in 0.9 % metastases were identified before the primary tumor was found. The metastatic lesions were localized most frequently in the lung (37.2 %), bones (16.5 %), intraspinally (15.2 %), and in the liver (9.2 %). Other locations were rarer. The size of the metastases varied from 0.6 to 28 cm (median size, 3 cm). There were no significant differences between sizes of the identified metastases in relation to tumor grading. 50.4 % of distant metastases were clinically manifest and 31.3 % were identified incidentally. In 18.3 % clinical signs were missing. In our review 31.3 % of metastatic meningiomas were found to be clinically silent. The prevalence of metastases in meningioma may be underreported.

 

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[370]

TÍTULO / TITLE:  - Forkhead-box A1 transcription factor is a novel adverse prognosis marker in human glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 16. pii: S0967-5868(12)00525-5. doi: 10.1016/j.jocn.2012.03.055.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.03.055

AUTORES / AUTHORS:  - Wang L; Qin H; Li L; Feng F; Ji P; Zhang J; Li G; Zhao Z; Gao G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tangdu Hospital, 569 Xinsi Road, Baqiao District, Xi’an City 710038, China.

RESUMEN / SUMMARY:  - Forkhead-box A1 (FOXA1), a member of the FOX family of transcription factors, has been implicated in certain tumor types including breast, prostate, lung, thyroid  and esophageal squamous cell carcinomas. The aim of this study was to investigate the clinicopathological significance of FOXA1 expression in human malignant glioma. FOXA1 expression in human glioma and non-neoplastic brain tissue was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry. The association of FOXA1 immunostaining with clinicopathological factors and prognosis in patients with glioma was also investigated. The expression levels of FOXA1 messenger RNA (mRNA) and protein in glioma tissues were significantly higher than those in corresponding non-neoplastic brain tissue (both p<0.001). In addition, the expression of FOXA1 was upregulated in high-grade glioma tissue compared with that in low-grade tissues, and increased with ascending World Health Organization (WHO) tumor grade (p=0.001). The increased expression of FOXA1 protein was also significantly correlated with low Karnofsky performance scale score (p=0.02). Moreover, the overall survival rate for patients with high FOXA1 protein expression was clearly lower than that for patients with low FOXA1 protein expression (p=0.01). Multivariate analysis showed that high FOXA1 protein expression was an independent prognostic factor for overall survival (p=0.02) in  patients with glioma. In conclusion, our results suggest, for the first time, that FOXA1 might be a potential regulator of progression of human glioma and its  upregulation might be closely associated with a poor clinical outcome for patients with this serious disease.

 

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[371]

TÍTULO / TITLE:  - The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Feb 9. pii: S0304-3835(13)00115-8. doi: 10.1016/j.canlet.2013.02.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.004

AUTORES / AUTHORS:  - Ajeawung NF; Joshi HC; Kamnasaran D

INSTITUCIÓN / INSTITUTION:  - Pediatric Research Unit, Centre de Recherche du CHUL, Quebec, QC, Canada G1V 4G2.

RESUMEN / SUMMARY:  - Low grade gliomas are a heterogeneous group of tumours representing the most common form of neoplasms in the central nervous system among children. Although gross total resection remains the principal treatment, it is often impractical especially for the resection of tumours within eloquent regions of the brain. Instead Radiotherapy is utilised in such cases, but because of its associated toxicities, it is refrained from use among younger children. These limitations coupled with hypersensitivity and toxicities associated with some commonly used chemotherapeutic agents, have ignited the need to search for safer and more effective treatments for paediatric low grade gliomas. In this study, we investigated the EM011 drug on the growth of two pilocytic and one diffuse paediatric astrocytoma cell lines, using an assortment of cancer assays. We discovered that treatments of low grade gliomas with EM011 abrogated cell viability by inducing a decrease in cell proliferation and an arrest in the S and G2M cell cycle phases, followed by a converse increase in apoptosis in a dose and time dependent manner. The cell migratory and invasion indices, as well as anchorage independent growth in soft agarose, were significantly attenuated. These findings were mechanistically associated with a transient release of AIF, a disruption of microtubule architecture, and a decline in the expression of key genes which drive cancer progression including EGFR, mTORC1, JUN and multiple MMPs. In fact, the activity of MMP2 was also perturbed by EM011. These findings,  in conjunction with the insignificant adverse side effects established from other studies, make EM011 an appealing chemotherapeutic agent for the treatment of paediatric low grade gliomas.

 

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[372]

TÍTULO / TITLE:  - Differential sensitivities of glioblastoma cell lines towards metabolic and signaling pathway inhibitions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 21. pii: S0304-3835(13)00248-6. doi: 10.1016/j.canlet.2013.03.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.020

AUTORES / AUTHORS:  - Kennedy CR; Tilkens SB; Guan H; Garner JA; Or PM; Chan AM

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Division of Hematology, Oncology, & BMT, Medical College of Wisconsin, 8701, Watertown Plank Road, MFRC-6033, Milwaukee, WI 53226, USA.

RESUMEN / SUMMARY:  - In glioblastoma multiforme (GBM), the activation of the phosphatidylinositol 3-kinase (PI3-K) pathway is known to promote aerobic glycolysis. The relative sensitivity of GBM towards PI3-K and metabolic inhibitors was examined in a panel of human GBM lines. We observed differential sensitivities towards oligomycin, an ATP synthase inhibitor that suppresses oxidative phosphorylation (OXPHOS). GBMs that were sensitive to oligomycin have greater intrinsic oxygen consumption. They also failed to undergo adaptive glycolytic switches in response to oligomycin, as reflected in the failure to activate AMPKalpha. On the other hand, GBM lines that were less sensitive to oligomycin could be rendered non-viable when simultaneously treated with the glycolysis inhibitor, 2-Deoxyglucose (2DG). Furthermore, inhibiting either PI3-K pathway or glycolysis was effective in suppressing cell migration. Inhibiting OXPHOS alone did not have any significant  effects on cell motility. However, both oligomycin and 2DG acted synergistically  in suppressing cell migration. We conclude that while there was less synergy by the combined inhibition of PI3-K and glycolysis, the simultaneous targeting of glycolysis and OXPHOS is highly effective in blocking GBM tumorigenic phenotypes.

 

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[373]

TÍTULO / TITLE:  - Analysis of CIC-associated CpG-island methylation in oligoastrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathol Appl Neurobiol. 2013 Mar 25. doi: 10.1111/nan.12045.

            ●● Enlace al texto completo (gratuito o de pago) 1111/nan.12045

AUTORES / AUTHORS:  - Sahm F; Lass U; Herold-Mende C; von Deimling A; Hartmann C; Mueller W

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Ruprecht-Karls-Universitat Heidelberg, D-69120, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.

RESUMEN / SUMMARY:  - AIMS: Combined deletion of the whole chromosomal arms 1p and 19q is a frequent event in oligodendroglial tumours. Recent identification of recurrent mutations in CIC on 19q and FUBP1 on 1p and their mutational patterns suggest a loss of function of the respective proteins. Surprisingly, oligoastrocytomas harbouring identical genetic characteristics regarding 1p/19q co-deletion and frequent IDH1/2 mutations have been shown to carry CIC mutations in a significantly lower  number of cases. The present study investigates whether epigenetic modification may result in silencing of CIC. METHODS: Since IDH1/2 mutation mediated DNA hypermethylation is a prominent feature of these tumours, we analyzed a set of CIC wild-type oligoastrocytomas and other diffuse gliomas with regard to 1p/19q status for presence of CIC-associated CpG-island methylation by methylation-specific PCR. RESULTS: Both methylation specific PCR and subsequent bisulfite-sequencing of selected cases revealed an unmethylated status in all samples. CONCLUSION: Despite the hypermethylator- phenotype in IDH1/2 mutant tumours and recent detection of gene silencing particularly on retained alleles in oligodendendroglial tumours, hypermethylation of CIC-associated CpG-islands does not provide an alternative mechanism of functional CIC protein abrogation.

 

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[374]

TÍTULO / TITLE:  - Natural history of a medulloblastoma: 30 months of wait and see in a child with a cerebellar incidentaloma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2077-9

AUTORES / AUTHORS:  - Zeilhofer UB; Scheer I; Warmuth-Metz M; Rushing EJ; Pietsch T; Boltshauser E; Grotzer MA; Gerber NU

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University Children’s Hospital, 8032, Zurich, Switzerland.

RESUMEN / SUMMARY:  - INTRODUCTION: With the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking, and little is known about their optimal management. CASE  REPORT: We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 14 months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable  radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression  was observed, the tumour was resected, 2(1/2) years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. DISCUSSION: To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The  long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic changes.

 

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[375]

TÍTULO / TITLE:  - Characteristics and management of occult intrasacral extradural cyst in children.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.764968

AUTORES / AUTHORS:  - Huang SL; Jiang HX; Cheng B; Ning N; He XJ

INSTITUCIÓN / INSTITUTION:  - Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University , Xi’an , P. R. China.

RESUMEN / SUMMARY:  - Occult intrasacral extradural cyst is a rare entity. Since little about this lesion has been reported in the literature, this study herein demonstrates by cases some of the clinical features and surgical treatment of occult intrasacral  extradural cyst in children. A series of 4 children, 2 boys and 2 girls aged from 4 years and 6 months to 11 years, with occult intrasacral extradural cyst were reviewed. All patients underwent neurological examinations and magnetic resonance imaging. Of these 4 patients two had urinary incontinence in daytime, one frequent micturition, and one numb in saddle area. There were no abnormal findings on physical or laboratory examination. Whole excision of the cyst and ligation of the tract between the cyst and thecal sac were performed for all the  patients. No complications such as cerebrospinal fluid leakage and infection were found after operation. All cases made complete recovery and have been asymptomatic at follow-up. The clinical and radiological features of occult intrasacral extradural cyst are characteristic in children. Magnetic resonance imaging is the choice of investigation and surgery is curative.

 

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[376]

TÍTULO / TITLE:  - Reconstruction of cranial base defects using the medpor titan implant: Cranioplasty applications in acoustic neuroma surgery.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Laryngoscope. 2013 Jan 31. doi: 10.1002/lary.23840.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23840

AUTORES / AUTHORS:  - Boghani Z; Choudhry OJ; Schmidt RF; Jyung RW; Liu JK

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, U.S.A.

 

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[377]

TÍTULO / TITLE:  - External drainage with an Ommaya reservoir for perioperative hydrocephalus in children with posterior fossa tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2078-8

AUTORES / AUTHORS:  - Jiang C; Wu X; Lin Z; Wang C; Kang D

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.

RESUMEN / SUMMARY:  - PURPOSE: This study aims to evaluate an external drainage using an Ommaya reservoir for relieving perioperative hydrocephalus and reducing postoperative complications in children with posterior fossa tumors. METHODS: We retrospectively analyzed the data from 48 children with posterior fossa tumors who underwent tumor resection between May 2006 and June 2012. An Ommaya reservoir was placed in the right lateral ventricle forehead for continuous perioperative drainage of cerebrospinal fluid (CSF). RESULTS: Tumors were successfully removed  from all patients. Intracranial infection occurred in nine patients and was controlled by antibiotic treatment. Preoperative obstruction and obstructive hydrocephalus were relieved, and the need for a shunt or endoscopic third ventriculostomy was avoided. One patient who underwent a second surgical procedure had intracranial infection, hydrocephalus, and occipital pseudomeningocele. After continuous drainage and anti-infective treatment, hydrocephalus and intracranial infection were effectively controlled. CONCLUSIONS: Using an Ommaya reservoir for perioperative external ventricular CSF drainage enabled tumors to be wholly and safely removed. Restoring CSF circulation provided an effective means of controlling and preventing hydrocephalus secondary to posterior fossa tumors in children.

 

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[378]

TÍTULO / TITLE:  - Recurrent Schwannoma Postirradiation: Histological Review Reveals Mixed Schwannoma and Meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Otolaryngol Head Neck Surg. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0194599813475572

AUTORES / AUTHORS:  - Kimmel RA; Doherty J; Slattery WH 3rd; Linthicum FH Jr

INSTITUCIÓN / INSTITUTION:  - House Research Institute, Eccles Temporal Bone Histopathology Laboratory, Los Angeles, California, USA.

 

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[379]

TÍTULO / TITLE:  - Concomitant Meningioma and Glioma Within the Same Optic Nerve in Neurofibromatosis Type 1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Child Neurol. 2013 Feb 17.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0883073812475157

AUTORES / AUTHORS:  - Buyukkapu-Bay S; Akca A; Karadogan M; Corapcioglu F; Anik Y

INSTITUCIÓN / INSTITUTION:  - 1Department of Pediatrics, Kocaeli University School of Medicine, Kocaeli, Turkey.

RESUMEN / SUMMARY:  - A patient with neurofibromatosis type 1 and the rare finding of concomitant meningioma and optic pathway glioma within the same optic nerve is presented. A 4-year-old boy was admitted to our hospital with right-sided proptosis. He also had numerous cafe-au-lait macules and axillary freckling on physical exam. According to National Institutes of Health (NIH) criteria, he met the diagnostic  criteria for neurofibromatosis type 1. On magnetic resonance imaging (MRI), a mass originating from the right optic nerve sheath with normal appearance of the  optic nerve was observed, which was consistent with optic nerve sheath meningioma. Another mass lesion was observed in the prechiasmatic region of the same optic nerve, which was consistent with optic nerve glioma. Two different types of optic pathway tumors in the same optic nerve is an extraordinary case. It is important to recognize imaging findings of these tumors and make correct diagnosis.

 

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[380]

TÍTULO / TITLE:  - STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pflugers Arch. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00424-013-1254-8

AUTORES / AUTHORS:  - Motiani RK; Hyzinski-Garcia MC; Zhang X; Henkel MM; Abdullaev IF; Kuo YH; Matrougui K; Mongin AA; Trebak M

INSTITUCIÓN / INSTITUTION:  - The College of Nanoscale Science and Engineering (CNSE), University at Albany, State University of New York, 257 Fuller Rd., Albany, NY, 12203, USA.

RESUMEN / SUMMARY:  - The Ca2+ sensor stromal interacting molecule 1 (STIM1) and the Ca2+ channel Orai1 mediate the ubiquitous store-operated Ca2+ entry (SOCE) pathway activated by depletion of internal Ca2+ stores and mediated through the highly Ca2+-selective, Ca2+ release-activated Ca2+ (CRAC) current. Furthermore, STIM1 and Orai1, along with Orai3, encode store-independent Ca2+ currents regulated by either arachidonate or its metabolite, leukotriene C4. Orai channels are emerging as important contributors to numerous cell functions, including proliferation, migration, differentiation, and apoptosis. Recent studies suggest critical involvement of STIM/Orai proteins in controlling the development of several cancers, including malignancies of the breast, prostate, and cervix. Here, we quantitatively compared the magnitude of SOCE and the expression levels of STIM1  and Orai1 in non-malignant human primary astrocytes (HPA) and in primary human cell lines established from surgical samples of the brain tumor glioblastoma multiforme (GBM). Using Ca2+ imaging, patch-clamp electrophysiology, pharmacological reagents, and gene silencing, we established that in GBM cells, SOCE and CRAC are mediated by STIM1 and Orai1. We further found that GBM cells show upregulation of SOCE and increased Orai1 levels compared to HPA. The functional significance of SOCE was evaluated by studying the effects of STIM1 and Orai1 knockdown on cell proliferation and invasion. Utilizing Matrigel assays, we demonstrated that in GBM, but not in HPA, downregulation of STIM1 and  Orai1 caused a dramatic decrease in cell invasion. In contrast, the effects of STIM1 and Orai1 knockdown on GBM cell proliferation were marginal. Overall, these results demonstrate that STIM1 and Orai1 encode SOCE and CRAC currents and control invasion of GBM cells. Our work further supports the potential use of channels contributed by Orai isoforms as therapeutic targets in cancer.

 

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[381]

TÍTULO / TITLE:  - The expression of AIB1 correlates with cellular proliferation in human prolactinomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Anat. 2013 Feb 4. pii: S0940-9602(13)00022-8. doi: 10.1016/j.aanat.2013.01.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.aanat.2013.01.009

AUTORES / AUTHORS:  - Carretero J; Blanco EJ; Carretero M; Carretero-Hernandez M; Garcia-Barrado MJ; Iglesias-Osma MC; Burks DJ; Font de Mora J

INSTITUCIÓN / INSTITUTION:  - Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, España; Laboratory of Neuroendocrinology, Institute of Neuroscience of  Castilla y Leon, University of Salamanca, España. Electronic address: jcar@usal.es.

RESUMEN / SUMMARY:  - Estrogens as well as certain growth factors strongly influence the development and growth of prolactinomas. However, the molecular mechanisms by which extracellular factors trigger prolactinomas are not well known. Amplified in breast cancer 1 (AIB1), also known as steroid receptor co-activator 3 (SRC-3), belongs to the p160/SRC family of nuclear receptor co-activators and is a major co-activator of the estrogen receptor. Here, we report that the estrogen receptor coactivator AIB1 is overexpressed in human prolactinomas and correlates with the  detection of aromatase and estrogen receptor alpha (ERalpha). Of the 87 pituitary tumors evaluated in women, 56%, corresponding to hyperoprolactinemic women, contained an enriched population of prolactin-positive cells and hence were further classified as prolactinomas. All prolactinomas stained positive for both  ERalpha and AIB1. Moreover, AIB1 sub-cellular distribution was indicative of the  cell-cycle status of tumors; the nuclear expression of AIB1 was correlated with proliferative markers whereas the cytoplasmic localization of AIB1 coincided with active caspase-3. Thus, our results demonstrate for the first time that AIB1 is expressed in prolactinomas and suggest its participation in the regulation of proliferation and apoptosis of tumoral cells. Because aromatase expression is also enhanced in these prolactinomas and it is involved in the local production of estradiol, both mechanisms, ER-AIB1 and aromatase could be related.

 

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[382]

TÍTULO / TITLE:  - Synchronous occurrence of paraganglioma of the glomus jugulare and olfactory groove meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300606

AUTORES / AUTHORS:  - Mittal S; Monsell EM; Narayanan S; Kupsky WJ; Guthikonda M; Mittal S

 

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[383]

TÍTULO / TITLE:  - Notch receptors in human choroid plexus tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Mar 12.

AUTORES / AUTHORS:  - Beschorner R; Waidelich J; Trautmann K; Psaras T; Schittenhelm J

INSTITUCIÓN / INSTITUTION:  - Institute for Pathology and Neuropathology, Department of Neuropathology, University of Tubingen, Tubingen, Germany. rudi.beschorner@med.uni-tuebingen.de.

RESUMEN / SUMMARY:  - Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3  has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression  of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid  plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (p0.0001) and Notch4 (p=0.046) was significantly higher, whereas Notch2 expression was significantly lower (p0.0001) in nCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (p0.0001 each). Expression of Notch2 and Notch4 showed a shift from a prevailing membranous/cytoplasmic expression in nCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.

 

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[384]

TÍTULO / TITLE:  - H magnetic resonance spectroscopy in the diagnosis of paediatric low grade brain  tumours.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Radiol. 2013 Mar 11. pii: S0720-048X(13)00070-3. doi: 10.1016/j.ejrad.2013.01.030.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.01.030

AUTORES / AUTHORS:  - Orphanidou-Vlachou E; Auer D; Brundler MA; Davies NP; Jaspan T; Macpherson L; Natarajan K; Sun Y; Arvanitis TN; Grundy RG; Peet AC

INSTITUCIÓN / INSTITUTION:  - School of Cancer Sciences, College of Medical and Dental Sciences, University of  Birmingham, Edgbaston, Birmingham, B15 2TT, UK; Birmingham Children’s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH, UK. Electronic address: eleni.orphanidou@googlemail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: Low grade gliomas are the commonest brain tumours in children but present in a myriad of ways, each with its own treatment challenges. Conventional MRI scans play an important role in their management but have limited ability to  identify likely clinical behaviour. The aim of this study is to investigate 1H magnetic resonance spectroscopy (MRS) as a method for detecting differences between the various low grade gliomas and related tumours in children. PATIENTS AND METHODS: Short echo time single voxel 1H MRS at 1.5 or 3.0T was performed prior to treatment on children with low grade brain tumours at two centres and five MR scanners, 69 cases had data which passed quality control. MRS data was processed using LCModel to give mean spectra and metabolite concentrations which  were compared using T-tests, ANOVA, Receiver Operator Characteristic curves and logistic regression in SPSS. RESULTS: Significant differences were found in concentrations of key metabolites between glioneuronal and glial tumours (T-test  p<0.05) and between most of the individual histological subtypes of low grade gliomas. The discriminatory metabolites identified, such as choline and myoinositol, are known tumour biomarkers. In the set of pilocytic astrocytomas and unbiopsied optic pathway gliomas, significant differences (p<0.05, ANOVA) were found in metabolite profiles of tumours depending on location and patient neurofibromatosis type 1 status. Logistic regression analyses yielded equations which could be used to assess the probability of a tumour being of a specific type. CONCLUSIONS: MRS can detect subtle differences between low grade brain tumours in children and should form part of the clinical assessment of these tumours.

 

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[385]

TÍTULO / TITLE:  - Steroid management in newly diagnosed glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1096-4

AUTORES / AUTHORS:  - Deutsch MB; Panageas KS; Lassman AB; Deangelis LM

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

RESUMEN / SUMMARY:  - Glucocorticoids ameliorate neurologic symptoms in patients with glioblastoma, but their adverse effects limit long-term use. This study sought to identify factors  associated with steroid taper success or failure in the early stages of glioblastoma treatment. We retrospectively reviewed steroid prescribing practices from date of surgery until one month following radiotherapy (RT) completion among 85 patients with newly diagnosed glioblastoma who were treated on a prospective clinical trial with RT and temozolomide. Sufficient information on steroid dosing was available in 72 patients included in the final analysis. The mean age was 54  years, and 65 % were men. Thirty-nine percent had a gross-total resection. Fifteen patients (21 %) tolerated steroid taper without requiring dose increase during the study. Men and patients with Karnofsky performance scale 90-100 were more likely to have a successful steroid taper. The most common symptom of taper  failure was headache, but the reason for steroid increase differed among the different time intervals examined: worsening neurologic deficit in the early post-operative period, headache and non-focal symptoms during RT, and headache and seizure post-RT. Of the 50 patients in whom steroid use during RT was known,  36 (72 %) underwent dose reduction and of those, 21 (58 %) required an increase.  The successful early taper of steroids in glioblastoma was associated with male gender and better functional status. Steroids are often tapered during RT, but there is frequent taper failure with this approach. A prospective trial with standardized steroid dosing regimens would be needed to verify these findings.

 

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[386]

- CASTELLANO -

TÍTULO / TITLE:Der Pseudotumor cerebri im Kindes- und Jugendalter - Ergebnisse einer Deutschland-weiten ESPED-Studie.

TÍTULO / TITLE:  - Pseudotumor Cerebri in Childhood and Adolescence - Results of a Germany-wide ESPED-survey.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Klin Padiatr. 2013 Mar;225(2):81-85. Epub 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0033-1333757

AUTORES / AUTHORS:  - Tibussek D; Distelmaier F; von Kries R; Mayatepek E

INSTITUCIÓN / INSTITUTION:  - Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Duesseldorf, Germany.

RESUMEN / SUMMARY:  - No valid epidemiological data on Pseudotumor cerebri (PTC) in childhood and adolescence are available. This national survey aims to raise awareness of the PTC in paediatrics and contribute to a better understanding of age-related characteristics.Over 1 year (January-December 2008) new cases of PTC in childhood and adolescence from all paediatric hospitals in Germany were collected by the German Paediatric Surveillance Unit for rare diseases (ESPED).With a total of 61  cases, an annual incidence of 0.5 per 100 000 children <18 years was found. Children of all age groups were affected. A female preponderance and obesity was  only found in adolescents. Clinical presentation was variable. Headaches represent the most common symptom affecting prepubertal children less frequently. A wide range of vision problems could be documented (papilledema, visual loss, double vision, visual field defects, disturbed colour and stereo vision). In 10 patients no papilledema was found. Comorbidities were reported in 23% of patients. 14 children gained remission after lumbar puncture without medication.  Acetazolamide was the drug of choice, with relatively low dosages used. Escalation strategies were variable. 2 patients were treated invasively (sinus venous stent, LP shunt).PTC in childhood and adolescence appears to be as frequent as in the general population. Unspecific clinical characteristics and the broad spectrum of ophthalmologic findings emphasize the importance of a skilful neuroophthalmological investigation. Inconsistent therapeutic approaches  are most likely due to a lack of diagnostic and therapeutic standards. Present diagnostic criteria and guidelines for the management of paediatric PTC do not sufficiently consider paediatric aspects.

 

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[387]

TÍTULO / TITLE:  - Expression of histone acetylases p300 and PCAF in pediatric astrocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2046-3

AUTORES / AUTHORS:  - Eguia-Aguilar P; Solis-Paredes M; Reyes-Cid P; Perezpena-Diazconti M; de Leon FC; Sadowinski-Pine S; Arenas-Huertero F

INSTITUCIÓN / INSTITUTION:  - Departamento de Patologia, Hospital Infantil de Mexico Federico Gomez, Dr. Marquez 162, Colonia Doctores, 06720, Mexico City, Mexico.

RESUMEN / SUMMARY:  - OBJECTS: The protein 300 (p300) and p300/CBP-binding protein-associated factor (PCAF) are enzymes with histone acetyltransferase (HAT) activity, a function that can become deregulated in different tumors and affect biological responses. METHODS: Due to the lack of information on the deregulation of these HATs in pediatric tumors, this study evaluated the expression of both the mRNA and proteins of p300 and PCAF in 54 samples of pediatric astrocytomas embedded in paraffin. RESULTS: PCAF was not expressed in normal brain tissue. In grade I tumors, the expression of p300 (1.1 +/- 0.1) and PCAF (1.2 +/- 0.11) was greater  than those observed in grade III tumors: 0.72 +/- 0.15 for p300 and 0.55 +/- 0.11 for PCAF, and grade IV tumors: 0.74 +/- 0.13 for p300 and 0.55 +/- 0.13 for PCAF  (p < 0.05). Immunohistochemical staining revealed the same tendency towards a decrease in the expression of the protein as the degree of clinical severity increased. Patients with recurrent grades I, III, and IV tumors had the highest levels of PCAF, compared to those who showed no recurrence (p < 0.05). CONCLUSIONS: This work describes and confirms that these HATs play important roles in regulating genes and in the biological behavior of pediatric astrocytomas.

 

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[388]

TÍTULO / TITLE:  - Gliomatosis peritonei as a natural experiment in tissue differentiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Dev Biol. 2012;56(10-12):969-74. doi: 10.1387/ijdb.120172fn.

            ●● Enlace al texto completo (gratuito o de pago) 1387/ijdb.120172fn

AUTORES / AUTHORS:  - Nogales FF; Preda O; Dulcey I

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, San Cecilio University Hospital, Granada, España. fnogales@ugr.es

RESUMEN / SUMMARY:  - Gliomatosis peritonei (GP) is an unusual condition in which nodules of mature astroglia, often miliary and microscopic in size, are widespread in the peritoneum and abdominal lymph nodes. Its behaviour is benign and it is usually found in association with ovarian teratoma and rarely with teratomas of other organs. Implants grow rapidly and can remain unchanged for life. Astroglia is the main component, but other neural lineage elements and many other tissues can be found. Cells are mature but not terminal, since they express SOX2. Secondary associated lesions include: a) degenerative astrocytic changes, b) granulomatous  and follicular chronic inflammatory changes, c) association with hormonally related changes, such as decidual peritoneal metaplasia and endometriosis and d)  endothelial and adventitial vascular hyperplasia leading to haemoperitoneum.Two pathogenetic mechanisms are considered: direct seeding of immature neural cells from a primary tumour with subsequent differentiation and metaplasia from peritoneal stem cells. The former proposal is supported by clinicopathologic data such as ample cellular heterogeneity, coexistence of mature astroglia with neural blastema, as well as the shed keratin and hairs from the ovarian neoplasm. However, metaplasia is sustained by a heterozygosity pattern of GP nodules, identical to the normal tissue and different from the coexistent ovarian teratoma. GP would constitute a response to growth factors from teratoma or macrophages. While an implantative origin from ovarian teratoma remains in most cases a more probable mechanism, metaplasia from peritoneal stem cells would explain cases of GP which present a monomorphic astrocytic cell population.

 

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[389]

TÍTULO / TITLE:  - Image-guided resection of spheno-orbital skull-base meningiomas with predominant  intraosseous component.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1662-8

AUTORES / AUTHORS:  - Marcus H; Schwindack C; Santarius T; Mannion R; Kirollos R

INSTITUCIÓN / INSTITUTION:  - Hamlyn Centre for Robotic Surgery, Imperial College London, London, UK, hani.marcus10@imperial.ac.uk.

RESUMEN / SUMMARY:  - BACKGROUND: Although meningiomas of the spheno-orbital region commonly result in  hyperostosis, intraosseous meningiomas, which feature extensive full thickness infiltration of the anterolateral skull base, are rare. In this study, we assess  the value of image guidance during surgery for intraosseous spheno-orbital skull-base meningiomas in achieving safe and maximal abnormal bone resection. METHOD: Only cases with a full thickness and extensive intraosseous component were included. Image guidance was used to guide drilling of hyperostotic bone. Extensive resulting defects of the orbital wall were reconstructed with titanium  mesh. Post-operative CT scans were used to assess completeness of abnormal bone resection in the skull base, and MRI scans used to evaluate residual intradural disease. Operative complications to neurovascular structures in adjacent foramina were recorded. RESULTS: Nineteen patients with full-thickness intraosseous spheno-orbital meningiomas underwent image-guided resection. Anterior clinoidectomy to variable extent was necessary in 11 cases with decompression of  the optic canal in five. In ten cases, hyperostotic bone was drilled from the middle fossa around the exit foramina of the trigeminal nerve and base of the pterygoid plates. Proptosis was corrected in all cases, and of 11 patients presenting with reduced visual acuity, symptoms improved or stabilized in ten cases. Post-operative CT scans confirmed gross resection of abnormal bone in all  cases, but limited residual tumor was present around the cavernous sinus or orbital apex in eight patients. One patient died from a pulmonary embolism, the only mortality of the series. One patient had worsening of pre-existing poor visual acuity, and three patients had worsening of pre-existing ophthalmoplegia.  Five patients developed new facial numbness post-operatively, which persisted in  three cases. CONCLUSIONS: Intra-operative image guidance allowed total or near-total resection of the hyperostotic skull base around the cranial nerve foramina with minimal morbidity in a group of patients with extensive spheno-orbital meningiomas.

 

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[390]

TÍTULO / TITLE:  - Total magnitude of diffusion tensor imaging as an effective tool for the differentiation of glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Radiol. 2013 May;82(5):857-61. doi: 10.1016/j.ejrad.2012.12.027. Epub 2013  Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.12.027

AUTORES / AUTHORS:  - Smitha KA; Gupta AK; Jayasree RS

INSTITUCIÓN / INSTITUTION:  - Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal  Institute for Medical Sciences & Technology, Thiruvananthapuram, India. Electronic address: mithamahesh@gmail.com.

RESUMEN / SUMMARY:  - OBJECTIVES: The study aims to evaluate the difference in diffusion properties between high grade glioma and low grade glioma by measuring the total magnitude of diffusion tensor (L), and its isotropic (p) and anisotropic (q) components. METHODS: The diffusion tensor parameters p, q, L and FA from the tumor area, adjacent area to the tumor and corresponding contra lateral normal area of 30 high grade glioma and 49 low grade glioma were calculated. Chi square analysis was done to find the changes in age and sex. One Way ANOVA was performed to compare the mean and ROC curve analysis to confirm the discriminative sensitivity. RESULTS: Major variation in the mean values of p, L and FA was observed in different brain areas considered. Variation in the p and L values between low grade and high grade glioma were statistically significant (p<0.001)  and their ROC curve analysis yielded 93.9% and 91.8% sensitivity and 53.3% specificity respectively. CONCLUSION: Measurement of the isotropic component p and the total value of diffusion tensor L can be effectively correlated with different grades of glioma and can be used to study the diffusion properties of tumor affected brain.

 

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[391]

TÍTULO / TITLE:  - Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biomaterials. 2013 Apr;34(12):2969-79. doi: 10.1016/j.biomaterials.2012.12.049. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2012.12.049

AUTORES / AUTHORS:  - Jiang X; Sha X; Xin H; Xu X; Gu J; Xia W; Chen S; Xie Y; Chen L; Chen Y; Fang X

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.

RESUMEN / SUMMARY:  - The treatment of cerebral tumor, especially advanced gliomas, represents one of the most formidable challenges in oncology. In this study, integrin-mediated poly(trimethylene carbonate)-based nanoparticulate system (c(RGDyK)-NP) was proposed as a delivery vehicle for enhancing drug penetration and chemotherapy of malignant gliomas. Following the recognition by integrin proteins on cell surface, c(RGDyK)-NP could be energy-dependently internalized by human U87MG glioma cells through a multiple endocytic pathway. The tumor penetration, homing  specificity and anticancer efficacy of PTX-loaded c(RGDyK)-NP (c(RGDyK)-NP/PTX) were performed on the 3D glioma spheroids, the U87MG glioma cells and the intracranial glioma mice model, respectively. Compared with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)-NP/PTX showed the strongest penetration and accumulation into 3D glioma spheroids, an obvious microtubule stabilization effect to U87MG glioma cells, a significant homing specificity to malignant glioma in vivo, and an extended median survival time in the intracranial glioma-bearing mice. Furthermore, preliminary in vivo subacute toxicity was also evaluated by measuring the histopathology, blood cell counts and clinical biochemistry parameters, and the results revealed no obvious subacute toxicity to hematological system, major organs or tissues were observed  post successive intravenous injection of c(RGDyK)-NP. Therefore, our results suggested that cyclic RGD-conjugated PEG-PTMC nanoparticle could be a promising vehicle for enhancing the penetration and cxhemotherapy of high-grade malignant gliomas.

 

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[392]

TÍTULO / TITLE:  - Expression of claudins relates to tumour aggressivity, location and recurrence in ependymomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Feb 20.

AUTORES / AUTHORS:  - Nordfors K; Haapasalo J; Sallinen P; Haapasalo H; Soini Y

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Centre for Laboratory Medicine, Pirkanmaa Hospital District, Tampere, Finland, and Department of Pathology, University of Tampere, Tampere, Finland. kristiina.nordfors@gmail.com.

RESUMEN / SUMMARY:  - The aim of our study was to assess the nature and importance of claudin expression in grade I-III ependymomas. The expression of claudins 2-5, 7, 10, TWIST, and ZEB1 were investigated in a series of 61 ependymomas using immunohistochemistry. All the claudins were expressed in ependymomas, except for  CLDN4. CLDN5 positive tumours were associated with higher grade (p = 0.049), whereas CLDN10 was lower in higher grade tumours (p = 0.039). CLDN5 and CLDN3 were overexpressed in ependymomas of cerebral location (p = 0.036, p = 0.007, respectively). CLDN5 positive tumours showed more nuclear atypia, endothelial proliferation, mitosis, and hypercellularity (p = 0.007, p = 0.018, p = 0.041, p  = 0.010, respectively). CLDN5 positivity correlated to higher proliferation (p =  0.015). CLDN7 was more often positive in primary tumours (p = 0.041). Positive ZEB1 expression was associated with CLDN2 negativity (p = 0.031). TWIST-negative  tumours were more often also CLDN5 and 10 negative (p = 0.013, p = 0.017, respectively). CLDN5 was related to more aggressive tumours compared to CLDN2 and 10, which tended to display a better degree of differentiation and a better prognosis. CLDN2 and CLDN5 were expressed commonly in ependymomas, while the parental ependymal cells in the central nervous system were usually negative. Evidently, claudins influence growth and differentiation in ependymomas.

 

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[393]

TÍTULO / TITLE:  - Noninvasive assessment of hypoxia with 3-[18F]-fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO): a PET study in  two experimental models of human glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biol Chem. 2013 Apr 1;394(4):529-39. doi: 10.1515/hsz-2012-0318.

            ●● Enlace al texto completo (gratuito o de pago) 1515/hsz-2012-0318

AUTORES / AUTHORS:  - Corroyer-Dulmont A; Peres EA; Petit E; Durand L; Marteau L; Toutain J; Divoux D; Roussel S; Mackenzie ET; Barre L; Bernaudin M; Valable S

RESUMEN / SUMMARY:  - Abstract Despite multiple advances in cancer therapies, patients with glioblastoma (GBM) still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a  reliable method to map hypoxia in preclinical human models may contribute to the  discovery and translation of future and more targeted therapies. The aim of this  study was to compare the hypoxic status of two commonly used human orthotopic glioma models (U87 and U251) developed in rats and studied by noninvasive hypoxia imaging with 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol-micro-positron emission tomography ([18F]-FMISO-muPET). In parallel, because of the relationships between angiogenesis and hypoxia, we used magnetic resonance imaging (MRI), histology, and immunohistochemistry to characterize the tumoral vasculature. Although all tumors were detectable in T2-weighted MRI and 2-deoxy-2-[18F]fluoro-d-glucose-muPET, only the U251 model exhibited [18F]-FMISO  uptake. Additionally, the U251 tumors were less densely vascularized than U87 tumors. Our study demonstrates the benefits of noninvasive imaging of hypoxia in  preclinical models to define the most reliable one for translation of future therapies to clinic based on the importance of intratumoral oxygen tension for the efficacy of chemotherapy and radiotherapy.

 

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[394]

TÍTULO / TITLE:  - Effects of perfusion on diffusion changes in human brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24042.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24042

AUTORES / AUTHORS:  - Cohen AD; Laviolette PS; Prah M; Connelly J; Malkin MG; Rand SD; Mueller WM; Schmainda KM

INSTITUCIÓN / INSTITUTION:  - Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

RESUMEN / SUMMARY:  - PURPOSE: To characterize the influence of perfusion on the measurement of diffusion changes over time when ADC is computed using standard two-point methods. MATERIALS AND METHODS: Functional diffusion maps (FDMs), which depict changes in diffusion over time, were compared with rCBV changes in patients with  brain tumors. The FDMs were created by coregistering and subtracting ADC maps from two time points and categorizing voxels where ADC significantly increased (iADC), decreased (dADC), or did not change (ncADC). Traditional FDMs (tFDMs) were computed using b = 0,1000 s/mm(2) . Flow-compensated FDMs (fcFDMs) were calculated using b = 500,1000 s/mm(2) . Perfusion’s influence on FDMs was determined by evaluating changes in rCBV in areas where the ADC change significantly differed between the two FDMs. RESULTS: The mean DeltarCBV in voxels that changed from iADC (dADC) on the tFDM to ncADC on the fcFDM was significantly greater (less) than zero. In addition, mean DeltarCBV in iADC (dADC) voxels on the tFDM was significantly higher (lower) than in iADC (dADC) voxels on the fcFDM. CONCLUSION: The ability to accurately identify changes in diffusion on traditional FDMs is confounded in areas where perfusion and diffusion changes are colocalized. Flow-compensated FDMs, which use only non-zero b-values, should therefore be the standard approach. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.

 

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[395]

TÍTULO / TITLE:  - Surgery for high-grade gliomas in the aging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurol Scand. 2013 Feb 21. doi: 10.1111/ane.12105.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ane.12105

AUTORES / AUTHORS:  - Konglund A; Helseth R; Lund-Johansen M; Helseth E; Meling TR

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.

RESUMEN / SUMMARY:  - OBJECTIVE: High-grade glioma (HGG) is the commonest primary brain tumor in adults. We prospectively assessed outcome following surgery and adjuvant treatment for HGG in older patients. MATERIALS AND METHODS: Patients >/= 60 years undergoing craniotomies for gliomas WHO grade 3 and 4 at Oslo and Haukeland University Hospitals 2008-2009 were included (n = 80). Outcome was assessed at six months, and overall mortality evaluated at two years. RESULTS: Forty-two males and 38 females of median age 68.5 (60-83) years were included, 35% attended a follow-up appointment at six months. Surgical mortality was 1.3%. Surgical morbidity included neurological sequela (10%), post-operative hematomas (3.8%) and hydrocephalus (1.3%). Median overall survival was 8.4 months and significantly increased by adjuvant radiochemotherapy. In univariate survival analyses, age >/= 80 years, subtotal resection, American Society of Anesthesiology (ASA) scores 3-4, Karnofsky performance scale (KPS) < 70, and mini-mental state examination (MMSE) score < 25 significantly reduced survival. CONCLUSIONS: Surgical treatment of HGG carries low mortality and acceptable morbidity in patients aged >/= 60 years. There is improved survival following bimodal adjuvant treatment. Maximum tumor resection should be attempted. Treatment might be less beneficial in patients aged >/= 80 years and in those with poor pre-operative function.

 

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[396]

TÍTULO / TITLE:  - Development and characterization of murine models of medulloblastoma extraneural  growth in bone.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Metastasis. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10585-013-9577-6

AUTORES / AUTHORS:  - Grunda JM; Wang D; Clines GA

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Alabama at Birmingham, Boshell Diabetes Building RM 730B, 1808 7th  Avenue South, Birmingham, AL, 35294-0012, USA.

RESUMEN / SUMMARY:  - Medulloblastoma is a malignant pediatric brain neoplasm with an unusual predilection for metastasis to the skeleton. The objective of this study was to generate and characterize murine models of medulloblastoma extraneural growth in  bone as ‘discovery tools’ for the identification of unrecognized signal transduction pathways and factors driving metastatic bone disease. To this end, the human Daoy and D283 medulloblastoma cell lines were inoculated into the intratibial medullary space of athymic nude mice. Daoy injected mice developed a  primarily osteolytic radiographic and histological phenotype. In contrast, both areas of osteolytic and osteosclerotic activity were evident in D283 inoculated bones. D283 and Daoy cell conditioned media increased in vitro osteoblast differentiation and is consistent with the enhanced bone turnover characteristic  of bone metastases. Daoy cells also significantly increased bone marrow osteoclast formation, consistent with the robust in vivo osteolytic phenotype. A  survey of secreted factors implicated in bone metastasis and expressed by D283 and Daoy was performed. High expression of the bone-homing factor, CXCR4, was observed in both Daoy and D283 tissues. Consistent with the skeletal phenotypes,  Daoy cells, while secreting the osteoblastic factor ET-1, abundantly produced the osteolytic factors RANKL, PTHrP and TNFalpha. D283 cells produced high levels of  both RANKL and ET-1. These newly described animal models of medulloblastoma bone  metastasis are expected to serve as platforms to aid in the elucidation of novel  bone metastasis signaling cascades and to test therapeutics that target both medulloblastoma metastasis and the primary tumor.

 

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[397]

TÍTULO / TITLE:  - Leptomeningeal carcinomatosis in sinonasal undifferentiated carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Head Neck. 2013 Mar 8. doi: 10.1002/hed.23225.

            ●● Enlace al texto completo (gratuito o de pago) 1002/hed.23225

AUTORES / AUTHORS:  - Liu SV; Wagle N; Zada G; Sun B; Go J; Rashtian A

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Keck University of Southern California School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, California. stephen.liu@usc.edu.

RESUMEN / SUMMARY:  - BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an uncommon neoplasm characterized by local extension and an aggressive course. Treatment often includes a combination of chemotherapy, radiation therapy, and surgery, although  the optimal strategy remains unclear. Here, we present the first reported case of leptomeningeal carcinomatosis from SNUC. METHODS AND RESULTS: A 28-year-old man with rapidly progressive headaches, congestion, and exophthalmos was found to have a nasal mass. Biopsy revealed sinonasal undifferentiated carcinoma. He had a transient response to chemotherapy followed by a sustained response to concurrent chemoradiation. At the completion of radiation, he developed subtle neurologic findings and MRI revealed diffuse, bulky leptomeningeal spread. He was able to receive only a single fraction of external beam radiation to his spinal axis before his disease rapidly progressed, leading to respiratory failure and death.  CONCLUSIONS: Sinonasal undifferentiated carcinoma can be associated with leptomeningeal carcinomatosis, which can lead to a fulminant clinical course. Head Neck, 2012.

 

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[398]

TÍTULO / TITLE:  - Visual and Neurological Outcomes Following Endovascular Stenting for Pseudotumor  Cerebri Associated With Transverse Sinus Stenosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neuroophthalmol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WNO.0b013e31827f18eb

AUTORES / AUTHORS:  - Radvany MG; Solomon D; Nijjar S; Subramanian PS; Miller NR; Rigamonti D; Blitz A; Gailloud P; Moghekar A

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology and Radiological Science (MGR, AB, PG) Neurology (DS, SN, PSS, NRM, AM) Ophthalmology (PSS, NRM), and Neurosurgery (PSS, NRM, DR), Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of Radiology (MGR) Department of Ophthalmology (PSS), Uniformed Services University of the Health Sciences, Bethesda, Maryland.

RESUMEN / SUMMARY:  - BACKGROUND:: Pseudotumor cerebri (PTC) is characterized by raised intracranial pressure (ICP) without an identifiable mass, evidence of hydrocephalus, or abnormal cerebrospinal fluid content. In the past, most cases of PTC appeared to  have no identifiable etiology, and thus, they were classified as “idiopathic intracranial hypertension” (IIH). Recently, however, a subset of patients with presumed IIH has been found to have evidence of cerebral dural sinus stenoses, particularly involving one or both transverse sinuses (TS). The belief that the stenoses are the cause, rather than an effect of the increased ICP, has led investigators to recommend stenting of the stenosed sinus for the treatment of the condition. We describe detailed visual and neurological outcomes after stenting for PTC associated with hemodynamically significant dural sinus stenosis. METHODS:: All patients with PTC had initial neurological, neuro-ophthalmological, and imaging assessments. Regardless of the findings, all  were treated with medical therapy. If medical therapy failed and TS stenosis was  detected on contrast-enhanced magnetic resonance or computed tomographic venography, catheter cerebral angiography with venous manometry was performed. If a mean pressure gradient (MPG) of 4 mm Hg or greater was present, unilateral transverse sinus stenting was performed. RESULTS:: Twelve patients with PTC and TS stenosis associated with an MPG of >4 mm Hg who failed medical therapy were identified. TS stenting significantly decreased the pressure gradient in all cases. Unilateral stenting was sufficient to reduce pressure gradients even when  the stenosis was bilateral. At a mean follow-up of 16 months (range, 9-36 months), tinnitus had improved in all patients, and 10 of 12 patients had improvement in visual function. Seven patients had significant improvement in headaches. CONCLUSION:: In this small series of patients with PTC associated with TS stenosis, endovascular stent placement was generally effective in treating visual dysfunction and tinnitus, although not headaches. The optimum gradient and vascular characteristics amenable for selection of patients for stenting needs further research.

 

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[399]

TÍTULO / TITLE:  - ID1 affects the efficacy of radiotherapy in glioblastoma through inhibition of DNA repair pathways.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):325. doi: 10.1007/s12032-012-0325-6. Epub 2013 Feb 3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0325-6

AUTORES / AUTHORS:  - Guo Q; Guo P; Mao Q; Lan J; Lin Y; Jiang J; Qiu Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is characterized by poor therapeutic response and poor overall survival. It is crucial that more effective therapies be developed for the treatment of GBM. Inhibitor of DNA binding protein-1 (ID1) has been shown to maintain the self-renewal capacity of neural stem cells and might be involved  in the therapeutic resistance of GBM. In the present study, we explored survival  data from the The Cancer Genome Atalas database that were based on ID1 expression for patients diagnosed with primary GBMs. Interestingly, patients with high ID1 expression had better survival than patients with low ID1 expression, and a strong correlation was found between radiotherapy efficacy, ID1 expression, and overall survival. We further investigated the relationship between ID1 expression and the radiosensitivity of glioblastoma using glioblastoma cell lines. The clonogenic formation assay showed that U87 ID1-shRNA cells were much less sensitive to radiation. Moreover, both the results of the gammaH2AX foci staining assay and the comet assay further revealed that ID1 negatively regulates DNA repair processes by downregulating the expression of genes such as DNA ligase IV  (LIG4) and ataxia-telangiectasia-mutated. Additionally, ID1 induces G2/M arrest in U87 cells. Taken together, these results suggest that ID1 may be a new prognostic marker for GBM and have important implications for the therapeutic strategies used to treat GBM patients.

 

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[400]

TÍTULO / TITLE:  - Preformed titanium cranioplasty after resection of skull base meningiomas - A technical note.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Craniomaxillofac Surg. 2013 Feb 20. pii: S1010-5182(13)00046-2. doi: 10.1016/j.jcms.2013.01.030.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcms.2013.01.030

AUTORES / AUTHORS:  - Schebesch KM; Hohne J; Gassner HG; Brawanski A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany. Electronic address: Karl-michael.schebesch@ukr.de.

RESUMEN / SUMMARY:  - INTRODUCTION: Meningiomas of the fronto-basal skull are difficult to manage as the treatment usually includes extensive resection of the lesion, consecutive reconstruction of the meninges and of the skull. Especially after removal of spheno-orbital and sphenoid-wing meningiomas, the cosmetic result is of utmost importance. In this technical note, we present our institutional approach in the  treatment of skull base meningiomas, focussing on the reconstruction of the neurocranium with individually preformed titanium cranioplasty (CRANIOTOP(®), CL Instruments, Germany). CASE REPORT: Two female patients (40 years, 64 years) are presented. Both patients presented with skull base lesions suggestive of meningiomas. The preoperative thin-sliced CT scan was processed to generate a 3D-model of the skull. On it, the resection was mapped and following a simulated  resection, the cranioplasty was manufactured. Intra-operatively, the titanium plate served as a template for the skull resection and was implanted after microsurgical tumour removal, consecutively. The cosmetic result was excellent. Immediate postoperative CT scan revealed accurate fitting and complete tumour removal. Control Magnetic Resonance Imaging (MRI) within 12 weeks was possible without any artifacts. DISCUSSION: The comprehensive approach described indicates only one surgical procedure for tumour removal and for reconstruction of the skull. The titanium plate served as an exact template for complete resection of the osseous parts of the tumour. Cosmetic outcome was excellent and control MRI was possible post operatively. CONCLUSION: CRANIOTOP(®) cranioplasty is a safe  and practical tool for reconstruction of the skull after meningioma surgery.

 

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[401]

TÍTULO / TITLE:  - Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1112-8

AUTORES / AUTHORS:  - Suswam EA; Shacka JJ; Walker K; Lu L; Li X; Si Y; Zhang X; Zheng L; Nabors LB; Cao H; King PH

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, University of Alabama at Birmingham, 1720 2nd Avenue South, WTI410C, Birmingham, AL, 35294-3300, USA, easuswam@uab.edu.

RESUMEN / SUMMARY:  - Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3’ untranslated region is one mechanism  for upregulating these and other growth factors. In glioma cells, we have shown that the post-transcriptional machinery is optimized for growth factor upregulation secondary to overexpression of the mRNA stabilizer, HuR. The negative regulator, tristetraprolin (TTP), on the other hand, may be suppressed because of extensive phosphorylation. Here we test that possibility by analyzing  the phenotypic effects of a mutated form of TTP (mt-TTP) in which 8 phosphoserine residues were converted to alanines. We observed a significantly enhanced negative effect on growth factor expression in glioma cells at the post-transcriptional and transcriptional levels. The protein became stabilized and displayed significantly increased antiproliferative effects compared to wild-type TTP. Macroautophagy was induced with both forms of TTP, but inhibition  of autophagy did not affect cell viability. We conclude that glioma cells suppress TTP function through phosphorylation of critical serine residues which in turn contributes to growth factor upregulation and tumor progression.

 

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[402]

TÍTULO / TITLE:  - Extracranial meningioma in the maxillary region.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Craniofac Surg. 2013 Mar;24(2):e142-4. doi: 10.1097/SCS.0b013e31827c7e9f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SCS.0b013e31827c7e9f

AUTORES / AUTHORS:  - Pinting L; Xiaofeng H; Zhiyong W; Wei H

INSTITUCIÓN / INSTITUTION:  - From the *Department of Oral and Maxillofacial Surgery, daggerCentral Laboratory  of Stomatology, and double daggerDepartment of Pathology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, China.

RESUMEN / SUMMARY:  - Extracranial meningioma consists of 1%-2% of all meningiomas. Because it is usually encountered by non-neurosurgeons and its main diagnosis is based on histological examination, it is really hard for “euro-laymen” to distinguish it from other common diseases. Herein we report a 59-year-old male patient with a large, painless mass on his maxilla, finally diagnosed as extracranial meningioma. This case is not frequently seen even in maxillofacial extracranial meningioma.

 

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[403]

TÍTULO / TITLE:  - Solitary dural plasmacytoma mimicking meningioma and invading calvarium.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Craniofac Surg. 2013 Mar;24(2):e175-7. doi: 10.1097/SCS.0b013e31827c85ba.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SCS.0b013e31827c85ba

AUTORES / AUTHORS:  - Hasturk AE; Basmaci M; Erten F; Cesur N; Yilmaz ER; Kertmen H

INSTITUCIÓN / INSTITUTION:  - From the *Department of Neurosurgery, Oncology Training and Research Hospital, Ankara, daggerDepartment of Pathology, Faculty of Medicine, Gazi University, Ankara, and double daggerDepartment of Neurosurgery, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey.

RESUMEN / SUMMARY:  - Solitary plasmacytoma comprises 2%-10% of all plasma cell diseases. Cranial localization of plasmacytoma is quite rare. They may emerge after years without systemic involvement and symptoms. They may be confused with other tumors as they are not remembered primarily in radiological diagnosis. The definite diagnosis is made upon histopathological examination. Surgical resection followed by radiotherapy is the first choice of therapy. Chemotherapy may be administered for secretory tumors. In this paper, we discussed a patient who underwent surgery with the prediagnosis of meningioma and histopathologically diagnosed with plasmacytoma.

 

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[404]

TÍTULO / TITLE:  - Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery-a feasibility study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):693-9. doi: 10.1007/s00701-013-1643-y. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1643-y

AUTORES / AUTHORS:  - Schebesch KM; Proescholdt M; Hohne J; Hohenberger C; Hansen E; Riemenschneider MJ; Ullrich W; Doenitz C; Schlaier J; Lange M; Brawanski A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital of Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany, karl-michael.schebesch@klinik.uni-regensburg.de.

RESUMEN / SUMMARY:  - OBJECTIVE: In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier  and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW  560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors. PATIENTS AND METHOD: A total of 200 mg of FL (3-4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy (‘helpful,’ ‘not helpful’) of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n = 5) for each surgical procedure. RESULTS: Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5  patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as ‘helpful’ in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects. CONCLUSION: The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.

 

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[405]

TÍTULO / TITLE:  - Central nervous system lymphoma initially diagnosed as tumefactive multiple sclerosis after brain biopsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Intern Med. 2013;52(4):483-8. Epub 2013 Feb 15.

AUTORES / AUTHORS:  - Ohe Y; Hayashi T; Mishima K; Nishikawa R; Sasaki A; Matsuda H; Uchino A; Tanahashi N

INSTITUCIÓN / INSTITUTION:  - Department of Neurology and Cerebrovascular Medicine, Saitama Medical University  International Medical Center, Japan. yooe@saitama-med.ac.jp

RESUMEN / SUMMARY:  - A 72-year-old man was admitted with left homonymous hemianopsia and hemiparesis.  Magnetic resonance imaging revealed a heterogeneously enhanced lesion in the right parietal lobe. A brain biopsy showed acute demyelination without malignancy, which led to a diagnosis of tumefactive multiple sclerosis (MS). The  patient received corticosteroid therapy and experienced clinical and radiological improvement. Six months later, new lesions appeared, and a second biopsy revealed proliferation of dysplastic lymphocytes. This led to a revised diagnosis of primary central nervous system lymphoma (PCNSL). Because PCNSL mimics MS both clinically and radiologically, PCNSL is difficult to diagnose. Performing repeated brain biopsies may therefore be required when PCNSL is strongly suspected.

 

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[406]

TÍTULO / TITLE:  - Maxillary swing approach for extended infratemporal fossa tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Laryngoscope. 2013 Mar 27. doi: 10.1002/lary.23947.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23947

AUTORES / AUTHORS:  - Otremba M; Adam S; Omay SB; Lowlicht R; Bulsara KR; Judson B

INSTITUCIÓN / INSTITUTION:  - Section of Otolaryngology, Head and Neck Surgery, Department of Surgery, New Haven, Connecticut, U.S.A.

 

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[407]

TÍTULO / TITLE:  - Lipomas of the cerebellopontine angle and internal auditory canal: Primum Non Nocere.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Laryngoscope. 2013 Feb 9. doi: 10.1002/lary.23882.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23882

AUTORES / AUTHORS:  - White JR; Carlson ML; Van Gompel JJ; Neff BA; Driscoll CL; Lane JI; Link MJ

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, 200 First Street S.W., Rochester, Minnesota, U.S.A.

RESUMEN / SUMMARY:  - OBJECTIVES/HYPOTHESIS: To describe the presentation and clinical course of cerebellopontine angle (CPA) and internal auditory canal (IAC) lipomas. STUDY DESIGN: Retrospective cohort study at a tertiary academic referral center. METHODS: All patients presenting with a CPA or IAC mass radiographically consistent with a lipoma on high-resolution magnetic resonance imaging (MRI) were identified. Data including presenting symptomatology, tumor characteristics, management strategy, and patient course were collected. RESULTS: Between 1996 and 2012, 15 patients were diagnosed with a CPA or IAC lipoma at the authors’ institution and were included in the analysis. The mean duration of radiological  and clinical follow-up was 3.4 years and 5.1 years, respectively. Eight lesions were confined to the IAC, while seven involved the CPA. The median tumor size at  diagnosis was 7.2 mm; one patient demonstrated tumor growth on serial MRI while the remaining subjects did not have radiological progression. The most common presenting symptoms were sensorineural hearing loss (40%) and tinnitus (33%); five patients were diagnosed after incidental discovery on MRI. Fourteen patients were managed with observation, while one subject underwent subtotal resection. None of the observed patients reported worsening symptoms at last follow-up. CONCLUSIONS: While rare, lipomas should be included in the differential diagnosis of CPA and IAC lesions. Owing to a generally benign clinical course and high morbidity associated with resection, microsurgery should only be considered in cases of definite tumor enlargement with intractable symptoms from mass effect. Careful radiological evaluation is critical for establishing an accurate diagnosis in order to prevent unnecessary morbidity associated with resection. LEVEL OF EVIDENCE: 2b.

 

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[408]

TÍTULO / TITLE:  - Oral-facial-digital syndrome type 1 with hypothalamic hamartoma and dandy-walker  malformation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Neurol. 2013 Apr;48(4):329-32. doi: 10.1016/j.pediatrneurol.2012.12.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pediatrneurol.2012.12.016

AUTORES / AUTHORS:  - Azukizawa T; Yamamoto M; Narumiya S; Takano T

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Nagahama Red Cross Hospital, Nagahama, Japan. Electronic address: takayuki.azukizawa@gmail.com.

RESUMEN / SUMMARY:  - We report a 1-year-old girl with oral-facial-digital syndrome type 1 with multiple malformations of the oral cavity, face, digits, and central nervous system, including agenesis of the corpus callosum, the presence of intracerebral  cysts, and agenesis of the cerebellar vermis, which is associated with the subarachnoid space separating the medial sides of the cerebellar hemispheres. This child also had a hypothalamic hamartoma and a Dandy-Walker malformation, which have not been reported previously. The clinical features, including cerebral malformations, in several types of oral-facial-digital syndrome, overlap with each other. Further accumulation of new case reports and identification of new genetic mutations in oral-facial-digital syndrome may provide novel and important insights into the genetic mechanisms of this syndrome.

 

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[409]

TÍTULO / TITLE:  - The “onco-functional balance” in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1653-9

AUTORES / AUTHORS:  - Duffau H; Mandonnet E

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Hopital Gui de Chauliac, Montpellier University Medical Center, 80 Av Augustin Fliche, 34295, Montpellier, France, h-duffau@chu-montpellier.fr.

RESUMEN / SUMMARY:  - Diffuse low-grade glioma (DLGG) is a growing pre-cancerous tumor, often diagnosed in patients with no or only mild deficit. Maximal and early surgical resection is currently the first therapeutic option, in order to delay the malignant transformation and thus increase the overall survival. Preserving the quality of  life (QoL) is nonetheless another priority. Here, our purpose is to weight the value of the extent of resection versus the neurological worsening that could be  voluntarily generated by a radical resection; that is, to study the “onco-functional balance” at the individual level. To this end, we will examine DLGG involving the supplementary motor area and DLGG involving visual pathways. We will consider the benefit-risk ratio of different strategies of resection, according to the brain structures actually invaded and their plastic potential. The aim is to increase both the quantity of life and the time with a normal QoL,  on the basis of strong interactions between the tumor course, brain reorganization and multistage surgical approach adapted to each patient over time. To this end, beyond the conceptual and technical issues, the most important point remains the honest and unique relationship between the surgical oncologist  and the patient, based on clear and complete information about the behavior of DLGG versus the expected medical and social consequences of a resection over years. In other words, in the era of “evidence-based medicine”, it is crucial to  not forget “individual-based medicine” by offering tailored resections adapted to each patient.

 

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[410]

TÍTULO / TITLE:  - TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Sci. 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10072-013-1326-8

AUTORES / AUTHORS:  - Ning S; Liang N; Liu B; Chen X; Pang Q; Xin T

INSTITUCIÓN / INSTITUTION:  - School of Medicine, Shandong University, Jinan, People’s Republic of China.

RESUMEN / SUMMARY:  - Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which  is associated with tumor development and progression in a variety of epithelial carcinomas, while its expression and role in gliomas have not been considered. The aim of the study was to investigate TROP2 expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis. Immuohistochemistry was used to determine TROP2 and Ki-67 expression and microvessel density (MVD) in tumor specimens and normal brain tissues from 69 glioma patients and the relationship between TROP2 and Ki-67 and MVD was investigated. Immunohistochemistry results showed that the TROP2 expression was found in 59 (85.5 %) of the 69 tumor specimens, but no expression in normal brain tissues. Furthermore, TROP2 expression is significantly higher in WHO grade III (P = 0.025) and WHO grade IV  (P = 0.011) gliomas than in WHO grade II gliomas. TROP2 expression correlates with Ki-67 (r = 0.676, P = 0.012) and MVD (r = 0.365, P = 0.035), but not with gender or age in human gliomas. These results suggested that the TROP2 correlated with malignancy, proliferation and angiogenesis in human gliomas. This is the first study describing TROP2 expression in gliomas and its proliferation and angiogenesis-related characteristic may serve as a potential therapeutic target for glioma treatment.

 

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[411]

TÍTULO / TITLE:  - Thickened area of external granular layer and Ki-67 positive focus are early events of medulloblastoma in Ptch1(+/-) mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Exp Toxicol Pathol. 2013 Jan 28. pii: S0940-2993(12)00149-2. doi: 10.1016/j.etp.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.etp.2012.12.005

AUTORES / AUTHORS:  - Matsuo S; Takahashi M; Inoue K; Tamura K; Irie K; Kodama Y; Nishikawa A; Yoshida M

INSTITUCIÓN / INSTITUTION:  - Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi,  Gifu 501-1193, Japan.

RESUMEN / SUMMARY:  - Patched1 (Ptch1) encodes a receptor for Sonic hedgehog (Shh) and is major gene related to human medulloblastoma (MB) in the Shh subgroup. MB is thought to arise from residual granule cell precursors (GCPs) located in the external granular layer (EGL) of the developing cerebellum. As the detailed preneoplastic changes of MB remain obscure, we immunohistochemically clarified the derived cell, early  events of MBs, and the cerebellar developmental processes of Ptch1(+/-) (Ptch1) mice, an animal model of human MB of the Shh subgroup. In Ptch1 mice, the earliest proliferative lesions were detected at PND10 as focal thickened areas of outer layer of the EGL. This area was composed of GCP-like cells with atypia and  nuclei disarrangement. In the latter cerebellar developmental period, GCP-like cell foci were detected at high incidence in the outermost area of the cerebellum. Their localization and morphological similarities indicated that the  foci were derived from GCPs in the EGL. There were two types of the foci. A Ki-67-positive focus was found in Ptch1 mice only. This type resembled the GCPs in the outer layer of EGL characterized by having proliferating activity and a lack of neuronal differentiation. Another type of focus, Ki-67-negative, was observed in both genotypes and exhibited many of the same features of mature internal granule cells, suggesting that the focus had no preneoplastic potential. Due to morphological, immunohistochemical characteristics, our results indicate that the focal thickened area of EGL and Ki-67-positive foci are preneoplastic lesions of MB.

 

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[412]

TÍTULO / TITLE:  - Unexpected Finding of Cerebral Meningioma on 11C-PiB PET.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Apr;38(4):292-3. doi: 10.1097/RLU.0b013e3182817c8f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182817c8f

AUTORES / AUTHORS:  - Yamamoto Y; Maeda Y; Kawai N; Kudomi N; Nishiyama Y

INSTITUCIÓN / INSTITUTION:  - From the *Departments of Radiology, daggerNeurosurgery, and double daggerMedical  Physics, Faculty of Medicine, Kagawa University, Kagawa, Japan.

RESUMEN / SUMMARY:  - A 69-year-old man with no history of neurologic or psychiatric disorders underwent C-PiB PET as a healthy volunteer for amyloid imaging study. C-PiB PET images demonstrated an unexpected increased PiB binding in the left frontal region. MR images demonstrated an extra-axial left frontal mass lesion with mild  enhancement, highly suggestive of meningioma. There is a limited amount of published information on the detection of meningioma with C-PiB PET.

 

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[413]

TÍTULO / TITLE:  - 18F-Fluoride PET/CT allows detection of hyperostosis and osseous involvement in meningioma: initial experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar;38(3):e125-31. doi: 10.1097/RLU.0b013e318279fd79.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279fd79

AUTORES / AUTHORS:  - Tateishi U; Tateishi K; Shizukuishi K; Shishikura A; Murata H; Inoue T; Kawahara N

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. utateish@yokohama-cu.ac.jp

RESUMEN / SUMMARY:  - PURPOSE: The present study was conducted to assess the diagnostic performance of  (18)F-fluoride PET/CT in evaluating hyperostosis and osseous involvement in patients with meningioma. PATIENTS AND METHODS: Thirty-four patients with meningioma (mean age, 61 years) underwent (18)F-fluoride PET/CT before surgery. In 24 patients (71%), (18)F-FDG PET/CT was also given before surgery, and the results were compared. The images were reviewed by 2 board-certified nuclear medicine specialists who were unaware of any clinical information and a consensus was reached. Uptake patterns and measurements of tracers were compared with pathological findings from resected specimens, with hyperostosis and osseous involvement as the reference standard. RESULTS: There were 27 grade I tumors (79%) and 7 grade II tumors (21%). The primary tumor focus was identified in each patient using both (18)‘F-fluoride PET/CT and (18)F-FDG PET/CT, but there were no significant correlations in the degree of uptake between the 2 tracers. The SUV(max), SUV(max) corrected for lean body mass (SUL(max)), and tumor metabolic volume (TMV) for (18)F-fluoride and (18)F-FDG were greater in grade II tumors than in grade I tumors. Hyperostosis and osseous involvement was identified in 12 tumors (38%). The SUV(max), SUL(max), and TMV of tumors visualized with (18)F-fluoride PET/CT were greater in tumors with hyperostosis and osseous involvement than in those without (P = 0.005, P = 0.003, and P = 0.006, respectively). In contrast, the SUV(max), SUL(max), and TMV of tumors visualized  with (18)F-FDG PET/CT were similar regardless of hyperostosis or osseous involvement. CONCLUSIONS: (18)F-fluoride PET/CT may improve detection of hyperostosis and osseous involvement in patients with meningioma.

 

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[414]

TÍTULO / TITLE:  - Pediatric Pseudotumor Cerebri Associated With Low Serum Levels of Vitamin A.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Child Neurol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0883073812474344

AUTORES / AUTHORS:  - Dotan G; Goldstein M; Stolovitch C; Kesler A

INSTITUCIÓN / INSTITUTION:  - 1Department of Ophthalmology, Sourasky Tel Aviv Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

RESUMEN / SUMMARY:  - The aim of this study was to describe the association between pediatric pseudotumor cerebri and low serum vitamin A levels. We retrospectively reviewed the charts of 6 children (5 boys, 1 girl; mean age 8 years) with increased intracranial pressure and low serum vitamin A levels (mean 16.0 +/- 8.8 microg/dL). The etiology of the vitamin A deficiency was a restricted diet (2 children), intestinal malabsorption caused by celiac disease (2 children), and undetermined cause (2 children). Only 1 child had ocular signs of xerosis. Poor visual acuity at presentation and lower serum vitamin A levels were associated with a poor visual outcome and development of optic atrophy. In conclusion, pseudotumor cerebri in children can be associated with vitamin A deficiency even  when other manifestations of xerophthalmia do not exist. Early recognition of this condition and appropriate therapy can prevent blindness.

 

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[415]

TÍTULO / TITLE:  - PCV for anaplastic oligodendrogliomas: back to the future or a step backwards? :  A point/counterpoint discussion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1100-z

AUTORES / AUTHORS:  - Villano JL; Wen PY; Lee EQ; Nayak L; Reardon DA; Rosenfeld MR

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine and Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

 

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[416]

TÍTULO / TITLE:  - Association of craniopharyngioma and pituitary adenoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrine. 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9892-3

AUTORES / AUTHORS:  - Guaraldi F; Prencipe N; di Giacomo V; Scanarini M; Gasco V; Gardiman MP; Berton AM; Ghigo E; Grottoli S

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, Citta della Salute e della Scienza Hospital, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy, federica.guaraldi@unito.it.

RESUMEN / SUMMARY:  - Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with  craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical,  laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion  affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting  with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

 

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[417]

TÍTULO / TITLE:  - Interferon regulatory factor 3 alters glioma inflammatory and invasive properties.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1109-3

AUTORES / AUTHORS:  - Tarassishin L; Lee SC

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA, leonid.tarassishin@einstein.yu.edu.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common, highly malignant primary tumor  of the brain with poor prognosis. Even with the improved therapy regimen including temozolomide, the average survival rate is less than 2 years. Additional approaches to therapy targeting multiple aspects of glioma progression are in need. In the present work, we have tested the possibility that upregulation of the transcription factor interferon regulatory factor 3 (IRF3) can inhibit glioma invasiveness, proliferation and production of pro-inflammatory and pro-angiogenic factors in cultures of malignant glioma cell lines (U271, U87  and SNB-19). IRF3 is an essential transcription factor involved in TLR3/4-mediated signaling and generation of type I interferons. Although IRF3 has been suggested as a potential tumor suppressor gene, its role in glioma remains uninvestigated. In this study, we find that human glioma immune activation is potently elicited by a cytokine combination, IL-1/IFNgamma (or poly IC), but not  by bacterial lipopolysaccharide (LPS), similar to primary human astrocytes. GBM biopsy specimens show little detectable IRF3 immunoreactivity, and in vitro adenovirus-mediated IRF3 gene transfer in glioma cells modulates IL-1/IFNgamma-induced cytokine and chemokine genes, resulting in upregulation of  IFNbeta and IP-10 (IRF3-stimulated genes) and downregulation of proinflammatory and angiogenic genes including IL-8, TNFalpha and VEGF (IRF3-represssed genes). Cytokines (IL-1beta and TNFalpha) also induce the expression of miR-155 and miR-155*, the microRNAs crucial in immunity and inflammation-induced oncogenesis  and this is dose-dependently suppressed by IRF3. Importantly, IRF3 also inhibits  glioma proliferation, migration and invasion. Together, these data suggest that IRF3 can suppress glioma progression. Agents that promote IRF3 activation and expression (such as IRF3 gene transfer) could be explored as potential future therapy.

 

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[418]

TÍTULO / TITLE:  - All-trans retinoic acid inhibits craniopharyngioma cell growth: study on an explant cell model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1080-z

AUTORES / AUTHORS:  - Li Q; You C; Zhou L; Sima X; Liu Z; Liu H; Xu J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, West China Hospital of Sichuan University, No. 37 Guoxue Road, Chengdu, 610041, People’s Republic of China.

RESUMEN / SUMMARY:  - The ratio between FABP5 and CRABPII determines cellular response to physiological level of retinoic acid; tumor cells undergo proliferation with high level of FABP5 and apoptosis with high level of CRABPII. We intended to study FABP5 and CRABPII expression in craniopharyngiomas, to establish craniopharyngioma cell model using explants method, and to study the effect of pharmacological dose of retinoic acid on craniopharyngioma cells. Expression of FABP5 and CRABPII in craniopharyngioma tissue from 20 patients was studied using immunohistochemistry. Primary craniopharyngioma cell cultures were established using tissue explants method. Craniopharyngioma cells were treated using various concentrations of all-trans retinoic acid, and cell growth curve, apoptosis, expression of FABP5, CRABPII and NF-kappaB were assayed in different groups. FABP5/CRABPII ratio was significantly higher in adamatinomatous group than that in papillary group. Cell  cultures were established in 19 cases (95 %). Pharmacological level retinoic acid inhibited cell growth and induced cellular apoptosis in dose dependent manner, and apoptosis rate cells treated with 30 muM retinoic acid for 24 h was 43 %. Also, retinoic acid increased CRABPII, and decreased FABP5 and NF-kappaB expression in craniopharyngioma cells. High FABP5/CRABPII ratio is observed in adamatinomatous craniopharyngioma. Retinoic acid at pharmacological level induced craniopharyngioma cell apoptosis via increasing FABP5/CRABPII ratio and inhibiting NF-kappaB signaling pathway. Our study demonstrated that all-trans retinoic acid might be a candidate for craniopharyngioma adjuvant chemotherapy in future.

 

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[419]

TÍTULO / TITLE:  - Geranylgeranyltransferase I regulates HIF-1alpha promoting glioblastoma cell migration and invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurooncol. 2013 Mar 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1081-y

AUTORES / AUTHORS:  - Zhou X; Liu Z; Shi Q; Jiao J; Bian W; Song X; Mo J; Sang B; Xu Y; Qian J; Chao Y; Yu R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China, xpzhou@xzmc.edu.cn.

RESUMEN / SUMMARY:  - Glioblastoma multiforme is a highly migratory and invasive brain tumor in which hypoxia inducible factor-1alpha (HIF-1alpha) plays important roles. However, the  underlying mechanisms regulating the action of HIF-1alpha in glioma cell migration and invasion ability remain unclear. We reported here that HIF-1alpha was regulated by geranylgeranyltransferase I (GGTI), a protein prenylation transferase, and then promoted glioma cell migration and invasion. The migratory  and invasive ability of glioma cells were enhanced by hypoxia treatment but inhibited by down-regulation of HIF-1alpha. GGTI activity inhibition or GGTI specific beta subunit (GGTI beta) knocking-down decreased HIF-1alpha protein level. In addition, down-regulation of GGTI beta inhibited migration and invasion of glioma cells under hypoxia, while GGTI beta over-expression promoted it. Furthermore, the effect of GGTI beta over-expression on cell migration and invasion was abolished by HIF-1alpha down-regulation. In summary, our study showed, for the first time, that HIF-1alpha was regulated by protein prenylation  transferase GGTI and mediated the effect of GGTI on glioma cell migration and invasion.

 

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[420]

TÍTULO / TITLE:  - A Rathke’s cleft cyst located entirely in the anterior pituitary lobe.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1666-4

AUTORES / AUTHORS:  - Kinoshita Y; Tominaga A; Usui S; Kurisu K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, y-kinoshita@hiroshima-u.ac.jp.

 

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[421]

TÍTULO / TITLE:  - Serum Prolactin Concentration at Presentation of Non-Functioning Pituitary Macroadenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Endocrinol Invest. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 3275/8815

AUTORES / AUTHORS:  - Behan LA; O’Sullivan EP; Glynn N; Woods C; Crowley RK; Tun TK; Smith D; Thompson CJ; Agha A

INSTITUCIÓN / INSTITUTION:  - Division of Neuro-endocrinology, Beaumont Hospital and the RCSI Medical School, Dublin, Ireland.

RESUMEN / SUMMARY:  - Objective: Serum prolactin levels at presentation may be useful in distinguishing between disconnection hyperprolactinaemia in non secretory pituitary adenomas and prolactinomas in order to guide appropriate therapy, however there is a debate regarding the discriminatory prolactin thresholds. We aimed to examine prolactin  concentrations at presentation in a cohort of histologically proven non-functioning pituitary adenomas (NFPAs). Design and Methods: Retrospective case note analysis was performed. Clinical, biochemical, histopathological and radiological data were recorded and analysed. Complete data was available for 250 subjects with NFPAs Results: 44.8% of patients were hyperprolactinaemic at presentation, 55.3% of whom were female. Of those with hyperprolactinaemia, 73.2% had prolactin <1000miU/l on presentation, 24.1% had prolactin between 1000-1999miU/l. Only 2.7% (n=3 females, 1.2% whole cohort) had prolactin >2000miU/l (94.3ng/ml), 2 of whom were pregnant. No male subject and no subjects  with an intrasellar macroadenoma had serum prolactin >1000miU/l (47.2ng/ml). Overall, serum prolactin was not higher among 43 subjects taking medications known to raise prolactin. Conclusions: Our data support recent evidence that the  serum prolactin concentration is rarely >1000miU/l in males, or >2000miU/l in females, with non-functioning macroadenomas and that once other contributing factors to the hyperprolactinaemia have been excluded, a trial of dopamine agonist therapy for such lesions is indicated.

 

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[422]

TÍTULO / TITLE:  - Management of an incidentally discovered hypoglossal paraganglioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Am Surg. 2013 Mar;79(3):114-5.

AUTORES / AUTHORS:  - Harmon L; Viney S; Frazee R; Van Husen R

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Texas Tech University Health Sciences, Center-Permian Basin, Odessa, Texas, USA.

 

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[423]

TÍTULO / TITLE:  - Hypertrophic olivary degeneration after surgical resection of brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Radiol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1258/ar.2012.120537

AUTORES / AUTHORS:  - Shinohara Y; Kinoshita T; Kinoshita F; Kaminou T; Watanabe T; Ogawa T

INSTITUCIÓN / INSTITUTION:  - Division of Radiology, Department of Pathophysiological Therapeutic Science, Faculty of Medicine, Tottori University, Yonago.

RESUMEN / SUMMARY:  - BackgroundHypertrophic olivary degeneration (HOD) can be seen as high signal intensity with enlargement of the inferior olivary nucleus (ION) on T2-weighted magnetic resonance (MR) images 4-6 months after injury of the Guillain-Mollaret triangle. To the best of our knowledge, there has been no systematic evaluation with regard to the relationship between neurosurgical intervention affecting this pathway and the appearance of HOD.PurposeTo evaluate MR findings of HOD after surgical resection of brain tumors with the temporal evolution in focus.Material  and MethodsMR images of seven patients that showed signal changes in the ION after surgical resection of brain tumors in the posterior fossa were retrospectively reviewed. T1-weighted imaging with and without gadolinium (Gd) contrast enhancement and T2-weighted imaging were performed in all patients before and after surgery.ResultsBefore surgery, no patient had a signal change in the ION. T2-high signal intensity of the ION initially appeared 5 days to 2.5 months after surgery. Five patients showed enlargement of the ION with T2-high signal intensity 11 days to 3.5 months after surgery: three patients showed the enlargement of the ION subsequent to the T2-signal change on serial follow-up MR  images. On Gd-enhanced T1-weighted images, there was no enhancement at the ION in any patient. Each signal change of the ION was consistent with HOD, according to  the relationship between the resection site of the tumor and the Guillain-Mollaret triangle on follow-up MRI.ConclusionHOD can be caused after neurosurgical intervention of brain tumors involving the Guillain-Mollaret triangle. It is important for radiologists to distinguish HOD from tumor recurrence.

 

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[424]

TÍTULO / TITLE:  - Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Sci. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10072-013-1358-0

AUTORES / AUTHORS:  - Gaviani P; Corsini E; Salmaggi A; Lamperti E; Botturi A; Erbetta A; Milanesi I; Legnani F; Pollo B; Silvani A

INSTITUCIÓN / INSTITUTION:  - Neuro-Oncology Department, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, 20133, Milan, Italy, paolagaviani@hotmail.com.

RESUMEN / SUMMARY:  - Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte®. In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte® regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte® (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte® cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte®, and  the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).

 

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[425]

TÍTULO / TITLE:  - Cortical ependymoma with unusual histologic features.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300593

AUTORES / AUTHORS:  - Hiniker A; Lee HS; Chang S; Berger M; Perry A

RESUMEN / SUMMARY:  - Cortical ependymomas are rare gliomas with classic ependymal features but are unusual in primarily involving the cerebral cortex. Here, we present a 19-yearold woman with new-onset seizures who was found to have a large, cortically based non-enhancing lesion with scalloping of the overlying calvarium. Abundant ependymal features were present including classic ependymal cytology, diffuse GFAP and dot-like EMA positivity, and well developed cilia, microvilli, and intercellular junctions on ultrastructural analysis. Additionally, the tumor showed areas of infiltrative growth similar to angiocentric glioma as well as striking mucin-filled microcystic spaces somewhat reminiscent of myxopapillary ependymoma. Thus far, the patient shows no evidence of recurrence following gross total resection. This case demonstrates detailed morphologic, immunohistochemical, and ultrastructural evidence supporting a relationship between cortical ependymoma and angiocentric glioma and suggesting that cortical  ependymomas can have myxopapillary as well as classic features.

 

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[426]

TÍTULO / TITLE:  - Lessons in the management of post-operative tension pneumocephalus complicating transcranial resection of advanced cutaneous tumours with free flap reconstruction.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Craniomaxillofac Surg. 2013 Feb 25. pii: S1010-5182(13)00058-9. doi: 10.1016/j.jcms.2013.01.042.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcms.2013.01.042

AUTORES / AUTHORS:  - Swan MC; Scholz AF; Pretorius PM; Johnson D; Martinez-Devesa P; Wall SA

INSTITUCIÓN / INSTITUTION:  - Oxford Craniofacial Unit (Head: Mr. Steven A. Wall), West Wing, Oxford University Hospitals NHS Trust, Headington, Oxford OX3 9DU, United Kingdom. Electronic address: marc.swan@nds.ox.ac.uk.

RESUMEN / SUMMARY:  - Tension pneumocephalus is a rare, but potentially life-threatening complication of transcranial surgery. Whilst commonly described in the field of neurosurgery,  little has been published in the context of craniofacial surgery. We describe two cases of post-operative extradural tension pneumocephalus occurring following free myocutaneous latissimus dorsi flap reconstruction of anterior cranial defects following extirpation of advanced recurrent skin carcinomas. These cases  illustrate the variation in clinical presentation of this condition, the importance of prompt recognition, urgent radiological investigation and timely decompression, and potential management strategies for minimising the risk of recurrent symptoms.

 

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[427]

TÍTULO / TITLE:  - Use of Collagen Conduits in Management of Painful Neuromas of the Foot and Ankle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Foot Ankle Int. 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1071100713478927

AUTORES / AUTHORS:  - Gould JS; Naranje SM; McGwin G Jr; Florence M; Cheppalli S

INSTITUCIÓN / INSTITUTION:  - University of Alabama at Birmingham, Birmingham, AL, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Painful neuromas of the foot and ankle frequently pose a treatment dilemma due to persistent pain or recurrence after resection. The purpose of this survey was to evaluate the clinical and functional outcomes in patients in which  collagen nerve conduits were used as an adjunct to the resection of a painful neuroma. Our prior experience with vein conduits for this purpose suggested that  we might have similar success with the use of these devices. MATERIALS AND METHODS: Chart reviews and telephone surveys were performed on patients operated  by the senior surgeon (JSG) at our medical center from June 2006 to June 2011. A  total of 50 patients underwent excision of painful single or multiple neuromas with the end of the resected nerve sutured into the collagen conduit. Each patient preoperatively was asked to describe the amount of pain he or she was experiencing on a scale from 1 to 10, with 10 indicating the most severe pain. In the telephone interview conducted during this study, the same question was asked  of each patient following revision. Patient ages ranged from 16 to 77 years, with a mean of 54 years. In all, 30 right and 20 left sides were operated, and 1 patient had bilateral involvement. Mean follow-up was 36 months (6-55 months). There were a total of 69 nerves that underwent conduit procedures. RESULTS: Of 69 nerve conduit constructs, 30 (43%) were painless at final outcome, 23 (33%) had pain scores of 1 to 4, 6 (9%) had pain scores of 5 to 7, and 10 (15%) had severe  symptoms with pain scores of 8 to 10. Satisfactory outcomes in which patients stated that they were significantly improved with the procedure and now functional occurred in 59/69 (85%). In all, 24 (48%) patients were completely symptom free, 13 (26%) had a pain score of 1 to 4, 6 (12%) had scores of 5 to 7,  and 10 (15%) had severe pain with scores of 8 to 10. Three patients had superficial infections (stitch abscesses): 2 resolved with oral antibiotics and 1 resolved spontaneously. Three patients developed complex regional pain syndrome.  One patient responded to a dorsal column stimulator and 2 responded to sympathetic blocks. No other complications were reported. CONCLUSION: Collagen conduits were safe and generally successful adjuncts to simple excision in the management of painful neuromas of the foot and ankle. LEVEL OF EVIDENCE: Level IV, retrospective case series.

 

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[428]

TÍTULO / TITLE:  - Visualization of angiographical arteriovenous shunting in perisylvian glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):715-9. doi: 10.1007/s00701-013-1650-z. Epub 2013 Feb 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1650-z

AUTORES / AUTHORS:  - Yoshikawa A; Nakada M; Kita D; Watanabe T; Kinoshita M; Miyashita K; Furuta T; Hamada JI; Uchiyama N; Hayashi Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Arteriovenous shunting visualized by angiography is one of the major  features of glioblastomas, and the visualization is dependent on the presence of  extensive shunting. Extensive arteriovenous shunting is associated with the risk  of poorly controlled intraoperative bleeding. When a tumor with extensive arteriovenous shunting is located in close proximity to the eloquent regions of the brain, a meticulous surgical procedure is necessary. In the present study, the site-oriented visualization of angiographical arteriovenous shunting was evaluated from the perspective of surgical treatment, with a particular focus on  the perisylvian region that is in close proximity to motor and language regions (dominant hemisphere), as well as large arteries and veins. METHODS: Twenty-six consecutive patients underwent a resection of glioblastoma between February 2007  and September 2012. All patients were presurgically examined using digital subtraction angiography. The patients were subdivided into the following two groups based on the location of the tumor: 1) perisylvian glioblastoma (18 patients) and 2) non-perisylvian glioblastoma (eight patients). Angiography to detect the arteriovenous shunting was performed. In addition, the number of intratumoral vessels, tumor proliferative activity (MIB-1 labeling index), and volume of intraoperative bleeding were evaluated and compared between the two groups. RESULTS: Angiographical arteriovenous shunting was definitively visualized in 13 of 18 (72 %) perisylvian glioblastomas, in contrast to only one  of eight (13 %) non-perisylvian glioblastomas (p = 0.007). There were no significant differences between the two groups with respect to the number of intratumoral vessels, MIB-1 labeling index, and volume of intraoperative bleeding. However, massive intraoperative bleeding of > 2,000 mL occurred in one  perisylvian glioblastoma patient. CONCLUSIONS: Glioblastomas in the perisylvian region tend to be associated with extensive arteriovenous shunting that can be definitively visualized by performing an angiography. Because arteriovenous shunting carries the risk of intraoperative bleeding, perisylvian glioblastomas-particularly in the dominant hemisphere-should be resected with a meticulous surgical procedure and strategy.

 

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[429]

TÍTULO / TITLE:  - Attention to normal brain volumes in glioblastoma radiotherapy: Potential role in tumor invasion and vasculogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Hypotheses. 2013 Apr;80(4):501-4. doi: 10.1016/j.mehy.2013.01.006. Epub 2013  Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mehy.2013.01.006

AUTORES / AUTHORS:  - Zhou W; Jiang Z; Xu YY; Li XG

INSTITUCIÓN / INSTITUTION:  - Department of Radiotherapy, Cancer Centre, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.

RESUMEN / SUMMARY:  - Glioblastoma is well known for frequent local recurrences even after radiation therapy. The significance of low-dose normal brain volume analysis is usually ignored by clinical radiotherapist. Recently, several reports have demonstrated that ionizing radiation to surrounding brain tissues augments the secretions of several mediators, including SDF-1alpha, VEGF and MMPs. They are essential for glioma invasion and vasculogenesis processes. It is hypothesized that irradiated  normal brain tissues promotes tumor invasion and vasculogenesis, resulting in glioma recurrence. This prompts new attention on the volumes of “normal” brain in radiation treatment for gliomas. Improvement of radiotherapy techniques is expected to decrease the doses and volumes of irradiated normal brain. The combination of radiation and inhibitors of these mediators would be a promising adjuvant therapy for glioblastoma.

 

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[430]

TÍTULO / TITLE:  - Potential roles for Gfi1 in the pathogenesis and proliferation of glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med Hypotheses. 2013 May;80(5):629-32. doi: 10.1016/j.mehy.2013.02.007. Epub 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mehy.2013.02.007

AUTORES / AUTHORS:  - Huang H; Xiang Y; Su B; Xiong W; Zhang X

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, 17 Changle Western Road, Xi’an, PR China; Department of Neurosurgery, Xiamen Hospital of Traditional Chinese Medicine (T.C.M.), 1739 Xianyue Road, Xiamen, PR China.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is a major form of adult brain tumour with relatively poor prognosis and high mortality. Temozolomide (TMZ)-based chemotherapy following neurosurgery and radiotherapy has been suggested as the first line of treatment and is proven to effectively prolong overall survival and enhance patient quality of life. However, not all patients benefit from this treatment because of drug resistance. Even patients with TMZ-sensitive GBM may become resistant, which is partly due to the restoration of activity of the DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT); thus, patients cannot evade eventual tumour recurrence. The cellular activity of MGMT is the most important determinant of TMZ-resistance. However, some patients with a low level of activated MGMT are also TMZ-resistant. The aberrant expression of HOXA9, one of the 39 class I homeobox genes, is a marker of poor prognosis, and its level gradually increases with histologic malignant progression, shorter time to  overall survival (OS) and free progression survival (FPS) in glioma patients, which further supports an oncogenic role for HOXA9 in gliomas. The HOXA9-PI3K signalling pathway is an important mechanism in GBM that is independent of MGMT promoter methylation status. The DNA binding sites of growth factor independent-1 (Gfi1) can overlap with the HOXA9 promoter through the “AATC” versus “GATT” core  sequence. The competition for this binding site inhibits the expression of HOXA9  and induces different transcriptional outcomes, which suggests a new direction for investigation of the mechanism underlying targeted therapy of malignant gliomas.

 

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[431]

TÍTULO / TITLE:  - Sensitivity of intraoperative 5-aminolevulinic acid fluorescence compared with PET using O-(2-(18)F-fluoroethyl)-L-tyrosine to detect cerebral gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Res. 2013 Apr;35(3):329-30. doi: 10.1179/1743132812Y.0000000140.

            ●● Enlace al texto completo (gratuito o de pago) 1179/1743132812Y.0000000140

AUTORES / AUTHORS:  - Langen KJ; Floeth FW; Galldiks N

INSTITUCIÓN / INSTITUTION:  - Institute of Neuroscience and Medicine, Forschungszentrum Julich, Germany.

 

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[432]

TÍTULO / TITLE:  - Cribriform Neuroepithelial Tumor Arising in the Lateral Ventricle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Dev Pathol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 2350/12-12-1287-CR.1

AUTORES / AUTHORS:  - Arnold M; Stallings-Archer K; Marlin E; Grondin R; Olshefski R; Biegel JA; Pierson CR

INSTITUCIÓN / INSTITUTION:  - a Nationwide Children’s Hospital, Pathology & Laboratory Medicine.

RESUMEN / SUMMARY:  - Abstract Cribriform neuroepithelial tumor (CRINET) is a recently recognized central nervous system neoplasm that arises in the ventricles of young children and is characterized by primitive, non-rhabdoid SMARCB1-deficient cells with prominent cribriform architecture. We report a 14-month-old male who presented with signs of increased intracranial pressure. Neuroimaging revealed a large solid and cystic mass in the lateral ventricle. Tumor cells were small, primitive appearing and arranged in cribriform and trabecular patterns with interspersed solid cellular areas. Rhabdoid cells were absent. Immunohistochemical staining showed no SMARCB1 (INI11, BAF47, hSNF5) expression and strong epithelial membrane antigen (EMA) immunoreactivity along luminal surfaces. Electron microscopy showed epithelial characteristics, including abundant basal lamina. Genetic analysis of  the tumor revealed deletion of one SMARCB1 allele, while the other contained an intronic point mutation predicted to disrupt splicing. This case further illustrates the distinct histopathologic and molecular genetic features of CRINET and identifies distinctive ultrastructural features.

 

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[433]

TÍTULO / TITLE:  - Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Semin Oncol. 2013 Feb;40(1):120-33. doi: 10.1053/j.seminoncol.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.009

AUTORES / AUTHORS:  - Strosberg JR

INSTITUCIÓN / INSTITUTION:  - Gastrointestinal and Neuroendocrine Tumor Division, H. Lee Moffitt Cancer Center  and Research Institute, Tampa, FL 33612, USA. jonathan.strosberg@moffitt.org

RESUMEN / SUMMARY:  - Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the “diffuse neuroendocrine system,” they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and  treatment of these rare neoplasms.

 

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[434]

TÍTULO / TITLE:  - Delayed cerebral vasospasm and systemic inflammatory response syndrome following  intraoperative rupture of cerebral hydatid cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1675-3

AUTORES / AUTHORS:  - Salunke P; Patra DP; Mukherjee KK

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, PGIMER, Sector 12, Chandigarh, India, 1600l2, drpravin_salunke@yahoo.co.uk.

 

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[435]

TÍTULO / TITLE:  - Recurrent multiple spinal paragangliomas as a manifestation of a metastatic composite paraganglioma-ganglioneuroblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1678-0

AUTORES / AUTHORS:  - Gempt J; Baldawa SS; Weirich G; Delbridge C; Hempel M; Lohse P; Meyer B; Ringel F

INSTITUCIÓN / INSTITUTION:  - Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str. 22, 81675, Munchen, Germany, Jens.Gempt@lrz.tum.de.

 

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[436]

TÍTULO / TITLE:  - The transventricular preforniceal approach for exophytic chiasmatic/hypothalamic  astrocytomas extending into the anterior third ventricle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):727-32. doi: 10.1007/s00701-013-1642-z. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1642-z

AUTORES / AUTHORS:  - Yoshimoto K; Shono T; Matsukado K; Sasaki T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan, kyoshimo@ns.med.kyushu-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Surgical treatment of large exophytic chiasmatic/hypothalamic astrocytomas extending into the anterior third ventricle remains a challenging task for neurosurgeons. In particular, when the tumor extends from the chiasmatic region upward to the foramen of Monro, damage to the fornix and other neurovascular structures is a major concern. OBJECTIVE: To describe the technique used in the transventricular preforniceal surgical approach to remove the superior and superoposterior part of the tumor in the third ventricle for treatment of exophytic chiasmatic/hypothalamic astrocytoma. METHODS: The transventricular preforniceal approach was used in two cases of exophytic chiasmatic/hypothalamic astrocytoma. The approach is summarized in 4 procedures:  1) exposure of the anterior horn of the lateral ventricle by the transcallosal approach, 2) identification of the foramen of Monro and the fornix, 3) incision of the septum pellucidum or the wall of the lateral ventricle, in front of the columns of the fornix, and 4) removal of the tumor through the space between the  anterior commissure and the columns of the fornix. RESULTS: Because the tumor compressed the foramen of Monro posteriorly and stretched the space between the anterior commissure and the columns of the fornix, the posterosuperior part of the tumor in the third ventricle was successfully removed through the surgical corridor in front of the columns of the fornix. In both cases, tumors were successfully removed using this approach without damaging the fornix and the anterior commissure. Residual tumor was removed using an anterior interhemispheric translamina terminalis approach in a two-stage surgery. CONCLUSIONS: The transventricular preforniceal approach can be applied for removing the superior part of exophytic chiasmatic/hypothalamic astrocytomas, because the space between the anterior commissure and the fornix is stretched by  the tumor, providing an appropriate surgical corridor.

 

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[437]

TÍTULO / TITLE:  - Nonglial tumors of the brainstem.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Semin Ultrasound CT MR. 2013 Apr;34(2):113-22. doi: 10.1053/j.sult.2013.01.002.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.sult.2013.01.002

AUTORES / AUTHORS:  - Pinero-Gonzalez de la Pena P; Rodriguez-Romero R

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, Virgen del Rocio Hospitals, Seville, España. Electronic address: pilarpingo@telefonica.net.

RESUMEN / SUMMARY:  - Nonglial tumors of the brainstem constitute a histologically heterogeneous group  of lesions with quite a different behavior and aggressiveness. Therefore, the diverse therapeutic options depend on a correct and prompt diagnosis. We can limit their differential diagnosis by using clinical and demographic data and imaging findings, which in most cases will be a translation of their histologic characteristics. The main clinical, neuroimaging, and pathologic features of these lesions are described according to the last updated classification of the World Health Organization for central nervous system tumors. We provide some useful clues, based on the direct correlation of the imaging appearance with its  gross pathologic and histologic appearance, for a comprehensive diagnostic approach. Embryonic tumors (medulloblastoma and primitive neuroectodermal tumor), cavernoma, lymphoma, hemangioblastoma, and ganglionic and mixed tumors as long as lesions affecting the central nervous system by external compression (arising from the skull, cerebrospinal fluid spaces, or extraaxial nervous and vascular elements) are included. All cases presented belong to the archive data of our hospital.

 

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[438]

TÍTULO / TITLE:  - Brainstem gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Semin Ultrasound CT MR. 2013 Apr;34(2):104-12. doi: 10.1053/j.sult.2013.01.001.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.sult.2013.01.001

AUTORES / AUTHORS:  - Ramos A; Hilario A; Lagares A; Salvador E; Perez-Nunez A; Sepulveda J

INSTITUCIÓN / INSTITUTION:  - Neuroradiology, Department of Radiology, Hospital 12 de Octubre, Madrid, España. Electronic address: ramosana3@yahoo.es.

RESUMEN / SUMMARY:  - Historically, brainstem gliomas have been considered as a single entity. Since the introduction of magnetic resonance (MR) imaging in the late 1980s, these tumors are now regarded as a heterogeneous group of neoplasms with different age  of onset, clinical and radiologic presentation, and varying behavior and natural  history. This article describes the different subtypes of brainstem gliomas in children and adults. We focus on recent advances in MR such as MR spectroscopy, MR perfusion, and diffusion tensor imaging that often strongly suggest the histopathologic diagnosis of the lesion.

 

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[439]

TÍTULO / TITLE:  - Sagittal sinus thrombosis with malignant brain oedema: pathophysiology of cortical veins after decompressive craniectomy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Apr;155(4):651-3. doi: 10.1007/s00701-013-1627-y. Epub 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-013-1627-y

AUTORES / AUTHORS:  - Weber J; Vida M; Greiner K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Steinenberg Clinic, Steinenbergstrasse 31, 72764, Reutlingen, Germany, palaeoweber@gmx.de.

 

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[440]

TÍTULO / TITLE:  - Up-regulation of USP2a and FASN in gliomas correlates strongly with glioma grade.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Feb 14. pii: S0967-5868(12)00492-4. doi: 10.1016/j.jocn.2012.03.050.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.03.050

AUTORES / AUTHORS:  - Tao BB; He H; Shi XH; Wang CL; Li WQ; Li B; Dong Y; Hu GH; Hou LJ; Luo C; Chen JX; Chen HR; Yu YH; Sun QF; Lu YC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, China.

RESUMEN / SUMMARY:  - Gliomas are the most common neoplasms in the central nervous system. The lack of  efficacy of glioma therapies necessitates in-depth studies of glioma pathology, especially of the underlying molecular mechanisms that transform normal glial cells into tumor cells. Here we report that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. Using real-time quantitative polymerase chain reaction (PCR), Western blot and immunohistochemistry, we examined the expression and cellular distribution of USP2a and FASN in human glioma tissues. The expression patterns of USP2a and FASN correlated with the pathologic and clinical characteristics of the patients. Real-time PCR analysis showed that the expression levels of USP2a and its substrate FASN were higher in  high-grade (World Health Organization [WHO] grades III and IV) glioma tissues than in low-grade (WHO grades I and II) glioma tissues. Western blot analysis indicated that the average optical densitometry ratio of USP2a and its substrate  FASN in high-grade gliomas was higher than in low-grade gliomas. Moreover, statistical analysis of grade-classified glioma samples showed that the level of  USP2a and FASN expression increased with the elevation of the WHO grade of glioma. USP2a protein expression was detected in the nucleus of glioma tissues and an increase in expression was significantly associated with the elevation of  the WHO grade of glioma by immunohistochemistry. These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas.

 

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[441]

TÍTULO / TITLE:  - Craniopharyngiomas of the third ventricle: topographical concepts of surgical interest.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Apr;27(2):268-9. doi: 10.3109/02688697.2013.772100. Epub 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.772100

AUTORES / AUTHORS:  - Pascual JM; Prieto R; Castro Dufourny I; Gil Simoes R; Carrasco R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, La Princesa University Hospital , Madrid , España E-mail: jmpasncj@hotmail.com.

 

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[442]

TÍTULO / TITLE:  - The Role of microRNAs in Medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Hematol Oncol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 3109/08880018.2013.783890

AUTORES / AUTHORS:  - Vidal DO; Marques MM; Lopes LF; Reis RM

INSTITUCIÓN / INSTITUTION:  - Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte  Vilela , Barretos, Sao Paulo , Brasil.

RESUMEN / SUMMARY:  - Medulloblastomas (MBs) are the most frequent brain tumors in children and remained a major therapeutic challenge. Clinical and histopathological features are used for disease classification and patient prognostication. Currently, several molecular studies using transcriptomic and genomic approaches suggested the existence of four molecular subtypes, increasing the complexity, and knowledge of MB biology. Despite these significant advances, the molecular basis  of MBs is not fully understood. MicroRNAs (miRNAs) are a group of small nonprotein coding RNA molecules that target genes by inducing mRNA degradation or translational repression. They represent an evolutionary conserved mechanism that controls fundamental cellular processes, such as development, differentiation, metabolism, proliferation, and apoptosis. Aberrant expression of miRNAs correlates with various cancers. This altered expression can arise from mutation, methylation, deletion, and gain of miRNA-encoding regions. We here review the knowledge of miRNAs in MBs. The expression patterns of miRNAs in MBs were comprehensively evaluated and their diagnostic, prognostic, and therapeutic biomarker role assessed. miRNAs are important players in MB tumorigenesis and their therapeutic exploitation can constitute an alternative approach to this devastating disease.

 

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[443]

TÍTULO / TITLE:  - FDG PET Differentiation of Tumor Recurrence From Post-Stereotactic Radiosurgical  Scar in a Central Neurocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 7.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318286bdea

AUTORES / AUTHORS:  - Liu Y

INSTITUCIÓN / INSTITUTION:  - From the Nuclear Medicine Service, Department of Radiology, University Hospital,  New Jersey Medical School, Newark, New Jersey.

RESUMEN / SUMMARY:  - Central neurocytoma is a rare benign tumor of neuronal origin. The tumor is often located in the ventricular system and can proliferate within the ventricle. Five  months after stereotactic radiosurgery for recurrent neurocytoma, a 33-year-old woman had a 2.0-cm lesion in the right third ventricle on the MRI. FDG PET demonstrated intense uptake of the lesion. The subsequent MRI follow-up showed growth of the lesion and confirmed recurrence.

 

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[444]

TÍTULO / TITLE:  - Supraorbital trans-eyebrow craniotomy and fluorescence-guided resection of fronto-basal high grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb 26. pii: S0303-8467(13)00062-0. doi: 10.1016/j.clineuro.2013.02.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.02.009

AUTORES / AUTHORS:  - Prat-Acin R; Galeano-Senabre I; Pancucci G; Evangelista R; Ayuso-Sacido A; Botella C

INSTITUCIÓN / INSTITUTION:  - Dptment of Neurocurgery, Hospital Universitari i Politecnic la Fe, España. Electronic address: ricprat@hotmail.com.

RESUMEN / SUMMARY:  - OBJECT: To determine the effectiveness of fluorescence-guided resection of fronto-basal high grade gliomas by using the supraorbital trans-eyebrow craniotomy. METHODS: We present a single-institution experience of 6 consecutive  patients presenting high grade brain glioma located on the fronto-basal area that were operated through a supraorbital trans-eyebrow craniotomy. Previous to surgery all patients were administered 20mg/kg of 5 aminolevulic acid so microscopic fluorescence-guided resection could be accomplished. Tumors were located on gyrus rectus (3 patients), medial orbital gyrus (2 patients), and anterior orbital gyrus (1 patient). RESULTS: Despite the narrow surgical corridor, fluorescence was useful in all cases. Fluorescence-guided resection allowed inclusion into the margins of resection of areas previously considered as normal under white light. Complete resection was obtained in 5 patients. No neurological postoperative new deficit was observed in this series. All six cases corresponded to glioblastoma. Only one case of superficial infection with delayed wound healing was reported as complication. All patients expressed a high level of satisfaction related to cosmetic result. CONCLUSIONS: Fluorescence-guided resection of fronto-basal high grade gliomas can be successfully achieved through supraorbital trans-eyebrow craniotomy. Benefits of supraorbital craniotomy in the management of fronto-basal high grade gliomas as well as usefulness of fluorescence-guided resection through a very narrow corridor are exposed.

 

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[445]

TÍTULO / TITLE:  - Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: A brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Mar 27. doi: 10.1111/neup.12028.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12028

AUTORES / AUTHORS:  - Miyata H; Hori T; Vinters HV

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Research Institute for Brain and Blood Vessels - Akita, Akita, Japan.

RESUMEN / SUMMARY:  - Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD), including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies, constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlations. However, results have been controversial, particularly in terms of post-surgical seizure outcome. Recently,  the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish  an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological studies. Meanwhile, we reviewed the neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and  severity of neuronal loss and gliosis within hippocampal formation, that is, HS type 1 (61%) equivalent to “classical” Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore, we performed a neuropathological comparative study  on mTLE-HS and dementia-associated HS (d-HS) in the elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes,  particularly Alzheimer type and TDP-43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated.

 

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[446]

TÍTULO / TITLE:  - Three new nor-dammarane triterpenoids from Dysoxylum hainanense with particular cytotoxicity against glioma cell line.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pharm Res. 2013 Mar;36(3):322-6. doi: 10.1007/s12272-013-0030-9. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12272-013-0030-9

AUTORES / AUTHORS:  - Cao P; Liang G; Gao X; Wang X; Li Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shenyang Northern Hospital, #83 Wenhua Road, Shenhe district, Shenyang, 110018, Liaoning Province, People’s Republic of China, atocaopeng@hotmail.com.

RESUMEN / SUMMARY:  - Three new nor-dammarane triterpenoids, 12beta-O-acetyl-15alpha-hydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanordammanr an (1), 12beta,28-O-diacetyl-15alpha-hydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanorda mmanran (2), 12beta-hydoxy-3,15-dioxo-20,21,22-23,24,25,26,27-octanordammanran (3), together with one known compound, 12beta-O-acetyl-15alpha,28-dihydoxy-3-oxo-17-en-20,21,22-23,24,25,26,27-octanorda mmanran (4), were isolated from the 95 % EtOH extract of Dysoxylum hainanense. The structures of the new compounds were elucidated by spectral methods. All the  triterpenoids were in vitro evaluated for their cytotoxic activities against four tumor cell lines (BGC-823, U251, HepG2 and SGC-7901). All the three nor-dammarane triterpenoids exhibited particular significant cytotoxic activities against glioma cell line.

 

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[447]

TÍTULO / TITLE:  - Reversible hypothalamic dysfunction in optic nerve germinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Craniofac Surg. 2013 Mar;24(2):468-9. doi: 10.1097/SCS.0b013e318275eb2b.

            ●● Enlace al texto completo (gratuito o de pago) 1097/SCS.0b013e318275eb2b

AUTORES / AUTHORS:  - Chen CH; Lin HL; Cho DY

INSTITUCIÓN / INSTITUTION:  - From the Department of Neurosurgery, China Medical University Hospital; and China Medical University, Taichung, Taiwan.

RESUMEN / SUMMARY:  - Primary optic apparatus germ cell tumors are rare. There have been only 6 cases reported in the literature. Although they often disturb the hypothalamus-pituitary-adrenal axis and cause progressive visual loss, the influence of treatment outcomes on hypothalamic autoregulation has never been mentioned. Here, we report a patient with an optic nerve germinoma who presented  with reversible visual and hypothalamic dysfunction, and we discuss the possible  mechanisms and pathogenesis.

 

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[448]

TÍTULO / TITLE:  - Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pharm Res. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12272-013-0089-3

AUTORES / AUTHORS:  - Cao P; Pan DS; Han S; Yu CY; Zhao QJ; Song Y; Liang Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Institue of Neurology, General Hospital of Shenyang Military Area Command, #83 Wenhua Road, Shenhe District, Shenyang, 110018, China.

RESUMEN / SUMMARY:  - Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and  (+)-3-hydroxy-anhydrolycorine N-oxide (4). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3). Alkaloids 1 and 2 exhibited particular cytotoxic activities  against astrocytoma and glioma cell lines with IC50 of 9.2-11.3 muM and 10.4-12.2 muM respectively.

 

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[449]

TÍTULO / TITLE:  - Primary intradural extraosseous Ewing’s sarcoma of the lumbar spine presenting with acute bleeding.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.772102

AUTORES / AUTHORS:  - Khalatbari MR; Jalaeikhoo H; Moharamzad Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Arad Hospital , Tehran , Iran.

RESUMEN / SUMMARY:  - We report the case of a 28-year-old female with primary extraosseous Ewing’s sarcoma who presented initially with a low back pain and a right S1 radicular pain. Before scheduled surgical removal, she suddenly developed an unusual complication of an acute hemorrhage and an acute cauda equina syndrome. Emergency surgery was done which demonstrated an acute bleeding. Treatment was followed by  the chemotherapy and the adjuvant radiotherapy. Follow-up has been done for 6 years after presentation.

 

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[450]

TÍTULO / TITLE:  - Tumour infiltrating T-cell subpopulations in glioblastomas: what is the significance of natural killer T-cells?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Apr;27(2):267. doi: 10.3109/02688697.2013.772099. Epub 2013  Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.772099

AUTORES / AUTHORS:  - Noorani I

INSTITUCIÓN / INSTITUTION:  - Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine University of Southampton , SO16 6YD , UK.

 

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[451]

TÍTULO / TITLE:  - An unusually mild presentation of megalencephalic leukoencephalopathy with subcortical cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb 25. pii: S0303-8467(13)00051-6. doi: 10.1016/j.clineuro.2013.01.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2013.01.024

AUTORES / AUTHORS:  - Kocaman G; Eryigit G; Abbink TE; Kilicarslan R; Asil T; Alkan A; Van der Knaap MS; Kocer A

INSTITUCIÓN / INSTITUTION:  - Bezmialem Vakif University, Faculty of Medicine, Department of Neurology, Turkey. Electronic address: drgkocaman@hotmail.com.

 

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[452]

TÍTULO / TITLE:  - Calculating the tumor volume of acoustic neuromas: Comparison of ABC/2 formula with planimetry method.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 31. pii: S0303-8467(13)00006-1. doi: 10.1016/j.clineuro.2012.12.029.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.029

AUTORES / AUTHORS:  - Yu YL; Lee MS; Juan CJ; Hueng DY

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

RESUMEN / SUMMARY:  - OBJECTIVE: The ABC/2 equation is commonly applied to measure the volume of intracranial hematoma. However, the precision of ABC/2 equation in estimating the tumor volume of acoustic neuromas is less addressed. The study is to evaluate the accuracy of the ABC/2 formula by comparing with planimetry method for estimating  the tumor volumes. METHODS: Thirty-two patients diagnosed with acoustic neuroma received contrast-enhanced magnetic resonance imaging of brain were recruited. The volume was calculated by the ABC/2 equation and planimetry method (defined as exact volume) at the same time. The 32 patients were divided into three groups by tumor volume to avoid volume-dependent overestimation (<3ml, 3-6ml and >6ml). RESULTS: The tumor volume by ABC/2 method was highly correlated to that calculated by planimetry method using linear regression analysis (R(2)=0.985). Pearson correlation coefficient (r=0.993, p<0.001) demonstrates nearly perfect association between two methods. CONCLUSIONS: The ABC/2 formula is an easy method in estimating the tumor volume of acoustic neuromas that is not inferior to planimetry method.

 

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[453]

TÍTULO / TITLE:  - Dermoid cysts of the posterior fossa - morbid associations of a benign lesion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.776667

AUTORES / AUTHORS:  - Raghunath A; Indira Devi B; Bhat DI; Somanna S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, National Institute of Mental Health and Neurosciences , Bangalore , India.

RESUMEN / SUMMARY:  - Dermoid cysts of posterior fossa are uncommon benign lesions. They differ from other lesions found in the infra tentorial compartment by virtue of their associated conditions. Due to their association with dermal sinus tracts, intracranial infection is a potential threat following infection of the cyst. Due to their embryologic origin, these cysts may also be associated with other congenital anomalies. In this article we detail our eleven-year-experience with posterior fossa dermoid cysts in fifteen patients. Despite the morbid presentation with severe life-threatening complications, the overall outcome was  excellent. Implications of the various associations are discussed.

 

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[454]

TÍTULO / TITLE:  - Identification of thymosins beta and beta in paediatric craniopharyngioma cystic  fluid.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2069-9

AUTORES / AUTHORS:  - Desiderio C; Martelli C; Rossetti DV; Di Rocco C; D’Angelo L; Caldarelli M; Tamburrini G; Iavarone F; Castagnola M; Messana I; Cabras T; Faa G

INSTITUCIÓN / INSTITUTION:  - Consiglio Nazionale delle Ricerche, Istituto di Chimica del Riconoscimento Molecolare, Rome, Italy, claudia.desiderio@icrm.cnr.it.

RESUMEN / SUMMARY:  - BACKGROUND: Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively  as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or  delay of the radical resection of the tumour mass and the collateral serious effects. METHODS: Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction. FINDINGS: Thymosin beta4 and beta10 peptides were for the first time  identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin beta4 and beta10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients. INTERPRETATION: The presence of beta-thymosins in the intracystic fluid of the tumour confirmed the secretion of  these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.

 

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[455]

TÍTULO / TITLE:  - A mass resulting from cerebral spinal fluid collection of ventriculopleural shunt: radiographic and radionuclide findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar;38(3):215-6. doi: 10.1097/RLU.0b013e31827a2518.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31827a2518

AUTORES / AUTHORS:  - Lu YY; Lin WY; Wang HY; Kao CH; Tsai SC

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

RESUMEN / SUMMARY:  - A 49-year-old man was brought to our hospital because of lethargy. His medical history was hydrocephalus with ventriculoperitoneal shunt initially. The ventriculoperitoneal shunt was replaced several times owing to malfunction, and it was later replaced with a right-sided ventriculopleural shunt. The chest radiograph revealed a mass at the right lung. The mass was a capsular collection  of cerebral spinal fluid (CSF) in the right pleural cavity diagnosed based on radionuclide shuntogram findings.

 

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[456]

TÍTULO / TITLE:  - Multifocal Extra-Adrenal Paraganglioma Evaluated With Different PET Tracers: Comparison Between 18F-FDG, 18F-DOPA and 68Ga DOTANOC PET/CT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31827088d9

AUTORES / AUTHORS:  - Treglia G; Cardillo G; Stefanelli A; Di Franco D; Enang GN; Giordano A; Rufini V

INSTITUCIÓN / INSTITUTION:  - From the *Department of Bioimaging and Radiological Sciences, Institute of Nuclear Medicine, Catholic University of the Sacred Heart; and daggerDepartment of Thoracic Surgery, Carlo Forlanini Hospital, Rome, Italy.

RESUMEN / SUMMARY:  - A 40-year-old female patient with suspected multifocal extra-adrenal paraganglioma, on the basis of biochemical, genetic, and conventional imaging data, underwent F-FDG, F-DOPA and Ga DOTANOC PET/CT. FDOPA- and FDG-PET/CT detected a multifocal mediastinal and cervical paraganglioma. Ga-DOTANOC PET/CT detected 2 additional lesions compared to the other PET/CT methods. In our case,  somatostatin receptor PET/CT with Ga-DOTANOC correctly assessed the extent of the disease in a patient with multifocal paraganglioma.

 

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[457]

TÍTULO / TITLE:  - MIBG Superscan of Metastatic Paraganglioma Occurring With Neurofibromatosis Type  1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182816777

AUTORES / AUTHORS:  - Harrison CE; Barron BJ

INSTITUCIÓN / INSTITUTION:  - From the Department of Radiology and Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Emory University, Atlanta, GA.

RESUMEN / SUMMARY:  - A Tc MDP bone superscan occurs when osseous activity is extremely intense and genitourinary and soft tissue activity is not identified. A similar phenomenon has been described with metaiodobenzylguanidine (MIBG) in metastatic pheochromocytoma and neuroblastoma. We present a case of metastatic paraganglioma resulting in an MIBG superscan. Neuroendocrine bone metastasis alters the biodistribution of MIBG such that the liver, heart, and urinary bladder are not well visualized. Our case occurred in association with neurofibromatosis type 1 and in the absence of an identified primary tumor.

 

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[458]

TÍTULO / TITLE:  - Organizing Intracerebral Hematoma Mimicking a Recurrent Brain Tumor on FDG-PET.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31827085ce

AUTORES / AUTHORS:  - Nakajima S; Okada T; Arakawa Y; Mikami Y; Togashi K

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Diagnostic Imaging and Nuclear Medicine, daggerNeurosurgery, and double daggerDiagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

RESUMEN / SUMMARY:  - A man underwent resection of low-grade astrocytoma, followed by radiation therapy at the age of 14 years old. He had been followed up for 33 years with no finding  of recurrent disease on brain images until the most recent CT and MRI scans showed a mass at the postoperative site in the left parieto-occipital lobe. F-FDG PET/CT showed increased uptake in the mass. Resection was conducted, and microscopic examination of the whole mass demonstrated an organizing hematoma. A  provisional diagnosis of organizing hematoma should be considered, along with other benign and malignant causes of increased FDG uptake.

 

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[459]

TÍTULO / TITLE:  - A bilateral infratentorial neurenteric cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 9. pii: S0967-5868(12)00509-7. doi: 10.1016/j.jocn.2012.04.026.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.04.026

AUTORES / AUTHORS:  - Ranguis SC; Chaganti JR; Winder MJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia.

RESUMEN / SUMMARY:  - We report a patient with a large infratentorial neurenteric (NE) cyst. Intracranial NE cysts, also known as enterogenous cysts, constitute a rare, generally benign entity of unknown aetiology. The presentation, imaging characteristics and management of the case is discussed, including illustrative peri-operative images.

 

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[460]

TÍTULO / TITLE:  - Neuroleptic malignant syndrome (parkinsonism-hyperpyrexia syndrome) after deep brain stimulation of the subthalamic nucleus.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 2. pii: S0967-5868(12)00507-3. doi: 10.1016/j.jocn.2012.04.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.04.024

AUTORES / AUTHORS:  - Urasaki E; Fukudome T; Hirose M; Nakane S; Matsuo H; Yamakawa Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nagasaki Kawatana Medical Center, Nishi-kyusyu Brain  and Nerve Center, Higashi Sonogi-gun, Kawatana-machi, Shimokumigo 2005-1, Nagasaki 859-3615, Japan. Electronic address: urasaki@nkmc1.jp.

RESUMEN / SUMMARY:  - Neuroleptic malignant syndrome (NMS), also called parkinsonism-hyperpyrexia syndrome (PHS), is a severe, general, sometimes fatal, physical reaction, induced by sudden and strong blockade of dopamine receptors. When subthalamic nucleus (STN)-deep brain stimulation (DBS) is used on patients with Parkinson disease (PD), dopaminergic medications are transiently stopped prior to the procedure, and a reduction in the use of drugs is routinely attempted after the procedure. Although a sudden stop or abrupt reduction of dopaminergic medications may set the stage for NMS/PHS, only three cases have been reported after STN-DBS surgery. Here, we describe a 75-year-old woman with PD who experienced delayed onset, yet  fatal, PHS after STN-DBS. Although STN-DBS might prevent or suppress PHS, its protective effect is not always complete. We must be aware that fatal PHS can occur when the use of medication for PD is reduced or altered, even when patients are under continuous STN stimulation.

 

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[461]

TÍTULO / TITLE:  - Anaplastic astrocytoma masquerading as hemorrhagic stroke.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Mar 16. pii: S0967-5868(13)00032-5. doi: 10.1016/j.jocn.2012.09.041.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.09.041

AUTORES / AUTHORS:  - Li L; Yin J; Li Y; Tian W; Qiao B; Tang Z; Shi J

INSTITUCIÓN / INSTITUTION:  - Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 500 W. Thomas Road, Phoenix, AZ 85013, USA; Department of Neurology, Affiliated Lianyungang Hospital of Nanjing University of Chinese Medicine, China.

RESUMEN / SUMMARY:  - Although primary and metastatic brain tumors can cause intracranial hemorrhage, thalamic hemorrhage as the first presentation of an anaplastic astrocytoma has not been reported. We report a 47-year-old man who first presented with hypertensive hemorrhagic stroke. He improved with aggressive blood pressure control and recovered with minimal residual deficit within 10days. This led to the initial misdiagnosis of uncontrolled hypertension as the cause of the stroke. He deteriorated rapidly 4months later. A biopsy revealed an anaplastic astrocytoma. Misdiagnosis of tumor as stroke can occur in patients with vascular  risk factors who do not have a previous history of neoplasia. Our case report is  to heighten the awareness of the incidence of tumor apoplexy masquerading as stroke.

 

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[462]

TÍTULO / TITLE:  - Dysembryoplastic neuroepithelial tumor, a pure glial tumor? Immunohistochemical and morphometric studies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuropathology. 2013 Mar 27. doi: 10.1111/neup.12033.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12033

AUTORES / AUTHORS:  - Komori T; Arai N

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine and Pathology (Neuropathology), Tokyo Metropolitan Neurological Hospital, Tokyo, Japan; Brain Pathology Research Center, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

RESUMEN / SUMMARY:  - Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal tumor, occurring in children and adolescents, typically associated with drug-resistant partial seizures. Pathologically, DNT is characterized by a specific glioneuronal element that is comprised of oligodendroglia-like cells (OLC) and floating neurons. The definition of DNT is currently controversial and the incidence of DNT varies among institutions. In this study we characterize the morphologic profiles of OLC and floating neurons by performing immunohistochemical and morphometric studies on seven cases of a simple form of DNT. While a majority of  OLC was positive for oligodendrocyte transcription factor 2 (Olig2), only floating neurons and a few small cells were positive for neuronal nuclear antigens (NeuN). Double immunofluorescence studies revealed co-localization of Olig2 and galectin 3 in OLC, but no co-localization of Olig2 and NeuN. The distribution pattern of NeuN-positive nuclei within the tumor tissue was not different from that in the adjacent neural tissue. A section cut perpendicular to the cortex stained with NeuN showed a continuous laminar arrangement with the adjacent cortex. Densities of NeuN-positive nuclei from tumors embedded in the white matter were significantly lower than those from tumors in the gray matter.  Our results suggest that the NeuN-positive small and large cells observed within  the specific glioneuronal element are in fact entrapped granular and pyramidal cells within the cortex and that OLCs are essentially glial and not neuronal in nature. DNT is thus a pure glial tumor rather than a glioneuronal tumor, that is, the equivalent of non-infiltrating oligodendroglioma, grade I.

 

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[463]

TÍTULO / TITLE:  - Operability of glioblastomas: “sins of action” versus “sins of non-action”

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Sci. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10072-013-1345-5

AUTORES / AUTHORS:  - Ferroli P; Schiariti M; Finocchiaro G; Salmaggi A; Castiglione M; Acerbi F; Tringali G; Farinotti M; Broggi M; Roberto C; Maccagnano E; Broggi G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Fondazione Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy, paolo.ferroli@istituto-besta.it.

RESUMEN / SUMMARY:  - Despite prognosis of glioblastomas is still poor, mounting evidence suggests that more extensive surgical resections are associated with longer life expectancy. However, the surgical indications, at present, are far from uniform and the concept of operability is extremely surgeon-dependant. The results of glioblastoma resection in 104 patients operated on between March 2005 and April 2011 were reviewed with the aim to shed some light on the limits between ‘sins of action’ (operating upon complex tumors causing a permanent severe deficit) and ‘sins of non-action’ (considering inoperable tumors that can be resected with good results). Fifty-five patients (54.4 %) (Group 1) presented with a ‘disputable’ surgical indication because of one or more of the following clinico-radiological aspects: involvement of motor and language areas (39.4 %), deep location (7.7 %), corpus callosum infiltration (13.4 %), or major vessels encasement (8.6 %). Forty-six (42.5 %) patients (Group 2) presented with an ‘indisputable’ surgical indication (readily accessible tumors in non-eloquent areas). Overall mortality was 2.9 %. The mean overall survival was 19.8 months and not significantly different in the two Groups (20.4 Group 2 and 19.5 months for Group 1; p = 0.7). Patients with GTR and <72 years had a longer survival (p = 0.004 and 0.03, respectively). Seventy patients (69.3 %) showed an uneventful post-operative course, without statistical significance difference between Group  1 and 2. The gross total removal of glioblastoma with many complexities (Group 1) was found to be feasible with acceptable mortality, morbidity and long-term survival rates.

 

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[464]

TÍTULO / TITLE:  - Response assessment criteria for glioblastoma: practical adaptation and implementation in clinical trials of antiangiogenic therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Neurol Neurosci Rep. 2013 May;13(5):347. doi: 10.1007/s11910-013-0347-2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11910-013-0347-2

AUTORES / AUTHORS:  - Chinot OL; Macdonald DR; Abrey LE; Zahlmann G; Kerloeguen Y; Cloughesy TF

INSTITUCIÓN / INSTITUTION:  - Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, 264 Rue  Saint Pierre, 13005, Marseille, France, olivier.chinot@ap-hm.fr.

RESUMEN / SUMMARY:  - Since 1990, the primary criteria used for assessing response to therapy in high-grade gliomas were those developed by Macdonald and colleagues, which incorporated 2-dimensional area measurements of contrast-enhancing tumor regions, corticosteroid dosing, and clinical assessment to arrive at a designation of response, stable disease, or progression. Recent advances in imaging technology and targeted therapeutics, however, have exposed limitations of the Macdonald criteria and have highlighted the need for reevaluation of response assessment criteria. In 2010, the Response Assessment in Neuro-Oncology (RANO) Working Group published updated criteria to address this need and to standardize response assessment for high-grade gliomas. In 2009, prior to the publication of the RANO  criteria, the randomized, placebo-controlled, multicenter, phase 3 AVAglio trial  was designed and initiated to investigate the effectiveness of radiotherapy and temozolomide with or without bevacizumab in newly diagnosed glioblastoma. The AVAglio protocol enacted specific measures to adapt the Macdonald criteria to the frontline treatment setting and to antiangiogenic agent evaluation, including the incorporation of a T2/fluid-attenuated inversion recovery component, qualitative  assessment of irregularly shaped contrast-enhancing lesions, and a decision tree  for confirming or ruling out pseudoprogression. Moreover, the protocol outlines practical means by which these adapted response criteria can be implemented in the clinic. This article describes the evolution of radiographic response criteria for high-grade gliomas and highlights the similarities and differences between those implemented in the AVAglio study and those subsequently published by RANO.

 

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[465]

TÍTULO / TITLE:  - A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1084-y

AUTORES / AUTHORS:  - Trouillas J; Roy P; Sturm N; Dantony E; Cortet-Rudelli C; Viennet G; Bonneville JF; Assaker R; Auger C; Brue T; Cornelius A; Dufour H; Jouanneau E; Francois P; Galland F; Mougel F; Chapuis F; Villeneuve L; Maurage CA; Figarella-Branger D; Raverot G

INSTITUCIÓN / INSTITUTION:  - Universite Lyon 1, Universite de Lyon, Lyon, France, jacqueline.trouillas@univ-lyon1.fr.

RESUMEN / SUMMARY:  - Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours  were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic).  The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

 

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[466]

TÍTULO / TITLE:  - A Distinct Reactive Oxygen Species Profile confers Chemoresistance in Glioma-Propagating Cells and Associates with Patient Survival Outcome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Antioxid Redox Signal. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1089/ars.2012.4999

AUTORES / AUTHORS:  - Koh L; Koh G; Ng F; Toh TB; Sandanaraj E; Chong YK; Phong M; Tucker-Kellogg G; Kon OL; Ng WH; Ng I; Clement MV; Pervaiz S; Ang BT; Tang C

INSTITUCIÓN / INSTITUTION:  - NNI, SG, Singapore; lynnette.louisakwh@gmail.com.

RESUMEN / SUMMARY:  - Aims We explore the role of elevated O2-:H2O2 ratio as a prosurvival signal in glioma-propagating cells (GPCs). We hypothesize that depleting this ratio sensitizes GPCs to apoptotic triggers. Results We observed that elevated O2-:H2O2 ratio conferred enhanced resistance in GPCs, and depletion of this ratio by pharmacological and genetic methods sensitized cells to apopotic triggers. We established the ROS Index as a quantitative measure of normalized O2-:H2O2 ratio  and determined its utility in predicting chemosensitivity. Importantly, mice implanted with GPCs of reduced ROS Index demonstrated extended survival. Analysis of tumor sections revealed effective targeting of CD133- and nestin-expressing neural precursors. Furthermore, we established the Connectivity Map to interrogate a gene signature derived from varied ROS Index for patterns of association with individual patient gene expression in 2 clinical databases. We showed that patients with reduced ROS Index demonstrate better survival. These data provide clinical evidence for the viability of our O2-:H2O2-mediated chemosensitivity profiles. Innovation and Conclusion Gliomas are notoriously recurrent and highly infiltrative, and have been shown to arise from stem-like cells. We implicate elevated O2-:H2O2 ratio as a prosurvival signal in GPC self-renewal and proliferation. The ROS Index provides quantification of O2-:H2O2-mediated chemosensitivity, an advancement in a previously qualitative field. Intriguingly, glioma patients with reduced ROS Index correlate with longer survival and the Proneural molecular classification, a feature frequently associated with tumors of better prognosis. These data emphasize the feasibility  of manipulating the O2-:H2O2 ratio as a therapeutic strategy.

 

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[467]

TÍTULO / TITLE:  - Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos334

AUTORES / AUTHORS:  - Li Y; Lupo JM; Parvataneni R; Lamborn KR; Cha S; Chang SM; Nelson SJ

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Biomedical Imaging, University of California, San Francisco, California (Y.L., J.M.L., S.C., S.J.N.); Department of Neurological Surgery, University of California, San Francisco, California, (R.P., K.R.L., S.M.C.); Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, (S.J.N.).

RESUMEN / SUMMARY:  - BackgroundThe objective of this study was to examine the predictive value of parameters of 3D (1)H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and  overall survival (OS).MethodsSixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables.ResultsAssociated  with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) >3 at baseline and an increase of the CNI within elevated CNI regions (>2)  at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at  F2mo had worse PFS6 and OS.ConclusionsOur study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients.

 

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[468]

TÍTULO / TITLE:  - Silver nanocrystals mediated combination therapy of radiation with magnetic hyperthermia on glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Nanosci Nanotechnol. 2012 Nov;12(11):8276-81.

AUTORES / AUTHORS:  - Jiang H; Wang C; Guo Z; Wang Z; Liu L

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Lianyungang Second Hospital, Lianyungang 222006, China.

RESUMEN / SUMMARY:  - Based on the study of apoptosis-induced and anti-proliferation behavior of silver nanoparticles (AgNPs) on cancer cells, the attractively therapeutic effect and potential application of AgNPs in anti-cancer field was gradually revealed. Here  we investigated the effect of 10 nm silver nanoparticles (AgNPs) on human glioma  U251 cells upon the combination treatment of ionizing radiation (IR) treatment with magnetic hyperthermia (MHT). AgNPs showed both radio and thermo sensitivity  on U251 cells from the surviving fraction curve. Besides, we found both X-rays and heat could enhance the content of cells uptake of AgNPs. As the amount of intracellular AgNPs accumulated, the apoptosis rate of U251 cells enhanced. Furthermore, we established a simplified model for calculating cell survival rate and demonstrated that after RT, MHT and RT combined with MHT, AgNPs could significantly inhibited cancer cell proliferation. Our results revealed that AgNPs could have a potential application in enhancing effect of RT with MHT combination therapy induced killing of cancer cells.

 

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[469]

TÍTULO / TITLE:  - A phase I trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not021

AUTORES / AUTHORS:  - Cohen KJ; Gibbs IC; Fisher PG; Hayashi RJ; Macy ME; Gore L

INSTITUCIÓN / INSTITUTION:  - The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Department of Radiation Oncology (I.C.G), Department of Neurology, Stanford University Medical Center, Palo Alto, California (P.G.F); Department of Pediatrics, Division of Hematology/Oncology, Washington University  School of Medicine, St. Louis, Missouri (R.J.H.); University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado (M.E.M., L.G.).

RESUMEN / SUMMARY:  - BackgroundArsenic trioxide (ATO) has demonstrated preclinical evidence of activity in the treatment of infiltrating astrocytomas.MethodsWe conducted a phase I trial of ATO given concomitantly with radiation therapy in children with  newly diagnosed anaplastic astrocytoma, glioblastoma, or diffuse intrinsic pontine glioma. Eligible patients received a fixed daily dose of 0.15 mg/kg of ATO once a week, with each subsequent cohort of patients receiving an additional  dose per week up to a planned frequency of ATO administration 5 days per week as  tolerated. Twenty-four children were enrolled and 21 children were evaluable.ResultsATO was well tolerated throughout the entire dose escalation, resulting in confirmation of safety when administered 5 days per week during irradiation.ConclusionsThe recommended dose of ATO during conventional irradiation is 0.15 mg/kg given on a daily basis with each fraction of radiation  therapy administered.

 

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[470]

TÍTULO / TITLE:  - Using susceptibility-weighted imaging to determine response to combined anti-angiogenic, cytotoxic, and radiation therapy in patients with glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):480-9. doi: 10.1093/neuonc/nos325. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos325

AUTORES / AUTHORS:  - Lupo JM; Essock-Burns E; Molinaro AM; Cha S; Chang SM; Butowski N; Nelson SJ

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Janine M. Lupo, PhD Byers Hall UCSF, Box 2532, 1700 4th St., Ste. 303, San Francisco, CA 94158. janine.lupo@ucsf.edu.

RESUMEN / SUMMARY:  - Background The goal of this study was to investigate whether the amount of hypointense signal on susceptibility-weighted imaging within the contrast-enhancing lesion (%SWI-h) on the pretreatment scan could determine response in patients with newly diagnosed glioblastoma multiforme who received external beam radiation therapy with concomitant anti-angiogenic therapy (enzastaurin) and cytotoxic chemotherapy (temozolomide). Methods Twenty-five patients were imaged before therapy (postsurgical resection) and scanned serially every 2 months until progression. Standard clinical MR imaging and SWI were performed on a 3T scanner. %SWI-h was quantified for each patient’s pretreatment  scan. Time to progression and death were used to characterize patients into non-, immediate-, and sustained-response groups for both events. Cox proportional hazards models were used to assess the association between %SWI-h and both progression-free survival (PFS) and overall survival (OS). Classification and regression tree analysis were used to determine optimal cutoffs on which to split %SWI-h. Results For both death- and progression-based response categories, %SWI-h was significantly higher in sustained responders than in nonresponders. Cox model coefficients showed an association between %SWI-h and PFS and OS, both in univariate analysis (PFS: hazard ratio [HR] = 0.966, 95% confidence interval [CI] = 0.942-0.988; and OS: HR = 0.945, 95% CI = 0.915-0.976) and when adjusting for baseline KPS, age, sex, and resection extent (PFS: HR = 0.968, 95% CI = 0.940 -0.994; and OS: HR = 0.943, 95% CI = 0.908 -0.976). A cutoff value of 38.1% significantly differentiated patients into 2 groups based on censored OS and into non- and intermediate-response categories based on time to progression. Conclusions These early differences suggest that SWI may be able to predict which patients would benefit most from similar combination therapies and may assist clinicians in making important decisions about patient care.

 

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[471]

TÍTULO / TITLE:  - Clinical value of O-(2-[(18)F]-fluoroethyl)-L-tyrosine positron emission tomography in patients with low-grade glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E3. doi: 10.3171/2012.12.FOCUS12336.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12336

AUTORES / AUTHORS:  - Rapp M; Floeth FW; Felsberg J; Steiger HJ; Sabel M; Langen KJ; Galldiks N

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Progress in morphological imaging has facilitated the diagnosis of low-grade glioma (LGG) and plays a decisive role in therapeutic decisions. To date, the method of choice is contrast-enhanced MRI including T1-/T2-weighted and FLAIR sequences. However, tumor delineation and the differentiation between neoplastic  and normal brain tissue can be difficult when using morphological MRI and may complicate the identification of anaplastic foci for biopsy and further treatment planning. Furthermore, therapy monitoring and the differentiation of tumor recurrence from unspecific post-therapeutic changes in the tissue are challenging. Additional information about tumor metabolism may be very helpful for the diagnostic assessment of LGG and can be provided by PET. In recent years, the PET amino acid tracer O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET) has been clinically validated for brain tumor diagnosis. This tracer has logistical advantages over the widely used PET tracer (11)C-methyl-L-methionine due to the longer half-life of the (18)F-label (109 vs 20 minutes, respectively). Additionally, it has been demonstrated that both tracers provide comparable diagnostic information. The authors provide an overview of the recent literature  regarding the value of various clinical applications of (18)F-FET PET in patients with LGG.

 

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[472]

TÍTULO / TITLE:  - Gene analysis and dynamics of tumor stem cells in human glioblastoma cells after  radiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hum Cell. 2013 Mar 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13577-013-0060-0

AUTORES / AUTHORS:  - Sasaki A; Nakajo T; Tsunoda Y; Yamamoto G; Kobayashi Y; Tsuji M; Udaka Y; Mizutani T; Oguchi K

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawaku, Tokyo, 142-8666, Japan, sakiko@med.showa-u.ac.jp.

RESUMEN / SUMMARY:  - Glioblastoma is the most malignant central nervous system tumor. Patients with glioblastoma are treated with a combination of surgery, radiotherapy and chemotherapy; however, this effect is not satisfactory with regard to the prognosis. It is reported that the tumor stem cells affect recurrence, and radio- and chemotherapy resistance of the tumor, and that these cells play an important  role in tumorigenesis and tumor progression. Using human glioblastoma cell lines  (T98G and A172), irradiated (0, 30, 60 Gy) glioblastoma cells were prepared under the same conditions as clinical therapy. We analyzed cell proliferation rate, side population analysis by fluorescence-activated cell sorting and isolation of  CD133+ cells, and performed genetic analysis (human stem cells) on these cells. We also investigated the difference in gene expression in the cells after radiation. The stem cell-related genes were highly expressed in the CD133+ cells  compared with the CD133- cells, suggesting that the cancer stem cells may be located in these CD133+ cells. In the T98G cell line, the cell proliferation rate of 30-Gy irradiated cells was higher than those of non-irradiated cells and 60-Gy irradiated cells. Stem cell-related genes were highly expressed in 30-Gy irradiated CD133+ T98G cells. In conclusion, we suggest that CD133+ cells may strongly affect tumor proliferation and the resistance against radiation therapy.

 

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[473]

TÍTULO / TITLE:  - Patterns of care and outcome for patients with glioblastoma diagnosed during 2008-2010 in España.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not013

AUTORES / AUTHORS:  - Graus F; Bruna J; Pardo J; Escudero D; Vilas D; Barcelo I; Brell M; Pascual C; Crespo JA; Erro E; Garcia-Romero JC; Estela J; Martino J; Garcia-Castano A; Mata E; Lema M; Gelabert M; Fuentes R; Perez P; Manzano A; Aguas J; Belenguer A; Simon A; Henriquez I; Murcia M; Vivanco R; Rojas-Marcos I; Munoz-Carmona D; Navas I; de Andres P; Mas G; Gil M; Verger E

INSTITUCIÓN / INSTITUTION:  - Service of Neurology (F.G.) and Radiotherapy, Hospital Clinic, Barcelona (E.V.);  Service of Neurology (J.B.), Hospital Universitari de Bellvitge, L’Hospitalet de  Llobregat. Service of Neurology, Hospital Quiron, Madrid (J.P.); Service of Neurology, Hospital Universitari Germans Trias i Pujol, Badalona (D.E., D.V.); Service of Neurology (I.B.), Neurosurgery, Hospital Son Espases, Mallorca (M.B.); Service of Neurology, Hospital Universitario Miguel Servet, Zaragoza (C.P., J.A.C.); Service of Neurology (E.E.), Neurosurgery, Complejo Hospitalario de Navarra, Pamplona (J.C.G.-R.); Service of Neurology, Hospital Parc Tauli, Sabadell (J.E.); Service of Neurosurgery (J.M.), Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander (A.G.-C., E.M.); Service of Neurology (M.L.), Neurosurgery (M.G.), Complejo Hospitalario Universitario de Santiago, Santiago de Compostela; Service of Radiotherapy (R.F.), Hospital Universitari Josep Trueta, Girona; Service of Medical Oncology, Hospital Clinico  San Carlos, Madrid (P.P., A.M.); Service of Neurosurgery, Hospital Clinico Universitario Lozano Blesa, Zaragoza (J.A.); Service of Neurology, Hospital General de Castello, Castello (A.B., A.S.); Service of Radiotherapy, Hospital Universitari de Sant Joan, Reus (I.H., M.M.); Service of Neurology, Hospital del  Mar, Barcelona (R.V.); Service of Neurology (I.R.-M.), Radiotherapy, Hospital General Juan Ramon Jimenez, Huelva (D.M.-C.); Service of Neurology (I.N.), Neurosurgery, Fundacion Jimenez Diaz. Madrid (P.A.); Service of Neurology, Hospital Francesc de Borja, Gandia (G.M.); Service of Medical Oncology, Institut  Catala d’Oncologia, L’Hospitalet de Llobregat, España (M.G.).

RESUMEN / SUMMARY:  - BackgroundTo assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008-2010 in España.MethodsRetrospective analysis  of clinical, therapeutic, and survival data collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals.ResultsWe identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent  predictor (Odds ratio [OR], 1.03; 95% confidence interval [CI],1.01-1.05; P = .006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT </=42 days was associated with longer progression-free survival (hazard ratio [HR], 0.8; 95% CI, 0.64-0.99; P = .042) but not with overall survival (HR, 0.79; 95% CI, 0.62-1.00; P = .055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8-14.9 months), compared with 17.0 months (95% CI, 15.5-18.4 months; P = .034) among younger patients with GBM treated with the same regimen.ConclusionsIn a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for  chemoradiation, initiation of RT </=42 days was associated with better progression-free survival.

 

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[474]

TÍTULO / TITLE:  - Imaging descriptors improve the predictive power of survival models for glioblastoma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos335

AUTORES / AUTHORS:  - Mazurowski MA; Desjardins A; Malof JM

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Duke University Medical Center, Durham, North Carolina,  (M.A.M.); The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina, (A.D.); Department of Electrical & Computer Engineering, Duke University, Durham, North Carolina (J.M.M.).

RESUMEN / SUMMARY:  - BackgroundBecause effective prediction of survival time can be highly beneficial  for the treatment of glioblastoma patients, the relationship between survival time and multiple patient characteristics has been investigated. In this paper, we investigate whether the predictive power of a survival model based on clinical patient features improves when MRI features are also included in the model.MethodsThe subjects in this study were 82 glioblastoma patients for whom clinical features as well as imaging exams were available. Twenty-six imaging features were assessed by radiologists based on the available MR scans. We used multivariate Cox proportional hazards regression to construct 2 survival models:  one that used 3 clinical features (age, gender, and KPS) as the covariates and 1  that used both the imaging features and the clinical features as the covariates.  Then, we used 2 measures to compare the predictive performance of these 2 models: area under the receiver operating characteristic curve for the 1-year survival threshold and overall concordance index. To eliminate any positive performance estimation bias, we used leave-one-out cross-validation.ResultsThe performance of the model based on both clinical and imaging features was higher than the performance of the model based on only the clinical features, in terms of both area under the receiver operating characteristic curve (P < .01) and the overall  concordance index (P < .01).ConclusionsImaging features assessed using a controlled lexicon have additional predictive value compared with clinical features when predicting survival time in glioblastoma patients.

 

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[475]

TÍTULO / TITLE:  - Genetics of pheochromocytoma and paraganglioma in Spanish pediatric patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Relat Cancer. 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0339

AUTORES / AUTHORS:  - Cascon A; Inglada-Perez L; Comino-Mendez I; de Cubas AA; Leton R; Mora J; Marazuela M; Galofre JC; Quesada-Charneco M; Robledo M

INSTITUCIÓN / INSTITUTION:  - A Cascon, Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, España.

RESUMEN / SUMMARY:  - Pheochromocytomas and paragangliomas are neuroendocrine tumors developed in the adrenal medulla and in the extra-adrenal thoraco-abdominal sympathetic and parasympathetic paraganglia, respectively. Although clinical diagnosis of these tumors is infrequent during childhood, there have been reports of pediatric patients either carrying germline alterations in one of ten major pheochromocytoma/paraganglioma susceptibility genes, or without known mutations.  While new PCC/PGL susceptibility genes have recently been identified, little is known regarding their involvement in pediatric tumor development. We discuss here clinical and genetic criteria relevant to management of pheochromocytoma/paraganglioma patients diagnosed before age 18 years. Clinical and genetic data obtained from 36 pediatric non-related probands, tested for alterations in nine major pheochromocytoma/paraganglioma susceptibility genes (VHL, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX), were compared to data obtained from 411 genetically characterized non-pediatric cases. Seventy percent of probands had germline mutations affecting SDHB, SDHD, VHL, RET or MAX, with an over-representation of truncating SDHB mutations in the pediatric cases compared to non-pediatric patients. Amongst cases without mutations, we found a significantly higher proportion of pediatric patients with clinical features (bilateral pheochromocytoma and coexistence of pheochromocytoma and paraganglioma) suggestive of a hereditary condition (p=0.008). Genetic screening  for mutations in the susceptibility genes SDHB, SDHD, VHL, RET and MAX is strongly recommended in children developing PCC/PGL, starting with the metastasis-related gene SDHB. Alterations affecting still unidentified PCC/PGL susceptibility genes are probably responsible for a high proportion of the mutation-negative pediatric cases.

 

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[476]

TÍTULO / TITLE:  - Prognostic significance of telomerase-associated parameters in glioblastoma: effect of patient age.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):423-32. doi: 10.1093/neuonc/nos329. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos329

AUTORES / AUTHORS:  - Lotsch D; Ghanim B; Laaber M; Wurm G; Weis S; Lenz S; Webersinke G; Pichler J; Berger W; Spiegl-Kreinecker S

INSTITUCIÓN / INSTITUTION:  - Corresponding Authors: Sabine Spiegl-Kreinecker, PhD, Department of Neurosurgery, Wagner-Jauregg Hospital; Wagner-Jauregg Weg 15, 4020 Linz, Austria. sabine.spiegl-kreinecker@gespag.at); Walter Berger, Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria (walter.berger@meduniwien.ac.at.

RESUMEN / SUMMARY:  - Background Glioblastoma multiforme (GBM) is a heterogeneous, highly aggressive primary brain tumor with strongly variable patient survival. Because reliable prognostic biomarkers are lacking, we investigated the relation between telomerase-associated parameters and the disease course. Methods Telomerase-associated parameters were determined in 100 GBM tissues and associated with clinical characteristics and overall survival. Expressions of telomere length, telomerase activity (TA), and human telomerase reverse transcriptase (hTERT) were analyzed by quantitative PCR, telomeric repeat amplification protocol assay, and reverse transcriptase-PCR, respectively. Mutation status of isocitrate dehydrogenase (IDH)1 was determined by direct sequencing, and O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation by methylation-specific PCR. Results Of 100 GBM tissues, 61 were positive for both hTERT mRNA and TA, with a highly significant correlation between both parameters (linear regression, P < .0001). Telomere length determination revealed a significant difference between the hTERT/TA-positive and -negative subgroups, with markedly longer telomeres in the hTERT/TA-negative cohort (unpaired Student’s t-test, P = .0001). Accordingly, significantly shorter telomeres were detected in GBM tissues derived from older patients (>60 y at diagnosis, P < .0001). While no association of telomere parameters with MGMT promoter status was found, all tumors with IDH1 mutation (6/100) were negative for both hTERT expression and TA and harbored significantly longer telomeres. Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively  on the younger patient subgroup (</=60 y, both P < .005; >60 y, both ns). Conclusions Telomerase activation is not an independent prognostic parameter in GBM but predicts aggressive tumor behavior solely in a younger patient cohort.

 

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[477]

TÍTULO / TITLE:  - EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell. 2013 Feb 11;23(2):238-48. doi: 10.1016/j.ccr.2013.01.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2013.01.007

AUTORES / AUTHORS:  - Day BW; Stringer BW; Al-Ejeh F; Ting MJ; Wilson J; Ensbey KS; Jamieson PR; Bruce ZC; Lim YC; Offenhauser C; Charmsaz S; Cooper LT; Ellacott JK; Harding A; Leveque L; Inglis P; Allan S; Walker DG; Lackmann M; Osborne G; Khanna KK; Reynolds BA; Lickliter JD; Boyd AW

INSTITUCIÓN / INSTITUTION:  - Brain Cancer Research Unit and Leukaemia Foundation Research Unit, Queensland Institute of Medical Research, Brisbane 4006, Australia. bryan.day@qimr.edu.au

RESUMEN / SUMMARY:  - Significant endeavor has been applied to identify functional therapeutic targets  in glioblastoma (GBM) to halt the growth of this aggressive cancer. We show that  the receptor tyrosine kinase EphA3 is frequently overexpressed in GBM and, in particular, in the most aggressive mesenchymal subtype. Importantly, EphA3 is highly expressed on the tumor-initiating cell population in glioma and appears critically involved in maintaining tumor cells in a less differentiated state by  modulating mitogen-activated protein kinase signaling. EphA3 knockdown or depletion of EphA3-positive tumor cells reduced tumorigenic potential to a degree comparable to treatment with a therapeutic radiolabelled EphA3-specific monoclonal antibody. These results identify EphA3 as a functional, targetable receptor in GBM.

 

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[478]

TÍTULO / TITLE:  - Sequence Variations in the von Hippel-Lindau Tumor Suppressor Gene in Patients with Intracranial Aneurysms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Stroke Cerebrovasc Dis. 2013 Feb 19. pii: S1052-3057(13)00022-0. doi: 10.1016/j.jstrokecerebrovasdis.2013.01.016.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jstrokecerebrovasdis.2013.01.016

AUTORES / AUTHORS:  - Klingler JH; Kruger MT; Lemke JR; Jilg C; Van Velthoven V; Zentner J; Neumann HP; Glasker S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.

RESUMEN / SUMMARY:  - BACKGROUND: The rupture of intracranial aneurysms leads to subarachnoid hemorrhage, which is often associated with poor outcome. Preventive treatment of  unruptured intracranial aneurysms is possible and recommended. However, the lack  of candidate genes precludes identifying patients at risk by genetic analyses. We observed intracranial aneurysms in 2 patients with von Hippel-Lindau (VHL) disease and the known disease-causing mutation c.292T > C (p.Tyr98His) in the VHL tumor suppressor gene. This study investigates whether the VHL gene is a possible candidate gene for aneurysm formation. METHODS: Patients with intracranial aneurysms admitted to our department between 2006 and 2009 were enrolled. The peripheral leukocyte DNA of 200 patients was investigated for sequence variations in the VHL gene using denaturing high performance liquid chromatography. Peripheral leukocyte DNA of 100 randomly sampled probands was investigated as a control group. The allelic frequencies of sequence variations between both groups were compared using the Fisher exact test. RESULTS: Fourteen of 200 patients with intracranial aneurysms had sequence variations at 6 different loci in the VHL gene. In contrast, no sequence variations were identified in 100 probands in the  control group (P = 0.0062). However, none of the single-sequence variations had a statistically significant difference in the allelic frequencies compared to the control group. CONCLUSIONS: There is accumulating evidence for a genetic basis of aneurysm development. Our investigations lead to the conclusion that the VHL gene is potentially involved in the formation of intracranial aneurysms in a subset of patients. Additional candidate genes need to be identified in order to develop sensitive genetic screening for at-risk patients.

 

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[479]

TÍTULO / TITLE:  - Meningioma 1 (MN1) expression: Refined risk stratification in acute myeloid leukemia with normal cytogenetics (CN-AML).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hematology. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1179/1607845412Y.0000000065

AUTORES / AUTHORS:  - Aref S; Ibrahim L; Morkes H; Azmy E; Ebrahim M

RESUMEN / SUMMARY:  - Prognostic stratification of cytogenetic normal acute myeloid leukemia (CN-AML) is an area of active research. The aim of this study was to determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in CN-AML. One hundred patients with CN-AML were diagnosed; MN1 expressions were analyzed using quantitative real-time polymerase chain reaction. High expressions were detected in 48 (48%) patients (expression range: 2.35-31.99, mean: 13.9 +/- 8.49) in comparison with 52 (52%) patients with low expression (expression range: 0.02-2.3, mean: 0.68 +/- 0.77). The course of the disease in patients with high MN1 expression was unfavorable. Patients with high MN1 expression was associated  with significant low complete remission rate (62.5 vs. 8.4%, high vs. low MN1, P  = 0.001) and high mortality rate (75% vs. 46.1, P = 0.03). AML patients with high MN1 expression tended to be refractory (37.5 vs. 19.2%, P = 0.00) and relapse risk (54.1 vs. 23%, P = 0.02). Multivariable analysis confirmed high MN1 expression as an independent risk factor for disease-free survival and overall survival. In conclusion, MN1 overexpression independently predicts bad clinical outcome in CN-AML patients.

 

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[480]

TÍTULO / TITLE:  - Insulin receptor, IRS1, IRS2, INSIG1, INSIG2, RRAD, and BAIAP2 gene expressions in glioma U87 cells with ERN1 loss of function: effect of hypoxia and glutamine or glucose deprivation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Regul. 2013 Jan;47(1):15-26.

AUTORES / AUTHORS:  - Minchenko DO; Kharkova AP; Hubenia OV; Minchenko OH

RESUMEN / SUMMARY:  - Objective. The purpose of this study was to examine: 1) the association between the expression of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1) and 2 (IRS2), insulin inducible gene 1 (INSIG1) and 2 (INSIG2), Ras-related associated with diabetes (RRAD), and brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) genes in glioma cells and 2) the function of the endoplasmic reticulum stress signaling, mediated by endoplasmic reticulum to nuclei-1 (ERN1) and regulation of these gene expressions by hypoxia  and glucose or glutamine deprivation.Methods. The expression of the INSR, IRS1, IRS2, INSIG1, INSIG2, RRAD, and BAIAP2 genes in the glioma cell line U87 and its  subline with ERN1 loss of function was studied by qPCR. The cells were exposed to a mix of 3 % oxygen and 5 % carbon dioxide and glucose or glutamine deprivation.Results. The blockade of the ERN1 signaling enzyme function in glioma cells leads to the gene expression increase in INSR, INSIG2, and IRS2 and decrease in the BAIAP2 and RRAD genes. Hypoxia affected the expression of the INSR, IRS1, IRS2, INSIG1, INSIG2, and BAIAP2 genes with more significant changes  in INSIG2 and IRS2 genes. Furthermore, the effect of hypoxia on expression of these genes was mostly dependent on the ERN1 signaling enzyme function. The data  also show that glucose or glutamine deprivation may change the expression of the  genes studied and that the suppression of the ERN1 enzyme function usually modifies the effect of the glucose or glutamine deprivation.Conclusions. Results  of this study demonstrated the dependence of INSR and related to insulin receptor signaling gene expressions in U87 glioma cells on ERN1 enzyme function indicating its participation in the regulation of metabolic and proliferative processes via  endoplasmic reticulum stress which is important component of tumor growth and metabolic diseases. Moreover, hypoxia and glucose or glutamine deprivation are controlled by the expression of insulin receptor and related to insulin signaling genes mostly via ERN1 enzyme signaling. Keywords: insulin receptor, IRS2, INSIG2, gene expressions, glioma U87 cells, ERN1, hypoxia, glucose deprivation.

 

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[481]

TÍTULO / TITLE:  - MiR-106a is an independent prognostic marker in patients with glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not001

AUTORES / AUTHORS:  - Zhao S; Yang G; Mu Y; Han D; Shi C; Chen X; Deng Y; Zhang D; Wang L; Liu Y; Hou X; Wang C; Wu J; Liu H; Wang L; Zhang G; Qi J; Fang X; Shi C; Ai J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China (S.Z., G.Y., Y.M., D.H., X.C., Y.D., D.Z., Y.L., X.H., C.W., J.W., H.L., L.W., G.Z.); Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China (S.Z., G.Y., Y.M., D.H., X.C., Y.D., D.Z., Y.L., X.H., C.W., J.W., H.L., L.W., G.Z.); Department of Neurosurgery, New York University Langone Medical Center and School of Medicine, New York, New York (C.S.); Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China (L.W., J.A.); Section of Neurosurgery, Department of Surgery, The University of Chicago Medical Center and Pritzker School of Medicine, Chicago, Illinois (C.S.); Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang  Province, People’s Republic of China (J.Q., X.F.).

RESUMEN / SUMMARY:  - BackgroundVery little is known regarding correlation of micro RNA (miR)-106a with clinical outcomes of patients with glioblastoma multiforme (GBM). This study determined whether miR-106a could be used as an independent prognostic biomarker  in those patients.MethodsA total of 156 GBM patients were divided into 2 cohorts. In the first cohort, matched fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples were collected from 24 GBM patients, while in the second cohort, only FFPE samples were collected from 132 GBM patients. MiR-106a expression levels were examined by quantitative real-time PCR in the 2 cohorts and further validated by in situ hybridization assay in the second cohort. The correlation between miR-106a expression levels and overall survival was evaluated in the second cohort of 114 GBM patients available for follow-up by a log-rank test and  a multivariate Cox proportional hazards model.ResultsOur data showed a very good  correlation of miR-106a or U6 expression between fresh frozen and FFPE GBM specimens, with Pearson’s correlation coefficients of 0.849 and 0.823, respectively (P < .001). Their expression levels in archival FFPE samples were quite stable for at least 7 years when stored at room temperature. Multivariate analysis revealed that the expression level of miR-106a was an independent and significant predictor of overall survival in GBM patients (P = .011).ConclusionsMiR-106a expression was relatively abundant and stable in a large cohort of archival FFPE GBM specimens and could be used as an independent prognostic biomarker in those patients. Thus, miR-106a can be used to predict prognosis and treatment response in individual GBM patients.

 

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[482]

TÍTULO / TITLE:  - Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Transl Med. 2013 Mar 20;11:69. doi: 10.1186/1479-5876-11-69.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-69

AUTORES / AUTHORS:  - Chu SH; Ma YB; Feng DF; Li ZQ; Jiang PC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shanghai 3rd People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 280 Mohe Road, Baoshan District, Shanghai 201900,  China. shenghuachu@126.com.

RESUMEN / SUMMARY:  - BACKGROUND: Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter  methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy. PATIENTS AND METHODS: SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients. RESULTS: SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall  survival were observed in 35 patients without TMZ therapy. CONCLUSIONS: These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.

 

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[483]

TÍTULO / TITLE:  - Multidisciplinary care of patients with brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Oncol Clin N Am. 2013 Apr;22(2):161-78. doi: 10.1016/j.soc.2012.12.011. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.soc.2012.12.011

AUTORES / AUTHORS:  - Huang T; Mueller S; Rutkowski MJ; Han SJ; Bloch O; Barani IJ; Parsa AT; Chang SM

INSTITUCIÓN / INSTITUTION:  - Division of Hematology Oncology, Department of Pediatrics, University of California, San Francisco, 505 Parnassus Avenue M649, San Francisco, CA 94143, USA.

RESUMEN / SUMMARY:  - Patients with brain tumors are some of the most complex patients in the medical system, necessitating treatment teams of multiple subspecialists for optimal care. This article examines the roles of these subspecialists, with the goal of summarizing standard-of-care practices, recent therapeutic advances, and ongoing  clinical investigations within each subspecialty.

 

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[484]

TÍTULO / TITLE:  - Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1100-2

AUTORES / AUTHORS:  - Koelsche C; Wohrer A; Jeibmann A; Schittenhelm J; Schindler G; Preusser M; Lasitschka F; von Deimling A; Capper D

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Ruprecht-Karls-Universitat Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Ganglioglioma is a rare CNS tumor with a benign biological behavior. Recently, the BRAF V600E mutation was identified in approximately 20 % of gangliogliomas. Here, we analyzed a total of 71 gangliogliomas for BRAF V600E mutational status by VE1 immunohistochemistry and direct DNA sequencing. The BRAF V600E mutation was detected in 41/71 (58 %) gangliogliomas by immunohistochemistry. DNA sequencing was concordant in 60 of 62 analyzed cases. BRAF status was compared with clinical, histological and immunohistochemical data. Presence of the BRAF V600E mutation was associated with expression of synaptophysin in the tumor (p =  0.0008), presence of dysplastic neurons (p = 0.011) and lymphocytic cuffs (p = 0.018), and with younger age (p = 0.0054). Extensive hemosiderin deposition within the tumor was significantly associated with BRAF wild-type status (p = 0.042). No significant association was found with proliferation (p = 0.053), presence of phospho ERK (p = 0.1) or senescence marker p16(INK4a) (p = 0.22). Using VE1, we localized the BRAF V600E-mutated protein predominantly to the neuronal compartment, indicating that BRAF mutations occur in cells that have the capacity to differentiate into ganglionic cells. In many cases mutant BRAF is additionally expressed by the glial compartment, indicating that in these cases the cell targeted by BRAF mutation was likely capable of differentiating along both the ganglionic and glial lineages. No cases with an exclusive expression of  BRAF V600E in the glial compartment were observed. Thus, using VE1 we identified  the neuronal compartment as an essential part of this mixed glioneuronal tumor.

 

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[485]

TÍTULO / TITLE:  - Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not020

AUTORES / AUTHORS:  - Miyatake SI; Furuse M; Kawabata S; Maruyama T; Kumabe T; Kuroiwa T; Ono K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan (S.-I.M., M.F., S.K., T.K.); Department of Neurosurgery, Tokyo Women’s Medical College, Shinjuku, Tokyo, Japan (T.M.); Department of Neurosurgery, Tohoku University, Miyagi, Japan (T.K.); Radiation Oncology and Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori, Osaka, Japan (K.O.).

RESUMEN / SUMMARY:  - BackgroundBevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas.MethodsTwo recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression.ResultsThe first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is  tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No  tumor progression was observed 8 months after BNCT.ConclusionsBevacizumab showed  marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.

 

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[486]

TÍTULO / TITLE:  - F-FDOPA PET/CT for detection of recurrence in patients with glioma: prospective comparison with F-FDG PET/CT.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2384-0

AUTORES / AUTHORS:  - Karunanithi S; Sharma P; Kumar A; Khangembam BC; Bandopadhyaya GP; Kumar R; Gupta DK; Malhotra A; Bal C

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

RESUMEN / SUMMARY:  - PURPOSE: Differentiation between recurrence and radiation necrosis in patients with glioma is crucial, since the two entities have completely different management and prognosis. The purpose of the present study was to compare the efficacies of 18F-FDG PET/CT and 3,4-dihydroxy-6-[18F]fluoro-phenylalanine (18F-FDOPA) PET/CT in detection of recurrent gliomas. METHODS: A total of 28 patients (age 38.82 +/- 1.25 years; 85.7 % men) with histopathologically proven glioma with clinical/imaging suspicion of recurrence were evaluated using 18F-FDG PET/CT and 18F-FDOPA PET/CT. 18F-FDG PET/CT and 18F-FDOPA PET/CT images were evaluated qualitatively and semiquantitatively. The combination of clinical follow-up, repeat imaging and/or biopsy (when available) was taken as the reference standard. RESULTS: Based on the reference standard, 21 patients were positive and 7 were negative for tumour recurrence. The sensitivity, specificity  and accuracy of 18F-FDG PET/CT were 47.6 %, 100 % and 60.7 %, respectively, and those of 18F-FDOPA PET/CT were 100 %, 85.7 % and 96.4 %, respectively. The results of 18F-FDG PET/CT and 18F-FDOPA PET/CT were concordant in 57.1 % of patients (16 of 28) and discordant in 42.9 % (12 of 28). The difference in the findings between 18F-FDG PET/CT and 18F-FDOPA PET/CT was significant (P = 0.0005, McNemar’s test). The difference was significant for low-grade tumours (P = 0.0039) but not for high-grade tumours (P = 0.250). CONCLUSION: 18F-FDOPA PET/CT  is highly sensitive and specific for detection of recurrence in glioma patients.  It is superior to 18F-FDG PET/CT for this purpose and is especially advantageous  in patients with low-grade gliomas.

 

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[487]

TÍTULO / TITLE:  - Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pituitary. 2013 Mar 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0473-5

AUTORES / AUTHORS:  - Alkabbani AG; Mon SY; Hatipoglu B; Kennedy L; Faiman C; Weil RJ; Hamrahian AH

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue/F-20, Cleveland, OH, 44195, USA.

RESUMEN / SUMMARY:  - The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time,  whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8 %) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent  of patients (n = 48) had a macroadenoma. Forty-two (52.5 %) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these  patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size,  is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

 

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[488]

TÍTULO / TITLE:  - Hippocampal metabolomics using ultrahigh-resolution mass spectrometry reveals neuroinflammation from Alzheimer’s disease in CRND8 mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anal Bioanal Chem. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00216-013-6825-1

AUTORES / AUTHORS:  - Lin S; Liu H; Kanawati B; Liu L; Dong J; Li M; Huang J; Schmitt-Kopplin P; Cai Z

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, China.

RESUMEN / SUMMARY:  - In the wake of genomics, metabolomics characterizes the small molecular metabolites revealing the phenotypes induced by gene mutants. To address the metabolic signatures in the hippocampus of the amyloid-beta (Abeta) peptides produced in transgenic (Tg) CRND8 mice, high-field ion cyclotron resonance-Fourier transform mass spectrometry supported by LC-LTQ-Orbitrap was introduced to profile the extracted metabolites. More than 10,000 ions were detected in the mass profile for each sample. Subsequently, peak alignment and the 80 % rule followed by feature selection based on T score computation were performed. The putative identification was also conducted using the highly accurate masses with isotopic distribution by interfacing the MassTRIX database as well as MS/MS fragmentation generated in the LTQ-Orbitrap after chromatographic separation. Consequently, 58 differentiating masses were tentatively identified while up to 44 differentiating elemental compositions could not be biologically annotated in the databases. Nonetheless, of the putatively annotated masses, eicosanoids in arachidonic acid metabolism, fatty acid beta-oxidation disorders as well as disturbed glucose metabolism were highlighted as metabolic traits of Abeta toxicity in Tg CRND8 mice. Furthermore,  a web-based bioinformatic tool was used for simulation of the metabolic pathways. As a result of the obtained metabolic signatures, the arachidonic acid metabolism dominates the metabolic perturbation in hippocampal tissues of Tg CRND8 mice compared to non-Tg littermates, indicating that Abeta toxicity functions neuroinflammation in hippocampal tissue and new theranostic opportunities might be offered by characterization of altered arachidonic acid metabolism for Alzheimer’s disease.

 

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[489]

TÍTULO / TITLE:  - Erratum to: Clinicopathological evaluation of cyclooxygenase-2 expression in meningioma: immunohistochemical analysis of 76 cases of low and high-grade meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0144-2

AUTORES / AUTHORS:  - Kato Y; Nishihara H; Mohri H; Kanno H; Kobayashi H; Kimura T; Tanino M; Terasaka S; Tanaka S

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Pathology, Hokkaido University, Graduate School of Medicine, Sapporo, Japan.

 

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[490]

TÍTULO / TITLE:  - Secondary hematological malignancies associated with temozolomide in patients with glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not036

AUTORES / AUTHORS:  - Momota H; Narita Y; Miyakita Y; Shibui S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan (H.M., Y.N., Y.M., S.S.).

RESUMEN / SUMMARY:  - BackgroundThe alkylating agent temozolomide (TMZ) is widely used for the treatment of gliomas. Although reports of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) associated with TMZ are accumulating, it remains unclear whether TMZ has the same leukemogenic potential as other alkylating agents.MethodsWe performed a  single-institution retrospective analysis using a database of 359 glioma patients given nimustine (ACNU)-based therapy, TMZ-based therapy, or combination therapy,  who were followed up for a minimum of 2 months, between January 1990 and December 2009, at the National Cancer Center Hospital in Japan.ResultsOf the 359 patients, 225 received ACNU alone or ACNU plus other chemotherapeutic drugs (ACNU-based group; median follow-up period, 31.4 mo), 63 patients received ACNU-based therapy followed by TMZ therapy (ACNU-TMZ group; median follow-up period, 19.1 mo), and 71 patients received TMZ alone or TMZ plus other chemotherapeutic drugs (TMZ-based group; median follow-up period, 16.9 mo). Three patients in the ACNU-based group developed MDS/AML (incidence rate: 2.9 cases per 1000 person-years), 2 patients in the ACNU-TMZ group developed MDS/AML (13.0 cases per 1000 person-years), and 1 patient in the TMZ-based group developed ALL (9.9 cases per 1000 person-years).ConclusionsDespite the limitations of this study, published reports and our results suggest that TMZ induces secondary hematological malignancies, particularly ALL, and might shorten the latency period when used in combination with other chemotherapeutic agents.

 

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[491]

TÍTULO / TITLE:  - Increased serum interleukin-22 levels in patients with PRL-secreting and non-functioning pituitary macroadenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pituitary. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0468-2

AUTORES / AUTHORS:  - Cannavo S; Ferrau F; Cotta OR; Saitta S; Barresi V; Cristani MT; Saija A; Ruggeri RM; Trimarchi F; Gangemi S

INSTITUCIÓN / INSTITUTION:  - Section of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico “G. Martino” (Pad. H, floor 4), Via Consolare Valeria 1, 98125, Messina, Italy.

RESUMEN / SUMMARY:  - Cytokines’ involvement in tumorigenesis has been hypothesized. Interleukin-22 (IL-22) is implicated in proliferative and anti-apoptotic pathways via its receptor IL-22R. Its role in pituitary adenomas has never been investigated. Twenty-seven patients with pituitary macroadenomas (PA, 21 males, mean age 53.8 +/- 14.4 years) and 30 healthy controls (19 males, mean age 50.4 +/- 8.4 years) were enrolled. Out of 27 PA patients, 17 had a non-functioning tumour (NFPA) and  10 a PRL-secreting adenoma (PRL-oma). Serum IL-22 levels were measured in both patients and controls. Immunohistochemical (IHC) tumoral IL-22R expression was evaluated in 10 patients with NFPA and 4 with PRL-oma. IL-22 levels were significantly higher in PA patients than in controls [32.47 (11.29-70.12) vs. 5.58 (0.19-21.46) pg/mL, p < 0.0001] but did not correlate with tumor maximum diameter and were not associated to pituitary function impairment. PRL-oma patients had significantly higher IL-22 levels than NFPA patients [37.18 (14.82-70.12) vs. 21.29 (11.29-56) pg/mL, p = 0.039]. IHC revealed a strong IL-22R staining in 100 % of PRL-omas and 60 % of NFPAs. We provide the first evidence of increased serum IL-22 levels in patients with pituitary macroadenoma, especially in PRL-omas, regardless of tumor size and/or degree of pituitary function impairment. We also demonstrated the expression of IL22R in all PRL-omas and in 60 % of NFPAs.

 

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[492]

TÍTULO / TITLE:  - M2 receptor activation inhibits cell cycle progression and survival in human glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Mol Med. 2013 Mar 14. doi: 10.1111/jcmm.12038.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jcmm.12038

AUTORES / AUTHORS:  - Ferretti M; Fabbiano C; Bari MD; Conte C; Castigli E; Sciaccaluga M; Ponti D; Ruggieri P; Raco A; Ricordy R; Calogero A; Tata AM

INSTITUCIÓN / INSTITUTION:  - Department of Biology and Biotechnologies Charles Darwin, Research Centre of Neurobiology Daniel Bovet, La Sapienza, University of Rome, P.le Aldo Moro, Roma, Italy.

RESUMEN / SUMMARY:  - Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated in their growth and propagation. In this work we have demonstrated that M2 muscarinic receptors are expressed in glioblastoma human specimens and in glioblastoma cell lines. Moreover, we have characterized the effects of the M2 agonist arecaidine on cell growth and survival both in two different glioblastoma cell lines (U251MG and U87MG) and in primary cultures obtained from different human biopsies. Cell growth analysis has demonstrated that the M2 agonist arecaidine strongly decreased cell proliferation in both glioma cell lines and primary cultures. This effect was dose and time dependent.  FACS analysis has confirmed cell cycle arrest at G1/S and at G2/M phase in U87 cells and U251 respectively. Cell viability analysis has also shown that arecaidine induced severe apoptosis, especially in U251 cells. Chemosensitivity assays have, moreover, shown arecaidine and temozolomide similar effects on glioma cell lines, although IC50 value for arecaidine was significantly lower than temozolomide. In conclusion, we report for the first time that M2 receptor activation has a relevant role in the inhibition of glioma cell growth and survival, suggesting that M2 may be a new interesting therapeutic target to investigate for glioblastoma therapy.

 

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[493]

TÍTULO / TITLE:  - Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain Tumor Symposium.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E9. doi: 10.3171/2012.12.FOCUS12349.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12349

AUTORES / AUTHORS:  - Jones PS; Dunn GP; Barker FG 2nd; Curry WT; Hochberg FH; Cahill DP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

RESUMEN / SUMMARY:  - Object The authors’ goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence. Methods On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development. Results The meeting consisted of 3 scientific sessions ranging  from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and  treatment. Conclusions The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation  and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease.

 

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[494]

TÍTULO / TITLE:  - Adoptive transfer of genetically modified Wilms’ tumor 1-specific T cells in a novel malignant skull base meningioma model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not007

AUTORES / AUTHORS:  - Iwami K; Natsume A; Ohno M; Ikeda H; Mineno J; Nukaya I; Okamoto S; Fujiwara H; Yasukawa M; Shiku H; Wakabayashi T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya , Aichi, Japan (K.I., A.N., M.O., T.W.); Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan (H.I., H.S.); Center for Cell and Gene Therapy, Takara Bio Inc., Otsu, Shiga , Japan (J.M., I.N., S.O.); Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Matsuyama, Ehime, Japan (H.F., M.Y.).

RESUMEN / SUMMARY:  - BackgroundMeningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat meningiomas. The goal of this study was to investigate the potential of build-in short interfering RNA-based Wilms’ tumor protein (WT1)-targeted adoptive immunotherapy in a reproducible mouse model of malignant  skull base meningioma that we recently established.MethodsWe compared WT1 mRNA expression in human meningioma tissues and gliomas by quantitative real-time reverse-transcription polymerase chain reaction. Human malignant meningioma cells (IOMM-Lee cells) were labeled with green fluorescent protein (GFP) and implanted  at the skull base of immunodeficient mice by using the postglenoid foramen injection (PGFi) technique. The animals were sacrificed at specific time points for analysis of tumor formation. Two groups of animals received adoptive immunotherapy with control peripheral blood mononuclear cells (PBMCs) or WT1-targeted PBMCs.ResultsHigh levels of WT1 mRNA expression were observed in many meningioma tissues and all meningioma cell lines. IOMM-Lee-GFP cells were successfully implanted using the PGFi technique, and malignant skull base meningiomas were induced in all mice. The systemically delivered WT1-targeted PBMCs infiltrated skull base meningiomas and significantly delayed tumor growth and increased survival time.ConclusionsWe have established a reproducible mouse model of malignant skull base meningioma. WT1-targeted adoptive immunotherapy appears to be a promising approach for the treatment of difficult-to-treat meningiomas.

 

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[495]

TÍTULO / TITLE:  - Which drug or drug delivery system can change clinical practice for brain tumor therapy?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not016

AUTORES / AUTHORS:  - Siegal T

INSTITUCIÓN / INSTITUTION:  - Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (T.S.).

RESUMEN / SUMMARY:  - The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers  and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice.The English literature was searched for defined search items.Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined.To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These  include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with  any tumor size and brain location.

 

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[496]

TÍTULO / TITLE:  - Magnetic Resonance Imaging Is the Preferred Method to Assess Treatment-Related Skeletal Changes in Children With Brain Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2013 Mar 22. doi: 10.1002/pbc.24536.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24536

AUTORES / AUTHORS:  - Kaste SC; Kaufman RA; Gajjar A; Broniscer A

INSTITUCIÓN / INSTITUTION:  - Department of Radiological Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MSN #220, Memphis, Tennessee 38105; Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee; Department of Radiology, University of Tennessee Health Science Center, Memphis, Tennessee.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the growing skeleton for potential altered skeletalgenesis associated with antiangiogenesis therapy. PATIENTS AND METHODS: Knee radiographs  and magnetic resonance imaging (MRI) were prospectively obtained on patients enrolled on two consecutive clinical trials using vandetanib, a potent oral (VEGF receptor 2) VEGFR-2 inhibitor alone or combined with dasatinib, a multiple tyrosine kinase inhibitor, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). RESULTS: Fifty-nine patients (32 females) underwent 119 MRIs; 51 patients underwent 89 radiographs of the knees. The median age at enrollment was 6.2 years (range, 2.4-17.6 years). The dose of vandetanib ranged from 50 to 145 mg/m2 /day. The median treatment duration was 205 days. Only two patients have not experienced disease progression after 18 and 60 months from diagnosis. MRI identified clinically significant premature physeal fusion in both knees of one patient, focal physeal thickening in one, osteonecrosis in eight patients (present at enrollment in one), and bony spicules crossing the physis in two patients (bilateral in one). MRI follow-up period averaged 5.3 months (range, 0-25.5 months; median, 3.5 months). Radiographs delineated normally fused physes  in two patients but no cases of premature physeal fusion, osteonecrosis or bony spicules. CONCLUSIONS: As MRI provided greater information than radiographs, and  thus would be a more sensitive test to assess skeletalgenesis in pediatric patients. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.

 

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[497]

TÍTULO / TITLE:  - Slower processing speed after treatment for pediatric brain tumor and acute lymphoblastic leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Psychooncology. 2013 Feb 28. doi: 10.1002/pon.3255.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pon.3255

AUTORES / AUTHORS:  - Kahalley LS; Conklin HM; Tyc VL; Hudson MM; Wilson SJ; Wu S; Xiong X; Hinds PS

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Section of Psychology, Baylor College of Medicine, Houston, TX, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Acute lymphoblastic leukemia (ALL) and brain tumor (BT) survivors are at risk for post-treatment IQ declines. The extent to which lower scores represent global cognitive decline versus domain-specific impairment remains unclear. This study examined discrepancies between processing speed and estimated IQ (EIQ) scores and identified clinical characteristics associated with score discrepancies in a sample of pediatric cancer survivors. PROCEDURE: Survivors (50 ALL, 50 BT) ages 12-17 years completed cognitive testing. The Wechsler Abbreviated Scale of Intelligence provided an untimed measure of general reasoning ability (EIQ). The age-appropriate Wechsler Intelligence Scale provided a Processing Speed Index (PSI) score. Scores were examined and compared. RESULTS: Survivors’ PSI scores were lower than their EIQ scores (BT t(45) = 6.3, p < 0.001; ALL t(49) = 6.9, p < 0.001). For BT survivors, lower PSI scores were associated with history of craniospinal irradiation, t(44) = 3.3, p < 0.01. For ALL survivors, lower PSI scores were associated with male gender, grade retention, and time since diagnosis, F(3, 46) = 10.1, p < 0.001. Clinically significant EIQ-PSI score discrepancies were identified in 41.3% of BT and 14.0%  of ALL survivors. CONCLUSIONS: Many pediatric BT and ALL survivors exhibit slower processing speed than expected for age, whereas general reasoning ability remains largely intact. Risk factors associated with larger EIQ-PSI discrepancies include the following: BT diagnosis, craniospinal irradiation (BT only), male gender, and younger age at diagnosis (ALL only). Grade retention was frequent and associated  with lower EIQ scores (both groups) and PSI scores (ALL only). Describing post-treatment cognitive declines using global measures of intellectual ability may underestimate dysfunction or fail to isolate specific underlying deficits contributing to impairment. Copyright © 2013 John Wiley & Sons, Ltd.

 

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[498]

TÍTULO / TITLE:  - The frequency, longitudinal course, clinical associations, and causes of emotional distress during primary treatment of cerebral glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not009

AUTORES / AUTHORS:  - Rooney AG; McNamara S; Mackinnon M; Fraser M; Rampling R; Carson A; Grant R

INSTITUCIÓN / INSTITUTION:  - Edinburgh Centre for Neuro-Oncology, Western General Hospital, Edinburgh, UK (A.G.R., S.M., R.G.); Beatson West of Scotland Cancer Centre, Gartnaval General Hospital, Glasgow, UK (M.M., M.F., R.R.); Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK (A.C.).

RESUMEN / SUMMARY:  - BackgroundRelatively little is known about the frequency, longitudinal course, independent associations, and reported causes of emotional distress in adults with primary cerebral glioma. We aimed to describe these features in an observational study.MethodsThis was a twin-center prospective cohort study. Eligible adults were those with a new histological diagnosis of glioma who were receiving active management. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and problem checklist. Subjects were sampled at 3 timepoints: T1 (shortly after starting chemo/radiotherapy), T2  (3 months later), and T3 (6 months later).ResultsT1 n = 154; T2 n = 103; T3 n = 83. Significant distress was present in 36.4 +/- 7.6% at T1, 35.9 +/- 9.3% at T2, and 33.7 +/- 10.2% at T3. Longitudinally, subjects with high distress at T1 (median Distress Thermometer score = 8; interquartile range [IQR] 7-9) remained highly distressed on follow-up (T2 median = 8, IQR 6-8; T3 median = 7, IQR 5-8) (Friedman test P = .304). Younger age, functional impairment, and concurrent major depressive disorder were independently associated with high distress (logistic regression chi(2) for model = 39.882, P < .001, R(2) = 0.312). The most frequently reported causes of distress were worry, fatigue, sleep difficulties, and sadness. Emotional difficulties were among the most common causes of distress at all 3 timepoints.ConclusionsAt each timepoint, one-third of patients reported  significant emotional distress, which persisted during follow-up among those initially highly distressed. Young, functionally impaired, and depressed glioma patients may particularly benefit from increased support.

 

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[499]

TÍTULO / TITLE:  - Unexpected clinical course during treatment of a TSH-secreting pituitary adenoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Pract. 2013 Mar 19:1-11.

            ●● Enlace al texto completo (gratuito o de pago) 4158/EP13036.CR

AUTORES / AUTHORS:  - Glynn N; Agha A

INSTITUCIÓN / INSTITUTION:  - Division of Neuroendocrinology, Beaumont Hospital & the RCSI Medical School, Dublin, Ireland.

RESUMEN / SUMMARY:  - Objective: To report the rare occurrence of transition from a thyrotropinoma into a secretory thyro-somatotroph adenoma during medical treatment with somatostatin  analogue.Methods: We report the case of a patient with a thyrotroph pituitary adenoma who developed de novo evidence of growth hormone co-secretion following one year of successful medical treatment.Results: A 78-year-old woman was diagnosed with a TSH-secreting pituitary macroadenoma (TSHoma) based on classical clinical and biochemical features. There was no clinical or biochemical evidence  of growth hormone (GH) co-secretion. She declined surgical resection and was treated with primary medical therapy - Octreotide LAR to which she had an anti-tumor and anti-secretory response. However, following twelve months of successful medical treatment she developed de novo hypersecretion of growth hormone despite involution of the tumour mass. TSH secreting pituitary adenomas may rarely become plurihormonal during apparently successful medical treatment. This may represent an unusual form of secondary resistance to somatostatin analogue or the rarer phenomenon of tumor transformation into a secretory thyro-somatotroph adenoma.Conclusion: The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with TSH secreting pituitary adenomas.

 

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[500]

TÍTULO / TITLE:  - Hypernatremia-associated myelinolysis following the management of sepsis in a patient with glioblastoma treated with radiotherapy and temozolomide.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neurol Belg. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13760-013-0177-7

AUTORES / AUTHORS:  - Dixit S; Salvage D; Rajaraman C; Hingorani M; Rowland-Hill C

INSTITUCIÓN / INSTITUTION:  - Department of Oncology and Haematology, Castle Hill Hospital, Hull and East Yorkshire Hospitals NHS Trust, Castle Road, Cottingham, Hull, HU16 5JQ, UK, sanjay.dixit@hey.nhs.uk.

 

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[501]

TÍTULO / TITLE:  - Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not028

AUTORES / AUTHORS:  - Kanno H; Nishihara H; Wang L; Yuzawa S; Kobayashi H; Tsuda M; Kimura T; Tanino M; Terasaka S; Tanaka S

INSTITUCIÓN / INSTITUTION:  - Laboratory of Cancer Research, Department of Pathology (H.K., S.Y., M.T., T.K., M.T., S.T.), Laboratory of Translational Pathology (H.N., L.W., S.T.), and Department of Neurosurgery (H.K., S.T.), Hokkaido University School of Medicine,  Sapporo, Japan.

RESUMEN / SUMMARY:  - BackgroundCD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients’ poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression.MethodsFirst, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated  its roles in tumor progression in vitro and in vivo.ResultsImmunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore,  CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay.ConclusionsTo our knowledge, this is the first  report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.

 

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[502]

TÍTULO / TITLE:  - Prevalence, associations, and predictors of apathy in adult survivors of infantile (<5 years of age) posterior fossa brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):497-505. doi: 10.1093/neuonc/nos320. Epub 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos320

AUTORES / AUTHORS:  - Carroll C; Watson P; Spoudeas HA; Hawkins MM; Walker DA; Clare IC; Holland AJ; Ring HA

INSTITUCIÓN / INSTITUTION:  - Corresponding author: Dr. Howard Ring, MD, Cambridge Intellectual and Developmental Disability Research Group, University of Cambridge. Douglas House,  18b Trumpington Rd., Cambridge, CB2 8AH, UK. har28@cam.ac.uk.

RESUMEN / SUMMARY:  - Background Apathy is associated with pervasive and disadvantageous effects on daily functioning. It has been observed transiently in some children after surgery for posterior fossa tumors. In this study, our objective was to examine prevalence, associations, and predictors of apathy in adult survivors of an infantile posterior fossa brain tumor (PFT). Methods One hundred seventeen adult  survivors of a childhood PFT diagnosed before age 5 years and 60 of their siblings were assessed in a cross-sectional study a mean of 32 years (range, 18-53 years) after survivors’ initial tumor diagnoses, using the Marin Apathy Evaluation Scale (AES), the Weschler Abbreviated Scale of Intelligence and the Composite International Diagnostic Interview for psychiatric disorders. Results Marin Apathy Evaluation Scale, the Weschler Abbreviated Scale of Intelligence reached or exceeded a criterion score for clinically significant apathy in 35% of survivors, compared with 18% in a sibling comparison group. In both siblings and  survivors, apathy was associated with lower verbal and full-scale IQ and, among survivors, with having undergone partial rather than total tumor resection (independent of irradiation status). Apathy was not related to presence of concurrent International Classification of Diseases, 10(th) Revision, depression. Female sex was associated with late apathy after a PFT, with increased likelihood of women reaching the apathy criterion relative to men if they were survivors. Conclusions Clinically significant and potentially treatable apathy occurs relatively commonly in adult survivors of an infantile childhood PFT, particularly women. Clinicians, including those managing posterior fossa pathology in very young children, should be aware of this association, and future research should clarify whether specific treatment-related variables are implicated in increasing this risk of apathy.

 

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[503]

TÍTULO / TITLE:  - Long-term follow-up of surgical treatment of spinal anaplastic astrocytoma in a cat.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Feline Med Surg. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1098612X13478266

AUTORES / AUTHORS:  - Tamura S; Hori Y; Tamura Y; Uchida K

INSTITUCIÓN / INSTITUTION:  - 1Tamura Animal Clinic, Hiroshima, Japan.

RESUMEN / SUMMARY:  - A 10-year-old spayed female chinchilla feline presented with gradually progressive tetraparesis and cervical pain that had begun 1 month before the onset of a 4-day tetraplegic episode. Magnetic resonance imaging revealed a large elliptical intramedullary mass at the fourth cervical vertebrae. The mass was removed surgically and diagnosed as an anaplastic astrocytoma. No neurological abnormalities were observed 3 weeks postsurgery. Magnetic resonance at 3.5 year follow-up revealed neither mass regrowth nor recurrence of signs.

 

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[504]

TÍTULO / TITLE:  - Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):506-10. doi: 10.1093/neuonc/nos321. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos321

AUTORES / AUTHORS:  - Laser BS; Merchant TE; Indelicato DJ; Hua CH; Shulkin BL; Snyder SE

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Thomas E. Merchant, DO, PhD, Division of Radiation Oncology, St Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis,  TN 38105. thomas.merchant@stjude.org.

RESUMEN / SUMMARY:  - Background Fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine ((11)C MET) has little uptake under normal conditions. We prospectively investigated the uptake of (18)F FDG and (11)C MET PET in patients with craniopharyngioma prior to proton therapy. Methods Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using (18)F FDG and (11)C MET. PET and MRI studies were registered to help identify tumor volume. Measurements of maximum standardized uptake value (SUVmax) were taken of the tumor and compared with noninvolved left frontal background white matter using a paired t-test. Uptake was graded using a 4-point scale. Results Median patient age was 9 years (range 5-19). Seven patients were diagnosed by pathology, 1 by cyst fluid aspiration, and 2 by neuroimaging. Median FDG SUVmax for tumor and background were 2.65 and 3.2, respectively. Median MET SUVmax for tumor and background were  2.2 and 1, respectively. There was a significant difference between MET tumor SUVmax and MET background SUVmax (P = .0001). The difference between FDG tumor SUVmax and FDG background SUVmax was not significant (P = .3672). Conclusion (11)C MET PET uptake is significantly greater within the tumor compared with noninvolved background white matter, making it more useful than FDG PET in identifying active tumor in patients with craniopharyngioma. Future work will focus on using (11)C MET PET to discriminate between active and inactive tumor after irradiation.

 

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[505]

TÍTULO / TITLE:  - Extracellular vesicles as prospective carriers of oncogenic protein signatures in adult and pediatric brain tumours.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proteomics. 2013 Mar 18. doi: 10.1002/pmic.201200360.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pmic.201200360

AUTORES / AUTHORS:  - Garnier D; Jabado N; Rak J

INSTITUCIÓN / INSTITUTION:  - Montreal Children’s Hospital, RI MUHC, McGill University, Montreal, Quebec, Canada.

RESUMEN / SUMMARY:  - Extracellular vesicles (EVs), including exosomes, act as biological effectors and carriers of oncogenic signatures in human cancer. The molecular composition and accessibility of EVs in biofluids open unprecedented diagnostic opportunities in  malignancies where tumour tissue is difficult to sample, especially in primary and metastatic brain tumours. The ongoing genetic discovery of driver mutations defines the ever increasing number of distinct molecular subtypes of brain tumours (orphan diseases), a complexity that may soon be translated into alterations in functional proteins and their oncogenic networks. This may likely  be extended to real time changes engendered by the disease progression, tumour heterogeneity, inter-individual variations and therapeutic responses. Realization of these opportunities is dependent on technological progress in such areas as: generation of mutation- and phospho-specific antibodies, antibody array platforms, nanotechnology, microfluidics, nuclear magnetic resonance spectroscopy (NMR), mass-spectrometry (MS) and multiple reaction monitoring (MRM) approaches of quantitative proteomics. Indeed, exploration of EVs as biomarkers and mediators of intercellular communication is associated with considerable challenges, which should not be underestimated. Still, vesiculation emerges as a  unique process that could be harnessed for the benefit of more individualized patient care.

 

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[506]

TÍTULO / TITLE:  - Difficulties in the diagnosis of thyroid paraganglioma: a clinical case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Ter. 2013 Jan;164(1):e35-9. doi: 10.7417/CT.2013.1519.

AUTORES / AUTHORS:  - Calo PG; Lai ML; Guaitoli E; Pisano G; Favoriti P; Nicolosi A; Pinna G; Sorrenti S

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Sciences, University of Cagliari; A.O.U. Presidio di Monserrato, Cagliari; Department of Surgical Sciences, Sapienza, University of Rome; Endocrinology, Nuova casa di cura Decimomannu, Cagliari, Italy.

RESUMEN / SUMMARY:  - Thyroid Paragangliomas are exceptionally rare tumors and only 35 documented cases have been reported in the literature. We report an additional unusual male case of thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A 45-year-old man presented with a solitary thyroid nodule. Physical examination revealed a smooth, well-circumscribed, firm, mobile, painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound examination  showed a 40 mm hypoechoic, non-homogeneous nodule with peri- and intra-nodular vascular flow. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3). He underwent a total thyroidectomy associated to VI level lymphectomy. Histology showed a thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma measuring 0.3 cm in the greatest dimension. Thyroid Paraganglioma  is an elusive tumor. It is difficult to diagnose and should be included in the differential diagnosis of all neuroendocrine tumors of the thyroid, even those arising in men or behaving in a locally aggressive fashion. Clin Ter 2013; 164(1):e35-39. doi:10.7417/CT.2013.1519.

 

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[507]

TÍTULO / TITLE:  - Trends in treatment and outcomes of pediatric craniopharyngioma, 1975-2011.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not026

AUTORES / AUTHORS:  - Cohen M; Bartels U; Branson H; Kulkarni AV; Hamilton J

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, The Hospital for Sick Children, Toronto, ON (M.C., J.H.); Paediatric Brain Tumour Program, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON (U.B.); Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON (H.B.); Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON (A.V.K.); The University of Toronto, ON,  Canada (M.C., U.B., H.B., A.V.K., J.H.).

RESUMEN / SUMMARY:  - BackgroundCraniopharyngioma tumors and their treatment can lead to significant long-term morbidity due to their proximity to vital structures. The optimal treatment has been debated for many years. We aimed to review the long-term outcomes of children treated for craniopharyngioma in our institution over the past decade and describe trends in treatment and outcomes over the past 3 decades.MethodsCharts of children with craniopharyngioma treated and followed at  The Hospital for Sick Children between 2001 and 2011 were reviewed. Data regarding findings at diagnosis, treatment, and long-term outcomes were analyzed. Comparison was made with previously published data from our institution.ResultsData from 33 patients are included; mean age at treatment, 10.7 +/- 4.8 years. In 18 children (55%), the initial surgical approach was tumor cyst decompression with or without adjuvant therapy, compared with only 0-2% in the preceding decades (P < .01). Diabetes insipidus occurred in 55% of children and panhypopituitarism in 58% compared with 88% (P < .01) and 86% (P < .01), respectively, in the previous 10 years. Overall, there was a 36% reduction in the number of children who developed severe obesity compared with the preceding decade. Body mass index at follow-up was associated with body mass index at diagnosis (P = .004) and tumor resection as an initial treatment approach (P = .028).ConclusionsA shift in surgical treatment approach away from gross total resection has led to improved endocrine outcomes. This may have beneficial implications for quality of life in survivors.

 

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[508]

TÍTULO / TITLE:  - Spontaneous resolution of pituitary apoplexy in a giant boy under 10 years old.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Endocrinol Metab. 2012;25(11-12):1177-9.

AUTORES / AUTHORS:  - Chentli F; Bey A; Belhimer F; Azzoug S

INSTITUCIÓN / INSTITUTION:  - Department of Endocrine, and Metabolic Diseases, Bab El Oued University Hospital, Algiers, Algeria. endofarida@hotamail.fr

RESUMEN / SUMMARY:  - AIM: Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association. OBSERVATION: A boy aged 9 years  and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record has been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of visual acuity with  diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient’s brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient’s vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH) = 39 ng/mL, n </= 5, prolactin ( PRL) = 470 ng/mL, n < 15].  Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor. CONCLUSION: This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.

 

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[509]

TÍTULO / TITLE:  - Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos338

AUTORES / AUTHORS:  - Rosati A; Poliani PL; Todeschini A; Cominelli M; Medicina D; Cenzato M; Simoncini EL; Magrini SM; Buglione M; Grisanti S; Padovani A

INSTITUCIÓN / INSTITUTION:  - Neurology Clinic (A.R., A.T., A.P.), Pathology Service (P.L.P., M.C., D.M.), Medical Oncology (S.G., E.L.S.), Neurosurgery Department (M.C.), and Radiotherapy Department (S.M.M., M.B.), Spedali Civili, University of Brescia, Brescia, Italy.

RESUMEN / SUMMARY:  - BackgroundGlutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in  patients with GBM with or without epilepsy and its correlation with survival.MethodsWe conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression.ResultsMedian age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5-58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O(6)-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity  pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses.ConclusionsAbsent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.

 

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[510]

TÍTULO / TITLE:  - Improved facial nerve outcomes using an evolving treatment method for large acoustic neuromas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Otol Neurotol. 2013 Feb;34(2):304-10.

AUTORES / AUTHORS:  - Porter RG; LaRouere MJ; Kartush JM; Bojrab DI; Pieper DR

INSTITUCIÓN / INSTITUTION:  - Michigan Ear Institute, 30055 Northwestern Highway, Farmington Hills, MI 48334, USA.

RESUMEN / SUMMARY:  - OBJECTIVE: To describe a successful paradigm for the treatment of large acoustic  neuromas (vestibular schwannomas). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: The charts of 2,875 acoustic neuroma patients at Michigan Ear Institute were reviewed to identify 153 patients who underwent surgical resection for large acoustic neuromas (>=3 cm) between 2000 and 2009. INTERVENTION(S): Staged surgical resection or single stage surgery with or without adjuvant stereotactic radiosurgery. MAIN OUTCOME MEASURE(S): Postoperative facial nerve outcomes are reported using the House-Brackmann (HB) facial nerve grading scale and compared with historical controls from a literature review. Rates of adverse outcomes are also reported. RESULTS: Seventy-five patients underwent staged surgical resection of their tumors, whereas 78 patients underwent either single stage surgery or surgery with subsequent stereotactic radiosurgery. Eighty-one percent of patients in the staged surgical resection group had a postoperative HB Grade I or II facial nerve function compared with 75% in the single stage surgical group. Overall, 78% of patients in the current study had HB Grade I or II after treatment compared with  a mean of 53% in the literature for similar sized tumors. Our methods including the decision to use staged surgery when necessary, dissection of tumor with stimulating dissector-directed intraoperative monitoring, and use of adjuvant stereotactic radiosurgery are described. CONCLUSION: Using the described paradigm, large acoustic neuromas can be successfully treated with either staged  or single-stage surgical resection with or without adjuvant radiosurgery to obtain more favorable facial nerve outcomes than historically reported controls while minimizing morbidity for the patient.

 

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[511]

TÍTULO / TITLE:  - Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not012

AUTORES / AUTHORS:  - He M; Zuo C; Wang J; Liu J; Jiao B; Zheng J; Cai Z

INSTITUCIÓN / INSTITUTION:  - Department of Pathology (M.H., J.Z., J.W.), Department of Nuclear Medicine (C.Z.), Department of Neurosurgery (J.L.) Changhai Hospital, Shanghai, China; Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China (Z.C., B.J.).

RESUMEN / SUMMARY:  - BackgroundPrimary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological variables of PCNS-DLBCL.MethodsAggregative perivascular tumor cells (APVTs) and reactive perivascular T cell infiltrates (RPVIs) in tumor samples from 62 immunocompetent patients with PCNS-DLBCL were histopathologically and immunohistochemically studied. A mouse brain DLBCL model was established to confirm the special morphological features of PCNS-DLBCL. The therapy, overall response rate (ORR), and overall survival (OS) among patients were followed up.ResultsAPVT was present in 54 (87%) of the 62 cases, whereas RPVI was present  in 20 (32%). Patients with APVT-positive lesions exhibited significantly worse OS, with intermediate to high International Extranodal Lymphoma Study Group (IELSG) scores, compared with patients with RPVI-positive lesions. Among cases of APVT-positive lymphoma, the semiquantitative score of immunostaining of X-box-binding protein (XBP1) and CD44 demonstrated prognostic significance. Multivariate analysis confirmed independent associations between APVT and XBP1 and between CD44 staining and survival.ConclusionsThe presence of APVT and staining of XBP1 and CD44 are independently associated with survival among patients with PCNS-DLBCL. These features could be routinely assessed in histopathological and immunohistochemical specimens.

 

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[512]

TÍTULO / TITLE:  - IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):469-79. doi: 10.1093/neuonc/nos317. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos317

AUTORES / AUTHORS:  - Leu S; von Felten S; Frank S; Vassella E; Vajtai I; Taylor E; Schulz M; Hutter G; Hench J; Schucht P; Boulay JL; Mariani L

INSTITUCIÓN / INSTITUTION:  - Corresponding Authors: Luigi Mariani, MD, Department of Biomedicine, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. lmariani@uhbs.ch); Jean-Louis Boulay, MD, Department of Biomedicine, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland (Jean-Louis.Boulay@unibas.ch.

RESUMEN / SUMMARY:  - Background Low-grade gliomas (LGGs) are rare brain neoplasms, with survival spanning up to a few decades. Thus, accurate evaluations on how biomarkers impact survival among patients with LGG require long-term studies on samples prospectively collected over a long period. Methods The 210 adult LGGs collected  in our databank were screened for IDH1 and IDH2 mutations (IDHmut), MGMT gene promoter methylation (MGMTmet), 1p/19q loss of heterozygosity (1p19qloh), and nuclear TP53 immunopositivity (TP53pos). Multivariate survival analyses with multiple imputation of missing data were performed using either histopathology or molecular markers. Both models were compared using Akaike’s information criterion (AIC). The molecular model was reduced by stepwise model selection to filter out  the most critical predictors. A third model was generated to assess for various marker combinations. Results Molecular parameters were better survival predictors than histology (DeltaAIC = 12.5, P< .001). Forty-five percent of studied patients died. MGMTmet was positively associated with IDHmut (P< .001). In the molecular model with marker combinations, IDHmut/MGMTmet combined status had a favorable impact on overall survival, compared with IDHwt (hazard ratio [HR] = 0.33, P< .01), and even more so the triple combination, IDHmut/MGMTmet/1p19qloh (HR = 0.18, P< .001). Furthermore, IDHmut/MGMTmet/TP53pos triple combination was a significant risk factor for malignant transformation (HR = 2.75, P< .05). Conclusion By integrating networks of activated molecular glioma pathways, the model based on genotype better predicts prognosis than histology and, therefore,  provides a more reliable tool for standardizing future treatment strategies.

 

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[513]

TÍTULO / TITLE:  - Dissecting the Inter-Substrate Navigation of Migrating Glioblastoma Cells with the Stripe Assay Reveals a Causative Role of ROCK.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Neurobiol. 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12035-013-8429-3

AUTORES / AUTHORS:  - Mertsch S; Oellers P; Wendling M; Stracke W; Thanos S

INSTITUCIÓN / INSTITUTION:  - Institute of Experimental Ophthalmology, School of Medicine, Westfalian-Wilhelms  University, Albert Schweitzer Campus 1, Building D15, 48149, Munster, Germany, Sonja.Mertsch@ukmuenster.de.

RESUMEN / SUMMARY:  - A hallmark of gliomas is the growth and migration of cells over long distances within the brain and proliferation within selected niches, indicating that the migrating cells navigate between complex substrates. We demonstrate in the present study a differential preference for migration that depends on Rho-associated coil kinase (ROCK) signaling, using the alternating Bonhoeffer stripe assay. Membrane fractions from nonmyelinated and myelinated brain areas from female rats, purified myelin also from female rats, and commercial extracellular matrix were used as substrates, with each substrate being tested against the others. The human tumor cell lines exhibited a clear preference for extracellular matrix over all other substrates and for myelinated over nonmyelinated tissue. ROCK signaling was different when cells were cultured on either substrate. The ROCK inhibitor Y27632 significantly attenuated and neutralized the preference for extracellular matrix and myelin, indicating that ROCK controls the substrate selectivity. The findings of this study pave the way  for navigation-targeted therapeutics.

 

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[514]

TÍTULO / TITLE:  - The Histone Deacetylase Inhibitor Sodium Butyrate Promotes Cell Death and Differentiation and Reduces Neurosphere Formation in Human Medulloblastoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Neurobiol. 2013 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12035-013-8441-7

AUTORES / AUTHORS:  - Nor C; Sassi FA; de Farias CB; Schwartsmann G; Abujamra AL; Lenz G; Brunetto AL; Roesler R

INSTITUCIÓN / INSTITUTION:  - Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

RESUMEN / SUMMARY:  - Increasing evidence suggests that alterations in epigenetic mechanisms regulating chromatin state play a role in the pathogenesis of medulloblastoma (MB), the most common malignant brain tumor of childhood. Histone deacetylase (HDAC) inhibitors, which increase chromatin relaxation, have been shown to display anticancer activities. Here we show that the HDAC inhibitor sodium butyrate (NaB) markedly increases cell death and reduces colony formation in human MB cell lines. In addition, NaB increased the mRNA expression of Gria2, a neuronal differentiation  marker, in D283 and DAOY cells and reduced the number of neurospheres in D283 cell cultures. Finally, NaB reduced the viability of D283 cells when combined with etoposide. These data show that NaB displays pronounced inhibitory effects on the survival of human MB cells and suggest that NaB might potentiate the effects of etoposide. In addition, our study suggests that HDAC inhibition might  promote the neuronal differentiation of MB cells and provides the first evidence  that an HDAC inhibitor might suppress the expansion or survival of MB cancer stem cells.

 

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[515]

TÍTULO / TITLE:  - Erratum to: Immunohistochemical molecular expression profile of metastatic brain  tumor for potent personalized medicine.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0143-3

AUTORES / AUTHORS:  - Kato Y; Nishihara H; Yuzawa S; Mohri H; Kanno H; Hatanaka Y; Kimura T; Tanino M; Tanaka S

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Pathology, Hokkaido University Graduate School of Medicine,  Sapporo, Japan.

 

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[516]

TÍTULO / TITLE:  - Molecular analysis of a recurrent glioblastoma treated with bevacizumab.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0142-4

AUTORES / AUTHORS:  - Furuta T; Nakada M; Misaki K; Sato Y; Hayashi Y; Nakanuma Y; Hamada JI

INSTITUCIÓN / INSTITUTION:  - Division of Neuroscience, Department of Neurosurgery, Graduate School of Medical  Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

RESUMEN / SUMMARY:  - We treated a case of recurrent glioblastoma (GBM) with bevacizumab and assessed its effect biologically. A 55-year-old man with a left frontal lobe GBM was experiencing recurrence 7 months postoperation. We administered bevacizumab concomitant with temozolomide (TMZ). Follow-up magnetic resonance imaging (MRI) showed dramatic but temporal tumor reduction; however, the patient died of re-recurrent disease 6 months after beginning bevacizumab. We obtained an autopsy and analyzed the detailed molecular change. In the autopsy specimen, the quantity of microvessels was significantly reduced. Vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were downregulated, most likely due to a negative feedback mechanism by blocking of VEGF signaling. Matrix metalloproteinase (MMP)-2 and membrane-type 1 MMP were upregulated, resulting in the higher activation of MMP-2 in the autopsy specimen. MIB-1 staining index and phosphorylation levels of p44/42-mitogen-activated protein kinase did not change, whereas phosphorylated protein kinase B (Akt) was decreased in the autopsy specimen, suggesting compensation and/or amplification of other proliferative signaling pathways such as suppression of apoptosis signaling. Consequently, bevacizumab might inhibit the VEGF autocrine loop, which then causes a change in  molecular expression related not only to enhancement of tumor invasion but also maintenance of tumor proliferation.

 

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[517]

TÍTULO / TITLE:  - Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E7. doi: 10.3171/2012.12.FOCUS12343.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12343

AUTORES / AUTHORS:  - Bagley JH; Babu R; Friedman AH; Adamson C

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Department of Surgery;

RESUMEN / SUMMARY:  - Object Low-grade gliomas (LGGs) are indolent tumors that have the potential to dedifferentiate into malignant high-grade tumors. Recent studies have demonstrated that cerebellar low-grade tumors have a better prognosis than supratentorial tumors, although no study has focused on the risk factors for poor prognosis in cerebellar LGGs in adults. The authors of the current study aimed to address both of these concerns by using a large cohort derived from a national cancer registry and a smaller cohort derived from their institution’s experience. Methods Adults with diagnosed Grade I and Grade II gliomas of the cerebellum were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox proportional hazard models were used to predict rates of survival, and the log-rank test was applied to evaluate differences in Kaplan-Meier survival curves. An institutional cohort was created by isolating all patients whose surgical pathology revealed an LGG of the cerebellum. Excluded from analysis were patients in whom a glioma was first diagnosed under the age of 18 years and those whose tumors could not be definitively determined to arise from the cerebellum. Results Data from the local cohort (11 patients) demonstrated that the most common presenting symptom was headache, which occurred in more than 70% of the cohort. Approximately half of the patients in this cohort had symptomatic improvement after treatment. Results from the SEER cohort (166 patients) revealed that adults with Grade I gliomas were slightly younger than those with Grade II tumors (p < 0.01), but no other demographic differences were  observed. Patients with Grade I tumors were twice as likely to undergo gross-total resection (54% vs 21%), and those with Grade II gliomas were much more likely to receive postoperative radiation (3% vs 48%). Five-year survival was greater in the patients with Grade I gliomas than in those with Grade II lesions (91% vs 70%). Multivariate analysis revealed that an age >/= 40 years (HR 7.30, 95% CI 3.55-15.0, p < 0.0001) and Grade II tumors (HR 2.76, 95% CI 1.12-6.84, p = 0.028) were risk factors for death, whereas female sex was protective (HR 0.28, 95% CI 0.14-0.59, p < 0.001). Log-rank tests revealed that a cerebellar location was protective (p < 0.0001), but this relationship was only true for Grade II tumors (p < 0.0001). Survival in patients with Grade I gliomas  was not different based on the various lesion locations (p = 0.21). Conclusions Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved  survival in patients with cerebellar Grade II gliomas.

 

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[518]

TÍTULO / TITLE:  - Expression Pattern of Id Proteins in Medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Oncol Res. 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9599-4

AUTORES / AUTHORS:  - Snyder AD; Dulin-Smith AN; Houston RH; Durban AN; Brisbin BJ; Oostra TD; Marshall JT; Kahwash BM; Pierson CR

INSTITUCIÓN / INSTITUTION:  - The Research Institute, Nationwide Children’s Hospital, Columbus, OH, USA.

RESUMEN / SUMMARY:  - Inhibitor of DNA binding or inhibitor of differentiation (Id) proteins are up regulated in a variety of neoplasms, particularly in association with high-grade, poorly differentiated tumors, while differentiated tissues show little or no Id expression. The four Id genes are members of the helix-loop-helix (HLH) family of transcription factors and act as negative regulators of transcription by binding  to and sequestering HLH complexes. We tested the hypothesis that Id proteins are  overexpressed in medulloblastoma by performing immunohistochemistry using a medulloblastoma tissue microarray with 45 unique medulloblastoma and 11 normal control cerebella, and antibodies specific for Id1, Id2, Id3, and Id4. A semi-quantitative staining score that took staining intensity and the proportion  of immunoreactive cells into account was used. Id1 was not detected in normal cerebella or in medulloblastoma cells, but 78 % of tumors showed strong Id1 expression in endothelial nuclei of tumor vessels. Id2 expression was scant in normal cerebella and increased in medulloblastoma (median staining score: 4). Id3 expression was noted in some neurons of the developing cerebellar cortex, but it  was markedly up regulated in medulloblastoma (median staining score: 12) and in tumor endothelial cells. Id4 was not expressed in normal cerebella or in tumor cells. Id2 or Id3 overexpression drove proliferation in medulloblastoma cell lines by altering the expression of critical cell cycle regulatory proteins in favor of cell proliferation. This study shows that Id1 expression in endothelial  cells may contribute to angiogenic processes and that increased expression of Id2 and Id3 in medulloblastoma is potentially involved in tumor cell proliferation and survival.

 

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[519]

TÍTULO / TITLE:  - CRN2 enhances the invasiveness of glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos388

AUTORES / AUTHORS:  - Ziemann A; Hess S; Bhuwania R; Linder S; Kloppenburg P; Noegel AA; Clemen CS

INSTITUCIÓN / INSTITUTION:  - Center for Biochemistry, Institute of Biochemistry I, Medical Faculty (A.Z., A.A.N., C.S.C.), Institute of Zoology (S.H., P.K.), Center for Molecular Medicine Cologne (S.H., P.K., A.A.N.), and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne (S.H., P.K., A.A.N.); and Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.B., S.L.).

RESUMEN / SUMMARY:  - BackgroundMovement of tumor cells involves dynamic remodeling of the actin cytoskeleton, which is regulated by actin binding proteins, such as CRN2 (synonyms: coronin 1C, coronin 3). In vitro, CRN2 participates in secretion, matrix degradation, protrusion formation, and cell migration. Furthermore, expression of CRN2 correlates with the malignant phenotype of human diffuse gliomas. CRN2’s effects on actin polymerization and F-actin bundling are abolished by protein kinase 2 (CK2) dependent phosphorylation at serine 463.MethodsWe generated human U373 glioblastoma cell lines with knock-down of CRN2 or over-expression of CRN2 variants and studied their behavior in vitro and  ex vivo in organotypic brain slice cultures.ResultsCRN2 over-expression and expression of the S463A phospho-resistant CRN2 variant increase proliferation, matrix degradation, and invasion but decrease adhesion and formation of invadopodia-like extensions in vitro. Knock-down of CRN2 and expression of S463D  phospho-mimetic CRN2 generally have opposite effects. Analysis of invadopodia-like cell extensions shows a diffuse relocalization of F-actin in CRN2 knockdown cells, whereas expression of S463A and S463D mutant CRN2 causes enrichments of F-actin structures at the center and rime zone, respectively. Fluorescence recovery after photobleaching studies of CRN2 and F-actin in lamellipodia show that both CRN2 variants decrease the turnover of actin filaments. Glioblastoma cells over-expressing wild-type or S463A CRN2, which were transplanted onto brain slices, characteristically developed into tumors with an  invasive phenotype.ConclusionsOverall, our data indicate that CRN2 participates in cancer progression via modulation of the actin cytoskeleton.

 

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[520]

TÍTULO / TITLE:  - NPV-LDE-225 (Erismodegib) inhibits epithelial mesenchymal transition and self-renewal of glioblastoma initiating cells by regulating miR-21, miR-128, and  miR-200.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not011

AUTORES / AUTHORS:  - Fu J; Rodova M; Nanta R; Meeker D; Van Veldhuizen PJ; Srivastava RK; Shankar S

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, The University of Kansas Cancer  Center, The University of Kansas Medical Center, Kansas City, Kansas (J.F., S.S.); Department of Pharmacology, Toxicology and Therapeutics, and Medicine, The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas (M.R., R.N., D.M., R.K.S.); Department of Internal Medicine,  The University of Kansas Medical Center, Kansas City, Kansas (P.J.V.).

RESUMEN / SUMMARY:  - BackgroundGlioblastoma multiforme is the most common form of primary brain tumor, often characterized by poor survival. Glioblastoma initiating cells (GICs) regulate self-renewal, differentiation, and tumor initiation properties and are involved in tumor growth, recurrence, and resistance to conventional treatments.  The sonic hedgehog (SHH) signaling pathway is essential for normal development and embryonic morphogenesis. The objectives of this study were to examine the molecular mechanisms by which GIC characteristics are regulated by NPV-LDE-225 (Smoothened inhibitor; (2,2’-[[dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N- dimethylbenzenamine).MethodsCell viability and apoptosis were measured by XTT and annexin V-propidium iodide assay, respectively. Gli translocation and transcriptional activities were measured by immunofluorescence and luciferase assay, respectively. Gene and protein expressions were measured by quantitative real-time PCR and Western blot analyses, respectively.Results and conclusionNPV-LDE-225 inhibited cell viability, neurosphere formation, and Gli transcriptional activity and induced apoptosis by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. NPV-LDE-225 increased the expression of  tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-R1/DR4, TRAIL-R2/DR5, and Fas and decreased the expression of platelet derived growth factor receptor-alpha and Bcl2, and these effects were abrogated by Gli1 plus Gli2 short hairpin RNAs. NPV-LDE-225 enhanced the therapeutic potential of FasL and TRAIL by upregulating Fas and DR4/5, respectively. Interestingly, NPV-LDE-225 induced expression of programmed cell death 4 and apoptosis and inhibited cell viability by suppressing micro RNA (miR)-21. Furthermore, NPV-LDE-225 inhibited pluripotency-maintaining factors Nanog, Oct4, Sox2, and cMyc. The inhibition of Bmi1 by NPV-LDE-225 was regulated by induction of miR-128. Finally, NPV-LDE-225 suppressed epithelial-mesenchymal transition by upregulating E-cadherin and inhibiting N-cadherin, Snail, Slug, and Zeb1 through modulating the miR-200 family. Our data highlight the importance of the SHH pathway for self-renewal and early metastasis of GICs.

 

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[521]

TÍTULO / TITLE:  - Anti-Angiogenic Therapy in High-Grade Glioma (Treatment and Toxicity).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Treat Options Neurol. 2013 Feb 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11940-013-0224-y

AUTORES / AUTHORS:  - Taylor J; Gerstner ER

INSTITUCIÓN / INSTITUTION:  - Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General  Hospital Cancer Center, Yawkey 9E, 55 Fruit Street, Boston, MA, 02114, USA.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Malignant gliomas continue to have a very poor prognosis and treatment responses at recurrence are very limited. Though anti-angiogenic therapy has not yet been shown to extend overall survival in this patient population, there is likely substantial benefit to reducing vasogenic edema, allowing for temporary improvement in neurologic function, and minimizing the side effects of prolonged corticosteroid use. A trial of bevacizumab should be considered in those with worsening vasogenic cerebral edema such as seen in recurrent malignant gliomas, radiation necrosis, or progressive brain metastases. However, not all patients respond to anti-angiogenic treatment and if no radiographic or clinical responses are seen, then patients are not likely to benefit from further infusions. Though it is commonly well tolerated, some side effects, while rare, may be life threatening, and should be discussed with patients and their families. These discussions should also outline the goals of initiating therapy and when treatment should be stopped.

 

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[522]

TÍTULO / TITLE:  - Identifying dysfunctional miRNA-mRNA regulatory modules by inverse activation, cofunction, and high interconnection of target genes: A case study of glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not018

AUTORES / AUTHORS:  - Xiao Y; Ping Y; Fan H; Xu C; Guan J; Zhao H; Li Y; Lv Y; Jin Y; Wang L; Li X

INSTITUCIÓN / INSTITUTION:  - College of Bioinformatics Science and Technology (Y.X., Y.P., H.F., C.X., J.G., H.Z., Y.L., Y.L., X.L.), Laboratory of Medical Genetics (Y.J.), and Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions (Y.J.); and Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China (L.W.).

RESUMEN / SUMMARY:  - BackgroundAccumulating evidence demonstrates that complex diseases may arise from cooperative effects of multiple dysfunctional miRNAs. Thus, identifying abnormal  functions cooperatively regulated by multiple miRNAs is useful for understanding  the pathogenesis of complex diseases.MethodsIn this study, we proposed a multistep method to identify dysfunctional miRNA-mRNA regulatory modules (dMiMRMs) in a specific disease, in which a group of miRNAs cooperatively regulate a group of target genes involved in a specific function. We identified dysfunctional miRNAs, which were differentially expressed and inversely regulated most of their target genes, by integrating paired miRNA and mRNA expression profiles and miRNA target information. Then, we identified cooperative functional units, in each of which a pair of miRNAs cooperatively repressed function-enriched and highly interconnected target genes. Finally, the cooperative functional units were assembled into dMiMRMs.ResultsWe applied our method to glioblastoma (GBM) and identified GBM-associated dMiMRMs at the population, subtype, and individual levels. We identified 5 common dMiMRMs using  all GBM samples, 3 of which were associated with the prognosis in patients with GBM and were better predictors of prognosis than were miRNAs or mRNAs alone. By applying our approach to GBM subtypes, we found consistent dMiMRMs across GBM subtypes, and some subtype-specific dMiMRMs were observed. Furthermore, personalized dMiMRMs were identified, suggesting significant individual differences in different patients with GBM.ConclusionsOur method provides the capability to identify miRNA-mediated dysfunctional mechanisms underlying complex diseases.

 

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[523]

TÍTULO / TITLE:  - How could a drug used to treat alcoholism also be effective against glioblastoma?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2013 Mar;13(3):239-41. doi: 10.1586/era.12.169.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.169

AUTORES / AUTHORS:  - Wang W; Darling JL

INSTITUCIÓN / INSTITUTION:  - Research Institute in Healthcare Science, School of Applied Sciences, University  of Wolverhampton, Wolverhampton, WV1 1LY, UK. w.wang2@wlv.ac.uk.

 

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[524]

TÍTULO / TITLE:  - Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - OMICS. 2013 Mar;17(3):136-49. doi: 10.1089/omi.2012.0098. Epub 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1089/omi.2012.0098

AUTORES / AUTHORS:  - Shao J; Zhang J; Zhang Z; Jiang H; Lou X; Huang B; Foltz G; Lan Q; Huang Q; Lin B

INSTITUCIÓN / INSTITUTION:  - 1 Systems Biology Division, Zhejiang-California International NanoSystems Institute, Zhejiang University , Hangzhou, China .

RESUMEN / SUMMARY:  - Abstract Alternative polyadenylation (APA) is widely present in the human genome  and plays a key role in carcinogenesis. We conducted a comprehensive analysis of  the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline,  RNAelements ( sysbio.zju.edu.cn/RNAelements/ ), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation  (RIP) analysis. We identified 4530 APA isoforms for 2733 genes in GBM, and found  that 182 APA isoforms from 148 genes showed significant differential expression between normal and GBM brain tissues. We then focused on three genes with long and short APA isoforms that show inconsistent expression changes between normal and GBM brain tissues. These were myocyte enhancer factor 2D, heat shock factor binding protein 1, and polyhomeotic homolog 1 (Drosophila). Using the RNAelements program, we found that RBP binding sites were enriched in the alternative regions between the first and the last polyadenylation sites, which would result in the short APA forms escaping regulation from those RNA binding proteins. To the best  of our knowledge, this report is the first comprehensive APA isoform dataset for  GBM and normal brain tissues. Additionally, we demonstrated a putative novel APA-mediated mechanism for controlling RNA stability and translation for APA isoforms. These observations collectively lay a foundation for novel diagnostics  and molecular mechanisms that can inform future therapeutic interventions for GBM.

 

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[525]

TÍTULO / TITLE:  - Prognostic value of EGFR expression in de novo and progressed atypical and anaplastic meningiomas: an immunohistochemical and fluorescence in situ hybridization pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Sci. 2013 Mar 13.

AUTORES / AUTHORS:  - Caltabiano R; Barbagallo GM; Castaing M; Cassenti A; Senetta R; Cassoni P; Albanese V; Lanzafame S

INSTITUCIÓN / INSTITUTION:  - Section of Anatomic Pathology, G.F. Ingrassia Department, University of Catania,  Catania, Italy - giuseppebarbagal@hotmail.com.

RESUMEN / SUMMARY:  - Aim: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues. Methods: We investigated whether there was a difference in the EGFR protein expression and the EGFR gene amplification between the so called de novo malignant meningiomas and recurrent meningiomas with or without malignant progression from a previously lower grade tumor. Our goal was to evaluate if EGFR expression was a useful marker to select patients affected by meningioma with a major risk of recurrences. We also assessed the prognostic value of the EGFR expression on overall survival. Results: Progression from benign meningiomas to atypical or anaplastic meningiomas correlated with an increase in the expression  of EGFR protein. Our study shows that EGFR immunostaining in meningiomas directly correlates to the tumor’s grade. The EGFR expression did not correlate with the overall survival and the recurrence-free survival of the patients affected by meningioma (de novo, recurrent and progressed). Conclusion: We submit that the EGFR expression is not a useful prognostic element to identify patients with a major risk of meningioma recurrence.

 

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[526]

TÍTULO / TITLE:  - Advances in stem cell therapy against gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Trends Mol Med. 2013 Mar 25. pii: S1471-4914(13)00041-5. doi: 10.1016/j.molmed.2013.03.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.molmed.2013.03.001

AUTORES / AUTHORS:  - Bovenberg MS; Degeling MH; Tannous BA

INSTITUCIÓN / INSTITUTION:  - Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center,  Department of Neurology, Massachusetts General Hospital, Boston, MA, 02129, USA;  Program in Neuroscience, Harvard Medical School, Boston, MA, USA; Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands.

RESUMEN / SUMMARY:  - Malignant gliomas are one of the most lethal cancers, and despite extensive research very little progress has been made in improving prognosis. Multimodality treatment combining surgery, radiation, and chemotherapy is the current gold standard, but effective treatment remains difficult due to the invasive nature and high recurrence of gliomas. Stem cell-based therapy using neural, mesenchymal, or hematopoietic stem cells may be an alternative approach because it is tumor selective and allows targeted therapy that spares healthy brain tissue. Stem cells can be used to establish a long-term antitumor response by stimulating the immune system and delivering prodrug, metabolizing genes, or oncolytic viruses. In this review, we discuss current trends and the latest developments in stem cell therapy against malignant gliomas from both the experimental laboratory and the clinic.

 

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[527]

TÍTULO / TITLE:  - Overcoming resistance to rapalogs in gliomas by combinatory therapies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochim Biophys Acta. 2013 Feb 8. pii: S1570-9639(13)00060-5. doi: 10.1016/j.bbapap.2013.01.041.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbapap.2013.01.041

AUTORES / AUTHORS:  - Grzmil M; Hemmings BA

INSTITUCIÓN / INSTITUTION:  - Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Electronic address: michal.grzmil@fmi.ch.

RESUMEN / SUMMARY:  - Glioblastoma is the most common and aggressive brain tumor type, with a mean patient survival of approximately 1year. Many previous analyses of the glioma kinome have identified key deregulated pathways that converge and activate mammalian target of rapamycin (mTOR). Following the identification and characterization of mTOR-promoting activity in gliomagenesis, data from preclinical studies suggested the targeting of mTOR by rapamycin or its analogs (rapalogs) as a promising therapeutic approach. However, clinical trials with rapalogs have shown very limited efficacy on glioma due to the development of resistance mechanisms. Analysis of rapalog-insensitive glioma cells has revealed  increased activity of growth and survival pathways compensating for mTOR inhibition by rapalogs that are suitable for therapeutic intervention. In addition, recently developed mTOR inhibitors show high anti-glioma activity. In this review, we recapitulate the regulation of mTOR signaling and its involvement in gliomagenesis, discuss mechanisms resulting in resistance to rapalogs, and speculate on strategies to overcome resistance. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).

 

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[528]

TÍTULO / TITLE:  - From genomics to the clinic: biological and translational insights of mutant IDH1/2 in glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E2. doi: 10.3171/2012.12.FOCUS12355.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12355

AUTORES / AUTHORS:  - Dunn GP; Andronesi OC; Cahill DP

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - The characterization of the genomic alterations across all human cancers is changing the way that malignant disease is defined and treated. This paradigm is  extending to glioma, where the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioma and other IDH-mutant cancers. The IDH1 mutations are present in the vast majority of low-grade gliomas and secondary glioblastomas. Rapidly emerging work  on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome, transcriptional programs, hypoxia-inducible factor biology, and development. In the brief time since its discovery, knowledge of the IDH mutation status has had significant translational implications, and diagnostic tools are being used to monitor its expression and function. The concept of IDH1-mutant versus IDH1-wild type will become a critical early distinction in diagnostic and  treatment algorithms.

 

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[529]

TÍTULO / TITLE:  - Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not024

AUTORES / AUTHORS:  - Kim YW; Koul D; Kim SH; Lucio-Eterovic AK; Freire PR; Yao J; Wang J; Almeida JS; Aldape K; Yung WK

INSTITUCIÓN / INSTITUTION:  - Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea, (Y.-W.K.), Brain Tumor Center, Department of Neuro-Oncology (D.K.,  S.H.K., A.K.L.-E., J.Y., K.A., W.K.A.Y.), and Department of Bioinformatics and Computational Biology (P.R.F., J.W., J.S.A.), The University of Texas MD Anderson Cancer Center, Houston, Texas.

RESUMEN / SUMMARY:  - BackgroundThe Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM).MethodsHere, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine correlates of subtypes that may be biologically significant.ResultsTo identify predictive survival models, we searched TCGA in 173 patients and identified 42 probe sets (P = .0005) that could be used to divide the tumor samples into 3 groups and showed a significantly (P = .0006) improved overall survival. Kaplan-Meier plots showed that the median survival of group 3 was markedly longer (127 weeks) than that of groups 1 and 2 (47 and 52 weeks, respectively). We then validated the 42 probe sets to stratify the patients according to survival in other public GBM gene expression datasets (eg, GSE4290 dataset). An overall analysis of the gene expression and copy number aberration using a multivariate Cox regression model showed that the 42 probe sets had a significant (P < .018) prognostic value independent of other variables.ConclusionsBy integrating multidimensional genomic data from TCGA, we identified a specific survival model in a new prognostic group of GBM and suggest that molecular stratification of patients with GBM into homogeneous subgroups may provide opportunities for the development of new treatment modalities.

 

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[530]

TÍTULO / TITLE:  - Intradural intramedullary spinal cord meningioma in a seven years old female child.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mymensingh Med J. 2013 Jan;22(1):180-5.

AUTORES / AUTHORS:  - Hafiz MG; Rahman MR; Yeamin MB

INSTITUCIÓN / INSTITUTION:  - Dr Md Golam Hafiz, Assistant Professor, Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka, Bangladesh; E-mail:golamhafiz59@yahoo.com.

RESUMEN / SUMMARY:  - Halima, a 7 years old female child was admitted initially in the Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka, Bangladesh with the complaints of burning sensation in the neck for last four month. Initially pain was mild and gradually it became severe and agonizing  at night which awakening her from sleep. Following fifteen days of admission, her left hand gradually became weak and numb. Subsequently, all four limbs became involved within one month. Magnetic resonance imaging (MRI) showed expansion of cervical cord with hypo-intense in T1 and inhomogeneous hyper-intense in T2 areas with widening of cervical canal. Post gadolinium diethylene triamine penta-acetic acid dimeglumine (Gd-DTPA) films showed mild heterogeneous contrast enhancement of the cord at the C2-C4 level. The cervical disc showed normal signal intensity  on T2WI. During surgical procedure, laminectomy was done at C1-C5 level to release compression and dura matter was opened. Biopsy from involved tissue was taken and sent for histopathological examination and reported as embronal rhabdomyosarcoma. Immunohistochemistry (IHC) of tumor showed negative reaction for desmin, focal positivity for pancytokeratin and positivity for S-100 protein. The tumor was then diagnosed as atypical meningioma,intradural-intramedullary (WHO grade-II). Then, following transfer to the Department of Pediatric Hematology and Oncology, BSMMU, protocol based chemotherapy was started followed  by subsequent radiotherapy. The child was gradually improving after decompression of dura matter, commencement of chemotherapy and following external beam radiotherapy. So, an awareness of varied clinical manifestation of atypical meningioma of intrdural-intramedullary spinal cord tumor should be suspected to establish a correct diagnosis when the presenting signs and symptoms are enigmatic, presenting with intractable burning sensation or pain in the neck and  investigation should be done accordingly.

 

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[531]

TÍTULO / TITLE:  - Dental X-rays: meningiomas?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Prescrire Int. 2013 Jan;22(134):16-7.

 

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[532]

TÍTULO / TITLE:  - Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Feb 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1095-8

AUTORES / AUTHORS:  - Fontebasso AM; Schwartzentruber J; Khuong-Quang DA; Liu XY; Sturm D; Korshunov A; Jones DT; Witt H; Kool M; Albrecht S; Fleming A; Hadjadj D; Busche S; Lepage P; Montpetit A; Staffa A; Gerges N; Zakrzewska M; Zakrzewski K; Liberski PP; Hauser P; Garami M; Klekner A; Bognar L; Zadeh G; Faury D; Pfister SM; Jabado N; Majewski J

INSTITUCIÓN / INSTITUTION:  - Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, QC, Canada.

RESUMEN / SUMMARY:  - Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30 % of HGGs). To identify additional driver mutations in HGGs, we investigated a cohort of 60 pediatric HGGs using whole-exome sequencing (WES) and compared them to 543 exomes from non-cancer control samples. We identified mutations in SETD2, a H3K36 trimethyltransferase, in 15 % of pediatric HGGs, a result that was genome-wide significant (FDR = 0.029). Most SETD2 alterations were truncating mutations. Sequencing the gene in this cohort and another validation cohort (123 gliomas from all ages and grades) showed SETD2 mutations to be specific to high-grade tumors affecting 15 % of pediatric HGGs (11/73) and 8 % of adult HGGs (5/65) while no SETD2 mutations were identified in low-grade diffuse gliomas (0/45). Furthermore, SETD2 mutations were mutually exclusive with H3F3A mutations in HGGs (P = 0.0492) while they partly overlapped with IDH1 mutations (4/14), and SETD2-mutant tumors were found exclusively in the cerebral hemispheres (P = 0.0055). SETD2 is the only H3K36 trimethyltransferase in humans, and SETD2-mutant tumors showed a substantial decrease in H3K36me3 levels (P < 0.001), indicating that the mutations are loss-of-function. These data suggest that loss-of-function SETD2 mutations occur in older children and young adults and are specific to HGG  of the cerebral cortex, similar to the H3.3 G34R/V and IDH mutations. Taken together, our results suggest that mutations disrupting the histone code at H3K36, including H3.3 G34R/V, IDH1 and/or SETD2 mutations, are central to the genesis of hemispheric HGGs in older children and young adults.

 

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[533]

TÍTULO / TITLE:  - Strategies to maximize resection of complex, or high surgical risk, low-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E5. doi: 10.3171/2012.12.FOCUS12338.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12338

AUTORES / AUTHORS:  - Wilden JA; Voorhies J; Mosier KM; O’Neill DP; Cohen-Gadol AA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of California, San Francisco, California;

RESUMEN / SUMMARY:  - Object Early and aggressive resection of low-grade gliomas (LGGs) leads to increased overall patient survival, decreased malignant progression, and better seizure control. This case series describes the authors’ approach to achieving optimal neurological and surgical outcomes in patients referred by outside neurosurgeons for stereotactic biopsy of tumors believed to be complex or a high  surgical risk, due to their diffuse nature on neuroimaging and their obvious infiltration of functional cortex. Methods Seven patients underwent individualized neuroimaging evaluation preoperatively, which included routine brain MRI with and without contrast administration for intraoperative neuronavigation, functional MRI with speech and motor mapping, diffusion tensor imaging to delineate white matter tracts, and MR perfusion to identify potential  foci of higher grade malignancy within the tumor. Awake craniotomy with intraoperative motor and speech mapping was performed in all patients. Tumor removal was initiated through a transsylvian approach for insular lesions, and through multiple corticotomies in stimulation-confirmed noneloquent areas for all other lesions. Resection was continued until neuronavigation indicated normal brain, cortical or subcortical stimulation revealed functional cortex, or the patient began to experience a minor neurological deficit on intraoperative testing. Results Gross-total resection was achieved in 1 patient and subtotal resection (> 80%) in 6 patients, as assessed by postoperative MRI. Over the average follow-up duration of 31 months, no patient experienced a progression or  recurrence. Long-term seizure control was excellent in 6 patients who achieved Engel Class I outcomes. Neurologically, all 7 patients experienced mild temporary deficits or seizures that completely resolved, and 1 patient continues to have mild expressive aphasia. Conclusions Significant resection of diffuse, infiltrating LGGs is possible, even in presumed eloquent cortex. Aggressive resection maximizes seizure control and does not necessarily cause permanent neurological deficits. Individualized preoperative neuroimaging evaluation, including tractography and awake craniotomy with intraoperative speech and motor  mapping, is an essential tool in achieving these outcomes.

 

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[534]

TÍTULO / TITLE:  - Bevacizumab Use for Recurrent High-Grade Glioma at McGill University Hospital.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Can J Neurol Sci. 2013 Mar;40(2):241-6.

AUTORES / AUTHORS:  - Sahebjam S; Garoufalis E; Guiot MC; Muanza T; Del Maestro R; Petrecca K; Sharma R; Kavan P

INSTITUCIÓN / INSTITUTION:  - Drug Development Program, Princess Margaret Hospital, Toronto, Ontario.

RESUMEN / SUMMARY:  - Background: Bevacizumab, a humanized recombinant anti-vascular endothelial growth factor antibody, was approved in Canada in 2010 for the treatment of high-grade glioma. We report the effectiveness and safety of bevacizumab in the treatment of patients with recurrent high-grade gliomas at a single institution. Methods: Twenty-seven consecutive patients with high-grade glioma (anaplastic glioma and glioblastoma) at first or subsequent relapse were treated with bevacizumab alone  or in combination with chemotherapy. The primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate, six month PFS, overall survival (OS), and safety profile. Results: The clinical benefit rate (complete and partial responses plus stable disease) was 59%. Median PFS was 4.3 (95% CI, 3.0-10.9) months, with a six month PFS rate of 43%. Median OS after  current relapse was 8.9 (95% CI, 5.8-not reached) months. Ten episodes of grade ¾ adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1). Conclusions: We consider the efficacy and safety profile of bevacizumab is comparable to other cohorts of patients treated for recurrent high-grade glioma at other international institutions.

 

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[535]

TÍTULO / TITLE:  - Differential Expression of Somatostatin Receptors, P44/42 MAPK, and mTOR Activation in Medulloblastomas and Primitive Neuroectodermal Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e3182813724

AUTORES / AUTHORS:  - Johnson MD; O’Connell MJ; Silberstein H; Korones D

INSTITUCIÓN / INSTITUTION:  - *Department of Pathology, Division of Neuropathology Departments of daggerPediatric Neurosurgery double daggerPediatric Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY.

RESUMEN / SUMMARY:  - Recently, somatostatin receptors (SSR) have been identified on medulloblastomas and proposed as a new target for chemotherapy including inhibitory somatostatin analogs. Activation of SSRs inhibit growth, in part, by activating phosphatases that dephosphorylate/deactivate growth stimulatory signaling of the MEK1-p44/42 MAPK and PI3K-Akt-mTOR pathways. These SSR-inhibited signaling pathways have not  been characterized or correlated with SSR expression in medulloblastomas or primitive neuroectodermal tumors (PNETs), yet may represent additional targets for combined chemotherapy. We evaluated the distribution and extent of SSR1 and SSR2 expression and correlated it with activation of downstream MEK1-p44/42 MAPK  and PI3K-Akt-mTOR pathways in medulloblastomas and PNETs. Sections from 22 medulloblastomas and 9 PNETs were compared using immunohistochemistry with monoclonal antibodies to SSR1, SSR2, p44/42 MAPK, phosphorylated p44/42 MAPK, and phosphorylated mTOR. SSR1 was detected in 50% of medulloblastomas, extensive in 46%, and similar in classic, desmoplastic, and large cell/anaplastic subtypes. SSR1 was detected in 78% of PNETs and extensive in the majority. SSR2 was found in 18% of medulloblastomas and 33% of PNETs. Activated/phosphorylated pMAPK 44/42 was detected in 82% of medulloblastomas, all subtypes, and in 62.5% of PNETs with coexpression of SSR1 in one third. Activated/phosphorylated mTOR was found in only 18% of medulloblastomas but in 88% of PNETs. SSR1 coexpression with activated/phosphorylated mTOR was identified in 75% of PNETs. These findings suggest that addition of an mTOR inhibitor may potentiate growth inhibitory effects of SSR agonists in the treatment of PNETs. Immunohistochemical identification of mTOR activation/phosphorylation in biopsies of initial and treatment-resistant PNETs may facilitate development of clinical trials and therapeutic decisions.

 

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[536]

TÍTULO / TITLE:  - Radiotherapy for Optic Nerve Sheath Meningioma: A Case for Earlier Intervention?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Oncol (R Coll Radiol). 2013 Mar 12. pii: S0936-6555(13)00117-9. doi: 10.1016/j.clon.2013.02.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clon.2013.02.004

AUTORES / AUTHORS:  - Adams G; Roos DE; Crompton JL

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. Electronic address: adams_gerard@hotmail.com.

RESUMEN / SUMMARY:  - AIMS: To assess tumour control, visual outcomes and toxicity after radiotherapy for all patients with optic nerve sheath meningiomas (ONSM) treated by a single radiation oncologist at a single institution over a 15 year period. To explore potential predictors of outcomes. MATERIALS AND METHODS: All patients underwent ophthalmological and radiological assessments before radiotherapy. These were repeated at regular intervals after treatment. A retrospective analysis of clinical, dosimetric and radiological data was carried out. Patients with useful  vision before radiotherapy were divided into two groups - those with maintained or improved vision and those with a deterioration in vision. The groups were compared using the Mann-Whitney U-test with regard to eight potential predictors  of outcome. RESULTS: Seventeen patients with 18 ONSM were treated with fractionated radiotherapy (46.8-55.8 Gy in 26-31 fractions). No evaluable tumours grew after treatment: control rate 100% (95% confidence interval 82-100%). Using  the most common definition of visual function described in the literature, vision was maintained or improved in 89% (95% confidence interval 67-97%) of cases. In those with useful vision before treatment (13 evaluable eyes), visual acuity was  maintained or improved in eight (62%, 95% confidence interval 36-82%). There was  a suggestion that the time from the onset of symptoms to radiotherapy may influence outcome. Those with stable or better visual acuity after radiotherapy had been observed for a shorter time compared with those who had worse visual acuity (median of 18 months versus 62 months). Acute and late toxicity from radiotherapy was manageable. CONCLUSION: Radiotherapy is an extremely effective modality in arresting the growth of ONSM. A longer time from symptom onset to the start of radiotherapy may predict for poorer outcomes.

 

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[537]

TÍTULO / TITLE:  - Pheochromocytoma in ectopic pregnancy: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Exp Obstet Gynecol. 2012;39(4):553-5.

AUTORES / AUTHORS:  - Le A; Shang L; Xiao T; Zhuo R; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of the Gynaecology, The affiliated Shenzhen Nanshan People’s Hospital, Guangdong Medical College, Shenzhen, China. leaiwen@126.com

RESUMEN / SUMMARY:  - OBJECTIVE: To study pregnancy characteristics in women with pheochromocytoma and  to improve awareness of this comorbidity among obstetricians and gynecologists. METHODS: The diagnosis and treatment of a case of ectopic pregnancy with pheochromocytoma is described. RESULTS: The patient was diagnosed with a ruptured left Fallopian tube isthmus due to pregnancy, with comorbid left adrenal pheochromocytoma. CONCLUSION: Ectopic pregnancy with heavy bleeding and elevated  blood pressure is indicative of pheochromocytoma. Measurement of the levels of urinary vanillylmandelic acid and urinary and serum catecholamines, as well as ultrasonography, can help diagnose this comorbidity.

 

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[538]

TÍTULO / TITLE:  - Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos331

AUTORES / AUTHORS:  - Pallud J; Blonski M; Mandonnet E; Audureau E; Fontaine D; Sanai N; Bauchet L; Peruzzi P; Frenay M; Colin P; Guillevin R; Bernier V; Baron MH; Guyotat J; Duffau H; Taillandier L; Capelle L

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Sainte-Anne Hospital, Paris (J.P.); University Paris  Descartes, Paris (J.P., E.A.); Reseau d’Etude des Gliomes, REG, Groland (J.P., M.B., E.M. D.F., L.B., P.P., M.F., P.C., R.G., V.B., M-H.B., J.G., H.D., L.T., L.C.); Department of Neuro-Oncology, Nancy Neurological Hospital, Nancy (M.B., L.T.); Department of Neurosurgery, Lariboisiere Hospital, Paris (E.M.); Biostatistics and Epidemiology Unit, Hotel-Dieu, Assistance Publique-Hopitaux de  Paris, Paris (E.A.); Department of Neurosurgery, CHU de Nice, Nice, France (D.F.); Department of Neurosurgery, CHU de Montpellier, Montpellier (L.B., H.D.); Department of Neurosurgery, CHU de Reims, Reims (P.P.); Centre Anti-Cancereux Antoine Lacassagne, Nice (M.F.); Polyclinique Courlancy, Reims (P.C.); Department of Neuroradiology, Pitie-Salpetriere Hospital, Paris (R.G.); Department of Radiotherapy, Centre A. Vautrin, Vandoeuvre-les-Nancy (V.B.); Department of Radiotherapy, Jean Perrin Center of Cancer Treatment, Clermont-Ferrand (M-H.B.);  Department of Neurosurgery, P. Wertheimer Neurological Hospital, Lyon (J.G.); and Department of Neurosurgery, Pitie-Salpetriere Hospital, Paris, France (L.C.); and Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona (N.S.).

RESUMEN / SUMMARY:  - BackgroundSupratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of  diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor.MethodsA total of 407 adult patients with newly diagnosed supratentorial diffuse low-grade gliomas in adults were studied.ResultsThe mean spontaneous velocity of diametric expansion before first-line treatment was 5.8 +/- 6.3 mm/year. During the follow-up (mean, 86.5 +/- 59.4 months), 209 patients  presented a malignant transformation, and 87 died. The malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (median, 103 and 249 months, respectively) than in cases of fast velocity of diametric expansion (median, 35 and 91 months, respectively; P < .001). In multivariate analyses, spontaneous velocity of diametric expansion as a categorical variable (<4, >/=4 and <8, >/=8 and <12, >/=12 mm/year) was an independent prognostic factor for malignant progression-free survival (P < .001; hazard ratio, 3.87; 95% confidence interval  [CI], 2.67-5.52) and for overall survival (P < .001; hazard ratio, 4.62; 95% CI,  2.58-7.97). Velocity of diametric expansion was also an independent prognostic factor for overall survival as a continuous predictor, showing a linear relationship between overall survival and spontaneous velocity of diametric expansion (hazard ratio, 1.09 per one unit increase; 95% CI, 1.06-1.12; P < .001).ConclusionsIndependent of the molecular status, the spontaneous velocity of diametric expansion allows the identification of rapidly growing diffuse low-grade gliomas (at higher risk of worsened evolution) during the pretherapeutic period and without delaying treatment.

 

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[539]

TÍTULO / TITLE:  - Intellectual and Academic Outcome Following Two Chemotherapy Regimens and Radiotherapy for Average-Risk Medulloblastoma: COG A9961.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2013 Feb 26. doi: 10.1002/pbc.24496.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24496

AUTORES / AUTHORS:  - Ris MD; Walsh K; Wallace D; Armstrong FD; Holmes E; Gajjar A; Zhou T; Packer RJ

INSTITUCIÓN / INSTITUTION:  - Departmentof Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas.

RESUMEN / SUMMARY:  - PURPOSE: Assess the intellectual and academic outcomes as well as risk factors associated with treatment for average-risk medulloblastoma in childhood using 23.4 Gy of craniospinal radiotherapy plus adjuvant chemotherapy. METHODS: From an overall sample of 379 enrolled in the parent study (COG A9961), 110 patients received a total of 192 assessments over more than 5 years with standardized IQ and academic achievement tests. Random coefficient models of the various outcomes were developed that incorporated covariates including chemotherapy regimen, age at diagnosis, sex, initial Full Scale IQ, and mutism. RESULTS: Participants in this study were found to be comparable to the overall sample in all demographic,  disease, and treatment factors, except there were more gross total resections in  the subsample undergoing intellectual and academic assessment. Major findings include significant decline in both intellectual and academic domains over time that were greater in children who were younger at diagnosis and had higher initial intelligence test scores. Children with mutism were at higher risk for initial effects on intelligence. No effects of sex were found. CONCLUSION: These  results show progressive decline over several years post-treatment in standardized intellectual and academic scores. Despite recent improvements in therapies for these children, most notably a decrease dose of craniospinal radiation, they remain at risk. The pursuit of less toxic treatments, particularly for younger children, should continue. Neuropsychological surveillance should be routine at centers treating children with brain tumors. Pediatr Blood Cancer.

 

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[540]

TÍTULO / TITLE:  - Growth factor receptor-Src-mediated suppression of GRK6 dysregulates CXCR4 signaling and promotes medulloblastoma migration.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer. 2013 Mar 5;12:18. doi: 10.1186/1476-4598-12-18.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-12-18

AUTORES / AUTHORS:  - Yuan L; Zhang H; Liu J; Rubin JB; Cho YJ; Shu HK; Schniederjan M; Macdonald TJ

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA. tobey.macdonald@emory.edu.

RESUMEN / SUMMARY:  - BACKGROUND: Metastasis in medulloblastoma (MB) is associated with poor survival.  Recent genetic studies revealed MB to comprise distinct molecular subgroups, including the sonic hedgehog (SHH) subgroup that exhibits a relatively high rate  of progression. To identify targeted therapeutics against metastasis, a better understanding of the regulation of MB cell migration is needed. G protein-coupled receptor kinases (GRKs) have been implicated in cancer metastasis through their regulation of G-protein coupled receptors (GPCRs) involved in growth factor (GF)-mediated cell migration. However, the specific roles and regulation of GRKs  in MB have not been investigated. METHODS: Microarray mRNA analysis was performed for GRKs, GPCRs, and GFs in 29 human MB, and real time RT-PCR was used to detect  GRK6 expression in MB cells. Lenti- or retro-virus infection, and siRNA or shRNA  transfection, of MB cells was used to overexpress and knockdown target genes, respectively. Western blot was used to confirm altered expression of proteins. The effect of altered target protein on cell migration was determined by Boyden chamber assay and xCELLigence migration assays. RESULTS: We observed co-overexpression of PDGFRA, CXCR4, and CXCL12 in the SHH MB subtype compared to  non-SHH MB (5, 7, and 5-fold higher, respectively). GRK6, which typically acts as a negative regulator of CXCR4 signaling, is downregulated in MB, relative to other GRKs, while the percentage of GRK6 expression is lower in MB tumors with metastasis (22%), compared to those without metastasis (43%). In SHH-responsive MB cells, functional blockade of PDGFR abolished CXCR4-mediated signaling. shPDGFR transfected MB cells demonstrated increased GRK6 expression, while PDGF or 10% FBS treatment of native MB cells reduced the stability of GRK6 by inducing its proteosomal degradation. Overexpression or downregulation of Src, a key mediator of GF receptor/PDGFR signaling, similarly inhibited or induced GRK6 expression, respectively. siRNA downregulation of GRK6 enhanced CXCR4 signaling and promoted MB migration, while lentiviral-GRK6 overexpression suppressed CXCR4  signaling, potentiated the effect of AMD3100, a CXCR4 antagonist, and impaired migration. CONCLUSIONS: Our findings demonstrate a novel mechanism of GF receptor/PDGFR-Src-mediated dysregulation of CXCR4 signaling that promotes MB cell migration, which could potentially be exploited for therapeutic targeting in SHH MB.

 

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[541]

TÍTULO / TITLE:  - The Significance of Immunohistochemical Expression of Merlin, Ki-67, and p53 in Meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e318289f490

AUTORES / AUTHORS:  - Pavelin S; Becic K; Forempoher G; Tomic S; Capkun V; Drmic-Hofman I; Mrklic I; Lusic I; Pogorelic Z

INSTITUCIÓN / INSTITUTION:  - daggerDepartment of Pathology, Forensic Medicine and Cytology, University of Split, School of Medicine, Soltanska 2 Departments of *Neurology double daggerPathology, Forensic Medicine and Cytology section signNuclear Medicine parallelPediatric Surgery, Split University Hospital Centre, University of Split, School of Medicine, Spinciceva 1, Split, Croatia.

RESUMEN / SUMMARY:  - Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade  and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing  merlin expression and p53 levels, statistically significant difference was found  (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.

 

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[542]

TÍTULO / TITLE:  - 3’-Deoxy-3’-[(18)F]-fluorothymidine ([(18)F]-FLT) transport in newly diagnosed glioma: correlation with nucleoside transporter expression, vascularization, and  blood-brain barrier permeability.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0136-2

AUTORES / AUTHORS:  - Shinomiya A; Miyake K; Okada M; Nakamura T; Kawai N; Kushida Y; Haba R; Kudomi N; Tokuda M; Tamiya T

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa, 761-0173, Japan, ashinomi@med.kagawa-u.ac.jp.

RESUMEN / SUMMARY:  - 3’-Deoxy-3’-[(18)F]-fluorothymidine ([(18)F]-FLT), a marker of cellular proliferation, has been used in positron emission tomography (PET) examination of gliomas. The aim of this study was to investigate whether the uptake of [(18)F]-FLT in glioma correlates with messenger RNA (mRNA) levels of the equilibrative nucleoside transporter 1 (ENT1), microvascular density (assessed by CD34 immunohistochemistry), and the blood-brain barrier (BBB) breakdown. A total  of 21 patients with newly diagnosed glioma were examined with [(18)F]-FLT PET. Tumor lesions were identified as areas of focally increased [(18)F]-FLT uptake, exceeding that of surrounding normal tissue. Dynamic analysis of [(18)F]-FLT PET  revealed correlations between the phosphorylation rate constant k (3) and ENT1 expression; however there was no correlation between the kinetic parameters and CD34 score. There was a good correlation between the gadolinium (Gd) enhancement  score (evaluating BBB breakdown) and ENT1 expression, CD34 score, and Ki-67 index. This preliminary study suggests that ENT1 expression might not reflect accumulation of [(18)F]-FLT in vivo due to BBB permeability in glioma.

 

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[543]

TÍTULO / TITLE:  - Meningeal osteochondroma simulating meningioma with metaplastic change: a rare golf-ball-like lesion of non-meningothelial mesenchymal origin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0138-0

AUTORES / AUTHORS:  - Majumdar K; Mandal S; Thakkar R; Saran RK; Srivastava AK

INSTITUCIÓN / INSTITUTION:  - G B Pant Hospital, Jawaharlal Nehru Marg, New Delhi, 110002, India.

RESUMEN / SUMMARY:  - Non-meningothelial mesenchymal tumors of the central nervous system (CNS), including those originating from the meninges, histologically correspond to tumors of soft tissue or bone. These individual entities arising from the meninges are rare, and probably have their origin in the multipotent primitive mesenchymal stem cells of the dura. Though it is a common bone tumor, the meningeal origin of osteochondroma has only very rarely been reported. We describe a case of a 35-year-old female with a well-demarcated, golf-ball-like osteochondroma of meningeal origin which was enucleated en bloc on craniotomy. Such a lesion can resemble a meningioma that exhibits metaplastic (osseous) change on imaging. However, provided that there is clinico-radiological awareness of such tumors, magnetic resonance imaging (MRI) can guide the way to this rare differential diagnosis, as it reflects the pathologic appearance of osteochondroma and allows the thickness of the cartilage cap to be estimated in order to check for rare malignant change. Complete excision along with the cartilage cap usually offers a favorable prognosis without recurrence.

 

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[544]

TÍTULO / TITLE:  - Rituximab is associated with improved survival for aggressive B cell CNS lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not032

AUTORES / AUTHORS:  - Gregory G; Arumugaswamy A; Leung T; Chan KL; Abikhair M; Tam C; Bajel A; Cher L; Grigg A; Ritchie D; Opat S

INSTITUCIÓN / INSTITUTION:  - Inter-hospital Multi-institution Project Alliance and Collaboration Taskforce (IMPACT) (G.G., A.A., T.L., K.-L.C., C.T., A.B., A.G., D.R., S.O.); Monash Medical Centre, Clayton, Australia (G.G., M.A., S.O.); Austin Health, Heidelberg, Australia (A.A., L.C., A.G.); Royal Melbourne Hospital, Parkville (T.L., A.B., D.R.); St Vincent’s Hospital, Fitzroy, Australia (K.-L.C., C.T.); University of Melbourne, Parkville, Australia (C.T., L.C., A.G., D.R.); and Monash University,  Clayton, Victoria, Australia (S.O.).

RESUMEN / SUMMARY:  - BackgroundThe optimal treatment strategy in patients with aggressive B cell central nervous system lymphoma suitable to receive intensive therapy is unknown. The benefit of incorporating rituximab in systemic therapy remains unclear. We performed a retrospective study examining the impact of rituximab in the context  of concomitant therapies, including methotrexate, cytarabine, and radiotherapy, in patients treated with curative intent at 4 university teaching hospitals during 1996-2011.MethodsA retrospective study of CNS lymphoma cases treated at the participating institutions was performed in accordance with institutional ethical guidelines. Patients were included if they received a diagnosis of primary diffuse large B cell lymphoma of the CNS, were HIV negative, and were treated with curative intent.ResultsOne hundred twenty patients aged 21-81 years  were identified. Rituximab recipients and nonrecipients were similar, except for  rituximab recipients being more likely to have received a diagnosis after 2004. The median follow-up of surviving patients was 30 months. The 5-year overall survival was 46%. Univariate analysis revealed age </=60 years, ECOG performance  status </=1, normal lactate dehydrogenase, diagnosis after 2004, and treatment with cytarabine and rituximab as predictive of favorable overall survival. Multivariate analysis identified age to be an independent predictor of overall survival, with a trend toward improved survival from the other variables that were significant in univariate analyses.ConclusionsIn this retrospective analysis, the addition of rituximab to high-dose methotrexate-based chemotherapy  in patients with aggressive B cell CNS lymphoma was associated with improved overall survival. Further studies are underway to prospectively validate these findings.

 

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[545]

TÍTULO / TITLE:  - Determination of gemcitabine and its metabolite in extracellular fluid of rat brain tumor by ultra performance liquid chromatography-tandem mass spectrometry using microdialysis sampling after intralesional chemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 1;919-920:10-9. doi: 10.1016/j.jchromb.2012.12.027. Epub 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jchromb.2012.12.027

AUTORES / AUTHORS:  - Sun Y; Tang D; Chen H; Zhang F; Fan B; Zhang B; Fang S; Lu Q; Wei Y; Yin J; Yin X

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, No.  209 Tongshan Road, Xuzhou 221004, Jiangsu, China.

RESUMEN / SUMMARY:  - The cytotoxic agent Gemcitabine (2’,2’-difluoro-2’-deoxycytidine) has been proved to be effective in the treatment of malignant gliomas. A rapid, sensitive and specific ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) assay using microdialysis sampling was developed and validated to quantify gemcitabine and its major metabolite 2’,2’-difluoro-2’-deoxyuridine (dFdU) in Sprague-Dawley rat bearing 9L glioma. Microdialysis probes were surgically implanted into the area of rat brain tumor in the striatal hemisphere, and artificial cerebrospinal fluid was used as a perfusion medium. The samples were analyzed directly by UPLC-MS/MS after the addition of 5-bromouracil as an internal standard (IS). Separation was achieved on Agilent SB-C(18) (50 mm x 2.1mm I.D., 1.8 mum) column at 40 degrees C using an isocratic elution method with acetonitrile and 0.1% formic acid (4:96, v/v) at a flow rate of 0.2 mL/min.  Detection was performed using electrospray ionization in positive ion selected reaction monitoring mode by monitoring the following ion transitions m/z 264.0-->112.0 (gemcitabine), m/z 265.1-->113.0 (dFdU) and m/z 190.9-->173.8 (IS). The calibration curves of gemcitabine and dFdU were linear in the concentration range of 0.66-677.08 ng/mL and 0.31-312.00 ng/mL, respectively. The lower limit of quantification of gemcitabine and dFdU were 0.66 ng/mL and 0.31 ng/mL, respectively. The lower limit of detection of gemcitabine and dFdU were calculated to be 0.2 ng/mL and 0.1 ng/mL, respectively. All the validation data,  such as intra- and inter-day precision, accuracy, selectivity and stability, were within the required limits. The validated method was simple, precise and accurate, which was successfully employed to determinate the concentrations of gemcitabine and dFdU in the extracellular fluid of rat brain tumor.

 

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[546]

TÍTULO / TITLE:  - Autonomic nervous system balance in children and adolescents with craniopharyngioma and hypothalamic obesity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Mar 12.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-1082

AUTORES / AUTHORS:  - Cohen M; Syme C; McCrindle B; Hamilton J

INSTITUCIÓN / INSTITUTION:  - M Cohen, Endocrinology, The hospital for Sick Children, Toronto, Canada.

RESUMEN / SUMMARY:  - OBJECTIVE: Dysregulation of the autonomic nervous system is thought to be involved in craniopharyngioma related hypothalamic obesity (CRHO). Increased parasympathetic activity and decreased sympathetic activity have been suggested.  We aimed to study autonomic activity using heart rate variability (HRV) and biochemical measures in youth with CRHO compared to controls and to explore relationships between obesity and autonomic indices. DESIGN: A CROSS SECTIONAL STUDY OF 16 YOUTH WITH CRHO AND 16 CONTROLS MATCHED FOR SEX, AGE AND BODY MASS INDEX.METHODS: Anthropometrics, fasting blood-work, resting energy expenditure, 24hr HRV and 24hr urine catecholamines were assessed. Quality of life, sleepiness and autonomic symptoms were evaluated. Power spectral analysis of the HRV was performed. RESULTS: HRV power spectral analysis parameters of both parasympathetic activity (mean high frequency (ms2) 611 +/- 504 vs. 459 +/- 336 P=0.325) and sympathetic activity (median low frequency/high frequency 1.62 [1.37,2.41] vs. 1.89 [1.44,2.99] p=0.650) did not differ between the groups. Parasympathetic activity negatively correlated with central adiposity in both groups (r= -0.53, p=0.034 and r= -0.54 p=0.029) and sympathetic activity positively correlated with central adiposity in CRHO (r=0.51, p=0.043). Youth with CRHO had significantly lower resting energy expenditures; lower health and activities scores in the quality of life questionnaires and higher sleepiness scores. CONCLUSIONS: autonomic activity was similar in CRHO and control subjects. The degree of central adiposity correlated negatively with parasympathetic activity and positively with sympathetic activity in children with CRHO. These results provide a new perspective regarding autonomic balance in this unique patient population.

 

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[547]

TÍTULO / TITLE:  - Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):442-50. doi: 10.1093/neuonc/nos323. Epub 2013 Feb 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos323

AUTORES / AUTHORS:  - Laviolette PS; Cohen AD; Prah MA; Rand SD; Connelly J; Malkin MG; Mueller WM; Schmainda KM

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Peter S. LaViolette, PhD, Department of Radiology, Medical  College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. plaviole@mcw.edu.

RESUMEN / SUMMARY:  - Background Standard pre- and postcontrast (T1 + C) anatomical MR imaging is proving to be insufficient for accurately monitoring bevacizumab treatment response in recurrent glioblastoma (GBM). We present a novel imaging biomarker that detects abnormal tumor vasculature exhibiting both arterial and venous perfusion characteristics. We hypothesized that a decrease in the extent of this  abnormal vasculature after bevacizumab treatment would predict treatment efficacy and overall survival. Methods Dynamic susceptibility contrast perfusion MRI was gathered in 43 patients with high-grade glioma. Independent component analysis separated vasculature into arterial and venous components. Voxels with perfusion  characteristics of both arteries and veins (ie, arterio-venous overlap [AVOL]) were measured in patients with de novo untreated GBM and patients with recurrent  high-grade glioma before and after bevacizumab treatment. Treated patients were separated on the basis of an increase or decrease in AVOL volume (+/-DeltaAVOL),  and overall survival following bevacizumab onset was then compared between +/-DeltaAVOL groups. Results AVOL in untreated GBM was significantly higher than  in normal vasculature (P < .001). Kaplan-Meier survival curves revealed a greater median survival (348 days) in patients with GBM with a negative DeltaAVOL after bevacizumab treatment than in patients with a positive change (197 days; hazard ratio, 2.51; P < .05). Analysis of patients with combined grade III and IV glioma showed similar results, with median survivals of 399 days and 153 days, respectively (hazard ratio, 2.71; P < .01). Changes in T1+C volume and DeltarCBV  after treatment were not significantly different across +/-DeltaAVOL groups, and  DeltaAVOL was not significantly correlated with DeltaT1+C or DeltarCBV. Conclusions The independent component analysis dynamic susceptibility contrast-derived biomarker AVOL adds additional information for determining bevacizumab treatment efficacy.

 

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[548]

TÍTULO / TITLE:  - Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Mar;125(3):351-8. doi: 10.1007/s00401-013-1093-x. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1093-x

AUTORES / AUTHORS:  - Reuss DE; Piro RM; Jones DT; Simon M; Ketter R; Kool M; Becker A; Sahm F; Pusch S; Meyer J; Hagenlocher C; Schweizer L; Capper D; Kickingereder P; Mucha J; Koelsche C; Jager N; Santarius T; Tarpey PS; Stephens PJ; Andrew Futreal P; Wellenreuther R; Kraus J; Lenartz D; Herold-Mende C; Hartmann C; Mawrin C; Giese N; Eils R; Collins VP; Konig R; Wiestler OD; Pfister SM; von Deimling A

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

RESUMEN / SUMMARY:  - Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern  of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and  52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While  KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations  in other non-NF2 meningiomas.

 

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[549]

TÍTULO / TITLE:  - Childhood brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Rev. 2013 Feb;34(2):63-78. doi: 10.1542/pir.34-2-63.

            ●● Enlace al texto completo (gratuito o de pago) 1542/pir.34-2-63

AUTORES / AUTHORS:  - Crawford J

INSTITUCIÓN / INSTITUTION:  - University of California San Diego and Rady Children’s Hospital, San Diego, CA, USA.

 

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[550]

TÍTULO / TITLE:  - Gliomas in Children.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Treat Options Neurol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11940-013-0225-x

AUTORES / AUTHORS:  - Minturn JE; Fisher MJ

INSTITUCIÓN / INSTITUTION:  - Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard, CTRB 4028, Philadelphia, PA, 19104, USA.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Gliomas are the most common brain tumor in children and represent nearly 50 % of all pediatric central nervous system (CNS) tumors. They  are a heterogeneous group of diseases, ranging from highly malignant and frequently fatal to histologically benign and curable by surgery alone. A uniform treatment approach to these tumors is not practical, due to their histological and biological heterogeneity. Low-grade gliomas (LGGs) are best treated with maximally safe surgical resection, generally achievable for hemispheric or cerebellar locations. Patients with deep midline, optic pathway/hypothalamic, and brain stem locations should undergo subtotal resection or biopsy only. If a complete resection is not feasible, subtotal resection followed by adjuvant chemotherapy or radiotherapy is the standard approach; however, observation alone with serial neuroimaging is used in some asymptomatic, surgically inaccessible lesions. Chemotherapy is used first-line in cases of residual or progressive disease, to avoid or delay radiation therapy and its associated side effects. Regimens demonstrating objective responses and increased progression free survival (PFS) include carboplatin and vincristine (CV), thioguanine/procarbazine/CCNU/vincristine (TPCV), or weekly vinblastine. High-grade gliomas (HGGs) are less common in children than in adults, though are  similar in their aggressive clinical behavior, resistance to therapy, and dismal  outcomes. There is not a single “standard of care” therapy for non-metastatic HGGs, but generally accepted is an aggressive attempt at a complete surgical resection, followed by multimodality therapy with focal radiation and chemotherapy. The use of temozolomide (TMZ) during and following radiotherapy is  common, though it appeared not to improve the outcome in a cooperative group clinical trial when compared to an historical control cohort. The angiogenesis inhibitor bevacizumab, used alone or in combination with irinotecan, is also commonly used as maintenance therapy after radiation. Current trials are prospectively comparing TMZ to newer agents (vorinostat, bevacizumab) in a randomized phase II trial. Brainstem gliomas are a unique category of childhood gliomas. Approximately 80 % of childhood brainstem gliomas arise within the pons  as diffuse intrinsic pontine gliomas (DIPG). When biopsied, these are usually HGGs and carry a dismal prognosis. Standard therapy is focal radiation (54-58 Gy), preferably on a clinical trial testing concurrent chemotherapy or biologic agent. No standard chemotherapy agent has impacted survival. The remaining 20 % of brainstem gliomas are low-grade, arise in the midbrain, dorsal medulla, or cervicomedullary junction, and are indolent in nature with a much better prognosis. Improvement in the outcome of all childhood gliomas will require increased knowledge of the underlying biology of these tumors, in order to treat  with more biologically based and precise therapies.

 

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[551]

TÍTULO / TITLE:  - Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pituitary. 2013 Mar 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0479-z

AUTORES / AUTHORS:  - Bakhtiar Y; Hanaya R; Tokimura H; Hirano H; Oyoshi T; Fujio S; Bohara M; Arita K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.

RESUMEN / SUMMARY:  - Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary  adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in  50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in  accordance with sellar anatomy. Intensity of T1-weighted image was not different  between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38 %). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

 

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[552]

TÍTULO / TITLE:  - Infantile holocord cellular ependymoma with communicating hydrocephalus: unusual  presentation of a rare case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0145-1

AUTORES / AUTHORS:  - Aryan S; Ghosal N; Aziz ZA; Hegde AS; Dadlani R

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Transfusion Medicine, Sri Sathya Sai Institute of Higher Medical Sciences (SSSIHMS), EPIP Area, Whitefield, Bangalore, 560066, India.

RESUMEN / SUMMARY:  - We present a case of infantile holocord ependymoma in a 4-month-old boy who presented with infection of ventriculoperitoneal shunt done elsewhere for a communicating hydrocephalus. On magnetic resonance imaging, a diffuse holocord T2-hyperintense, T1-hypointense intramedullary bulky lesion with syringomyelia in the cervical level was seen. To the best of our knowledge, this is the first case of infantile holocord ependymoma. As the extent of morbidity associated with a spinal cord tumor is high, an increased level of suspicion and the need for a complete spinal cord screening in a case of infantile hydrocephalus without obvious clinical and radiological evidence of intracranial abnormality is emphasized.

 

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[553]

TÍTULO / TITLE:  - 1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not027

AUTORES / AUTHORS:  - Jiang H; Ren X; Cui X; Wang J; Jia W; Zhou Z; Lin S

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery (H.J., X.R., W.J., S.L.) and Pharmacy (X.C.), Beijing Tiantan Hospital, Capital Medical University, and Beijing Neurosurgical Institute (J.W.), Beijing, China; and Blood Center Station of Fuzhou, Fuzhou, China (Z.Z.).

RESUMEN / SUMMARY:  - BackgroundAnaplastic astrocytoma (AA), anaplastic oligoastrocytoma (AOA), and anaplastic oligodendroglioma (AO) are the major histological subtypes of World Health Organization grade III gliomas. More evidence suggests that AOA is unlikely to be a distinct entity, and re-evaluation of this issue has been recommended. In this study, we divided AOA into 2 subgroups, according to molecular biomarkers, and compared the survivals between them.MethodsOne hundred  nine patients with histological diagnosis of anaplastic gliomas enrolled in the study. Molecular biomarkers evaluated included 1p/19q codeletion and IDH1/2 mutation. Kaplan-Meier plots were compared by log-rank method.ResultsThere was no significant difference between AA and AOA with regard to the frequencies of biomarkers and survival plots. According to the status of biomarkers, AOA was classified into 2 subgroups (AOA1 and AOA2), for which Kaplan-Meier plots were significantly different (P = .001 for both progression-free survival [PFS] and overall survival [OS]). AOA1 with 1p/19q codeletion and/or IDH1/2 mutation showed similar Kaplan-Meier plots with AO (P = .169 for PFS and P = .523 for OS). AOA2 without either biomarker showed similar Kaplan-Meier plots with AA (P = .369 for  PFS and P = .271 for OS). In addition, patients with AO and AOA1 had significantly longer PFS and OS than did patients with AA and AOA2 (P < .001 for  both PFS and OS).ConclusionsAOA is a heterogeneous group and can be divided into  2 subgroups with significantly different prognoses according to the status of 1p/19q and IDH1/2. This will be helpful in estimating patients’ prognosis and guiding reasonable therapy for patients with anaplastic gliomas.

 

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[554]

TÍTULO / TITLE:  - Immunohistochemical actinin-4 expression in infiltrating gliomas: association with WHO grade and differentiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0139-z

AUTORES / AUTHORS:  - Fukushima S; Yoshida A; Honda K; Maeshima AM; Narita Y; Yamada T; Shibui S; Tsuda H

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, shfukush@ncc.go.jp.

RESUMEN / SUMMARY:  - Actinin-4 is an isoform of nonmuscular alpha-actinin and actin-bundling protein that plays an important role in cancer invasion and metastasis by enhancing cellular motility. Recent studies have revealed an association between several clinicopathological profiles and actinin-4 overexpression in human cancers. In this study, we investigated the immunohistochemical actinin-4 expression in 39 infiltrating gliomas. The specimens included three diffuse astrocytomas, three oligodendrogliomas, one oligoastrocytoma, two anaplastic astrocytomas, four anaplastic oligodendrogliomas, three anaplastic oligoastrocytomas, 17 glioblastomas, four gliosarcomas, and two glioblastomas with oligodendroglial component. All seven World Health Organization (WHO) grade II tumors were negative for actinin-4, whereas 20 of 22 tumors with strong actinin-4 expression  were WHO grade IV. Actinin-4 expression was significantly associated with histological grade (P < 0.0001) and proliferative activity measured by Ki-67 staining (P = 0.0045). Notably, actinin-4 expression was more pronounced in high-grade astrocytic tumors than oligodendroglial tumors (P < 0.0001). Additionally, pseudopalisading cells in glioblastoma exhibited stronger actinin-4 expression than the rest, likely reflecting enhanced cellular motility in pseudopalisades. This study is the first to demonstrate significant correlation between actinin-4 expression and tumor grade using clinical glioma samples. Although diagnostic utility of this marker awaits future exploration, actinin-4 may help distinguish between astrocytic and oligodendroglial lines of differentiation.

 

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[555]

TÍTULO / TITLE:  - miR-92b controls glioma proliferation and invasion through regulating Wnt/beta-catenin signaling via Nemo-like kinase.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not004

AUTORES / AUTHORS:  - Wang K; Wang X; Zou J; Zhang A; Wan Y; Pu P; Song Z; Qian C; Chen Y; Yang S; Wang Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Hangzhou Xiasha Hospital, Sir Run Run Shaw Hospital,  Medical College, Zhejiang University, Hangzhou , People’s Republic of China (K.W., Z.S.); Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University , Beijing, People’s Republic of China (X.W.); Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University,  Hangzhou , People’s Republic of China (J.Z.); Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin , People’s Republic of China (A.Z.,  P.P.); Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin , People’s Republic of China (A.Z., P.P.); Department of Neurosurgery, Sir Run Run  Shaw Hospital, Medical College, Zhejiang University, Hangzhou, People’s Republic  of China (C.Q., Y.C., S.Y., Y.W.).

RESUMEN / SUMMARY:  - BackgroundNemo-like kinase (NLK) is an evolutionarily conserved protein kinase involved in Wnt/beta-catenin signaling, which has been reported to be associated  with gliomagenesis. In the present study, we aimed to identify a concrete mechanism of Wnt/beta-catenin pathway regulation by microRNAs (miRNAs) in glioma.MethodsQuantitative reverse-transcription polymerase chain reaction and in situ hybridization were conducted to detect the expression of miR-92b. The cell proliferation rate and cell cycle kinetics were detected using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and flow cytometry, cell invasion and migration were evaluated using Transwell assay  and wound healing assay, and cell apoptosis was detected using annexin V staining. Furthermore, the relevant molecules regulating proliferation and invasion were examined using Western blot analysis, immunohistochemistry, and immunofluorescence staining. Luciferase reporter assay was used to identify the direct regulation of NLK by miR-92b and beta-catenin/TCF4 activity.ResultsWe first showed that the expression of miR-92b was elevated in both glioma samples and glioma cells. Furthermore, down-regulation of miR-92b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro and in  vivo. Luciferase assay and Western blot analysis revealed that NLK is a direct target of miR-92b. Restoring expression of NLK inhibited glioma proliferation and invasion. Mechanistic investigation revealed that miR-92b deletion suppressed beta-catenin/TCF-4 transcription activity by targeting NLK. Moreover, expression  of NLK was inversely correlated with miR-92b in glioma samples and was predictive of patient survival in a retrospective analysis.ConclusionsOur findings identify  a role for miR-92b in glioma proliferation and invasion after activation of Wnt/beta-catenin signaling via NLK.

 

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[556]

TÍTULO / TITLE:  - Prevalence of spinal meningeal cyst in the sacrum.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Med Chir (Tokyo). 2013;53(2):91-4.

AUTORES / AUTHORS:  - Tani S; Hata Y; Tochigi S; Ohashi H; Isoshima A; Nagashima H; Akiyama M; Abe T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan. tani@jikei.ac.jp

RESUMEN / SUMMARY:  - Spinal meningeal cysts in the sacrum (SMC) are known to be occasionally symptomatic with low back pain as well as leg pain, but no distinct prevalence of this pathological entity including asymptomatic lesions has been described. This  prospective study investigated the prevalence of SMCs based on magnetic resonance (MR) myelography in 102 consecutive Japanese women with gynecological problems, who underwent pelvic conventional MR imaging. Ten of 102 patients were suspected  of being positive for SMC (9.8%), but pseudo-positive findings were possible. A high probability of positive SMC was found in 7/102 (6.9%). MR myelography was better to detect SMCs than conventional MR imaging. Multiplicity and female preponderance may be other features of SMC. The speculated prevalence of SMCs in  Japanese females ranged from 6.9% to 9.8%.

 

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[557]

TÍTULO / TITLE:  - Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not015

AUTORES / AUTHORS:  - Agarwal S; Sharma MC; Jha P; Pathak P; Suri V; Sarkar C; Chosdol K; Suri A; Kale SS; Mahapatra AK; Jha P

INSTITUCIÓN / INSTITUTION:  - Departments of Pathology (S.A., M.C.S., P.J., P.P., V.S., C.S.), Biochemistry (K.C), and Neurosurgery (A.S., S.S.K., A.K.M.), All India Institute of Medical Sciences, Delhi, India; All India Institute of Medical Sciences, New Delhi (P.J.); and Institute of Genomics and Integrative Biology, Delhi, India (P.J.).

RESUMEN / SUMMARY:  - BackgroundMutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high  proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study  compares results of IHC with DNA sequencing in diffuse gliomas.Materials and methodsFifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations.ResultsConcordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were  immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells.ConclusionsIHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.

 

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[558]

TÍTULO / TITLE:  - Discriminating survival outcomes in patients with glioblastoma using a simulation-based, patient-specific response metric.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e51951. doi: 10.1371/journal.pone.0051951. Epub 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051951

AUTORES / AUTHORS:  - Neal ML; Trister AD; Cloke T; Sodt R; Ahn S; Baldock AL; Bridge CA; Lai A; Cloughesy TF; Mrugala MM; Rockhill JK; Rockne RC; Swanson KR

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Washington, Seattle, Washington, United States of America. mneal@uw.edu

RESUMEN / SUMMARY:  - Accurate clinical assessment of a patient’s response to treatment for glioblastoma multiforme (GBM), the most malignant type of primary brain tumor, is undermined by the wide patient-to-patient variability in GBM dynamics and responsiveness to therapy. Using computational models that account for the unique geometry and kinetics of individual patients’ tumors, we developed a method for assessing treatment response that discriminates progression-free and overall survival following therapy for GBM. Applying these models as untreated virtual controls, we generate a patient-specific “Days Gained” response metric that estimates the number of days a therapy delayed imageable tumor progression. We assessed treatment response in terms of Days Gained scores for 33 patients at the time of their first MRI scan following first-line radiation therapy. Based on Kaplan-Meier analyses, patients with Days Gained scores of 100 or more had improved progression-free survival, and patients with scores of 117 or more had improved overall survival. Our results demonstrate that the Days Gained response  metric calculated at the routinely acquired first post-radiation treatment time point provides prognostic information regarding progression and survival outcomes. Applied prospectively, our model-based approach has the potential to improve GBM treatment by accounting for patient-to-patient heterogeneity in GBM dynamics and responses to therapy.

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[559]

TÍTULO / TITLE:  - Thoracolumbar extradural arachnoid cyst—three surgical case reports.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol Med Chir (Tokyo). 2013;53(2):129-33.

AUTORES / AUTHORS:  - Tomii M; Mizuno J; Takeda M; Matsushima T; Itoh Y; Numazawa S; Matsuoka H; Watanabe K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Southern TOHOKU Research Institute for Neuroscience,  Southern TOHOKU General Hospital, Koriyama, Fukushima, Japan. masatotomii@ybb.ne.jp

RESUMEN / SUMMARY:  - Three cases of symptomatic extradural arachnoid cyst were treated by surgery. Total excision of the cyst followed by tight closure of the fistula by suture was achieved in all 3 cases. Surgery improved the neurological deficits but urinary incontinence persisted in all three patients. Obliteration of the fistula is considered to be important at surgery from the etiological perspective of the cyst. There are many surgical options, but surgical removal of the cyst and obliteration of the communication usually leads to prompt improvement in neurological deficits. Instability, malalignment, and worsening scoliosis are well-recognized postoperative complications of excessive laminotomy, but the exposure should be wide enough to cover the cyst completely at the operation. Wide exposure of the entire cyst is preferable to avoid missing the fistula and to identify any adhesions or fistula between the cyst and the dura. Identification of the fistula location based on preoperative imaging studies is also important.

 

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[560]

TÍTULO / TITLE:  - The Cancer Genome Atlas expression profiles of low-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E8. doi: 10.3171/2012.12.FOCUS12351.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12351

AUTORES / AUTHORS:  - Gonda DD; Cheung VJ; Muller KA; Goyal A; Carter BS; Chen CC

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q  status, should facilitate accurate and reliable pathological diagnosis of LGGs.

 

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[561]

TÍTULO / TITLE:  - Aberrant miRNA expression in brain tumors: a subject attracting an increasing amount of attention.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):405. doi: 10.1093/neuonc/not045.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not045

AUTORES / AUTHORS:  - James CD

 

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[562]

TÍTULO / TITLE:  - High incidence of extraadrenal paraganglioma in families with SDHx syndromes detected by functional imaging with [(18)F]fluorodihydroxyphenylalanine PET.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Feb 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2346-6

AUTORES / AUTHORS:  - Miederer M; Fottner C; Rossmann H; Helisch A; Papaspyrou K; Bartsch O; Mann WJ; Musholt TJ; Weber MM; Lackner KJ; Schreckenberger M

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany, Matthias.miederer@unimedizin-mainz.de.

RESUMEN / SUMMARY:  - PURPOSE: Knowledge of the genetic backgrounds of hereditary syndromes, which are  increasingly being characterized, enables genetic screening of family members of  affected patients. Upon detection of a mutation, genetic counselling and clinical screening including imaging modalities and biochemical analyses are commonly performed. METHODS: Unaffected, mutation-positive relatives of index patients with hereditary paraganglioma syndromes were offered PET imaging with [(18)F]fluorodihydroxyphenylalanine and the incidence of pathological findings was retrospectively analysed in relation to mutations of the succinate dehydrogenase enzyme complex. PET only or PET/CT was performed in 21 individuals  from eight families with SDHD, one family with SDHC and two families with SDHB mutations. Screening was offered every 2 to 5 years. RESULTS: Of the 21 individuals, 14 showed paraganglioma during screening. In particular, in only 2 of 15 patients with a SDHD mutation were the findings completely unremarkable on  PET screening. However, false-negative lesions for abdominal manifestations in two SDHD-positive patients were detected. CONCLUSION: FDOPA PET is a sensitive imaging modality which should be offered to patients with a detected SDHx (SDHD)  mutation, preferably using a hybrid technique.

 

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[563]

TÍTULO / TITLE:  - Stereotactic Radiosurgery of a Papillary Tumor of the Pineal Region: Case Report  and Review of the Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stereotact Funct Neurosurg. 2013 Feb 27;91(3):186-189.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000344023

AUTORES / AUTHORS:  - Riis P; van Eck AT; Dunker H; Bergmann M; Borm W

INSTITUCIÓN / INSTITUTION:  - Neurosurgical Department, Diakonissenanstalt zu Flensburg, Flensburg, Germany.

RESUMEN / SUMMARY:  - Background/Aims: Papillary tumors of the pineal region are a recently described very rare group of primary CNS neoplasms. Because of their rarity, it has proven  to be difficult to establish the optimal therapy. Furthermore, microsurgical resection of pineal region neoplasms is associated with quite a high morbidity. We report the first case of stereotactic radiosurgery of a histologically confirmed papillary tumor of the pineal region. Methods: After establishing the diagnosis by stereotactic biopsy, the patient was treated with stereotactic radiosurgery in a Gamma Knife unit. Results: Five years after treatment, the tumor size is still decreasing, showing a good response to the treatment. Conclusions: Stereotactic radiosurgery should be considered a treatment option in these surgically challenging tumors.

 

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[564]

TÍTULO / TITLE:  - A case of pleomorphic xanthoastrocytoma with anaplastic features in the pineal gland.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0137-1

AUTORES / AUTHORS:  - Katayama K; Asano K; Shimamura N; Ogasawara Y; Naraoka M; Ohkuma H; Kurose A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Hirosaki University Graduate School of Medicine, Zaifu-cho 5, Hirosaki, Aomori, 036-8562, Japan, k.kosuke@cc.hirosaki-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND AND IMPORTANCE: Different types of tumor have been reported in the pineal gland, but pleomorphic xanthoastrocytoma (PXA) in this region is extremely rare. CLINICAL PRESENTATIONS: A 61-year-old man had gait disturbance and dementia for 1 month. Radiological examination revealed a 22 x 26 x 22-mm-diameter mass in the pineal gland and remarkable hydrocephalus. Biopsy of the tumor was performed  and histological examination confirmed diagnosis of PXA with anaplastic features. Radiation therapy with concomitant temozolomide was performed, and tumor reduction was achieved. CONCLUSION: We report the first case of PXA with anaplastic features in the pineal gland. This case indicates that temozolomide and radiation therapy are effective for treating PXA with anaplastic features.

 

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[565]

TÍTULO / TITLE:  - Meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Neurol Neurosci Rep. 2013 Apr;13(4):337. doi: 10.1007/s11910-013-0337-4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11910-013-0337-4

AUTORES / AUTHORS:  - Fathi AR; Roelcke U

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Cantonal Hospital, 5001, Aarau, Switzerland. Ali-Reza.Fathi@ksa.ch

RESUMEN / SUMMARY:  - Meningiomas represent the most common primary brain tumor and comprise 3 World Health Organization (WHO) grades, the most frequent being WHO grade I (90%). Surgery is mandatory to establish the diagnosis and to remove the tumor; however, complete resection can be achieved in only <50% of patients. Depending on the extent of resection, tumor location and the WHO grade radiation therapy can be applied. The issue of systemic treatment such as chemotherapy or targeted therapy (eg, somatostatin receptors, antiangiogenic agents) is yet not solved, particularly as current data are derived from small uncontrolled series in patients with long-standing disease and after several pretreatments. A more thorough understanding of molecular genetics, signaling pathways and prognostic factors in meningiomas should lead to the design of studies which stratify according to these factors. These studies have to be conducted in newly diagnosed patients after incomplete resection and in tumors of WHO grade II and III.

 

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[566]

TÍTULO / TITLE:  - Identifying the mesenchymal molecular subtype of glioblastoma using quantitative  volumetric analysis of anatomic magnetic resonance images.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not008

AUTORES / AUTHORS:  - Naeini KM; Pope WB; Cloughesy TF; Harris RJ; Lai A; Eskin A; Chowdhury R; Phillips HS; Nghiemphu PL; Behbahanian Y; Ellingson BM

INSTITUCIÓN / INSTITUTION:  - Department of Radiological Sciences (K.M.N., W.B.P., R.J.H., Y.B., B.M.E.); Department of Biomedical Physics (R.J.H., B.M.E.); Department of Biomedical Engineering (B.M.E.); Department of Neurology (T.F.C., A.L., R.C., P.L.N.); Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California (A.E.); Department of Tumor Biology and Angiogenesis, Genentech, Inc., San Francisco, California (H.S.P.).

RESUMEN / SUMMARY:  - BackgroundSubtypes of glioblastoma multiforme (GBM) based on genetic and molecular alterations are thought to cause alterations in anatomic MRI owing to downstream biological changes, such as edema production, blood-brain barrier breakdown, and necrosis. The purpose of the current study was to identify a potential relationship between imaging features and the mesenchymal (MES) GBM subtype, which has the worst patient prognosis.MethodsMRIs from 46 patients with  histologically confirmed GBM were retrospectively analyzed. The volume of contrast enhancement, regions of central necrosis, and hyperintensity of T2/fluid attenuated inversion recovery (FLAIR) were measured. Additionally, the ratio of T2/FLAIR hyperintense volume to the volume of contrast enhancement and necrosis was calculated.ResultsThe volume of contrast enhancement, volume of central necrosis, combined volume of contrast enhancement and central necrosis, and the ratio of T2/FLAIR to contrast enhancement and necrosis were significantly different in MES compared with non-MES GBM (Mann-Whitney, P < .05). Receiver-operator characteristics indicated that these 4 metrics were all significant predictors of the MES phenotype. The volume ratio of T2 hyperintensity to contrast enhancement and central necrosis was significantly lower in MES vs non-MES GBM (P < .0001), was a significant predictor of the MES phenotype (area under the curve = 0.93, P < .001), and could be used to stratify  short- and long-term overall survival (log-rank, P = .0064 using cutoff of 3.0).  These trends were also present when excluding isocitrate dehydrogenase 1 mutant tumors and incorporating covariates such as age and KPS score.ConclusionsResults  suggest that volume ratio may be a simple, cost-effective, and noninvasive biomarker for quickly identifying MES GBM.

 

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[567]

TÍTULO / TITLE:  - Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not002

AUTORES / AUTHORS:  - Pafundi DH; Laack NN; Youland RS; Parney IF; Lowe VJ; Giannini C; Kemp BJ; Grams MP; Morris JM; Hoover JM; Hu LS; Sarkaria JN; Brinkmann DH

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology (D.H.P., N.N.L., M.P.G., J.N.S., D.H.B.); Mayo Medical School (R.S.Y.); Department of Neurologic Surgery (I.F.P., J.M.H.); Department of Nuclear Medicine (V.J.L., B.J.K.); Department of Anatomic Pathology (C.G.); Department of Radiology, Mayo Clinic, Rochester, Minnesota (J.M.M.); Department of Radiology, Mayo Clinic, Scottsdale, Arizona (L.S.H.).

RESUMEN / SUMMARY:  - BackgroundDelineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer 18F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares 18F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation.MethodsConventional MR and 18F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant 18F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. 18F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios.ResultsPathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained  from regions of elevated 18F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal 18F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, 18F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity.Conclusions18F-DOPA PET SUVmax may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.

 

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[568]

TÍTULO / TITLE:  - Treatment outcomes and survival in patients with primary central nervous system lymphomas treated between 1995 and 2010 - a single centre report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiol Oncol. 2012 Dec;46(4):346-53. doi: 10.2478/v10019-012-0048-5. Epub 2012 Nov 9.

            ●● Enlace al texto completo (gratuito o de pago) 2478/v10019-012-0048-5

AUTORES / AUTHORS:  - Jezersek Novakovic B

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.

RESUMEN / SUMMARY:  - BACKGROUND.: Primary central nervous system lymphomas (PCNSL) are rare variants of extranodal non-Hodgkin’s lymphomas that are nowadays primarily treated with high-dose methotrexate or methotrexate-based chemotherapy with or without radiation therapy. The optimal treatment of PCNSL is still unknown and there are  differences in clinical practice. PATIENTS AND METHODS.: With a retrospective research we evaluated our series of patients with PCNSL in regards to the patient’s characteristics, treatment results, disease specific survival and overall survival. Fifty nine patients who attended the Institute of Oncology Ljubljana between 1995 and 2010 were treated according to the protocol that was valid at the time of the patient’s admission. Between 1995 and 1999, the systemic treatment was classical CHOP (cyclophosphamide, doxorubicin, vincristine, steroids) chemotherapy, and later on high-dose methotrexate either alone or in combination with other agents. From 1999 onwards, radiation therapy was applied according to the patient’s age and response to chemotherapy, prior to that all patients treated with CHOP were also irradiated. Patients ineligible for the systemic treatment were treated with sole radiation therapy. RESULTS.: There was  a strong female predominance in our series and the median age at diagnosis was 59.8 years. Patients had predominantly aggressive B cell lymphomas (69.5%), one patient had marginal cell lymphoma and two patients T cell lymphoma. In total, 20.3% of patients were treated just with chemotherapy, 33.9% with combined therapy and 42.4% with sole radiation therapy. The overall response rate to the primary treatment in patients treated with sole chemotherapy was 33.3%, in patients treated with combined therapy 65% and in patients treated only with radiation therapy 56%, respectively. In terms of response duration, significantly better results were achieved with combined therapy or radiation therapy alone compared to sole chemotherapy (p<0.0006). The median overall survival of the whole cohort was 11 months and the overall survival was significantly affected by the patient’s age. The longest overall survival was observed in patients treated  with combined therapy (median survival of 39 months). Patients treated just with  radiation therapy had a median overall survival of 9 months and those treated with sole chemotherapy of 4.5 months, respectively. CONCLUSIONS.: The treatment outcomes in ordinary clinical practice are definitely inferior to the ones reported in clinical trials. The now standard treatment with high-dose methotrexate with or without radiation therapy is sometimes too aggressive and, therefore, a careful selection on the basis of patient’s age, performance status  and concomitant diseases of those eligible for such treatment is mandatory. According to our results from a retrospective study, radiation therapy should not be excluded from the primary treatment.

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[569]

TÍTULO / TITLE:  - Secondary glioblastomas with IDH1/2 mutations have longer glioma history from preceding lower-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0140-6

AUTORES / AUTHORS:  - Ohno M; Narita Y; Miyakita Y; Matsushita Y; Yoshida A; Fukushima S; Ichimura K; Shibui S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

RESUMEN / SUMMARY:  - Isocitrate dehydrogenase (IDH)1/2 mutations have been proposed as a genetic marker for secondary glioblastoma (sGBM). This study aimed to evaluate the impact of the IDH1/2 mutations on the clinical course and genetic alterations of sGBMs,  which histopathologically progressed from lower-grade gliomas. We investigated 18 sGBMs, including 8 sGBMs with IDH1/2 mutations (sGBM-Mut) and 10 with wild-type IDH1/2 (sGBM-Wt). The median overall survival time of patients with sGBM-Mut was  significantly longer than that of patients with sGBM-Wt (68.2 vs. 25.3 months). The median time from initial diagnosis to sGBM diagnosis was also significantly longer for sGBM-Mut than for sGBM-Wt (50.1 vs. 13.4 months). There was no difference in the median survival time from the sGBM diagnosis between sGBM-Mut and sGBM-Wt (6.75 vs. 6.8 months). All sGBM-Mut (7 of 7) and 6 of 9 sGBM-Wt had TP53 mutations, and the remaining one-thirds of sGBM-Wt had neither TP53 mutations nor 1p/19q codeletion. These observations suggest that IDH1/2 mutations have an impact on the glioma history of sGBM with different genetic pathway. The  aggressive progression to sGBM-Wt suggest the need for more intense treatment to  the IDH1/2 wild-type tumors.

 

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[570]

TÍTULO / TITLE:  - IDH1 and IDH2 Mutations in Gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Neurol Neurosci Rep. 2013 May;13(5):345. doi: 10.1007/s11910-013-0345-4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11910-013-0345-4

AUTORES / AUTHORS:  - Cohen AL; Holmen SL; Colman H

INSTITUCIÓN / INSTITUTION:  - Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA, adam.cohen@hci.utah.edu.

RESUMEN / SUMMARY:  - Mutations in isocitrate dehydrogenase (IDH) 1 and 2, originally discovered in 2008, occur in the vast majority of low-grade gliomas and secondary high-grade gliomas. These mutations, which occur early in gliomagenesis, change the function of the enzymes, causing them to produce 2-hydroxyglutarate, a possible oncometabolite, and to not produce NADPH. IDH mutations are oncogenic, although whether the mechanism is through alterations in hydroxylases, redox potential, cellular metabolism, or gene expression is not clear. The mutations also drive increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have improved prognosis compared with gliomas with wild-type IDH. Mutated IDH can now  be detected by immunohistochemistry and magnetic resonance spectroscopy. No drugs currently target mutated IDH, although this remains an area of active research.

 

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[571]

TÍTULO / TITLE:  - Hypodipsic hypernatremia leading to reversible renal failure following surgery for craniopharyngioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Endocrinol Metab. 2012;25(9-10):1027-30. doi: 10.1515/jpem-2012-0176.

            ●● Enlace al texto completo (gratuito o de pago) 1515/jpem-2012-0176

AUTORES / AUTHORS:  - Kwon AR; Ann JM; Shin JI; Chae HW; Kim HS

INSTITUCIÓN / INSTITUTION:  - Yonsei University College of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - Thirst is stimulated by increases in effective plasma osmolality that are detected by cerebral osmoreceptors located in the vascular organ of the lamina terminalis. However, surgical destruction or organic lesions of the lamina terminalis decrease the sensation of thirst in response to increased plasma osmolality. A 17-year-old boy who was diagnosed with craniopharyngioma at the age of 10 years and underwent tumor resection and gamma knife surgery was admitted for non-symptomatic severe hypernatremia. Although the sodium level was 173 mmol/L and serum osmolality was also high (371 mOsm/kg), the patient did not report increased thirst. Laboratory analysis revealed hypertonic dehydration and  acute non-oliguric renal failure due to dehydration. Treatment was based on correction of hypernatremia with hydration and education about regular, periodic  water ingestion. The patient’s hypernatremia and acute non-oliguric renal failure resolved with controlled daily fluid intake. To our knowledge, this is the first  report of decreased thirst sensation secondary to craniopharyngioma and tumor resection leading to severe hypernatremia and non-oliguric renal failure in an adolescent.

 

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[572]

TÍTULO / TITLE:  - Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pituitary. 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0481-5

AUTORES / AUTHORS:  - Guzzo MF; Carvalho LR; Bronstein MD

INSTITUCIÓN / INSTITUTION:  - Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.

RESUMEN / SUMMARY:  - Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor  pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in  physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke’s pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

 

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[573]

TÍTULO / TITLE:  - Technical nuances for surgery of insular gliomas: lessons learned.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E6. doi: 10.3171/2012.12.FOCUS12342.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12342

AUTORES / AUTHORS:  - Rey-Dios R; Cohen-Gadol AA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Mississippi; and.

RESUMEN / SUMMARY:  - Insular gliomas were traditionally considered a nonsurgical entity due to the high morbidity associated with resection. For the past 20 years, advances in microsurgical and brain mapping techniques have allowed neurosurgeons to resect insular gliomas with acceptable morbidity rates. Maximizing the extent of resection is nowadays the goal of surgery since this has proven to be an independent factor contributing to longer survival. Despite much progress, insular tumors remain a challenge for the neurosurgeon due to the complex anatomy of the region and technical expertise required to minimize morbidity during surgery. Herein, the authors describe the current surgical nuances, based on their experience and a literature review, that will allow the surgeon to achieve  a thorough resection while ensuring patient safety. The key factors for successful surgery in the insular region include detailed knowledge of the surgical anatomy, mastery of the nuances of cortical and subcortical mapping methods, and meticulous microsurgical technique.

 

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[574]

TÍTULO / TITLE:  - The molecular biology of WHO Grade II gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Feb;34(2):E1. doi: 10.3171/2012.12.FOCUS12283.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.FOCUS12283

AUTORES / AUTHORS:  - Marko NF; Weil RJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; and.

RESUMEN / SUMMARY:  - The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors  of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the “low-grade gliomas,” these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular  features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors’ goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

 

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[575]

TÍTULO / TITLE:  - Left Cerebellopontine Angle Lipoma With Mild Brainstem Compression in a 13-Year-Old Female.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Otol Neurotol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MAO.0b013e3182814d6e

AUTORES / AUTHORS:  - Crowson MG; Symons SP; Chen JM

INSTITUCIÓN / INSTITUTION:  - *Department of Otolaryngology-Head and Neck Surgery, and daggerDivision of Neuroradiology, Department of Medical Imaging, University of Toronto, Sunnybrook  Health Sciences Centre, Toronto, Ontario, Canada.

 

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[576]

TÍTULO / TITLE:  - PTEN suppresses SPARC-induced pMAPKAPK2 and inhibits SPARC-induced Ser78 HSP27 phosphorylation in glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Apr;15(4):451-61. doi: 10.1093/neuonc/nos326. Epub 2013 Feb 3.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos326

AUTORES / AUTHORS:  - Alam R; Schultz CR; Golembieski WA; Poisson LM; Rempel SA

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Sandra A. Rempel, PhD, Barbara Jane Levy Laboratory of Molecular Neuro-Oncology, Hermelin Brain Tumor Center, Department of Neurosurgery, Room 3096, Education and Research Bldg., Henry Ford Hospital, 2799  West Grand Blvd., Detroit, MI 48202. srempel1@hfhs.org.

RESUMEN / SUMMARY:  - Background Secreted protein acidic and rich in cysteine (SPARC) is overexpressed  in astrocytomas (World Health Organization grades II-IV). We previously demonstrated that SPARC promotes glioma migration and invasion-in part, by activating the P38 mitogen-activated protein kinase (MAPK)-heat shock protein (HSP)27 signaling pathway. The commonly lost tumor suppressor phosphatase and tensin homolog (PTEN) suppresses SPARC-induced migration, which is accompanied by suppression of Shc-Ras-Raf-MEK-ERK1/2 and Akt signaling. As PTEN completely suppresses SPARC-induced migration, we proposed that PTEN must also interfere with SPARC-induced HSP27 signaling. Therefore, this study determined the effects  of PTEN expression on SPARC-induced expression and phosphorylation of HSP27. Methods Control and SPARC-expressing clones transfected with control- or PTEN-expression plasmids were plated on fibronectin-coated tissue culture plates  for 3, 6, 24, and 48 h and then lysed. Equal amounts of protein were subjected to Western blot and densitometric analyses. Results The results show that SPARC enhances phosphorylated (p)P38 MAPK, phosphorylated MAPK-activated protein kinase 2 (pMAPKAPK2), and serine (Ser)78 HSP27 phosphorylation relative to total HSP27.  PTEN suppresses pAkt and pMAPKAPK2, suggesting that PTEN effects are downstream of pP38 MAPK. PTEN suppressed SPARC-induced sustained phosphorylation at Ser78 HSP27. As the level of total HSP27 differed based on the presence of SPARC or PTEN, the ratios of phosphorylation-specific to total HSP27 were examined. The data demonstrate that SPARC-induced phosphorylation at Ser78 remains elevated despite increasing levels of total HSP27. In contrast, PTEN inhibits SPARC-induced increases in Ser78 HSP27 phosphorylation relative to total HSP27. Conclusion These data describe a novel mechanism whereby PTEN inhibits SPARC-induced migration through suppression and differential regulation of pAkt and the P38 MAPK-MAPKAPK2-HSP27 signaling pathway.

 

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[577]

TÍTULO / TITLE:  - High Frequency of Temperature-Sensitive Mutants of p53 in Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Oncol Res. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9596-7

AUTORES / AUTHORS:  - Smardova J; Liskova K; Ravcukova B; Kubiczkova L; Sevcikova S; Michalek J; Svitakova M; Vybihal V; Kren L; Smarda J

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic, janasmarda@seznam.cz.

RESUMEN / SUMMARY:  - Glioblastoma is the most common and the most aggressive type of brain cancer. Aberrations of the RTK/RAS/PI3K-, p53-, and RB cell signaling pathways were recognized as a core requirement for pathogenesis of glioblastoma. The p53 tumor  suppressor functions as a transcription factor transactivating expression of its  target genes in response to various stress stimuli. We determined the p53 status  in 36 samples of glioblastoma by functional analyses FASAY and split assay. Seventeen p53 mutations were detected and further analyzed by cDNA and gDNA sequencing in 17 patients (47.2 %). Fifteen (88.2 %) of the mutations were missense mutations causing amino acid substitutions, seven of them exhibited temperature-sensitivity. Two mutations were determined as short deletions, one of them causing formation of premature termination codon in position 247. Fluorescent in situ hybridization revealed the loss of the p53-specific 17p13.3 locus in four of 33 analyzed samples (12 %). In 12 out of 30 samples (40 %), the  p53 protein accumulation was shown by immunoblotting. There was high (80 %) concordance between the presence of the clonal p53 mutation and the p53 protein accumulation.

 

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[578]

TÍTULO / TITLE:  - Surgical management of a giant cervical ganglioneuroma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Auris Nasus Larynx. 2013 Feb 19. pii: S0385-8146(13)00040-0. doi: 10.1016/j.anl.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.anl.2013.01.005

AUTORES / AUTHORS:  - Urata S; Yoshida M; Ebihara Y; Asakage T

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Otolaryngology, Medical Center, Saitama Medical University, Saitama, Japan. Electronic address: uraurashinjix@nifty.com.

RESUMEN / SUMMARY:  - An 18-year-old patient presented with a major complaint of a mass in the right side of the neck. At the previous clinic, the patient underwent an open biopsy because the mass could not be diagnosed by fine needle aspiration. The patient was introduced to our institution after mass was diagnosed as ganglioneuroma by open biopsy. In our outpatient clinic, magnetic resonance imaging (MRI) and computed tomography (CT) were performed. Gradual growth of the mass was accompanied by sleep apnea syndrome. Ultimately, the patient was only able to sleep with nasal continuous positive airway pressure. Pathological examination confirmed the ganglioneuroma. MRI revealed expansion of the ganglioneuroma from the nasopharynx to the right upper mediastinum, occupying the surroundings of the contralateral carotid artery via the retropharyngeal space. CT revealed a tumor mass of 160mmx60mmx190mm in size. The mass was surgically resected without any postoperative neurological disorder including Horner syndrome. The clinical course was successful without recurrence. This is the first report of a successful treatment of a large ganglineuroma that had continuously expanded to the contralateral neck via the retropharyngeal space.

 

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[579]

TÍTULO / TITLE:  - Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome secondary to an epidermoid tumor in the cerebellopontine angle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Mar;34(3):E1. doi: 10.3171/2013.1.FOCUS12233.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.FOCUS12233

AUTORES / AUTHORS:  - Rodgers SD; Marascalchi BJ; Strom RG; Huang PP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, New York University Langone Medical Center, New York, New York.

RESUMEN / SUMMARY:  - Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is classified under trigeminal autonomic cephalalgias. This rare headache syndrome is infrequently associated with secondary pathologies. In this paper the authors report on a patient with paroxysmal left retroorbital pain with associated autonomic symptoms of ipsilateral conjunctival injection and lacrimation, suggestive of SUNCT syndrome. After failed medical treatment an MRI sequence was obtained in this patient, demonstrating an epidermoid tumor in the left cerebellopontine angle. The patient’s symptoms completely resolved after a gross-total resection of the tumor. This case demonstrates the effectiveness of resection as definitive treatment for SUNCT syndrome associated with tumoral compression of the trigeminal nerve. Early MRI studies should be considered in all patients with SUNCT, especially those with atypical signs and symptoms.

 

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[580]

TÍTULO / TITLE:  - Resection of filum terminale ependymoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Spine J. 2013 Mar;22(3):681-2. doi: 10.1007/s00586-013-2704-x.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00586-013-2704-x

AUTORES / AUTHORS:  - Ringel F; Meyer B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany.

 

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[581]

TÍTULO / TITLE:  - Laparoscopic excision of a retroperitoneal ganglioneuroma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JSLS. 2012 Oct-Dec;16(4):668-70. doi: 10.4293/108680812X13517013316799.

            ●● Enlace al texto completo (gratuito o de pago) 4293/108680812X13517013316799

AUTORES / AUTHORS:  - Alimoglu O; Caliskan M; Acar A; Hasbahceci M; Canbak T; Bas G

INSTITUCIÓN / INSTITUTION:  - Department of General Surgery, Umraniye Education and Research Hospital, Istanbul, Turkey. orhanalimoglu@gmail.com

RESUMEN / SUMMARY:  - OBJECTIVE: Ganglioneuromas are rare benign tumors originating from ganglion cells. Ganglioneuromas are detected incidentally because they are asymptomatic. We report a case of laparoscopic excision of a retroperitoneal ganglioneuroma. Case Description: A 49-y-old female was admitted to our medical center with the complaint of abdominal pain. Abdominal ultrasound showed a hypoechoic solid lesion at the level of the liver hilum, adjacent to the pancreas. Computerized tomography scan confirmed the presence of a thin walled mass 44 mm in diameter, adjacent to the pancreas and liver. Laparoscopic excision of the retroperitoneal  mass was planned. The tumor was removed en bloc, and the pathologic diagnosis was ganglioneuroma. The patient was discharged from the hospital on the third postoperative day without any complications. CONCLUSION: Minimally invasive surgery has been shown to be safe and reliable in patients with retroperitoneal tumors.

 

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[582]

TÍTULO / TITLE:  - Alternative splicing of iodothyronine deiodinases in pituitary adenomas. Regulation by oncoprotein SF2/ASF.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Biochim Biophys Acta. 2013 Jun;1832(6):763-72. doi: 10.1016/j.bbadis.2013.02.013. Epub 2013 Feb 24.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbadis.2013.02.013

AUTORES / AUTHORS:  - Piekielko-Witkowska A; Kedzierska H; Poplawski P; Wojcicka A; Rybicka B; Maksymowicz M; Grajkowska W; Matyja E; Mandat T; Bonicki W; Nauman P

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical  Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland. Electronic address: pieklo@cmkp.edu.pl.

RESUMEN / SUMMARY:  - Pituitary tumors belong to the group of most common neoplasms of the sellar region. Iodothyronine deiodinase types 1 (DIO1) and 2 (DIO2) are enzymes contributing to the levels of locally synthesized T3, a hormone regulating key physiological processes in the pituitary, including its development, cellular proliferation, and hormone secretion. Previous studies revealed that the expression of deiodinases in pituitary tumors is variable and, moreover, there is no correlation between mRNA and protein products of the particular gene, suggesting the potential role of posttranscriptional regulatory mechanisms. In this work we hypothesized that one of such mechanisms could be the alternative splicing. Therefore, we analyzed expression and sequences of DIO1 and DIO2 splicing variants in 30 pituitary adenomas and 9 non-tumorous pituitary samples.  DIO2 mRNA was expressed as only two mRNA isoforms. In contrast, nine splice variants of DIO1 were identified. Among them, five were devoid of exon 3. In silico sequence analysis of DIO1 revealed multiple putative binding sites for splicing factor SF2/ASF, of which the top-ranked sites were located in exon 3. Silencing of SF2/ASF in pituitary tumor GH3 cells resulted in change of ratio between DIO1 isoforms with or without exon 3, favoring the expression of variants without exon 3. The expression of SF2/ASF mRNA in pituitary tumors was increased  when compared with non-neoplastic control samples. In conclusion, we provide a new mechanism of posttranscriptional regulation of DIO1 and show deregulation of  DIO1 expression in pituitary adenoma, possibly resulting from disturbed expression of SF2/ASF.

 

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[583]

TÍTULO / TITLE:  - Primary Central Nervous System Lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Treat Options Oncol. 2013 Mar 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11864-013-0227-7

AUTORES / AUTHORS:  - Doucet S; Kumthekar P; Raizer J

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Division of Hematology-Oncology, Northwestern University, Feinberg School of Medicine, 676 North St. Clair, suite 850, Chicago, IL, 60611,  USA, stephane.doucet@northwestern.edu.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Primary central nervous system lymphoma (PCNSL) comprises approximately 5 % of all primary brain tumors. During the past two decades the incidence of PCNSL has increased, and as a result clinical research to determine  the optimal treatment for PCNSL patients also has increased. Diagnosis is based on histopathologic findings traditionally established by biopsy only. More recent data raise controversy and challenges this biopsy-only paradigm, showing a potential advantage for surgical resection with progression-free survival (PFS) and overall survival (OS). Using high-dose intravenous (IV) methotrexate-based chemotherapy alone or as part of a regimen can lead to disease cure. The role of  whole brain radiotherapy (WBRT) remains controversial and more frequently is omitted to avoid potential delayed neurocognitive effects, especially in patients older than age 60 years. Newer data from Memorial Sloan Kettering Cancer Center (MSKCC) using five cycles of Rituximab, Methotrexate, Vincristine, and Procarbazine (R-MVP) followed by low-dose WBRT (2,340 cgy), and then two cycles of Ara-C had excellent disease control with low neuro-toxicity and is now the basis of an ongoing RTOG (Radiation Treatment Oncology Group) trial comparing early versus delayed WBRT. Other chemotherapeutics and novel treatments, such as  autologous stem cell transplantation, are being studied for potential use in PCNSL. Unlike many other primary brain tumors seen in adults, PCNSL is potentially curable; therefore, balancing treatment decisions with long-term neurocognitive effects and toxicities is crucial.

 

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[584]

TÍTULO / TITLE:  - Array CGH in brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Methods Mol Biol. 2013;973:325-38. doi: 10.1007/978-1-62703-281-0_20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-281-0_20

AUTORES / AUTHORS:  - Mohapatra G; Sharma J; Yip S

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

RESUMEN / SUMMARY:  - Alterations in the copy number of the cancer genome are frequently observed in brain tumors especially gliomas. Some pertinent examples include amplification of the EGFR locus in chromosome 7p and loss of the PTEN locus in 10q in glioblastoma. Meningiomas are often associated with loss of the NF2 locus in 22q. Array CGH or aCGH probes provide a reliable, consistent, and economical method of profiling genome-wide copy number alterations (CNAs) of cancer specimens at fairly robust resolution. This has allowed for the systematic assessment of brain tumors for recurrent genomic CNAs. In addition, recent technical advancements have increased the robustness of this technique to accommodate DNA derived from formalin-fixed paraffin-embedded (FFPE) tissue. Lastly, novel technologies such as next-generation sequencing and multiplex digital gene counting technology such as NanoString will expand the -repertoire of techniques for assessing CNAs in brain tumors.

 

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[585]

TÍTULO / TITLE:  - Chronic spinal subdural abscess mimicking an intradural-extramedullary tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Spine J. 2013 Feb 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00586-013-2700-1

AUTORES / AUTHORS:  - Lim HY; Choi HJ; Kim S; Kuh SU

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Gangnam Severance Spine Hospital, Yonsei University College of Medicine, 146-92, Dogok-dong, Gangnam-gu, Seoul, 135-720, South Korea.

RESUMEN / SUMMARY:  - Spinal subdural abscesses (SSA) are very rare disease. The etiologies of SSA are  hematogenous spread, iatrogenic contamination, and local extension. Elevated WBC  counts, ESR, and C-reactive protein are usually found in laboratory tests. But they are not sensitive indicators of SSA, especially chronic abscesses patient tend to have a less specific characteristic. We report the case of a healthy man  with chronic subdural abscess referred to our hospital as an intradural-extramedullary (IDEM) tumor. The patient presented with voiding difficulty and pain in the back and left leg. In a contrast MRI scan, a rim-enhanced mass-like lesion was seen at the L5/S1 level. But adjacent ill-defined epidural fat enhancement that are unusual imaging manifestation for IDEM tumors was seen. He had no fever and normal WBC, ESR, and CRP. In addition,  the patient had no previous infection history or other disease, but he did have an epidural block for back pain at another hospital 2 years previously. So, we repeated the MRI with a high-resolution 3-T scanner. The newly taken MR images in our hospital revealed a clear enlargement of lesion size compared to the previous MRI taken 1 week before in other hospital. We suspected a chronic spinal subdural abscess with recent aggravation and immediately performed surgical evacuation. In the surgical field, tensed dura was observed and pus was identified after opening the abscess capsule. Because chronic spinal subdural abscesses are difficult to diagnose, we could differentiate with IDEM tumor exactly and an exact history taking, contrast MRI are required.

 

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[586]

TÍTULO / TITLE:  - Pituitary Carcinoma in Situ.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocr Pract. 2013 Feb 20:1-15.

            ●● Enlace al texto completo (gratuito o de pago) 4158/EP12351.CR

AUTORES / AUTHORS:  - Pasquel FJ; Vincentelli C; Brat DJ; Oyesiku NM; Ioachimescu AG

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

RESUMEN / SUMMARY:  - Objective: Pituitary carcinomas are extremely rare tumors associated with poor prognosis despite surgery, radiation and chemotherapy. The hallmark of diagnosis  implies subarachnoid, brain, or systemic tumor spread.Methods: We report a case of rapid transformation of atypical non-functioning pituitary adenoma to a carcinoma.Results: A 64-year-old woman presented with sudden onset of ophtalmoplegia. MRI scan showed a pituitary macroadenoma (2.2 x 2.1 cm) with invasion of the right cavernous sinus. Biochemical data was consistent with a non-functioning pituitary adenoma. Pathology showed a pituitary adenoma with negative immunohistochemistry for pituitary hormones. The patient returned a month later with weakness, lethargy, and a dilated non-reactive right pupil. MRI  showed an invasive large mass (5 x 4.7 cm). After an emergent second transsphenoidal surgery, histopathologic examination revealed a widely infiltrative neoplasm invading the overlying mucosa and showing a high mitotic activity and necrosis and a very high Ki-67 (MIB-1) proliferation index (80%). MIB-1 retrospectively performed on the first specimen was also elevated (30%.). Soon after the second surgery, MRI showed a 7.9 x 8.0 cm mass that metastasized to dura mater, and extended into the right orbit, right middle cranial fossa, nasopharynx, clivus, posterior fossa, and along the right tentorium cerebelli, resulting in significant compression of the brainstem.Conclusion: Development of  a pituitary carcinoma from an adenoma is an exceptional occurrence, and predictors of such course are currently lacking. A very high Ki-67 proliferation  index should raise concern of a pituitary carcinoma in situ or premetastatic carcinoma.

 

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[587]

TÍTULO / TITLE:  - Accumulation of 2-hydroxyglutarate is not a biomarker for malignant progression in IDH-mutated low-grade gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not006

AUTORES / AUTHORS:  - Juratli TA; Peitzsch M; Geiger K; Schackert G; Eisenhofer G; Krex D

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery (T.A.J., G.S., D.K.), Department of Clinical Chemistry and Laboratory Medicine (M.P., G.E.), and Institute of Neuropathology (K.G.), University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Dresden, Germany.

RESUMEN / SUMMARY:  - ObjectivesTo determine whether accumulation of 2-hydroxyglutarate in IDH-mutated  low-grade gliomas (LGG; WHO grade II) correlates with their malignant transformation and to evaluate changes in metabolite levels during malignant progression.MethodsSamples from 54 patients were screened for IDH mutations: 17 patients with LGG without malignant transformation, 18 patients with both LGG and their consecutive secondary glioblastomas (sGBM; n = 36), 2 additional patients with sGBM, 10 patients with primary glioblastomas (pGBM), and 7 patients without  gliomas. The cellular tricarboxylic acid cycle metabolites, citrate, isocitrate,  2-hydroxyglutarate, alpha-ketoglutarate, fumarate, and succinate were profiled by liquid chromatography-tandem mass spectrometry. Ratios of 2-hydroxyglutarate/isocitrate were used to evaluate differences in 2-hydroxyglutarate accumulation in tumors from LGG and sGBM groups, compared with pGBM and nonglioma groups.ResultsIDH1 mutations were detected in 27 (77.1%) of 37 patients with LGG. In addition, in patients with LGG with malignant progression (n = 18), 17 patients were IDH1 mutated with a stable mutation status during their malignant progression. None of the patients with pGBM or nonglioma tumors had an IDH mutation. Increased 2-hydroxyglutarate/isocitrate ratios were seen in  patients with IDH1-mutated LGG and sGBM, in comparison with those with IDH1-nonmutated LGG, pGBM, and nonglioma groups. However, no differences in intratumoral 2-hydroxyglutarate/isocitrate ratios were found between patients with LGG with and without malignant transformation. Furthermore, in patients with paired samples of LGG and their consecutive sGBM, the 2-hydroxyglutarate/isocitrate ratios did not differ between both tumor stages.ConclusionAlthough intratumoral 2-hydroxyglutarate accumulation provides a marker for the presence of IDH mutations, the metabolite is not a useful biomarker for identifying malignant transformation or evaluating malignant progression.

 

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[588]

TÍTULO / TITLE:  - Pituitary macroadenoma due to hypothyroidism.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Endocrinol Metab. 2012 Nov 24:1-2. doi: 10.1515/jpem-2012-0323.

            ●● Enlace al texto completo (gratuito o de pago) 1515/jpem-2012-0323

AUTORES / AUTHORS:  - Eklioglu BS; Atabek ME; Akyurek N

RESUMEN / SUMMARY:  - No abstract available.

 

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[589]

TÍTULO / TITLE:  - Paraneoplastic brain stem encephalitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Treat Options Neurol. 2013 Apr;15(2):201-9. doi: 10.1007/s11940-013-0221-1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11940-013-0221-1

AUTORES / AUTHORS:  - Blaes F

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Gummersbach Hospital, Wilhelm-Breckow-Allee 20, 51643, Gummersbach, Giessen, Germany, Franz.Blaes@kkh-gummersbach.de.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment. Brain stem encephalitis with anti-Ma2 often improves after immunotherapy and/or tumor therapy, whereas only a minority of anti-Ri positive patients respond to immunosuppressants or tumor treatment. The Opsoclonus-myoclonus syndrome (OMS) in children, almost exclusively associated with neuroblastoma, shows a good response to steroids, ACTH, and rituximab, some  patients do respond to intravenous immunoglobulins or cyclophosphamide. In adults, OMS is mainly associated with small cell lung cancer or gynecological tumors and only a small part of the patients show improvement after immunotherapy. Earlier diagnosis and treatment seem to be one major problem to improve the prognosis of both, paraneoplastic brain stem encephalitis, and OMS.

 

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[590]

TÍTULO / TITLE:  - “Leiomyomatoid angiomatous neuroendocrine tumor” (LANT) of the pituitary reflects idiosyncratic angiogenesis in adenomas of the gonadotroph cell lineage.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pathol Res Pract. 2013 Mar;209(3):155-60. doi: 10.1016/j.prp.2013.01.003. Epub 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.prp.2013.01.003

AUTORES / AUTHORS:  - Schurch C; Birrer M; Estella I; Kappeler A; Hewer E; Vajtai I

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Pathology, Institute of Pathology, University of Bern, Switzerland.

RESUMEN / SUMMARY:  - Based on a single-case observation, the descriptive label “leiomyomatoid angiomatous neuroendocrine tumor” (LANT) has been tentatively applied to what was perceived as a possible novel type of dual-lineage pituitary neoplasm with biphasic architecture. We report on two additional examples of an analogous phenomenon encountered in male patients, aged 59 years (Case 1) and 91 years (Case 2). Both tumors were intra- and suprasellar masses, measuring 5.6cmx4.4cmx3.4cm, and 2.7cmx2cmx1.7cm, respectively. Histologically, Case 1 was  an FSH-cell adenoma interwoven by vascularized connective tissue septa that tended to exhibit incremental stages of adventitial overgrowth. The epithelial component of Case 2 corresponded to an LH-cell adenoma, and lay partitioned by a  maze of paucicellular to hyalinized vascular axes. Irrespective of architectural  variations, perivascular spindle cells exhibited immunopositivity for vimentin, muscular actin, and smooth muscle actin. Conversely, negative results were obtained for CD34, EMA, S100 protein, GFAP, and TTF-1. Ultrastructural study failed to reveal metaplastic cell forms involving transitional features between adenohypophyseal-epithelial and mesenchymal-contractile phenotype. We propose that LANT be regarded as a peculiar reflection of maladaptive angiogenesis in some pituitary adenomas, rather than a genuine hybrid neoplasm. While no mechanistic clue is forthcoming to account for this distinctive pattern, hemodynamic strain through direct arterial - rather than portal - supply of the adenoma’s capillary bed may be one such explanatory factor. The apparent predilection of the LANT pattern for macroadenomas of the gonadotroph cell lineage remains unexplained.

 

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[591]

TÍTULO / TITLE:  - Inhibition of prolyl 4-hydroxylase, beta polypeptide (P4HB) attenuates temozolomide resistance in malignant glioma via the endoplasmic reticulum stress  response (ERSR) pathways.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not005

AUTORES / AUTHORS:  - Sun S; Lee D; Ho AS; Pu JK; Zhang XQ; Lee NP; Day PJ; Lui WM; Fung CF; Leung GK

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, People’s Republic of China (S.S., D.L., A.S.W.H., J.K.S.P., X.Q.Z., N.P.L., W.M.L., C.F.F., G.K.K.L.); Interdisciplinary Molecular Medicine, The Manchester Institute of Biotechnology,  University of Manchester, Manchester, UK (P.J.R.D.).

RESUMEN / SUMMARY:  - BackgroundGlioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor of the central nervous system, is characterized by a relentless disease recurrence despite continued advancement in surgery, radiotherapy, and chemotherapy. Resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, remains a major challenge. Understanding the mechanisms behind TMZ resistance can direct the development of novel strategies for the prevention, monitoring, and treatment of tumor relapse.Methods and resultsOur research platform, based on the establishment of 2 pairs of TMZ-sensitive/resistant GBM cells (D54-S and D54-R; U87-S and U87-R), has successfully identified prolyl 4-hydroxylase, beta polypeptide (P4HB) over-expression to be associated with an increased IC(50) of TMZ. Elevated P4HB expression was verified using in vivo xenografts developed from U87-R cells. Clinically, we found that P4HB was relatively up-regulated in the recurrent GBM specimens that were initially responsive to TMZ but later developed acquired resistance, when compared with treatment-naive tumors. Functionally, P4HB inhibition by RNAi knockdown and bacitracin inhibition could sensitize D54-R and U87-R cells to TMZ in vitro and in vivo, whereas over-expression of P4HB in vitro conferred resistance to TMZ in  both D54-S and U87-S cells. Moreover, targeting P4HB blocked its protective function and sensitized glioma cells to TMZ through the PERK arm of the endoplasmic reticulum stress response.ConclusionsOur study identified a novel target together with its functional pathway in the development of TMZ resistance. P4HB inhibition may be used alone or in combination with TMZ for the treatment of TMZ-resistant GBM.

 

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[592]

TÍTULO / TITLE:  - Progressive late-onset of cutaneous angiomatosis as possible sign of cerebral cavernous malformations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dermatol Online J. 2013 Feb 15;19(2):2.

AUTORES / AUTHORS:  - Campione E; Diluvio L; Terrinoni A; Di Stefani A; Orlandi A; Chimenti S; Bianchi L

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, University of Rome Tor Vergata.

RESUMEN / SUMMARY:  - BACKGROUND: Cerebral cavernous malformations (CCM) comprise enlarged capillary cavities in the central nervous system, with possible retinal or cutaneous vascular malformations. This condition is associated with CCM1, CCM2, and CCM3 gene mutations. OBJECTIVE: Cutaneous clinical, histological and cerebral MRI findings, including CCM1, CCM2, and CCM3 gene sequencing, of two unrelated, neurological symptom-free patients who consulted for late-onset of deep multiple  cutaneous angiomatoid lesions, are described. RESULTS: The diagnosis of multiple  cutaneous angiomatosis was confirmed and related to CCM as detected by MRI in both cases. Analysis of our patients showed normal nucleotide sequences of the genes proposed. CONCLUSIONS: A progressive late-onset of multiple, deep cutaneous venous malformations may indicate the need to investigate a potential coexistence of CCM by MRI. Early diagnosis and prompt treatment is required in these patients. The absence of CCM1, CCM2, and CCM3 mutations might indicate that different genes could be involved in the pathogenesis of these late-onset patients. Careful questioning about family history of CCM is important; our first patient’s daughter had a history of cerebral cavernoma.

 

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[593]

TÍTULO / TITLE:  - STAT3 silencing inhibits glioma single cell infiltration and tumor growth.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not025

AUTORES / AUTHORS:  - Priester M; Copanaki E; Vafaizadeh V; Hensel S; Bernreuther C; Glatzel M; Seifert V; Groner B; Kogel D; Weissenberger J

INSTITUCIÓN / INSTITUTION:  - Experimental Neurosurgery, Goethe University Hospital, Neuroscience Center, Frankfurt, Germany (M.P., S.H., D.K., J.W.); Institute of Clinical Neuroanatomy,  Goethe University, Neuroscience Center, Frankfurt, Germany (E.C.); Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt, Germany (V.V., B.G.); Institute of Neuropathology, University Medical Center Hamburg-Eppendorf,  Hamburg, Germany (C.B., M.G.); Department of Neurosurgery, Center of Neurology and Neurosurgery, Goethe University Hospital, Frankfurt, Germany (V.S.).

RESUMEN / SUMMARY:  - BackgroundDiffuse infiltration remains the fulcrum of glioblastoma’s incurability, leading inevitably to recurrence. Therefore, uncovering the pathological mechanism is imperative. Because signal transducer and activator of  transcription 3 (STAT3) correlates with glioma malignancy and predicts poor clinical outcome, we determined its role in glioma single cell infiltration and tumor growth.MethodsSTAT3 was silenced in Tu-2449 glioma cells via lentiviral gene transfer. Target gene expression was measured by real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Microvilli were visualized by staining with wheat germ agglutinin. Migration and invasion were measured by Scratch and Matrigel chamber assays. Diffuse infiltration was studied in 350-mum-thick organotypic tissue cultures over 14 days using cells tagged with enhanced green fluorescent protein and live confocal laser scanning microscopy. Survival of tumor-bearing syngeneic, immunocompetent B6C3F1 mice was analyzed by  Kaplan-Meier plots.ResultsSTAT3 silencing reduced cell migration and invasion in  vitro and stopped single cell infiltration ex vivo, while STAT3-expressing cells  disseminated through the neuropil at approximately 100 microm/day. STAT3 silencing reduced transcription of several tumor progression genes. Mice with intracranial STAT3 knockdown tumors had a significant (P< .0007) survival advantage over controls, yielding 27% long-term survival. STAT3 knockdown reduced podoplanin expression 50-fold and inhibited concurrent microvilli formation. STAT3 knockdown tumors exhibited a weaker podoplanin immunoreactivity compared with controls. Podoplanin staining was diffuse, preferentially at tumor margins,  and absent in normal brain.ConclusionsOur results show compelling evidence that STAT3 is a key driver of diffuse infiltration and glioma growth and might therefore represent a promising target for an anti-invasive therapy.

 

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[594]

TÍTULO / TITLE:  - Malignant paraganglioma of the thyroid gland with synchronous bilateral carotid body tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ear Nose Throat J. 2013 Feb;92(2):E20-3.

AUTORES / AUTHORS:  - Mohyuddin N; Ferrer K; Patel U

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.

RESUMEN / SUMMARY:  - We describe a case of primary malignant paraganglioma of the thyroid gland that was found in a 55-year-old woman who had undergone surgery for bilateral carotid  body tumors. The paraganglioma was treated with a total thyroidectomy followed by radiation therapy, and the patient was disease-free after more than 2 years of follow-up. Malignant paragangliomas of the thyroid gland are extremely rare. The  diagnosis of malignancy is based on histopathologic findings, tumor behavior, and metastasis. These tumors can be misdiagnosed as other types of thyroid malignancies, thus resulting in less than optimal treatment. A genetic etiology was suspected in our patient.

 

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[595]

TÍTULO / TITLE:  - EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1101-1

AUTORES / AUTHORS:  - Talasila KM; Soentgerath A; Euskirchen P; Rosland GV; Wang J; Huszthy PC; Prestegarden L; Skaftnesmo KO; Sakariassen PO; Eskilsson E; Stieber D; Keunen O; Brekka N; Moen I; Nigro JM; Vintermyr OK; Lund-Johansen M; Niclou S; Mork SJ; Enger PO; Bjerkvig R; Miletic H

INSTITUCIÓN / INSTITUTION:  - Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway.

RESUMEN / SUMMARY:  - Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however,  it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon that is particularly evident by the infiltrative growth of malignant brain tumors, such as glioblastomas (GBMs). In these tumors, amplification or overexpression of wild-type (wt) or truncated and constitutively activated epidermal growth factor receptor (EGFR) are regarded as important events in GBM development, where the complex downstream signaling events have been implicated in tumor cell invasion, angiogenesis and proliferation. Here, we show that amplification and in particular activation of wild-type EGFR represents an underlying mechanism for non-angiogenic, invasive tumor growth. Using a clinically relevant human GBM xenograft model, we show that tumor cells with EGFR gene amplification and activation diffusely infiltrate normal brain tissue independent of angiogenesis and that transient inhibition of EGFR activity by cetuximab inhibits the invasive tumor growth. Moreover, stable, long-term expression of a dominant-negative EGFR leads to a mesenchymal to epithelial-like  transition and induction of angiogenic tumor growth. Analysis of human GBM biopsies confirmed that EGFR activation correlated with invasive/non-angiogenic tumor growth. In conclusion, our results indicate that activation of wild-type EGFR promotes invasion and glioblastoma development independent of angiogenesis,  whereas loss of its activity results in angiogenic tumor growth.

 

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[596]

TÍTULO / TITLE:  - Implications of Tumor Location on Subtypes of Medulloblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2013 Mar 19. doi: 10.1002/pbc.24511.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24511

AUTORES / AUTHORS:  - Teo WY; Shen J; Su JM; Yu A; Wang J; Chow WY; Li X; Jones J; Dauser R; Whitehead W; Adesina AM; Chintagumpala M; Man TK; Lau CC

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Division of Hematology-Oncology, Texas Children’s Cancer Center, Baylor College of Medicine, Houston, Texas.

RESUMEN / SUMMARY:  - BACKGROUND: Medulloblastoma (MB) comprises of four molecular subtypes, Sonic hedgehog (SHH), Wingless (WNT), Groups 3 and 4. WNT-subtype MBs were found to arise from midline of the brainstem occupying the fourth ventricle while SHH-subtype occupied the cerebellar hemisphere in a small subset of patients. PROCEDURE: We tested this hypothesis in a large cohort of pediatric MBs comprising of all four molecular subtypes. RESULTS: We validated in the first comprehensive analysis of tumor location of 60 human MBs representative of the four molecular subtypes, that hemispheric tumors are significantly associated with SHH-subtype MBs while midline tumors with WNT-subtype, Group 3 and 4 MBs (P  < 0.001). Nearly half of SHH-subtype MBs were midline. CONCLUSIONS: Tumor location should not be generalized to MB subtypes. SHH-subtype MBs are not exclusively hemispheric and hemispheric MBs are not always SHH-activated. It is imperative to identify subtypes in conjunction with tumor location when exploring currently available targeted therapy. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.

 

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[597]

TÍTULO / TITLE:  - Immunophenotype of Myxopapillary Ependymomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e318283980a

AUTORES / AUTHORS:  - Lamzabi I; Arvanitis LD; Reddy VB; Bitterman P; Gattuso P

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Rush University Medical Center, Chicago, IL.

RESUMEN / SUMMARY:  - Myxopapillary ependymoma (MPE) is a slow-growing tumor occurring almost exclusively in the region of conus medullaris, cauda equina, and filum terminale. On microscopic examination, some of these tumors show solid sheets of cells with  an epithelioid morphology mimicking a metastatic carcinoma. Several immunohistochemical studies addressed this issue with discordant results. We report the immunohistochemical findings of 9 additional cases of MPE. From 2004 to 2011, a total of 9 cases of MPE were recorded in our surgical pathology files. The histologic material and clinical data were reviewed for each case. There were 6 female and 3 male patients. The ages ranged from 15 to 58 years (mean, 31 y). Eight cases were intradural, lumbosacral (L1-S1), and 1 case was located in the sacrum. All tumors expressed CD99 and GFAP (100%). Eight tumors were positive for CD56 (89%). All tumors (100%) expressed focally CKAE1/AE3. One tumor (11%) was focally positive for CK8/18 and CK7. D2-40 was focally positive in 1 case (11%).  PLAP and AFP were both negative in all cases. Synaptophysin was focally positive  in 1 case. NSE was positive in all cases. All tumors were negative for CK5/6, CK20, E-cadherin, and TTF-1. Our study shows that the vast majority of MPE are positive for CD99, CD56, and GFAP. In selective cases, especially when the material obtained for pathologic evaluation is scanty and the tumor displays epithelioid appearance, the diagnosis may be challenging owing to cytokeratin positivity suggesting metastatic carcinoma. However, the clinical and radiologic  features in addition to the positivity for GFAP should prompt pathologists to consider MPE in the differential diagnosis of such cases. Interestingly, we found that MPE are positive for NSE, which suggests a neuroglial differentiation.

 

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[598]

TÍTULO / TITLE:  - Surgical treatment of intracranial arachnoid cyst in adult patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol India. 2013 Jan-Feb;61(1):60-4. doi: 10.4103/0028-3886.108013.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.108013

AUTORES / AUTHORS:  - Wang C; Liu C; Xiong Y; Han G; Yang H; Yin H; Wang J; You C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.

RESUMEN / SUMMARY:  - Background: Intracranial arachnoid cyst (IAC) is a benign cystic lesion filled with cerebrospinal fluid (CSF). Different surgical treatments were evaluated to determine the most effective technique among several. Materials and Methods: A consecutive series of 68 adult patients (43 males, mean age 30.3 years, range 18-42 years) with IAC were surgically treated between January 2004 and January 2011. The cysts were supratentorial in location in 53 and infratentorial in 15 patients. Symptoms at presentation, location of the IAC, surgical treatment modalities, and postoperative complications were evaluated. Results: Of the 51 patients with headache, 44 (86.27%) patients had complete relief of the headache, five (9.80%) patients had significant improvement, and two (3.92%) had no worthwhile change. Three of the four patients with hydrocephalus and gait disturbances had relief of the symptoms and one patient had significant improvement. Of the five patients with cognitive decline and weakness, three (60.00%) patients showed improvement, and two (40.00%) patients had no significant change. Five (62.50%) of the eight patients with epilepsy had seizure remission, two (25.00%) patients had non-disabling seizures, and one had no change. Follow-up computed tomography (CT) scans showed variable change in the mass effect of IAC in 68 patients; cystic size was significantly reduced in 51 patients, no significant change in two patients of supratentorial arachnoid cysts. Cystic size was reduced in seven patients, but no significant change was observed in eight patients of infratentorial cysts. Three patients with enlarged  head circumference had no further increase in the head circumference. Conclusion: Adult patients with IAC symptoms should be treated efficiently. Surgical treatment is associated with significant improvement in the symptoms and signs.

 

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[599]

TÍTULO / TITLE:  - Unsuspected pheochromocytoma multisystem crisis: a fatal outcome in a young male  patient.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Assoc Physicians India. 2012 Aug;60:53-6.

AUTORES / AUTHORS:  - Gundgurthi A; Gupta S; Garg MK; Ganguly P; Bhardwaj R

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantt.  110010

RESUMEN / SUMMARY:  - Pheochromocytoma is a great mimicker and has varied presentation. It can present  as medical emergency with hypertensive emergencies, acute cardiac event, neurological manifestations, systemic inflammatory response syndrome, acute respiratory distress syndrome, and metabolic emergencies. Here we report a young  individual who after a bout of exercise developed breathlessness and rapidly developed multiorgan failure which was fatal and post mortem examination revealed pheochromocytoma in right adrenal gland. Pheochromocytoma multisystem crisis is discussed.

 

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[600]

TÍTULO / TITLE:  - Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neoplasia. 2013 Feb;15(2):192-203.

AUTORES / AUTHORS:  - Velpula KK; Gogineni VR; Nalla AK; Dinh DH; Rao JS

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology and Pharmacology, University of Illinois College of  Medicine at Peoria, Peoria, IL.

RESUMEN / SUMMARY:  - Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers uPA expression in meningioma cells.

 

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[601]

TÍTULO / TITLE:  - Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Feb;126(3):482-7.

AUTORES / AUTHORS:  - Chen BB; Xu XP; Shen L; Han TJ; Lin ZG; Chen Z; Kang H; Huang B; Lin GW

INSTITUCIÓN / INSTITUTION:  - Department of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.

RESUMEN / SUMMARY:  - BACKGROUND: Clinical outcome in patients with primary central nervous lymphoma (PCNSL) is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL. METHODS: One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxp1, and LMO2 were performed. All cases were followed-up regularly. RESULTS: The common sites of involvement were frontal lobe (54.8%) and thalamus (16.5%). Diffuse large B-cell lymphoma composed of 96.5% of  the cases. The median overall survival was 22 (4 - 41) months, and the 5-year survival rate was 22.8%. Age > 65 years, serum globulin > 40 g/L, large size of tumor, lymphocyte count >/= 1 x 10(9)/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxp1, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size,  and high serum globulin were independent prognostic factors for PCNSL. CONCLUSIONS: PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.

 

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[602]

TÍTULO / TITLE:  - Clinical Outcomes of Gamma Knife Radiosurgery in the Salvage Treatment of Patients with Recurrent High-Grade Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 8. pii: S1878-8750(13)00295-7. doi: 10.1016/j.wneu.2013.02.030.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.030

AUTORES / AUTHORS:  - Elaimy AL; Mackay AR; Lamoreaux WT; Demakas JJ; Fairbanks RK; Cooke BS; Lamm AF; Lee CM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Gamma Knife of Spokane; Department of Radiation Oncology, Gamma Knife of Spokane and Cancer Care Northwest.

RESUMEN / SUMMARY:  - BACKGROUND: Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external-beam radiation therapy and chemotherapy when compared to patients treated with external-beam radiation therapy and chemotherapy alone. In recent years, Gamma Knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of Gamma Knife radiosurgery for patients who suffer from this malignancy. METHODS: Retrospective, prospective, and randomized clinical studies  published between the years 2000 and 2012 analyzing Gamma Knife radiosurgery for  patients with high-grade glioma were reviewed. RESULTS: After assessing patient age, Karnofsky Performance Status, tumor histology, and extent of resection, Gamma Knife radiosurgery is a viable, minimally-invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that Gamma Knife radiosurgery provides patients with a high local tumor control rate and a median survival following tumor recurrence ranging from 13 to 26 months. Gamma Knife radiosurgery followed  by chemotherapy for recurrent high-grade glioma may provide select patients with  increased levels of survival. However, further investigation into this matter is  needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities  of fractionated Gamma Knife radiosurgery due to its potential to limit treatment-associated morbidity. CONCLUSIONS: Gamma Knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating patients in specific clinical situations.

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[603]

TÍTULO / TITLE:  - DTI of the visual pathway in cerebral lesions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Bull Soc Sci Med Grand Duche Luxemb. 2012;(2):15-24.

AUTORES / AUTHORS:  - Hana A; Husch A; Hana A; Boecher-Schwarz H; Hertel F

INSTITUCIÓN / INSTITUTION:  - Neurosurgery Department, Centre Hospitalier de Luxembourg, Luxembourg.

RESUMEN / SUMMARY:  - Diffusion tensor imaging (DTI) can be used to localise the visual pathway (VP). In the service of the neurosurgery we have been working since the beginning of this year to develop a protocol which is suitable for the every day clinical routine to show the tracts of the white matter. Many lesions of the brain concern the white matter. Up to date it is still difficult to portray the visual pathway. Many centers all around the world are actually trying to localize the visual pathway, yet it is still used for the research. The application of the DTI-data for surgical interventions remains still a rarity. We believe that using this technique it would reduce the intraoperative risk and improve the postoperative outcome. From the beginning of this year we have been able to localize the visual pathway in 14 patients with different illnesses and we performed also postoperative controls. Using this new technique we were able to minimize the intraoperative risk in our patients.

 

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[604]

TÍTULO / TITLE:  - Deltex-1 Activates Mitotic Signaling and Proliferation and Increases the Clonogenic and Invasive Potential of U373 and LN18 Glioblastoma Cells and Correlates with Patient Survival.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e57793. doi: 10.1371/journal.pone.0057793. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057793

AUTORES / AUTHORS:  - Huber RM; Rajski M; Sivasankaran B; Moncayo G; Hemmings BA; Merlo A

INSTITUCIÓN / INSTITUTION:  - Department of Biomedicine, University of Basel, Basel, Basel-Stadt, Switzerland ; Mechanisms of Cancer Program, Friedrich Miescher Institute for Biomedical Research, Basel, Basel-Stadt, Switzerland.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is a highly malignant primary tumor of the central nervous system originating in glial cells. GBM results in more years of life lost than any other cancer type. Low levels of Notch receptor expression correlates with prolonged survival in various high grade gliomas independent of other markers. Different downstream pathways of Notch receptors have been identified. We tested  if the Notch/Deltex pathway, which is distinct from the canonical, CSL-mediated pathway, has a role in GBM. We show that the alternative or non-canonical Notch pathway functioning through Deltex1 (DTX1) mediates key features of glioblastoma  cell aggressiveness. For example, DTX1 activates the RTK/PI3K/PKB and the MAPK/ERK mitotic pathways and induces anti-apoptotic Mcl-1. The clonogenic and growth potential of established glioma cells correlated with DTX1 levels. Microarray gene expression analysis further identified a DTX1-specific, MAML1-independent transcriptional program - including microRNA-21- which is functionally linked to the changes in tumor cell aggressiveness. Over-expression  of DTX1 increased cell migration and invasion correlating to ERK activation, miR-21 levels and endogenous Notch levels. In contrast to high and intermediate expressors, patients with low DTX1 levels have a more favorable prognosis. The alternative Notch pathway via DTX1 appears to be an oncogenic factor in glioblastoma and these findings offer new potential therapeutic targets.

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[605]

- CASTELLANO -

TÍTULO / TITLE:Namen sind Schall und Rauch : Intrakranielle periphere primitive neuroektodermale Tumoren und primitive neuroektodermale Tumoren des zentralen Nervensystems sind nicht dasselbe.

TÍTULO / TITLE:  - What’s in a name? : Intracranial peripheral primitive neuroectodermal tumors and  CNS primitive neuroectodermal tumors are not the same.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Strahlenther Onkol. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00066-013-0315-4

AUTORES / AUTHORS:  - Muller K; Diez B; Muggeri A; Pietsch T; Friedrich C; Rutkowski S; von Hoff K; von Bueren AO; Zwiener I; Bruns F

INSTITUCIÓN / INSTITUTION:  - Department of Radiotherapy and Radio-Oncology, University of Leipzig, Stephanstr. 9a, 04103, Leipzig, Germany, Klaus.Mueller@medizin.uni-leipzig.de.

RESUMEN / SUMMARY:  - BACKGROUND: Intracranial peripheral primitive neuroectodermal tumors (P-PNET) are extremely rare. They can be easily misdiagnosed as central nervous system primitive neuroectodermal tumors (CNS-PNET) or meningiomas. Little is known about the optimal treatment and prognosis of these tumors. PATIENTS AND METHODS: We evaluated the treatment and outcome of 17 patients with intracranial, nonmetastatic, genetically confirmed P-PNET. Three patients were treated at our institutions. Thirteen other cases providing sufficient treatment and follow-up information were extracted from the literature. RESULTS: The median age at diagnosis was 17 years. All patients underwent initial surgery. Complete resection was achieved in 9 of the 17 cases (53 %). Combined adjuvant treatment consisting of radiotherapy (focal, n = 10; craniospinal, n = 1) and chemotherapy  was administered to 11 of the 17 patients (59 %). The median follow-up time was 1.4 years. In 8 of the 17 patients (47 %), the disease progressed; 4 of the 17 patients (24 %) died. The 2-year progression-free and overall survival rates were 64 % and 76 %, respectively. CONCLUSION: The differential diagnosis for intracranial, meningeal-based, small, round-cell tumors should include P-PNET. It is highly probable that complete resection has a positive impact on survival-as previously reported for extracranial P-PNET-but this cannot be shown by our data. Intensive adjuvant treatment consisting of radiotherapy and chemotherapy seems to be essential. A statistically grounded recommendation for the appropriate target  volume and radiation dose is not yet possible. However, in most case reports of primary intracranial P-PNET published to date, patients were treated with focal irradiation. The optimal chemotherapy regimen has yet to be established, with both the Ewing tumor and CNS-PNET protocols being promising candidates for effective treatment.

 

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[606]

TÍTULO / TITLE:  - A Case of Glioblastoma Invasion Clearly Demonstrated on 11C-methionine Positron Emission Tomography.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Clin Oncol. 2013 Apr;43(4):448. doi: 10.1093/jjco/hyt044.

            ●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt044

AUTORES / AUTHORS:  - Ohno M; Narita Y

 

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[607]

TÍTULO / TITLE:  - Quality assurance of radiotherapy in the ongoing EORTC 22042-26042 trial for atypical and malignant meningioma: results from the dummy runs and prospective individual case Reviews.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Jan 30;8:23. doi: 10.1186/1748-717X-8-23.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-23

AUTORES / AUTHORS:  - Coskun M; Straube W; Hurkmans CW; Melidis C; de Haan PF; Villa S; Collette S; Weber DC

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Ankara Oncology Hospital, Ankara, Turkey.

RESUMEN / SUMMARY:  - BACKGROUND: The ongoing EORTC 22042-26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the  Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. MATERIAL/METHODS: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (atc.wustl.edu/) and were  assessed prospectively. RESULTS: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. CONCLUSIONS:  A substantial number of protocol deviations were observed in this prospective QA  study. The number of cases accrued per institution was a significant determinant  for protocol deviation. These data suggest that successful DR is not a guarantee  for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations.

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[608]

TÍTULO / TITLE:  - Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ScientificWorldJournal. 2013;2013:951343. doi: 10.1155/2013/951343. Epub 2013 Mar 3.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/951343

AUTORES / AUTHORS:  - Li LQ; Shen F; Xu XY; Zhang H; Yang XF; Liu WG

INSTITUCIÓN / INSTITUTION:  - Department of Intensive Care Unit, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.

RESUMEN / SUMMARY:  - Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase  (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment  strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo sensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test  the in vitro efficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in vitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under  clinical setting.

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[609]

TÍTULO / TITLE:  - Bilateral pheochromocytoma as first manifestation of von Hippel-Lindau disease: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Turk J Pediatr. 2012 Sep-Oct;54(5):532-5.

AUTORES / AUTHORS:  - Catli G; Abaci A; Neumann HC; Altincik A; Demir K; Bober E

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Endocrinology, Department of Pediatrics, Dokuz Eyliil University Faculty of Medicine, Izmir, Turkey. gonulcatli@gmail.com

RESUMEN / SUMMARY:  - Von Hippel-Lindau syndrome is an autosomal dominant disorder that includes susceptibility to hemangioblastomas of the eyes and central nervous system, renal clear cell carcinoma, multiple pancreatic cysts, serous cystadenomas and pancreatic neuroendocrine tumors, pheochromocytoma, endolymphatic sac tumors, and cystadenomas of the epididymis and broad ligament. We present a 16-year-old male  who had been followed for having bilateral adrenal, and in addition, extraadrenal multifocal pheochromocytoma for six years. At the age of 16, he presented with bilateral retinal hemangioblastomas, which led to the diagnosis of von Hippel-Lindau disease type 2A confirmed by genetic analysis. The patient’s mother also had bilateral adrenal pheochromocytoma with no other von Hippel Lindau-associated tumor. In children, pheochromocytoma may be the only and/or initial manifestation of the disease with delayed manifestations of the syndrome  in other organs. Von Hippel-Lindau disease is a complex multidisciplinary disorder that requires well-coordinated medical care. Surveillance of these patients and asymptomatic relatives may prevent morbidity and mortality and improve long- term prognosis. Molecular analysis of the von Hippel-Lindau gene is useful for early diagnosis of the disease in individuals who do not yet fulfill the clinical diagnostic criteria and is instrumental in the management and follow-up of the affected family.

 

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[610]

TÍTULO / TITLE:  - Pediatric primary lymphoma of the pituitary stalk: A different disease entity from the adult form?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Formos Med Assoc. 2013 Mar;112(3):171-2. doi: 10.1016/j.jfma.2012.02.005. Epub  2012 May 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jfma.2012.02.005

AUTORES / AUTHORS:  - Huang AP; Wu MZ; Kuo MF

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan.

 

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[611]

TÍTULO / TITLE:  - Phase I study of hypofractionated intensity modulated radiation therapy with concurrent and adjuvant temozolomide in patients with glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Feb 20;8(1):38. doi: 10.1186/1748-717X-8-38.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-38

AUTORES / AUTHORS:  - Jastaniyah N; Murtha A; Pervez N; Le D; Roa W; Patel S; Mackenzie M; Fulton D; Field C; Ghosh S; Fallone G; Abdulkarim B

INSTITUCIÓN / INSTITUTION:  - Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, 11560, University Avenue, Edmonton, AB, T6G 1Z2, Canada. bassam.abdulkarim@mcgill.ca.

RESUMEN / SUMMARY:  - PURPOSE: To determine the safety and efficacy of hypofractionated intensity modulated radiation therapy (Hypo-IMRT) using helical tomotherapy (HT) with concurrent low dose temozolomide (TMZ) followed by adjuvant TMZ in patients with  glioblastoma multiforme (GBM). METHODS AND MATERIALS: Adult patients with GBM and KPS > 70 were prospectively enrolled between 2005 and 2007 in this phase I study. The Fibonacci dose escalation protocol was implemented to establish a safe radiation fractionation regimen. The protocol defined radiation therapy (RT) dose level I as 54.4 Gy in 20 fractions over 4 weeks and dose level II as 60 Gy in 22  fractions over 4.5 weeks. Concurrent TMZ followed by adjuvant TMZ was given according to the Stupp regimen. The primary endpoints were feasibility and safety of Hypo-IMRT with concurrent TMZ. Secondary endpoints included progression free survival (PFS), pattern of failure, overall survival (OS) and incidence of pseudoprogression. The latter was defined as clinical or radiological suggestion  of tumour progression within three months of radiation completion followed by spontaneous recovery of the patient. RESULTS: A total of 25 patients were prospectively enrolled with a median follow-up of 12.4 months. The median age at  diagnosis was 53 years. Based on recursive partitioning analysis (RPA) criteria,  16%, 52% and 32% of the patients were RPA class III, class IV and class V, respectively. All patients completed concurrent RT and TMZ, and 19 patients (76.0%) received adjuvant TMZ. The median OS was 15.67 months (95% CI 11.56 - 20.04) and the median PFS was 6.7 months (95% CI 4.0 - 14.0). The median time between surgery and start of RT was 44 days (range of 28 to 77 days). Delaying radiation therapy by more than 6 weeks after surgery was an independent prognostic factor associated with a worse OS (4.0 vs. 16.1 months, P = 0.027). All recurrences occurred within 2 cm of the original gross tumour volume (GTV). No cases of pseudoprogression were identified in our cohort of patients. Three patients tolerated dose level I with no dose limiting toxicity and hence the remainder of the patients were treated with dose level II according to the dose escalation protocol. Grade 3-4 hematological toxicity was limited to two patients and one patient developed Grade 4 Pneumocystis jiroveci pneumonia. CONCLUSION: Hypo-IMRT using HT given with concurrent TMZ is feasible and safe. The median OS  and PFS are comparable to those observed with conventional fractionation. Hypofractionated radiation therapy offers the advantage of a shorter treatment period which is imperative in this group of patients with limited life expectancy.

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[612]

TÍTULO / TITLE:  - Necrosis Score, Surgical Time, and Transfused Blood Volume in Patients Treated with Preoperative Embolization of Intracranial Meningiomas. Analysis of a Single-Centre Experience and a Review of Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuroradiol. 2013 Mar 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-013-0215-0

AUTORES / AUTHORS:  - Nania A; Granata F; Vinci S; Pitrone A; Barresi V; Morabito R; Settineri N; Tomasello F; Alafaci C; Longo M

INSTITUCIÓN / INSTITUTION:  - Department of Radiological Sciences, Neuroradiology Unit, University of Messina,  Via Malafata N degrees 43, Messina, Italy.

RESUMEN / SUMMARY:  - PURPOSE: Several authors have demonstrated that preoperative embolization of meningiomas reduces blood loss during surgery. However, preoperative embolization is still under debate. Aim of this study is the retrospective evaluation of necrosis score, surgical time, and transfused blood volume, on patients affected  by intracranial meningiomas treated with preoperative embolization before surgery, compared with a control group treated only with surgery. METHOD: Twenty-eight patients with meningiomas were subjected to a preoperative embolization with polyvinyl alcohol (PVA). These patients were divided into two groups: group 1, patients with preoperative embolization performed at least 7 days before surgery; and group 2, patients with preoperative embolization performed less than 7 days before surgery. A statistical evaluation was made by comparing necrosis score, surgical time, and transfused blood volume of these groups. Then, we compared these parameters also with group 3, which included patients with surgically treated meningioma who did not undergo preoperative embolization. RESULTS: Surgery time and transfused blood volume were significantly lower in patients who had been embolized at least 7 days before definitive surgery. Furthermore, large confluent areas of necrosis were significantly more frequent in patients with a larger time span between embolization and surgery. CONCLUSION: Preoperative embolization with PVA in patients with intracranial meningiomas is safe and effective, as it reduces the volume of transfused blood during surgical operation. However, patients should undergo surgery at least 7 days after embolization, as a shorter time interval has been correlated with a longer surgical time and a higher transfused blood volume.

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[613]

TÍTULO / TITLE:  - MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - RNA. 2013 Apr;19(4):552-60. doi: 10.1261/rna.035972.112. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1261/rna.035972.112

AUTORES / AUTHORS:  - Shi ZM; Wang XF; Qian X; Tao T; Wang L; Chen QD; Wang XR; Cao L; Wang YY; Zhang JX; Jiang T; Kang CS; Jiang BH; Liu N; You YP

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs) are single-stranded, 18- to 23-nt RNA molecules that function  as regulators of gene expression. Previous studies have shown that microRNAs play important roles in human cancers, including gliomas. Here, we found that expression levels of miR-181b were decreased in gliomas, and we identified IGF-1R as a novel direct target of miR-181b. MiR-181b overexpression inhibited cell proliferation, migration, invasion, and tumorigenesis by targeting IGF-1R and its downstream signaling pathways, PI3K/AKT and MAPK/ERK1/2. Overexpression of IGF-1R rescued the inhibitory effects of miR-181b. In clinical specimens, IGF-1R was overexpressed, and its protein levels were inversely correlated with miR-181b expression. Taken together, our results indicate that miR-181b functions in gliomas to suppress growth by targeting the IGF-1R oncogene and that miR-181b may serve as a novel therapeutic target for gliomas.

 

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[614]

TÍTULO / TITLE:  - Polymorphisms in DNA repair genes and risk of glioma and meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2013;14(1):449-52.

AUTORES / AUTHORS:  - Luo KQ; Mu SQ; Wu ZX; Shi YN; Peng JC

INSTITUCIÓN / INSTITUTION:  - Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China E-mail : swgaokun_tiantan@126.com.

RESUMEN / SUMMARY:  - Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type  genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

 

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[615]

TÍTULO / TITLE:  - 18F]fluoroethyltyrosine-Positron Emission Tomography-Based Therapy Monitoring after Stereotactic Iodine-125 Brachytherapy in Patients with Recurrent High-Grade Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Imaging. 2013 May 1;12(3):137-47.

AUTORES / AUTHORS:  - Jansen NL; Suchorska B; Schwarz SB; Eigenbrod S; Lutz J; Graute V; Bartenstein P; Belka C; Kreth FW; la Fougere C

RESUMEN / SUMMARY:  - AbstractTherapy monitoring of glioma after stereotactic iodine-125 brachytherapy  (SBT) remains challenging because posttherapeutic changes in magnetic resonance imaging can mimic tumor progression. We evaluated the prognostic value of serial  [18F]fluoroethyltyrosine (FET)-positron emission tomographic (PET) scans for therapy monitoring of high-grade glioma (HGG) after SBT. Thirty-three patients with recurrent HGG were included. Serial FET-PET scans were performed prior to therapeutic intervention and at 3-month intervals during the first year after SBT. FET-PET evaluation was performed by both conventional data analysis and kinetic analysis. Prognostic factors were obtained from proportional hazard models. Median local progression-free survival (LPFS) was 11.1 months. Maximal standardized background uptake value (SUVmax/BG) and biologic tumor volume (BTV)  differentiated accurately between therapeutic effects and local tumor progression at the 6-month and subsequent examinations. Increasing uptake kinetics at baseline (p < .05) and during follow-up (p < .01) were stringently associated with a longer LPFS. Early increase in FET uptake after SBT is not unequivocally associated with tumor progression; it might be induced by reactive changes and could easily lead to a misclassification of the tumor status (pseudoprogression). Six months after SBT (or later), however, increased SUVmax/BG and BTV values are  associated with a worse prognosis. Multivariate analysis stresses the prognostic  importance of dynamic studies.

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[616]

TÍTULO / TITLE:  - Glioblastoma: approach to treat elderly patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Einstein (Sao Paulo). 2012 Dec;10(4):512-8.

AUTORES / AUTHORS:  - Pontes Lde B; Karnakis T; Malheiros SM; Weltman E; Brandt RA; Guendelmann RA

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Oncology, Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection  and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

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[617]

TÍTULO / TITLE:  - Exosomes from Murine-derived GL26 Cells Promote Glioblastoma Tumor Growth by Reducing Number and Function of CD8+T Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2013;14(1):309-14.

AUTORES / AUTHORS:  - Liu ZM; Wang YB; Yuan XH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China E-mail : xianhou_yuan2012@163.com.

RESUMEN / SUMMARY:  - Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles  released from many cell types. Examples from GL26 cells were here purified using  density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells  producing intracellular cytokines were analyzed by FACS. Results: In this study,  exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26  cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

 

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[618]

TÍTULO / TITLE:  - Serum S100B in patients with brain tumours undergoing craniotomy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Coll Physicians Surg Pak. 2013 Feb;23(2):112-5. doi: 02.2013/JCPSP.112115.

AUTORES / AUTHORS:  - Syeda T; Muhammad Hashim AS; Rizvi HA; Hadi SM

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Jinnah University for Women, Karachi.

RESUMEN / SUMMARY:  - OBJECTIVE: To determine pre- and postoperative serum S100B concentrations in patients with intracranial tumours that underwent craniotomy and compare the values with healthy controls. STUDY DESIGN: An observational, comparative study.  PLACE AND DURATION OF STUDY: Neurosurgical Ward, Jinnah Postgraduate Medical Centre. Karachi, from May 2007 to April 2008. METHODOLOGY: Serum S100B was measured pre- and postoperatively on days 1, 2 and 7 in 18 healthy controls and similar number of patients who underwent craniotomy for intracranial tumours. Mean pre-operative patients and control values were compared using Mann-Whitney (unpaired) or Wilcoxon (paired) tests for comparing between pre- and postoperative values. The p-value was considered significant at < 0.05. RESULTS:  Serum S100B concentrations were significantly higher in patients with mean value  of 0.19 +/- 0.12 mug/L than in healthy controls (mean 0.03 +/- 0.01, p < 0.0005). Significantly raised serum S100B concentrations were observed in all postoperative samples when compared with pre-operative samples. S100B concentrations significantly increased on postoperative day 1 (mean = 0.90 +/- 1.07 mug/L, p < 0.0005), decreased on day 2 (mean = 0.84 +/- 0.57 mug/L, p < 0.0005). The concentrations further declined on day 7 (mean = 0.44 +/- 0.43 mug/L, p = 0.005). CONCLUSION: The significantly high postoperative concentrations of S100B in patients appear as a consequence of tissue damage due  to surgical procedures. The absence of fall of the S100B concentration in serum from the peak value on postoperative day 1 and day 2 could provide early warning  of brain tissue damage leading to neurological deterioration.

 

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[619]

TÍTULO / TITLE:  - Spinal cord metastasis in a patient treated with bevacizumab for glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0270-0

AUTORES / AUTHORS:  - Lomax AJ; Yannakou CK; Rosenthal MA

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, 3050, Australia, annalomax@y7mail.com.

RESUMEN / SUMMARY:  - Spinal metastases from glioblastoma are extremely rare and may be misdiagnosed leading to a delay in investigation and treatment. Patient outcomes are poor with a high morbidity and mortality. Metastases are seen in the context of increasing  survival due to improvements in glioblastoma therapies. We report a case of a patient developing a thoracic spinal cord metastasis while receiving anti-angiogenesis therapy with bevacizumab.

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[620]

TÍTULO / TITLE:  - An overview of therapeutic approaches to brain tumor stem cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med J Islam Repub Iran. 2012 Feb;26(1):31-40.

AUTORES / AUTHORS:  - Khoshnevisan A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - Primary and secondary malignant central nervous system (CNS) tumors are devastating invasive tumors able to give rise to many kinds of differentiated tumor cells. Glioblastoma multiform (GBM), is the most malignant brain tumor, in  which its growth and persistence depend on cancer stem cells with enhanced DNA damage repair program that also induces recurrence and resists current chemo- and radiotherapies. Unlike non-tumor stem cells, tumor stem cells lack the normal mechanisms that regulate proliferation and differentiation, resulting in uncontrolled production and incomplete differentiation of tumor cells. In current paper recent developments and new researches in the field of brain tumor stem cells have been reviewed.

 

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[621]

TÍTULO / TITLE:  - Clinicopathological Features of Growth Hormone-Producing Pituitary Adenomas in 242 Acromegaly Patients: Classification according to Hormone Production and Cytokeratin Distribution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ISRN Endocrinol. 2013;2013:723432. doi: 10.1155/2013/723432. Epub 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/723432

AUTORES / AUTHORS:  - Mori R; Inoshita N; Takahashi-Fujigasaki J; Joki T; Nishioka H; Abe T; Fujii T; Yamada S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan.

RESUMEN / SUMMARY:  - The aim of this study was to clarify the relationship between the histological features of GH-producing adenomas surgically resected at the Toranomon Hospital and the clinical features of the patients. Histological examinations, including immunohistochemistry for anterior pituitary hormones and cytokeratin (CK), were performed on 242 consecutively excised GH-producing pituitary adenomas. Immunohistochemistry showed 45% of the adenomas to be monohormonal and 55% to be  plurihormonal, producing GH-PRL (77%), GH-TSH (13%), and GH-PRL-TSH (10%). One-fourth of the monohormonal GH adenomas had a dot-like pattern of CK immunoreactivity in the majority of the tumor cells (>80%); they were significantly more common in female or younger patients and usually tended to be  larger and more invasive than monohormonal GH adenomas with perinuclear CK. Interestingly, CK-immunonegative adenomas were found in only 5% of the patients;  they also showed a tendency to be larger, suggesting that they are a distinct type of GH adenoma with clinically aggressive features. Serum hormone levels correlated well with tumor size only in GH-producing adenomas with a perinuclear  pattern of CK immunoreactivity. Each histological subtype of adenoma, classified  according to the pattern of CK immunoreactivity, was associated with distinct clinical characteristics. This information is useful for understanding the pathophysiology of acromegaly-causing GH-producing adenomas.

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[622]

TÍTULO / TITLE:  - IgG4-related hypophysitis presenting as a pituitary adenoma with systemic disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian J Surg. 2013 Apr;36(2):93-7. doi: 10.1016/j.asjsur.2012.04.013. Epub 2012 May 24.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.asjsur.2012.04.013

AUTORES / AUTHORS:  - Hsing MT; Hsu HT; Cheng CY; Chen CM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Changhua Christian Hospital, Changhua, Taiwan.

RESUMEN / SUMMARY:  - Hypophysitis is a rare inflammatory disorder that can mimic a pituitary tumor clinically or radiologically. Furthermore, immunoglobulin G4 (IgG4)-related systemic disease is only a just recently characterized disorder. It can manifest  as a systemic disease involving multiple organs, including the pancreas, salivary glands, lungs, liver, bile duct, gallbladder, kidneys, and retroperitoneum. It is characterized by a high serum level of IgG4 clinically and dense lymphoplasmacytic infiltration with sclerosis and phlebitis histologically. Herein, we report the case of a man 66 years of age who presented with nausea, vomiting, and poor appetite with a body weight loss of 4 kg. Image study revealed a pituitary infundibulum mass, right-posterior mediastinal and paraspinal masses, as well as infiltrating masses in bilateral kidneys. Therefore, he received a thoracoscopic biopsy for the right-posterior mediastinal and paraspinal masses and a pathologic examination reported an IgG4-related inflammatory pseudotumor. Then, transsphenoidal removal of the infundibulum mass was performed. Histologically, the infundibulum mass represented a IgG4-related hypophysitis manifested as an infiltration of plasma cells, lymphocytes, histiocytes, and some eosinophils with a fair number of IgG4-immunoreactive plasma cells. After the operation was complete, the patient took 5 mg of prednisolone every 2 days for 3  months. A follow-up computed tomography scan revealed improvement of the infiltrating masses in the bilateral kidneys.

 

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[623]

TÍTULO / TITLE:  - High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e56185. doi: 10.1371/journal.pone.0056185. Epub 2013 Feb 18.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056185

AUTORES / AUTHORS:  - Yost SE; Pastorino S; Rozenzhak S; Smith EN; Chao YS; Jiang P; Kesari S; Frazer KA; Harismendy O

INSTITUCIÓN / INSTITUTION:  - Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America.

RESUMEN / SUMMARY:  - Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models. Here, we report the comprehensive identification of somatic coding mutations and copy number aberrations in four glioblastoma (GBM) primary tumors and their matched pre-clinical models: serum-free neurospheres, adherent cell cultures, and mouse xenografts. We developed innovative methods to  improve the data quality and allow a strict comparison of matched tumor samples.  Our analysis identifies known GBM mutations altering PTEN and TP53 genes, and new actionable mutations such as the loss of PIK3R1, and reveals clear patient-to-patient differences. In contrast, for each patient, we do not observe  any significant remodeling of the mutational profile between primary to model tumors and the few discrepancies can be attributed to stochastic errors or differences in sample purity. Similarly, we observe approximately 96% primary-to-model concordance in copy number calls in the high-cellularity samples. In contrast to previous reports based on gene expression profiles, we do not observe significant differences at the DNA level between in vitro compared to in vivo models. This study suggests, at a remarkable resolution, the genome-wide  conservation of a patient’s tumor genetics in various pre-clinical models, and therefore supports their use for the development and testing of personalized targeted therapies.

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[624]

TÍTULO / TITLE:  - Genetics: New disease entity identified for meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Clin Oncol. 2013 Apr;10(4):182. doi: 10.1038/nrclinonc.2013.25. Epub 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2013.25

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[625]

TÍTULO / TITLE:  - Therapeutic Links between Alzheimer’s Disease and Brain Cancer: Drug Discovery Consequences.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ChemMedChem. 2013 Feb 26. doi: 10.1002/cmdc.201300006.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cmdc.201300006

AUTORES / AUTHORS:  - Kraus JL

INSTITUCIÓN / INSTITUTION:  - Institut de Biologie du Developpement de Marseille Luminy, UMR-CNRS 7288 IBDML, Campus de Luminy, 13288 Marseille cedex 09 (France). kraus@univ-amu.fr.

RESUMEN / SUMMARY:  - It was recently reported that female survivors of breast cancer have a lower risk of Alzheimer’s disease (AD). This observation led to the hypothesis that there is a link between cancer and AD. This Viewpoint provides an analysis of the consequences of this hypothesis, not only from the perspective of drug discovery  for new treatments, but above all, the awareness that any AD chemotherapy will require drug administration over longer periods of time before any cognitive effects are observed. Because such drugs will probably act as neuroprotective agents, slowing the progression of AD rather than curing it, they should be prescribed as soon as the first AD symptoms are detected. After a general survey  of anticancer drugs that have potential therapeutic value for AD chemotherapy, new drugs that could affect specific signal transduction pathways known to be activated by anticancer drugs are presented, with the unfolding protein response  pathway being one of the most relevant biological targets for new AD chemotherapeutic agents.

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[626]

TÍTULO / TITLE:  - The glial fibrillary acidic protein promoter directs sodium/iodide symporter gene expression for radioiodine therapy of malignant glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Feb;5(2):669-674. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1055

AUTORES / AUTHORS:  - Li W; Tan J; Wang P; Li N; Zhang F

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, P.R. China.

RESUMEN / SUMMARY:  - Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid  cancers may be treated with radio-iodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumor-specific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promoter-modulated expression of the hNIS gene in an experimental model of radioiodine-based treatment for malignant glioma. Cells were transfected using a  recombination adeno-virus and evaluated in cells by studying the transfected transgene expression through western blot analysis, (125)I uptake and efflux, clonogenicity following (131)I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells  showed 95-70-fold higher (125)I uptake compared with the control cells transfected with Ad-cytomegalovirus (CMV)-enhanced green fluorescent protein (EGFP). The western blotting revealed bands of approximately 70, 49 and 43 kDa, consistent with the hNIS, GFAP and beta-actin proteins. The clonogenic assay indicated that, following exposure to 500 muCi of (131)I-iodide for 12 h, >90% of cells transfected with the hNIS gene were killed. Ad-GFAP-hNIS-transfected and 2  mCi (131)I-injected U87 xenograft nude mice survived the longest of the three groups. The hNIS-expressing tumor tissue accumulated (99m)TcO(4) rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that  effective (131)I therapy was achieved in the malignant glioma cell lines following the induction of tumor-specific iodide uptake activity by GFAP promoter-directed hNIS gene expression in vitro and in vivo. (131)I therapy retarded Ad-GFAP-hNIS transfected-tumor growth following injection with (131)I in U87 xenograft-bearing nude mice.

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[627]

TÍTULO / TITLE:  - Psychosocial care for the caregivers of primary malignant brain tumor patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Soc Work End Life Palliat Care. 2013 Jan;9(1):74-95. doi: 10.1080/15524256.2012.758605.

            ●● Enlace al texto completo (gratuito o de pago) 1080/15524256.2012.758605

AUTORES / AUTHORS:  - Wasner M; Paal P; Borasio GD

INSTITUCIÓN / INSTITUTION:  - a Interdisciplinary Center for Palliative Medicine , University Hospital Grosshadern , Munich , Germany.

RESUMEN / SUMMARY:  - Despite clinical experience that suggests a high burden of care among relatives of individuals with a primary malignant brain tumor (PMBT), little is known about their actual needs. In this study, the caregivers’ personal experiences, quality  of life, burden of care, and psychological well-being were examined. Fifty-nine percent did not receive any financial aid for home care, 33% had increased risk for psychosomatic problems, 45% had anxiety, and 33% increased depression levels. The caregiver’s quality of life was most strongly affected by the burden of care  (p < .001) and the patient’s mental state (p < .03). To improve the situation, empathetic professionals and an early implementation of palliative care and social work are required.

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[628]

TÍTULO / TITLE:  - Managing the patient with transsphenoidal pituitary tumor resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosci Nurs. 2013 Apr;45(2):101-7; quiz E1-2. doi: 10.1097/JNN.0b013e3182828e28.

            ●● Enlace al texto completo (gratuito o de pago) 1097/JNN.0b013e3182828e28

AUTORES / AUTHORS:  - Yuan W

INSTITUCIÓN / INSTITUTION:  - Kaiser Permanente Foundation Hospitals, Los Angeles Medical Center, Los Angeles,  CA, USA. wendyla3@gmail.com

RESUMEN / SUMMARY:  - Patients who undergo transsphenoidal pituitary tumor resection require a multidisciplinary team approach, consisting of a neurosurgeon, an endocrinologist, and nurses. Successful transsphenoidal surgery needs expert nursing care for early identification and prompt treatment of pituitary dysfunction and neurosurgical complications. Pituitary dysfunction includes adrenal insufficiency, diabetes insipidus, syndrome of inappropriate antidiuretic hormone, and cerebral salt wasting syndrome. Neurosurgical complications may include visual disturbance, cerebrospinal fluid leak, subdural hematoma, and epistaxis.

 

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[629]

TÍTULO / TITLE:  - De-repression of PDGFRbeta transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Mar 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0502

AUTORES / AUTHORS:  - Akhavan D; Pourzia AL; Nourian AA; Williams KJ; Nathanson D; Babic I; Villa GR; Tanaka K; Nael A; Yang H; Dang J; Vinters HV; Yong WH; Flagg M; Tamanoi F; Sasayama T; James CD; Kornblum HI; Cloughesy TF; Cavenee WK; Bensinger SJ; Mischel PS

INSTITUCIÓN / INSTITUTION:  - 1Molecular and Medical Pharmacology, UCLA.

RESUMEN / SUMMARY:  - Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting  physiologically regulated receptors has not been addressed. Here we demonstrate the first example of this alternate mechanism in brain tumors by showing that EGFR-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing PDGFRbeta. Mechanistic studies demonstrate that EGFRvIII signaling  actively suppresses PDGFRbeta transcription in an mTORC1 and ERK-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRbeta signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRbeta signaling potently suppresses tumor growth in vivo. These data identify a novel, non-genetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy.

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[630]

TÍTULO / TITLE:  - Unusual appearance and presentation of supratentorial subependymoma in an adult patient.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Radiol Case Rep. 2012 Aug;6(8):8-16. doi: 10.3941/jrcr.v6i8.999. Epub 2012 Aug  1.

            ●● Enlace al texto completo (gratuito o de pago) 3941/jrcr.v6i8.999

AUTORES / AUTHORS:  - Abdel-Aal AK; Hamed MF; Al Naief NS; Vattoth S; Bag A

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Alabama at Birmingham (UAB), AL, USA. akamel@uabmc.edu

RESUMEN / SUMMARY:  - We report a case of a large, heterogeneously enhancing, pathologically proven, supratentorial subependymoma in a 31-year-old male patient presenting with headache, nausea and vomiting as well as gait disturbances. Although most supratentorial subependymomas have distinctive MR features, our case demonstrated imaging findings that made it indistinguishable from other more aggressive malignant supratentorial intraventricular lesions. It is of paramount importance  to consider supratentorial subependymomas in the differential diagnosis of supratentorial lesions, even if their radiological features were atypical.

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[631]

TÍTULO / TITLE:  - Prevalence of hepatitis B and C in patients with meningiomas and glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Mar;5(3):783-786. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1126

AUTORES / AUTHORS:  - Cabanne MB; Ma QD; Mecum L; Jandial R; Siddiqi J; Chen MY

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Arrowhead Regional Medical Center, Colton, CA 92324;

RESUMEN / SUMMARY:  - The prevalence of hepatitis B and C in patients with glioblastoma multiforme or meningiomas has not been described. These infections are known to modulate the activity of the immune system, which potentially influences the development and course of cancer. We hypothesized that chronic hepatitis infection, which activates the immune system, decreases the risk of brain tumors, particularly those that are highly malignant. We performed a retrospective study to examine the prevalence of hepatitis B and C in patients with meningiomas and glioblastomas. The combined prevalence of hepatitis B and C in the USA from 1999-2008 was 5.7%. The prevalence of hepatitis B and C in patients with meningiomas was 2.4%; while among glioblastoma patients, the prevalence of hepatitis B and C was 1.38%. The odds ratio of having hepatitis B or C with glioblastoma versus meningiomas was 0.56, with a confidence interval of 0.19-1.6  and a P-value of 0.29. Compared with historical controls, the prevalence of hepatitis B and C in meningioma and glioblastoma patients was decreased. However, this difference may be attributed to the retrospective nature of our data and the natural history of hepatitis B and C infections. The prevalence of these viral infections was not statistically different in patients with meningiomas and glioblastomas. This suggests that hepatitis B and C primarily influence slow-growing, benign tumors and more aggressive cancers equally, if at all. To definitively test our hypothesis, future studies in which data are prospectively  gathered are likely to be required.

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[632]

TÍTULO / TITLE:  - Tissue and Plasma Thioredoxin Reductase Expressions in Patients with Glioblastoma Multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1333422

AUTORES / AUTHORS:  - Kemerdere R; Kacira T; Hanimoglu H; Kucur M; Tanriverdi T; Canbaz B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

RESUMEN / SUMMARY:  - Background and Study Aims Thioredoxin reductase (TrxR) is a redox protein that is considered to play a role in tumor progression. The purpose of this study was to  assess the expression of TrxR in blood and tumor samples of glioblastoma multiforme (GBM) patients.Patients TrxR levels were evaluated in blood and GBM tissues extracted from 27 patients, in normal brain tissues of 12 autopsy cases,  and in blood samples of 12 healthy subjects. The results were compared between tumor and control groups.Results The mean level of TrxR in GBM tissues (74.5 +/-  14.9 U/g wet tissue) was remarkably higher than in normal brain tissues (14.8 +/- 3.4 U/g wet tissue). The mean TrxR levels in blood were significantly higher in GBM patients (296.3 +/- 43.6 U/mL) than in the controls (203.0 +/- 11.3 U/mL).Conclusions These findings suggest that high levels of TrxR may be related  to progression of GBM.

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[633]

TÍTULO / TITLE:  - Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol India. 2013 Jan-Feb;61(1):40-4. doi: 10.4103/0028-3886.107928.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.107928

AUTORES / AUTHORS:  - Zhou P; Ma W; Yin S; Li Y; Jiang S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

RESUMEN / SUMMARY:  - Background: Meningiomas account for 35.5% of central nervous system (CNS) tumors, of which 21-37.8% are atypical or anaplastic/malignant. High-grade meningiomas have higher rates of recurrence and worse outcome than grade I/II meningiomas. Thus, it is of importance to assess the tumor biology before treatment initiation. Materials and Methods: This study reviewed 1737 patients with histologically confirmed meningioma at a single institution. Meningiomas were classified according to World Health Organization (WHO) 2007 grading and the location of the tumor was confirmed from the operation records and preoperative imaging. Univariate and multivariate logistic regression were used to analyze the potential risk factors for high-grade pathology. Results: Young men and pediatric patients were less likely to have meningioma, but they had high-grade meningioma. Tumors originated from non-skull base and lateral intracranial are more likely to be grade II/III meningioma. Conclusions: Lateral and non-skull base location, male sex, and the younger patients increase the risk for grade II and III pathology. These factors should be considered while deciding treatment choice, surgical resection, and prognosis as well.

 

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[634]

TÍTULO / TITLE:  - Atypical meningioma as a solitary malignancy in a patient with Rothmund-Thompson  syndrome.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3:148. doi: 10.4103/2152-7806.104742. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.104742

AUTORES / AUTHORS:  - Pencovich N; Margalit N; Constantini S

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Neurosurgery, Dana-Dwek Children’s Hospital, Tel-Aviv, Israel.

RESUMEN / SUMMARY:  - BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by genomic instability and increased risk of various malignancies, especially osteosarcoma and squamous cell carcinoma. We report the  first RTS patient who developed a central nervous system (CNS)-related neoplasm.  CASE DESCRIPTION: A 28-year-old male, previously diagnosed with RTS , developed a massive parasagital lesion, detected by magnetic resonance imaging. The tumor was surgically removed and histologically diagnosed as atypical meningioma. Preoperative symptoms were dramatically improved. CONCLUSIONS: This is the first  description of a CNS-related malignancy in RTS patients. Although rare, the genomic instability and additional risk factors of this syndrome should be considered in choosing the course of treatment.

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[635]

TÍTULO / TITLE:  - Health-related quality of life and cognitive functioning at on- and off-treatment periods in children aged between 6-13 years old with brain tumors: a prospective  longitudinal study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Yonsei Med J. 2013 Mar 1;54(2):306-14. doi: 10.3349/ymj.2013.54.2.306.

            ●● Enlace al texto completo (gratuito o de pago) 3349/ymj.2013.54.2.306

AUTORES / AUTHORS:  - An KJ; Joung YS; Sung KW; Kim JH

INSTITUCIÓN / INSTITUTION:  - Department of Psychiatry, Seoul Metropolitan Eunpyeong Hospital, Samsung Medical  Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.

RESUMEN / SUMMARY:  - PURPOSE: Our study aimed to examine the relationship between intelligence and health-related quality of life (HRQOL) in children (6-13 years old) diagnosed as  having a brain tumor. MATERIALS AND METHODS: We administered a Korean version of  the Wechsler Intelligence Scale for Children-III, the Pediatric Quality of Life Inventory, version 4.0 (PedsQL), the Korean version of the Parenting Stress Index-Short Form, and the Korean Version of the Parenting Sense of Competence (K-PSOC) scale before or after initial radiotherapy (T1) and after treatment termination (T2). In total, 13 patients completed both the T1 and T2 interviews.  RESULTS: Scores significantly declined between T1 and T2 on the full-scale intelligence quotients (FIQ), verbal intelligence quotients (VIQ), performance intelligence quotients (PIQ), similarity and coding tests, as well as the K-PSOC, which measures parental anxiety. FIQ scores at T1 were correlated with the self-reported PedsQL total scores (r=0.739) and the parent proxy-report PedsQL scores for school functioning (r=0.706) at T2. Also, the FIQ scores at T2 were correlated with the self-reported PedsQL total scores (r=0.748) and scores for physical health (r=0.728) at T2. CONCLUSION: The cognitive ability and intelligence level of the patients significantly declined between on and off treatment periods, and higher intelligence functioning at both on and off treatment was correlated with long-term higher HRQOL. Further investigations that monitor intelligence, HRQOL and parenting stress over a longer period, using a greater number of participants, are needed.

 

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[636]

TÍTULO / TITLE:  - EMMPRIN Is an Independent Negative Prognostic Factor for Patients with Astrocytic Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e58069. doi: 10.1371/journal.pone.0058069. Epub 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058069

AUTORES / AUTHORS:  - Tian L; Zhang Y; Chen Y; Cai M; Dong H; Xiong L

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China.

RESUMEN / SUMMARY:  - Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein  expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by  immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of  patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical  staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.

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[637]

TÍTULO / TITLE:  - The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by Fak Inhibitor Y15 and Combination of Y15 and Temozolomide.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anticancer Agents Med Chem. 2013 Jan 24.

AUTORES / AUTHORS:  - Huang G; Ho B; Conroy J; Liu S; Qiang H; Golubovskaya V

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY,USA 14263. Vita.Golubovskaya@roswellpark.org.

RESUMEN / SUMMARY:  - Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide  and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in  DBTRG and U87 cells, respectively (p<0.05). Moreover, DBTRG and U87 cells treated with Y15 changed gene expression of 1332 and 462 genes more than 1.5 fold, p<0.05, respectively and had 237 common genes affected by Y15. The common genes up-regulated by Y15 included GADD45A, HSPA6 (heat-shock 70); DUSP1, DUSP 5 (dual-phosphatase 5); CDKN1A (p21) and common down-regulated genes included kinesins, such as KIF11, 14, 20A, 20B; topoisomerase II, TOP2A; cyclin F; cell cycle protein: BUB1; PARP1, POLA1. In addition, we detected genes affected by temozolomide and by combination of Y15 and temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and temozolomide more significantly than by each  agent alone were: COX7B; interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and to combination of Y15 with temozolomide that is important for glioblastoma therapy.

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[638]

TÍTULO / TITLE:  - Photofrin based photodynamic therapy and miR-99a transfection inhibited FGFR3 and PI3K/Akt signaling mechanisms to control growth of human glioblastoma In vitro and in vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e55652. doi: 10.1371/journal.pone.0055652. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055652

AUTORES / AUTHORS:  - Chakrabarti M; Banik NL; Ray SK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA.

RESUMEN / SUMMARY:  - Glioblastoma is the most common malignant brain tumor in humans. We explored the  molecular mechanisms how the efficacy of photofrin based photodynamic therapy (PDT) was enhanced by miR-99a transfection in human glioblastoma cells. Our results showed almost similar uptake of photofrin after 24 h in different glioblastoma cells, but p53 wild-type cells were more sensitive to radiation and  photofrin doses than p53 mutant cells. Photofrin based PDT induced apoptosis, inhibited cell invasion, prevented angiogenic network formation, and promoted DNA fragmentation and laddering in U87MG and U118MG cells harvoring p53 wild-type. Western blotting showed that photofrin based PDT was efficient to block the angiogenesis and cell survival pathways. Further, photofrin based PDT followed by miR-99a transfection dramatically increased miR-99a expression and also increased apoptosis in glioblastoma cell cultures and drastically reduced tumor growth in athymic nude mice, due to down regulation of fibroblast growth factor receptor 3  (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apoptosis. Therefore, our  results indicated that the anti-tumor effects of photofrin based PDT was strongly augmented by miR-99a overexpression and this novel combination therapeutic strategy could be used for controlling growth of human p53 wild-type glioblastomas both in vitro and in vivo.

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[639]

TÍTULO / TITLE:  - Combined bevacizumab and triamcinolone acetonide injections for macular edema in  a patient with astrocytic hamartomas and tuberous sclerosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ophthalmic Surg Lasers Imaging Retina. 2013 Jan 1;44(1):85-90. doi: 10.3928/23258160-20121221-19.

            ●● Enlace al texto completo (gratuito o de pago) 3928/23258160-20121221-19

AUTORES / AUTHORS:  - Lonngi M; Gold AS; Murray TG

RESUMEN / SUMMARY:  - Retinal astrocytic hamartoma or retinal astrocytoma is the best-known ocular manifestation of tuberous sclerosis complex, a neurocutaneous syndrome characterized by the development of multiple disseminated hamartomas. It can have several clinical presentations, ranging from unilateral transparent, noncalcified lesions to bilateral multinodular, mulberrylike calcified tumors. Symptoms appear if the tumor involves the macula and can cause visual loss on the basis of progressive retinal degeneration. The authors report a case of a patient with tuberous sclerosis, bilateral astrocytic hamartomas, and macular edema with intraretinal hemorrhage in the left eye that has responded well to treatment with bevacizumab and intravitreal triamcinolone acetonide.

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[640]

TÍTULO / TITLE:  - Treatment of primary brain tumours in adults.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nurs Stand. 2012 Dec 5-11;27(14):42-7.

AUTORES / AUTHORS:  - McNamara S

INSTITUCIÓN / INSTITUTION:  - Edinburgh Centre for Neuro-oncology, Edinburgh. Shanne.McNamara@luht.scot.nhs.uk

RESUMEN / SUMMARY:  - This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse’s contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

 

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[641]

TÍTULO / TITLE:  - Phospholipid Metabolites in Recurrent Glioblastoma: In Vivo Markers Detect Different Tumor Phenotypes before and under Antiangiogenic Therapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e56439. doi: 10.1371/journal.pone.0056439. Epub 2013 Mar 8.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056439

AUTORES / AUTHORS:  - Hattingen E; Bahr O; Rieger J; Blasel S; Steinbach J; Pilatus U

INSTITUCIÓN / INSTITUTION:  - Institute of Neuroradiology, Goethe-University Hospital Frankfurt, Frankfurt, Germany.

RESUMEN / SUMMARY:  - PURPOSE: Metabolic changes upon antiangiogenic therapy of recurrent glioblastomas (rGBMs) may provide new biomarkers for treatment efficacy. Since in vitro models  showed that phospholipid membrane metabolism provides specific information on tumor growth we employed in-vivo MR-spectroscopic imaging (MRSI) of human rGBMs before and under bevacizumab (BVZ) to measure concentrations of phosphocholine (PCho), phosphoethanolamine (PEth), glycerophosphocholine (GPC), and glyceroethanolamine (GPE). METHODS: (1)H and (31)P MRSI was prospectively performed in 32 patients with rGBMs before and under BVZ therapy at 8 weeks intervals until tumor progression. Patients were dichotomized into subjects with  long overall survival (OS) (>median OS) and short OS (<median OS) survival time from BVZ-onset. Metabolite concentrations from tumor tissue and their ratios were compared to contralateral normal-appearing tissue (control). RESULTS: Before BVZ, (1)H-detectable choline signals (total GPC and PCho) in rGBMs were elevated but significance failed after dichotomizing. For metabolite ratios obtained by (31)P  MRSI, the short-OS group showed higher PCho/GPC (p = 0.004) in rGBMs compared to  control tissue before BVZ while PEth/GPE was elevated in rGBMs of both groups (long-OS p = 0.04; short-OS p = 0.003). Under BVZ, PCho/GPC and PEth/GPE in the tumor initially decreased (p = 0.04) but only PCho/GPC re-increased upon tumor progression (p = 0.02). Intriguingly, in normal-appearing tissue an initial PEth/GPE decrease (p = 0.047) was followed by an increase at the time of tumor progression (p = 0.031). CONCLUSION: An elevated PCho/GPC ratio in the short-OS group suggests that it is a negative predictive marker for BVZ efficacy. These gliomas may represent a malignant phenotype even growing under anti-VEGF treatment. Elevated PEth/GPE may represent an in-vivo biomarker more sensitive to GBM infiltration than MRI.

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[642]

TÍTULO / TITLE:  - Suppression of the proliferation of human U-87 MG glioblastoma cells by new antagonists of growth hormone-releasing hormone in vivo and in vitro.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0264-y

AUTORES / AUTHORS:  - Jaszberenyi M; Schally AV; Block NL; Zarandi M; Cai RZ; Vidaurre I; Szalontay L; Jayakumar AR; Rick FG

INSTITUCIÓN / INSTITUTION:  - Veterans Affairs Medical Center, Miami, FL, 33125, USA, cleofide1731@gmail.com.

RESUMEN / SUMMARY:  - Five-year survival of patients afflicted with glioblastoma multiforme (GBM) is rare, making this cancer one of the most feared malignancies. Previously, we reported that growth hormone-releasing hormone (GHRH) is a potent growth factor in cancers. The present work evaluated the effects of two antagonistic analogs of GHRH (MIA-604 and MIA-690) on the proliferation of U-87 MG GBM tumors, in vivo as well as in vitro. Both analogs were administered subcutaneously and dose-dependently inhibited the growth of tumors transplanted into nude mice (127  animals in seven groups). The analogs also inhibited cell proliferation in vitro, decreased cell size, and promoted apoptotic and autophagic processes. Both antagonists stimulated contact inhibition, as indicated by the expression of the  E-cadherin-beta-catenin complex and integrins, and decreased the release of humoral regulators of glial growth such as FGF, PDGFbeta, and TGFbeta, as revealed by genomic or proteomic detection methods. The GHRH analogs downregulated other tumor markers (Jun-proto-oncogene, mitogen-activated protein  kinase-1, and melanoma cell adhesion molecule), upregulated tumor suppressors (p53, metastasis suppressor-1, nexin, TNF receptor 1A, BCL-2-associated agonist of cell death, and ifkappaBalpha), and inhibited the expression of the regulators of angiogenesis and invasion (angiopoetin-1, VEGF, matrix metallopeptidase-1, S100 calcium binding protein A4, and synuclein-gamma). Our findings indicate that GHRH antagonists inhibit growth of GBMs by multiple mechanisms and decrease both  tumor cell size and number.

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[643]

TÍTULO / TITLE:  - Cerebral Revascularization for Difficult Skull Base Tumors: A Contemporary Series of 18 Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 8. pii: S1878-8750(13)00293-3. doi: 10.1016/j.wneu.2013.02.028.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.028

AUTORES / AUTHORS:  - Yang T; Tariq F; Chabot J; Madhok R; Sekhar LN

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of Washington, Seattle, Washington.

RESUMEN / SUMMARY:  - OBJECTIVE: Cerebral revascularization has been used in treating difficult skull base tumors when the preservation of the involved native arteries is deemed challenging, and the patients are at risk to develop vascular complications. We aimed to evaluate a recent series of patients who needed high-flow cerebral bypasses as part of the surgical treatment strategies for their difficult skull base tumors; to assess current indications and the results of such treatments. METHODS: A prospectively collected consecutive series of patients who received high-flow cerebral bypasses in conjunction with surgical resections of the skull  base tumors over a 9-year period were studied. RESULTS: A total of 20 high-flow bypasses on 18 patients were performed, as part of the treatment plan for skull base tumors. Median age was 41 years. Four patients had preoperative transient ischemic attack (TIA) symptoms, three of which had progressed to acute strokes preoperatively. Thirteen patients (72.2%) had gross-total resection (GTR). There  were no acute perioperative stroke or graft occlusions. The mean follow-up was 47 months (2-104 months). One patient developed asymptomatic graft stenosis 8 months from surgery, which was surgically corrected. Fifteen patients had achieved good  clinical outcomes (modified Rankin Scale < 2) at the latest follow-up, one patient died post-operatively and two died of their disease. CONCLUSION: High-flow bypass for cerebral revascularization is a good surgical option for treating certain difficult skull base tumors. High rate of graft patency and low  risk of perioperative stroke can be achieved in experienced hands with concurrent high rate of GTR of the tumor and good clinical outcome of the patients.

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[644]

TÍTULO / TITLE:  - Distinct Genomic Aberrations between Low-Grade and High-Grade Gliomas of Chinese  Patients.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e57168. doi: 10.1371/journal.pone.0057168. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057168

AUTORES / AUTHORS:  - Li Y; Wang D; Wang L; Yu J; Du D; Chen Y; Gao P; Wang DM; Yu J; Zhang F; Fu S

INSTITUCIÓN / INSTITUTION:  - First Hospital of Jilin University, Changchun, PR China ; Jilin University, Changchun, PR China.

RESUMEN / SUMMARY:  - BACKGROUND: Glioma is a type of tumor that develops in the central nerve system,  mainly the brain. Alterations of genomic sequence and sequence segments (such as  copy number variations or CNV and copy neutral loss of heterozygosities or cnLOH) are thought to be a major determinant of the tumor grade. METHODS: We mapped genomic variations between low-grade and high-grade gliomas (LGG and HGG) in Chinese population based on Illumina’s Beadchip and validated the results using real-time qPCR. RESULTS: AT THE CYTOBAND LEVEL, WE DISCOVERED: (1) unique losses  in LGG on 5q, 8p and 11q, and in HGG on 6q, 11p, 13q and 19q; (2) unique gains in the LGG on 1p and in HGG at 5p, 7p, 7q and 20q; and (3) cnLOH in HGG only on 3q,  8q, 10p, 14q, 15q, 17p, 17q, 18q and 21q. Subsequently, we confirmed well-characterized oncogenes among tumor-related loci (such as EGFR and KIT) and  detected novel genes that gained chromosome sequences (such as AASS, HYAL4, NDUFA5 and SPAM1) in both LGG and HGG. In addition, we found gains, losses, and cnLOH in several genes, including VN1R2, VN1R4, and ZNF677, in multiple samples.  Mapping grade-associated pathways and their related gene ontology (GO) terms, we  classified LGG-associated functions as “arachidonic acid metabolism”, “DNA binding” and “regulation of DNA-dependent transcription” and the HGG-associated as “neuroactive ligand-receptor interaction”, “neuronal cell body” and “defense response to bacterium”. CONCLUSION: LGG and HGG appear to have different molecular signatures in genomic variations and our results provide invaluable information for the diagnosis and treatment of gliomas in patients with variable  duration or diverse tumor differentiation.

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[645]

TÍTULO / TITLE:  - Neuro-oncology: Study reveals extent of intratumour heterogeneity in patients with glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Neurol. 2013 Apr;9(4):184. doi: 10.1038/nrneurol.2013.52. Epub 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2013.52

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[646]

TÍTULO / TITLE:  - Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Surg Oncol. 2013 Mar 5;11:55. doi: 10.1186/1477-7819-11-55.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-55

AUTORES / AUTHORS:  - Grah JJ; Katalinic D; Stern-Padovan R; Paladino J; Santek F; Juretic A; Zarkovic K; Plestina S; Supe M

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University Hospital Centre (KBC Zagreb), University of Zagreb School of Medicine, Kispaticeva 12, Zagreb HR-10000, Croatia. josipjoachimgrah@yahoo.com.

RESUMEN / SUMMARY:  - Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with  primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery  and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very  poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

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[647]

TÍTULO / TITLE:  - Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Endocrinol Nutr. 2013 Feb 14. pii: S1575-0922(12)00291-4. doi: 10.1016/j.endonu.2012.09.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.endonu.2012.09.005

AUTORES / AUTHORS:  - Sanchez-Tejada L; Sanchez-Ortiga R; Moreno-Perez O; Montanana CF; Niveiro M; Tritos NA; Alfonso AM

INSTITUCIÓN / INSTITUTION:  - Endocrinology Department, Research Unit, Hospital General Universitario Alicante, Alicante, España.

RESUMEN / SUMMARY:  - INTRODUCTION AND OBJECTIVE: The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGFIR), and Ki-67. MATERIALS AND METHODS: In this retrospective study, the normalized copy number (NCN) of PTIG and IGFIR mRNA was  measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46+/-36 months. RESULTS: Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGFIR expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20%  during follow-up (10.69+/-3.84 NCN vs. 5.44+/-3.55 NCN, p=0.014). CONCLUSIONS: Our results suggest that the IGFIR is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.

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[648]

TÍTULO / TITLE:  - Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Rep. 2013 Apr;7(4):1229-34. doi: 10.3892/mmr.2013.1319. Epub 2013 Feb 11.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1319

AUTORES / AUTHORS:  - Cao ZH; Tao Y; Sang JR; Gu YJ; Bian XJ; Chen YC

INSTITUCIÓN / INSTITUTION:  - Department of Intensive Care Unit, Affiliated Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China.

RESUMEN / SUMMARY:  - Previous data have shown that the type II cGMPdependent protein kinase (PKG II) inhibits the EGFinduced MAPK signaling pathway. In order to thoroughly investigate PKG, it is necessary to elucidate the function of another type of PKG, PKG I. The aim of this study was to investigate the possible inhibitory effect of PKG II and PKG I activity on the basic fibroblast growth factor (bFGF)induced proliferation and migration of U251 human glioma cells and the possible underlying mechanisms. U251 cells were infected with adenoviral constructs encoding cDNA of PKG I (AdPKG I) or PKG II (AdPKG II) to increase the  expression levels of PKG I or PKG II and then treated with 8BrcGMP and 8pCPTcGMP, respectively, to activate the enzyme. An MTT assay was used to detect the proliferation of the U251 cells. The migration of the U251 cells was analyzed using a Transwell migration assay. Western blot analysis was used to detect the phosphorylation/activation of the fibroblast growth factor receptor (FGFR), MEK and ERK and the nuclear distribution of p-ERK. The results showed that bFGF treatment increased the proliferation and migration of U251 cells, accompanied by increased phosphorylation of FGFR, MEK and ERK. Furthermore, the nuclear distribution of p-ERK increased following bFGF treatment. Increasing the activity of PKG II through infection with Ad-PKG II and stimulation with 8-pCPT-cGMP significantly attenuated the aforementioned effects of the bFGF treatment, while  increased PKG I activity did not inhibit the effects of bFGF treatment. These data suggest that increased PKG II activity attenuates bFGFinduced proliferation  and migration by inhibiting the MAPK/ERK signaling pathway, whereas PKG I does not.

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[649]

TÍTULO / TITLE:  - Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55665. doi: 10.1371/journal.pone.0055665. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055665

AUTORES / AUTHORS:  - Knizhnik AV; Roos WP; Nikolova T; Quiros S; Tomaszowski KH; Christmann M; Kaina B

INSTITUCIÓN / INSTITUTION:  - Department of Toxicology, Medical University Center, Mainz, Germany.

RESUMEN / SUMMARY:  - Apoptosis, autophagy, necrosis and cellular senescence are key responses of cells that were exposed to genotoxicants. The types of DNA damage triggering these responses and their interrelationship are largely unknown. Here we studied these  responses in glioma cells treated with the methylating agent temozolomide (TMZ),  which is a first-line chemotherapeutic for this malignancy. We show that upon TMZ treatment cells undergo autophagy, senescence and apoptosis in a specific time-dependent manner. Necrosis was only marginally induced. All these effects were completely abrogated in isogenic glioma cells expressing O(6)-methylguanine-DNA methyltransferase (MGMT), indicating that a single type of DNA lesion, O(6)-methylguanine (O(6)MeG), is able to trigger all these responses. Studies with mismatch repair mutants and MSH6, Rad51 and ATM knockdowns revealed  that autophagy induced by O(6)MeG requires mismatch repair and ATM, and is counteracted by homologous recombination. We further show that autophagy, which precedes apoptosis, is a survival mechanism as its inhibition greatly ameliorated the level of apoptosis following TMZ at therapeutically relevant doses (<100 microM). Cellular senescence increases with post-exposure time and, similar to autophagy, precedes apoptosis. If autophagy was abrogated, TMZ-induced senescence was reduced. Therefore, we propose that autophagy triggered by O(6)MeG adducts is a survival mechanism that stimulates cells to undergo senescence rather than apoptosis. Overall, the data revealed that a specific DNA adduct, O(6)MeG, has the capability of triggering autophagy, senescence and apoptosis and that the decision between survival and death is determined by the balance of players involved. The data also suggests that inhibition of autophagy may ameliorate the  therapeutic outcome of TMZ-based cancer therapy.

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[650]

TÍTULO / TITLE:  - Pulmonary and Pleural Metastases from Benign Meningeal Meningioma: A Case Report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Thorac Cardiovasc Surg. 2013 Jan 31.

AUTORES / AUTHORS:  - Nakayama Y; Horio H; Horiguchi S; Hato T

INSTITUCIÓN / INSTITUTION:  - Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan.

RESUMEN / SUMMARY:  - Meningiomas are generally benign tumors, but rarely metastasize outside of the central nervous system. A 25-year-old female was admitted to our institute because of an abnormal shadow on her chest x-ray. A computed tomography (CT) scan showed a 3-cm, well- circumscribed mass in the right lower lobe of the lung. We performed thoracotomy and resected three pulmonary tumors at the right lung and diaphragm. Histological examination revealed a benign meningothelial meningioma.  Six months later, she complained of heaviness of her head and a head CT scan revealed an intracranial mass. A craniotomy was performed and a brain tumor was found to be histologically identical to the lung tumors. During the 21 years since the first operation, we performed three times of pulmonary and pleural metastasectomies and two times of resection of intracranial local recurrences. All of those tumors were meningothelial meningioma without malignant change. The  patient is alive without metastasis after the last resection of metastatic tumors.

 

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[651]

TÍTULO / TITLE:  - Gene expression profile of glioblastoma peritumoral tissue: an ex vivo study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e57145. doi: 10.1371/journal.pone.0057145. Epub 2013 Mar 5.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057145

AUTORES / AUTHORS:  - Mangiola A; Saulnier N; De Bonis P; Orteschi D; Sica G; Lama G; Pettorini BL; Sabatino G; Zollino M; Lauriola L; Colabianchi A; Proietti G; Kovacs G; Maira G; Anile C

INSTITUCIÓN / INSTITUTION:  - Institute of Neurosurgery, Faculty of Medicine, Catholic University of Rome, Rome, Italy.

RESUMEN / SUMMARY:  - The gene expression pattern of glioblastoma (GBM) is well documented but the expression profile of brain adjacent to tumor is not yet analysed. This may help  to understand the oncogenic pathway of GBM development. We have established the genome-wide expression profiles of samples isolated from GBM tumor mass, white matter adjacent to tumor (apparently free of tumor cells), and white matter controls by using the Affymetrix HG-U133 arrays. Array-CGH (aCGH) was also performed to detect genomic alterations. Among genes dysregulated in peritumoral  white matter, 15 were over-expressed, while 42 were down-regulated when compared  to white matter controls. A similar expression profile was detected in GBM cells. Growth, proliferation and cell motility/adhesion-associated genes were up-regulated while genes involved in neurogenesis were down-regulated. Furthermore, several tumor suppressor genes along with the KLRC1 (a member of natural killer receptor) were also down-regulated in the peritumoral brain tissue. Several mosaic genomic lesions were detected by aCGH, mostly in tumor samples and several GBM-associated mosaic genomic lesions were also present in the peritumoral brain tissue, with a similar mosaicism pattern. Our data could be explained by a dilution of genes expressed from tumor cells infiltrating the peritumour tissue. Alternatively, these findings could be substained by a relevant amount of “apparently normal” cells presenting a gene profile compatible with a precancerous state or even “quiescent” cancer cells. Otherwise, the recurrent tumor may arise from both infiltrating tumor cells and from an interaction and recruitment of apparently normal cells in the peritumor tissue by infiltrating tumor cells.

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[652]

TÍTULO / TITLE:  - Treatment outcome and prognostic factors of adult glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Egypt Natl Canc Inst. 2013 Mar;25(1):21-30. doi: 10.1016/j.jnci.2012.11.001. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jnci.2012.11.001

AUTORES / AUTHORS:  - Ahmadloo N; Kani AA; Mohammadianpanah M; Nasrolahi H; Omidvari S; Mosalaei A; Ansari M

INSTITUCIÓN / INSTITUTION:  - Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

RESUMEN / SUMMARY:  - INTRODUCTION: This study aimed to report the characteristics, prognostic factors  and treatment outcome of 223 patients with glioblastoma multiforme (GBM). SUBJECTS AND METHOD: This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients’ follow up ranged from 1 to 69months (median 11months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. RESULTS: There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11  (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the  extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. CONCLUSION: The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and  overall survival.

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[653]

TÍTULO / TITLE:  - Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Photodiagnosis Photodyn Ther. 2013 Feb;10(1):42-50. doi: 10.1016/j.pdpdt.2012.06.003. Epub 2012 Jul 20.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pdpdt.2012.06.003

AUTORES / AUTHORS:  - Sun W; Kajimoto Y; Inoue H; Miyatake S; Ishikawa T; Kuroiwa T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan; Department of Neurosurgery, Pu Nan Hospital, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - BACKGROUND: Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro. MATERIALS AND METHODS: Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01-1.0muM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro. RESULTS: At concentrations of 0.1muM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells. CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.

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[654]

TÍTULO / TITLE:  - Treatment of Cystic Craniopharyngioma by Endocavitary Instillation of Yttrium90 Radioisotope-Still a Valuable Treatment Option.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0033-1341413

AUTORES / AUTHORS:  - Vanhauwaert D; Hallaert G; Baert E; Van Roost D; Okito JP; Caemaert J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, UZ Gent, Gent, Belgium.

RESUMEN / SUMMARY:  - Craniopharyngiomas are a challenging pathology in neurosurgery because of their anatomic localization in the (supra)sellar region and their contact with diencephalic structures around the third ventricle. Among the different treatment modalities, stereotactic intracavitary treatment by instillation of yttrium90 radioisotope is a minimally invasive technique of particular use in the treatment of cystic or partially cystic craniopharyngiomas. It can be performed under local anesthesia during a short hospitalization and has a long-lasting effect. This treatment can be repeated or used in combination with other treatment modalities  such as microsurgery, endoscopy, conformal external radiation therapy, or stereotactic radiosurgery. Thus, this old and perhaps almost forgotten treatment  option is still valuable in the treatment of cystic craniopharyngiomas.

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[655]

TÍTULO / TITLE:  - Epidermal growth factor receptor mutation status and rad51 determine the response of glioblastoma to multimodality therapy with cetuximab, temozolomide, and radiation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:13. doi: 10.3389/fonc.2013.00013. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00013

AUTORES / AUTHORS:  - Wachsberger PR; Lawrence RY; Liu Y; Rice B; Daskalakis C; Dicker AP

INSTITUCIÓN / INSTITUTION:  - Molecular Radiation Biology, Department of Radiation Oncology, Thomas Jefferson University Philadelphia, PA, USA.

RESUMEN / SUMMARY:  - Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolomide (TMZ), and radiation therapy (RT).Methods and Materials:In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR) and the other overexpressing EGFRvIII (U87EGFRvIII).Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro  experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing.Conclusion: The difference in sensitivity between EGFR-expressing and  EGFRvIII-expressing tumors to combined modality treatment may help in the future  tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.

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[656]

TÍTULO / TITLE:  - Left-sided hemianopia as an unrecognized symptom of brain tumor and head injury.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Klin Oczna. 2012;114(3):204-7.

AUTORES / AUTHORS:  - Obuchowska I

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Medical University of Bialystok, Poland. iwonaobu@wp.pl

RESUMEN / SUMMARY:  - Homonymous hemianopia (HH) is a visual field defect characterized by the involvement of two right or left halves of the visual field in both eyes. Patients with HH complain of difficulties with reading and scanning scenes in sufficiently rapid fashion to make sense of things as a whole. Some of these patients are not aware of their visual field defect. We report two cases of left-sided hemianopia in which visual field defects were detected “quite” accidentally. In the case of the first patient, revealing HH facilitated the detection of brain tumor and its treatment. In the case of the other patient, identifying HH, which was caused by a head injury, and making the patient aware of this fact, prevented potential harmful consequences associated with driving a  car by a person with severe deficits in cognitive visual functions. homonymous hemianopia, brain tumor, head trauma.

 

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[657]

TÍTULO / TITLE:  - Retinal astrocytic hamartoma and Bourneville’s disease.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oman J Ophthalmol. 2012 Sep;5(3):198-9. doi: 10.4103/0974-620X.106108.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0974-620X.106108

AUTORES / AUTHORS:  - Ali MJ; Honavar SG; Naik MN

INSTITUCIÓN / INSTITUTION:  - Ocular Oncology Service, L.V. Prasad Eye Institute, Hyderabad, Andhra Pradesh, India.

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[658]

TÍTULO / TITLE:  - Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Feb 21;8(1):39.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-39

AUTORES / AUTHORS:  - Siviero-Miachon AA; Spinola-Castro AM; Lee ML; Andreoni S; Geloneze B; Lederman H; Guerra-Junior G

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in  this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. METHODS: A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. RESULTS: Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. CONCLUSIONS: Adolescent and young adult survivors of childhood acute lymphocytic  leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.

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[659]

TÍTULO / TITLE:  - Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Mar 21;4:e550. doi: 10.1038/cddis.2013.77.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.77

AUTORES / AUTHORS:  - Zhang YB; Gong JL; Xing TY; Zheng SP; Ding W

INSTITUCIÓN / INSTITUTION:  - 1] Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China [2] Department of Immunology and Pathogen Biology, Liaoning Medical University, Jinzhou, China.

RESUMEN / SUMMARY:  - HAMLET is a complex of oleic acids and decalcified alpha-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation  of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET  treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

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[660]

TÍTULO / TITLE:  - Chordoid meningioma: a retrospective study of 17 cases at a single institution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Feb;126(4):789-91.

AUTORES / AUTHORS:  - Zhu HD; Chen H; Xie Q; Gong Y; Mao Y; Zhong P; Che XM; Jiang CC; Huang FP; Zheng K; Li SQ; Gu YX; Bao WM; Yang BJ; Wu JS; Wang Y; Xie LQ; Zheng MZ; Tang HL; Wang DJ; Chen XC; Zhou LF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040,  China.

 

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[661]

TÍTULO / TITLE:  - The antiproliferative effect of indomethacin-loaded lipid-core nanocapsules in glioma cells is mediated by cell cycle regulation, differentiation, and the inhibition of survival pathways.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Nanomedicine. 2013;8:711-28. doi: 10.2147/IJN.S40284. Epub 2013 Feb 18.

            ●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S40284

AUTORES / AUTHORS:  - Bernardi A; Frozza RL; Hoppe JB; Salbego C; Pohlmann AR; Battastini AM; Guterres SS

INSTITUCIÓN / INSTITUTION:  - Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil. andressabernardi@yahoo.com.br

RESUMEN / SUMMARY:  - Despite recent advances in radiotherapy, chemotherapy, and surgical techniques, glioblastoma multiforme (GBM) prognosis remains dismal. There is an urgent need for new therapeutic strategies. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intense interest in recent years because  they can provide sustained, controlled, and targeted delivery. Here, we investigate the mechanisms involved in the antiproliferative effect of indomethacin-loaded lipid-core nanocapsules (IndOH-LNC) in glioma cells. IndOH-LNC were able to reduce cell viability by inducing apoptotic cell death in  C6 and U138-MG glioma cell lines. Interestingly, IndOH-LNC did not affect the viability of primary astrocytes, suggesting that this formulation selectively targeted transformed cells. Mechanistically, IndOH-LNC induced inhibition of cell growth and cell-cycle arrest to be correlated with the inactivation of AKT and beta-catenin and the activation of GSK-3beta. IndOH-LNC also induced G0/G1 and/or G2/M phase arrest, which was accompanied by a decrease in the levels of cyclin D1, cyclin B1, pRb, and pcdc2 and an increase in the levels of Wee1 CDK inhibitor p21(WAF1). Additionally, IndOH-LNC promoted GBM cell differentiation, observed as upregulation of glial fibrillary acidic protein (GFAP) protein and downregulation of nestin and CD133. Taken together, the crosstalk among antiproliferative effects, cell-cycle arrest, apoptosis, and cell differentiation should be considered when tailoring pharmacological interventions aimed at reducing glioma  growth by using formulations with multiples targets, such as IndOH-LNC.

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[662]

TÍTULO / TITLE:  - Pure intrasellar meningioma located under the pituitary gland: case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Korean J Radiol. 2013 Mar;14(2):321-3. doi: 10.3348/kjr.2013.14.2.321. Epub 2013  Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 3348/kjr.2013.14.2.321

AUTORES / AUTHORS:  - Cha SW; Park DW; Park CK; Lee YJ; Lee SR; Pyo JY

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, College of Medicine, Hanyang University, Guri Hospital,  Guri 471-701, Korea.

RESUMEN / SUMMARY:  - Most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae. Subglandular meningiomas located under the pituitary gland are extremely rare. Intrasellar meningiomas in the subdiaphragmatic and subglandular region probably  originate from the dura in the sellar floor. We report a case of a subglandular meningioma along with a review of the literature.

 

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[663]

TÍTULO / TITLE:  - P27/Kip1 Is Responsible for Magnolol-Induced U373 Apoptosis in Vitro and in Vivo.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Agric Food Chem. 2013 Mar 7.

            ●● Enlace al texto completo (gratuito o de pago) 1021/jf400542m

AUTORES / AUTHORS:  - Chen LC; Lee WS

INSTITUCIÓN / INSTITUTION:  - Graduate Institutes of Medical Sciences, College of Medicine, double daggerDepartment of Physiology, School of Medicine, College of Medicine, and section signCancer Research Center, Taipei Medical University , Taipei 110, Taiwan.

RESUMEN / SUMMARY:  - Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis , at low concentrations (3-10 muM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 muM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 muM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT  but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 muM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.

 

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[664]

TÍTULO / TITLE:  - Primary adult infradiaphragmatic craniopharyngiomas: Clinical features, management and outcomes in one Chinese institution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 5. pii: S1878-8750(13)00276-3. doi: 10.1016/j.wneu.2013.02.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.011

AUTORES / AUTHORS:  - Wang L; Ni M; Jia W; Jia G; Du J; Li G; Zhang J; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, and Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, P R China. Electronic address: saintage7@126.com.

RESUMEN / SUMMARY:  - OBJECTIVE: : This study was designed to evaluate the clinical, radiologic, histologic and surgical outcome characteristics of this disease treated in a single institution. METHODS: : 16 adult patients underwent trans-sphenoidal microsurgery from October 2005 to December 2010 at Neurosurgical Center of Beijing Tiantan Hospital. The clinical, radiological, operative, and pathological findings of the patients were reviewed retrospectively. RESULTS: : Pituitary dysfunction was presented in 12 patients, visual acuity and/or field deterioration was found in 11 patients, and headache was complained in 8 patients. Hyperprolactinemia was presented in 7 of 9 female patients. All lesions were resected by transsphenoidal microsurgery as the primary procedure.A GTR was  achieved in 3 of 16 patients, a radical subtotal resection was attained in the rest 13 patients. 9 cases were histologically classified as adamantinous subtype. After a mean follow-up of 50 months, 2 patients experienced recurrence. All female patients who had hyperprolactinemia experienced a gain of function postoperatively. 6 patients experienced new diabetes insipidus. Visual field improved or normalized in 8 of 9 patients. Visual acuity improved in 1 cases and  worsened in 1 patient. CONCLUSION: : Primary adult infradiaphagmic craniopharyngiomas are relatively rare lesions occurring in young adults. Pituitary dysfunction, visual acuity and/or field deterioration and headache were the most common chief symptoms. Transsphenoidal surgery, including tearing the cyst walls off the diaphragma sellae and protecting normal pituitary tissue as much as possible, is recommended. Though at the risk of impairing the function of anterior pituitary ,trans-sphenoidal surgery results in a high rate of both visual field and hyperprolactinemia improvement with a low associated risk of recurrence. In terms of pathological aspects, the adamantinous subtype was more common.

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[665]

TÍTULO / TITLE:  - Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Opin Endocrinol Diabetes Obes. 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MED.0b013e32835fcc45

AUTORES / AUTHORS:  - Vicha A; Musil Z; Pacak K

INSTITUCIÓN / INSTITUTION:  - aDepartment of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University, University Hospital Motol bInstitute of Biology and Medical Genetics, 1st Faculty of Medicine, Charles University, General Teaching Hospital, Prague, Czech Republic cProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA.

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: To summarize the recent advances in the genetics of pheochromocytoma and paraganglioma (PHEO/PGL), focusing on the new susceptibility genes and dividing PHEOs/PGLs into two groups based on their transcription profile. RECENT FINDINGS: Recently, TMEM127, MYC-associated factor X, and hypoxia-inducible factor (HIF) 2alpha have been described in the pathogenesis of  PHEOs/PGLs. Thus, now about 30-40% of these tumors are linked to the germline mutations, which also include mutations in the VHL, RET, NF1, SDHx, and SDHAF2 genes. Furthermore, PHEOs/PGLs have been divided into two groups, cluster 1 (SDHx/VHL) and cluster 2 (RET/NF1), based on the transcription profile revealed by genome-wide expression microarray analysis. SUMMARY: PHEOs/PGLs are the most inherited tumors among (neuro)endocrine tumors. Future approaches in genetics, including whole-genome sequencing, will allow the discovery of additional PHEO/PGL susceptibility genes. The current division of PHEOs/PGLs into cluster 1  and 2 provides us with additional knowledge related to the pathogenesis of these  tumors, including the introduction of new treatment options for patients with metastatic PHEOs/PGLs. New discoveries related to the role of the HIF-1/HIF-2alpha genes in the pathogenesis of almost all inherited PHEOs/PGLs may call for a new regrouping of these tumors and discoveries of new treatment targets.

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[666]

TÍTULO / TITLE:  - Adult Cerebellar Glioblastoma: Understanding Survival and Prognostic Factors Using A Population-Based Database from 1973 - 2009.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 6. pii: S1878-8750(13)00275-1. doi: 10.1016/j.wneu.2013.02.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.010

AUTORES / AUTHORS:  - Adams H; Chaichana KL; Avendano J; Liu B; Raza SM; Quinones-Hinojosa A

INSTITUCIÓN / INSTITUTION:  - Neuro-Oncology Surgical Outcomes Research Laboratory, Department of Neurosurgery  and Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - OBJECTIVE: : Glioblastoma (GB) is rarely in the cerebellum. Because of its rarity, it is poorly understood if cerebellar GB (CGB) behaves similarly to supratentorial GB. Studies have been limited to case reports and small case series. A better understanding of CGB may help guide treatment strategies. METHODS: : Surveillance, Epidemiology and End Results (SEER) database was analyzed from 1973-2009 for all adult patients with GB located in the cerebellum. Stepwise multivariate proportional hazards regression analyses were used to identify factors independently associated with survival. RESULTS: : 208(0.9%) patients with CGB were identified from 23,329 GB patients with known locality. The mean age was 58years. Median survival was 8 months, with 1, 2 and 5-year survival rates of 21%, 13%, and 2%. When compared to supratentorial GB, CGB occurred in younger patients (58+/-16 vs. 61+/-13 years, p=0.001), less commonly  in “Whites” (85.6% vs. 91.3%, p=0.005), and were smaller (3.7+/-1.1 vs. 4.5+/-1.7 cm, p=0.001). A cerebellar location independently predicted poorer survival when  compared to other GB locations (p=0.048). In multivariate analysis for patients with CGB, younger age (p<0.001), “Asian or Pacific Islander” race (p=0.046), and  radiation therapy (p<0.001) were independently associated with prolonged survival. CONCLUSION: CGB are difficult to analyze using institutional series because of their rarity. This study shows they are clinically different than supratentorial GB. Among patients with CGB, radiation therapy may prolong survival for patients with the rare lesions. This may help guide treatment strategies aimed at prolonging survival for patients with these extremely rare lesions.

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[667]

TÍTULO / TITLE:  - Secretory meningiomas: clinical, radiological and pathological findings in 70 consecutive cases at one institution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(3):358-74. Epub 2013 Feb 15.

AUTORES / AUTHORS:  - Wang DJ; Xie Q; Gong Y; Wang Y; Cheng HX; Mao Y; Zhong P; Huang FP; Zheng K; Wang YF; Bao WM; Yang BJ; Chen H; Xie LQ; Zheng MZ; Tang HL; Zhu HD; Chen XC; Zhou LF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Fudan University Shanghai, China.

RESUMEN / SUMMARY:  - Secretory meningioma (SM) is a rare, benign subtype of meningioma. Between January 2005 and December 2010, 70 SMs were operated on at the Department of Neurosurgery, Huashan Hospital, Fudan University. We retrospectively analyzed the clinical data, radiological and immunohistochemical findings, and patient outcome to discuss the specific features of SMs. Cranial base preference, hyper-signal in T2 weighted MR image, “xenon light” gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement were frequently observed in the 70 cases. Non-skull base SMs, which received more complete resection (p<0.01) and had better short-term and long-term outcome, were observed with more severe peritumoral brain edema (PTBE) (p<0.001). In follow-up, only 1 cranial base SM case showed tumor progression. 3 cases died after operation, all with cranial base SMs. As for the 10 cases given Simpson grade 3 or 4 resection who were available at follow-up, 3 died, 5 received gamma-knife therapy, and the other 2 cases received no treatment at all. Only one of the 2 residual SMs without postoperative radiation presented minor progression at a median of 48 months follow-up. In conclusion, cranial base preference, hyper-signal T2 weighted MR image and “xenon light” GD-DTPA enhancement are specific for SMs. Prognosis of SMs is related with operation completeness and surgical risks, rather than the extent of PTBE. Residual SM grows slowly and reacts well to gamma-knife therapy.

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[668]

TÍTULO / TITLE:  - Perfusion-weighted imaging of peritumoral edema can aid in the differential diagnosis of glioblastoma mulltiforme versus brain metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Isr Med Assoc J. 2013 Feb;15(2):103-5.

AUTORES / AUTHORS:  - Neiman OH; Sadetzki S; Chetrit A; Raskin S; Yaniv G; Hoffmann C

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel. osnatx@gmail.com

RESUMEN / SUMMARY:  - BACKGROUND: MRI differentiation between metastases and high grade gliomas is a challenging task. Contrast enhancement and size of edema do not provide clear-cut differentiators. The differences in the properties of the peritumoral edema between these tumor types may be exploited to distinguish between them, using MRI perfusion sequences, which are capable of imaging edema in the clinical setting and may be a reliable method to make this differentiation. OBJECTIVES: To assess  the ability of perfusion-weighted imaging to differentiate between high grade gliomas andbrain metastases. METHODS: During 5 months, 21 patients (age 40-85, median age 61, 16 males and 5 females) with either glioblastoma multiforme (GBM)  or metastasis (pathology proven), underwent MRI for assessment of the tumor prior to surgery. Most of the scans were done at 3 Tesla. The scans included perfusion-weighted imaging sequences. Perfusion in the tumor, in the peritumoral  edema and in normal tissue were assessed using Functool software. The ratios of tumor perfusion and peritumoral edema perfusion to normal tissue perfusion were calculated and compared. RESULTS: Bleeding artifact precluded perfusion assessment in four patients. There was no statistically significant difference between the tumor perfusion ratios of high grade gliomas and those of metastases. The edema perfusion ratios were higher in GBM than in metastases (P = 0.007). CONCLUSIONS: Perfusion-weighted imaging of peritumoral edema can help to differentiate between GBM and metastases.

 

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[669]

TÍTULO / TITLE:  - VEGF Promotes Proliferation of Human Glioblastoma Multiforme Stem-Like Cells through VEGF Receptor 2.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - ScientificWorldJournal. 2013;2013:417413. doi: 10.1155/2013/417413. Epub 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/417413

AUTORES / AUTHORS:  - Xu C; Wu X; Zhu J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai 200040, China.

RESUMEN / SUMMARY:  - Cancer stem-like cells, which have been described as tumor-initiating cells or tumor-propagating cells, play a crucial role in our fundamental understanding of  glioblastoma multiforme (GBM) and its recurrence. GBM is a lethal cancer, characterized by florid vascularization and aberrantly elevated vascular endothelial growth factor (VEGF). VEGF promotes tumorigenesis and angiogenesis of human GBM stem-like cells (GBSCs). However, whether and how VEGF contributes to GBSCs proliferation remain largely uncertain. In this study, human GBSCs were isolated from surgical specimens of glioblastoma and cultured in medium favored for stem cell growth. Neural Colony-Forming Cell Assay and ATP assay were performed to measure GBSC proliferation under normoxia (20% O2) and hypoxia (1% O2). Our observations demonstrate that exogenous VEGF stimulates GBSC proliferation in a dose-dependent manner via VEGF Receptor 2 (VEGFR2); while VEGF Receptor 1 (VEGFR1) has a negative feedback effect on VEGFR2 when cells were exposed to higher concentration of VEGF. These results suggest that suppressing VEGFR2-dependent GBSC proliferation is a potentially therapeutic strategy in GBM.

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[670]

TÍTULO / TITLE:  - Upregulation of glutathione peroxidase-1 expression and activity by glial cell line-derived neurotrophic factor promotes high-level protection of PC12 cells against 6-OHDA and H2O2 toxicities.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rejuvenation Res. 2013 Mar 9.

            ●● Enlace al texto completo (gratuito o de pago) 1089/rej.2012.1390

AUTORES / AUTHORS:  - Gharib E; Gardaneh M; Shojaei S

INSTITUCIÓN / INSTITUTION:  - Tehran, Iran, Islamic Republic of; sonick74ir2000@yahoo.com.

RESUMEN / SUMMARY:  - We examined the impact of strong co-presence and function of glutathione peroxidase-1 (GPX-1) and glial cell line-derived neurotrophic factor (GDNF) on protecting rat dopaminergic pheochromocytoma cell line PC12 against 6-OHDA and H2O2 toxicities. Primarily, GPX-1 overexpression by PC12 cells infected with pLV-GPX1 lentivirus vectors significantly increased cell survival against 6-OHDA  toxicity (P<0.01). Addition of conditioned medium collected from growing wild-type astrocytes (Control astro-CM) increased survival rate of pLV-GPX1 infectants by 10% compared to their un-treated counterparts (P<0.05) and 20% compared to their treated empty vector control (P<0.01). Treatment of pLV-GPX1 cells with astro-CM of GDNF-oversecreting astrocytes (Test astro-CM) significantly induced GPX-1 expression, peroxidase enzymatic activity and intracellular glutathione levels. These changes paralleled with protection of 90% of GDNF+/GPX1+ PC12 cells against toxicity, a rate that was 37% up from their un-infected un-treated (GDNF-/GPX1-) controls (P<0.001), and 12% up from pLV-GPX1 cells that received only Control astro-CM (GPX-1+/GDNF-) (P<0.01). GPX-1 overexpression per se suppressed intracellular H2O2 elevation upon 6-OHDA exposure and addition of GDNF medium significantly accelerated this suppression (P<0.01). Substitution of 6-OHDA with H2O2 induced similar intracellular changes  and comparable protection levels. In all cell groups, increased cell survival against either compound was further confirmed by increased live cell counts measured by double staining. Following depletion of intracellular glutathione (GSH), only 46% of pLV-GPX1 cells survived 6-OHDA toxicity, whereas over 70% of them were saved upon GDNF treatment (P<0.001). Moreover, capase-3 activation was  induced in pLV-GPX1 cells and maximized by addition of GDNF. Comparison analyses  well established correlations between GPX-1-GDNF co-presence and both accelerated cell protection and diminished levels of activated caspase-3. Our data collectively indicate that GDNF is capable of inducing anti-oxidant activities of intracellular GPX-1 and that growth promoting potential of GDNF and anti-oxidant  properties of GPX-1 can, in concert, maximize survival of dopaminergic neurons.

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[671]

TÍTULO / TITLE:  - Pediatric gliosarcoma with fibrosarcomatous differentiation: Report of a rare case.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Pathol Microbiol. 2012 Oct;55(4):521-4. doi: 10.4103/0377-4929.107797.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0377-4929.107797

AUTORES / AUTHORS:  - Ravisankar S; Chander RV; Devadoss PK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Institute of Neurology, Madras Medical College, Chennai, India.

RESUMEN / SUMMARY:  - Gliosarcoma is a rare variant of glioblastoma with a biphasic pattern showing glial and mesenchymal differentiation. It is seen in adults during their fifth to sixth decades of life and is extremely rare in children. We report a case of primary gliosarcoma with fibrosarcomatous differentiation in an 11-year-old boy presenting with headache and vomiting. Imaging showed a contrast-enhancing isodense space-occupying lesion with areas of calcification in the right temporoparietal cortex. A total excision was done and, on histopathologic examination, a differential diagnostic consideration of gliosarcoma and teratoma  with malignant transformation was made. After immunohistochemical analysis, a final diagnosis of gliosarcoma with fibrosarcomatous differentiation was then made. Primary gliosarcoma is a very rare tumor in children with a poor prognosis.

 

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[672]

TÍTULO / TITLE:  - In vivo dynamic monitoring of the biological behavior of labeled C6 glioma by MRI.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Rep. 2013 Mar 13. doi: 10.3892/mmr.2013.1369.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1369

AUTORES / AUTHORS:  - Liao J; Xia R; Liu T; Feng H; Ai H; Song B; Gao F

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

RESUMEN / SUMMARY:  - Gliomas are the most common type of intracranial tumor and have the highest rate  of mortality. The aims of this study were to investigate the long-term course and biological behavior of orthotopically implanted C6 gliomas and to dynamically monitor the distribution of superparamagnetic iron oxide (SPIO) nanocomposite-labeled C6 glioma cells in rats using 7.0T MRI. We observed that in the MRI of the rats implanted with SPIO-labeled cells, there were pronounced hypointense signal bands, which faded over time, but remained visible up to day 27 after implantation. We observed that the first tumors were detected as early as 2 days after implantation, presenting as slightly hyperintense regions with indefinite boundaries in the T1-weighted images (T1WIs). On the 9th day, thick tumor feeder vessels, ~0.2 mm in diameter, were observed and these increased rapidly over time. Edema was observed in the labeled and unlabeled groups in the  T2WIs. Both the central hypointense signal area and the peripheral cogwheel-shaped hypointense signal band in the tumor were observed on the post-contrast T1WIs, in accordance with the necrosis observed in the photomicrographs following hematoxylin and eosin (HE) staining. In conclusion, labeling tumor cells with SPIO and performing an MRI scan dynamically monitors the development and biological behavior of glioma at a very early stage.

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[673]

TÍTULO / TITLE:  - Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Plays a Key Role in Vasculogenic Mimicry Formation, Neovascularization and Tumor Initiation by Glioma Stem-like Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e57188. doi: 10.1371/journal.pone.0057188. Epub 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057188

AUTORES / AUTHORS:  - Yao X; Ping Y; Liu Y; Chen K; Yoshimura T; Liu M; Gong W; Chen C; Niu Q; Guo D; Zhang X; Wang JM; Bian X

INSTITUCIÓN / INSTITUTION:  - Institute of Pathology and Southwest Cancer Center, Third Military Medical University, Chongqing, China ; Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America.

RESUMEN / SUMMARY:  - Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical  role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the “stemness” of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.

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[674]

TÍTULO / TITLE:  - Rescue of MHC-1 Antigen Processing Machinery by Down-Regulation in Expression of  IGF-1 in Human Glioblastoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e58428. doi: 10.1371/journal.pone.0058428. Epub 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058428

AUTORES / AUTHORS:  - Pan Y; Trojan J; Guo Y; Anthony DD

INSTITUCIÓN / INSTITUTION:  - Division of General Medical Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America ; Department of Medicine, University Hospitals of Cleveland, Cleveland, Ohio, United States of America.

RESUMEN / SUMMARY:  - Escape from immune recognition has been hypothesized to be a factor in carcinogenesis. It may be mediated for many cancers through down-regulation in the MHC class 1 antigen processing and presentation pathway. TAP-1, TAP-2, tightly linked to LMP-2 and LMP-7 are multiple components of the endogenous, antigen presentation pathway machinery. We addressed the question of alterations  in this pathway in human Glioblastoma (HGB) and of its relationship to modulation in expression of IGF-1 that is highly expressed in this cancer. Deficiencies in expression of TAP-1 were demonstrated by RT-PCR and/or by immuno-flow cytometry in the HGB cell line T98G obtained from ATCC, and in 3 of 4 human cell lines established from patients with Glioblastoma Multiforme. Deficiencies in expression of TAP-2 were observed in 3 of 4, deficiencies in expression of LMP-2  in 4 of 4 and deficiencies in LMP-7 in 3 of 4 HGB cell lines examined by RT-PCR and Western blot. Following down-regulation of IGF-1 by transfection with the pAnti IGF-1 vector that expresses IGF-1 RNA in antisense orientation, or by the exogenous addition of IGF-1 receptor monoclonal antibody to cell culture media, the deficiencies in components of the MHC-1 antigen presentation pathway were up-regulated and/or rescued in all HGB cell lines tested. Moreover, this up-regulation in expression was aborted by addition of 100 ng/ml of IGF-1 to the  culture media. Unlike in the case of IFN-gamma, the restoration of TAP-1 and LMP-2 by down-regulation of IGF-1 in Glioblastoma cells was not correlated to the tyrosine phosphorylation of STAT 1. In summary, the simultaneous reversion in expression of the multiple constituents of MHC-1 antigen processing path and up-regulation in expression of MHC-1 occurring with down-regulation in IGF-1 may  have a role in reinforcement of immunity against tumor antigen(s) in some animal  cancers and in humans with Glioblastoma Multiforme.

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[675]

TÍTULO / TITLE:  - Clinicopathological analysis of metaplastic meningioma: report of 15 cases in Huashan Hospital.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2013 Feb;25(1):112-8. doi: 10.3978/j.issn.1000-9604.2013.01.10.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2013.01.10

AUTORES / AUTHORS:  - Tang H; Sun H; Chen H; Gong Y; Mao Y; Xie Q; Xie L; Zheng M; Wang D; Zhu H; Che X; Zhong P; Zheng K; Li S; Bao W; Zhu J; Wang X; Feng X; Chen X; Zhou L

INSTITUCIÓN / INSTITUTION:  - Neurosurgery Department of Huashan Hospital, Shanghai 200040, China;

RESUMEN / SUMMARY:  - OBJECTIVE: Metaplastic meningioma is a rare subtype of benign meningiomas, classified as WHO grade I with well prognosis. Here we presented our experiences  on 15 cases of metaplastic meningioma, to investigate the clinicopathological features, therapies and prognosis of these cases. METHODS: 15 patients underwent  surgical treatment for intracranial metaplastic meningioma between 2001 and 2010  at Neurosurgery Department of Huashan Hospital, Shanghai, China. The clinical data, radiological manifestation, treatment strategy, pathological findings and prognosis of all patients were analyzed retrospectively. RESULTS: Among the 15 cases (10 males and 5 females), the age ranged from 22 to 74 years old (the mean  age was 50.67-year old). The clinical manifestations include headache, dizziness, seizure attack, vision decrease, and weakness of bilateral lower limbs. All the patients received surgical treatment, combined with radiotherapy in some cases. In the follow-up period, recurrence occurred in 2 cases, of which 1 patient died  of other system complications. CONCLUSIONS: Metaplastic meningiomas are characterized by focal or widespread mesenchymal differentiation with formation of bone, cartilage, fat, and xanthomatous tissue elements. Surgical removal is the optimal therapy, and the overall prognosis is well. But recurrence may occur  in some cases, thus radiotherapy is necessary for such kind of patients.

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[676]

TÍTULO / TITLE:  - Polymorphisms in DNA repair genes and susceptibility to glioma in a chinese population.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2013 Feb 5;14(2):3314-24. doi: 10.3390/ijms14023314.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14023314

AUTORES / AUTHORS:  - Pan WR; Li G; Guan JH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shengjing Affiliated Hospital of China Medical University, Shenyang 110004, China. panweiran5432@126.com.

RESUMEN / SUMMARY:  - The excision repair cross-complementing rodent repair deficiency complementation  group 1 (ERCC1), and X-ray repair cross-complementing group 1 (XRCC1) genes appear to protect mammalian cells from the harmful effects of ionizing radiation. We conducted a large case-control study to investigate the association of polymorphisms in ERCC1 C118T, ERCC1 C8092A, XRCC1 A194T, XRCC1 A194T, and XRCC3 C241T, with glioma risk in a Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped, using the MassARRAY IPLEX platform, in 443 glioma cases and 443 controls. Association analyses based on an chi2 test and binary logistic regression were performed to determine the odds ratio (OR) and a  95% confidence interval (95% CI) for each SNP. For XRCC1 Arg194Trp, the variant genotype T/T was strongly associated with a lower risk of glioma cancer when compared with the wild type C/C (OR = 2.45, 95% CI = 1.43-4.45). Individuals carrying the XRCC1 399A allele had an increased risk of glioma (OR = 1.33, 95% CI = 1.02-1.64). The XRCC3 241T/T genotype was associated with a strong increased glioma risk (OR = 3.78, 95% CI = 1.86-9.06). Further analysis of the interactions of two susceptibility-associated SNPs, XRCC1 Arg194Trp and XRCC3 Thr241Met, showed that the combination of the XRCC1 194T and XRCC3 241T alleles brought a large increase in glioma risk (OR = 2.75, 95% CI = 1.54-4.04). XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 C241T, appear to be associated with susceptibility to  glioma in a Chinese population.

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[677]

TÍTULO / TITLE:  - FoxQ1 promotes glioma cells proliferation and migration by regulating NRXN3 expression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55693. doi: 10.1371/journal.pone.0055693. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055693

AUTORES / AUTHORS:  - Sun HT; Cheng SX; Tu Y; Li XH; Zhang S

INSTITUCIÓN / INSTITUTION:  - Institute of Traumatic Brain Injury and Neurology of the Chinese People’s Armed Police Forces, Tianjin, China.

RESUMEN / SUMMARY:  - BACKGROUND: Forkhead box Q1 (FoxQ1) is a member of the forkhead transcription factor family, and it has recently been found to participate in cancer development. However, whether FoxQ1 expression contributes to glioma development  and progression is not known. We investigate FoxQ1 expression in gliomas and the  role of FoxQ1 during tumorgenesis. METHODS: Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to determine the FoxQ1 and Neurexins 3 (NRXN3) expression in gliomas. Chromatin immunoprecipitation (ChIP) and luciferase assays were used to determine the regulation between FoxQ1 and NRXN3. We established depleted FoxQ1 stable clones in U-87MG cells and overexpressed FoxQ1 stable clones in SW1088 cells. MTT and transwell were used to evaluate the ability of proliferation and migration, respectively. RESULTS: FoxQ1 mRNA and protein were up-regulated in gliomas and negatively related to the NRXN3 expression (r = -0.373, P = 0.042). FoxQ1 directly binds to NRXN3 promoter region and suppresses the promoter activity. Furthermore, the ability of proliferation and migration is reduced in depleted FoxQ1 cells. CONCLUSION: FoxQ1 promotes glioma cell proliferation and migration by down-regulation of NRXN3 expression.

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[678]

TÍTULO / TITLE:  - Radiation necrosis of the pons after radiotherapy for nasopharyngeal carcinoma: diagnosis and treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Radiol Case Rep. 2012 Jul;6(7):9-16. doi: 10.3941/jrcr.v6i7.1108. Epub 2012 Jul 1.

            ●● Enlace al texto completo (gratuito o de pago) 3941/jrcr.v6i7.1108

AUTORES / AUTHORS:  - DeSalvo MN

INSTITUCIÓN / INSTITUTION:  - Harvard Medical School, Boston, MA 02115, USA. matthew_desalvo@hms.harvard.edu

RESUMEN / SUMMARY:  - We report a case of radiation necrosis in an unusual location, the pons, in a patient who had received chemoradiation for nasopharyngeal carcinoma (NPC) over one year prior to presentation. This patient presented with subacute onset of ataxic hemiparesis and slurred speech. Initial magnetic resonance imaging (MRI) studies showed two 1-2 cm peripherally contrast-enhancing lesions in the pons with extensive surrounding edema. Proton magnetic resonance spectroscopy (MRS) played a key role in narrowing the differential diagnosis to radiation necrosis.  The patient underwent biweekly bevacizumab therapy and has remained clinically stable with radiologic improvement of his lesion. In addition to this case, we present an overview of the use of advanced neuroimaging in distinguishing radiation necrosis of the central nervous system (CNS) from other entities as well as the role of bevacizumab in treatment.

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[679]

TÍTULO / TITLE:  - Early volumetric change and treatment outcome of metastatic brain tumors after external beam radiotherapy: differential radiotherapy for brain metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1016-2

AUTORES / AUTHORS:  - Lee DS; Kim YS; Lee CG; Lim JH; Suh CO; Kim HJ; Cho J

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the treatment outcomes of low-dose whole brain radiation therapy (WBRT)-based differential radiation therapy (RT) for metastatic brain tumors. METHODS: A total of 242 targets (metastatic brain lesions) were analyzed  in the present study. Median WBRT dose and number of fractions were 25 (range 25-35) Gy and 10 (range 8-15) fractions, respectively. A median normalized total  dose (NTD) of 1.8 Gy (NTD(1.8Gy)) to the metastatic lesion was 45 (range 27-64.8) Gy. We numbered and contoured each metastatic lesion sequentially using computed  tomography fused with serial magnetic resonance imaging to evaluate volumetric changes. RESULTS: The 6-month and 1-year freedom from remote intracranial failure rates were 87.7 and 58.5 %, respectively. The 6-month actuarial local control (LC) rate was 93.4 %. Tumor diameter was a major determinant for LC, and tumor histology was a significant parameter predicting the volume reduction rate. With  overall complete response (CR) rate of 56.6 % after RT, CR rate, if the target was more than 1 cm in size, was 25 % with a median NTD(1.8Gy) of 45 Gy, requiring dose escalation to achieve better target regression. CONCLUSIONS: Low-dose WBRT with selective boost was feasible and effective. Our results pose the rationale of future trial of differential radiation therapy (RT), which prescribes different radiation dose according to the tumor density in metastatic brain tumors.

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[680]

TÍTULO / TITLE:  - In vitro study of low intensity ultrasound combined with different doses of PDT:  Effects on C6 glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Feb;5(2):702-706. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1060

AUTORES / AUTHORS:  - Li JH; Chen ZQ; Huang Z; Zhan Q; Ren FB; Liu JY; Yue W; Wang Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Fourth College Hospital of Harbin Medical University, Harbin, P.R. China ;

RESUMEN / SUMMARY:  - The aim of this study was to study the effects of killing C6 glioma cells induced by hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy combined  with photodynamic therapy (SPDT). In the SPDT group, the cells were treated with  sonication at an intensity of 0.5 W/cm(2) and a frequency of 1 MHz, followed by different doses of light irradiation. The growth inhibition rate following treatment was determined by MTT assay. The apoptotic rate was examined by a flow  cytometry. Cleavage of caspase 3, 8 and 9 was investigated by immunoblotting. Reactive oxygen species (ROS) were measured by a fluorescence microplate reader.  The effect of SPDT on the glioma cells was also studied in the absence or presence of various ROS scavengers. The growth inhibition rate of C6 glioma cells treated with SPDT was significantly higher compared with sonodynamic therapy (SDT) or photodynamic therapy (PDT) alone at light doses <200 J/cm(2). The growth inhibition rate of C6 glioma cells treated with SPDT did not rise significantly when the light dose increased to >120 J/cm(2). The apoptosis rate was the highest in the SPDT group, when the light dose was at 80 J/cm(2). A greater amount of ROS were generated in the SPDT group than in the groups treated with SDT or PDT alone. The addition of NaN(3) or mannitol resulted in a decrease in the growth inhibition rate with SPDT. In conclusion, our data indicate that SPDT powerfully  kills C6 glioma cells in vitro through the synergistic effects of SDT and PDT. The pathway of PDT inducing C6 glioma cell apoptosis includes both the mitochondrial and death receptor pathways. Furthermore, ROS may play an important role in SPDT.

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[681]

TÍTULO / TITLE:  - The involvement of xanthohumol in the expression of annexin in human malignant glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Open Biochem J. 2013;7:1-10. doi: 10.2174/1874091X01307010001. Epub 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 2174/1874091X01307010001

AUTORES / AUTHORS:  - Festa M; Caputo M; Cipolla C; D’Acunto C; Rossi A; Tecce M; Capasso A

INSTITUCIÓN / INSTITUTION:  - University of Salerno, Department of Pharmacy, Italy.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common malignant and resistant tumor of the central nervous system in humans and new therapeutic strategies are urgently  required. Recently, we have shown that the potential chemotherapeutic polyphenol  xanthohumol (XH), isolated from Humulus Lupulus, induces apoptosis of human T98G  glioblastoma cells by increasing reactive oxygen species and activating MAPK pathways. Then we have found, by western blotting and microscopic analysis, that  XH up-regulates cytosolic levels of ANXA1 and induces translocation of the protein on the cell membrane of T98G cells in a time-dependent manner with significant effects observed after 24 h. On the basis of the above evidence, the  aim of this work was to investigate the role of intracellular and cell membrane localized ANXA1 in GBM cells. RT-PCR analysis has shown that XH up-regulates mRNA levels of ANXA1 after 16 h treatment. To demonstrate the involvement of ANXA1 in  apoptosis of GBM cells we down-regulated ANXA1 expression with small interfering  RNA (siRNA) and then analysed apoptosis in the presence and absence of apoptotic  stimuli. Importantly, apoptosis induced by XH was reduced in siRNA-ANXA1 transfected cells where western blot analysis shows a significant reduction of ANXA1 protein levels. To investigate the role of ANXA1 expression on the cell membrane of T98G cells as potential “eat-me” signal we studied phagocytosis of apoptotic cells by human macrophages. We incubated apoptotic T98G cells with human blood monocyte derived macrophages (M=). After co-incubation period we analysed the percentage of M= phagocytosing the apoptotic cells by cytofluorimetric FACS analysis and by confocal microscopy. Our results show that  XH induces phagocytosis of apoptotic T98G cells by human M= in a concentration-effect manner, a processes that is dependent on caspase mediated apoptosis. ANXA1 acts as an “eat-me” signal on the cell membrane of T98G cells, and interestingly, apoptotic siRNA-ANXA1 transfected cells are not completely ingested by M=. These results were confirmed by incubating apoptotic cells with a neutralizing anti-ANXA1 antiboby and ANXA1 membrane depletion by EDTA washing. ANXA1 was also detected in supernatants of apoptotic cells and the incubation of  enriched supernatants enhanced the percentage of phagocytosis by M=. These results demonstrated that ANXA1 is involved both in the apoptosis and phagocytosis of glioblastoma cells. This study shows a possible role of ANXA1 in  maintenance of brain homeostasis and may lead to novel therapeutic approaches for neuro-inflammatory diseases and chemotherapy targets in the treatment of glioblastoma multiforme.

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[682]

TÍTULO / TITLE:  - Suppression of chloride channel 3 expression facilitates sensitivity of human glioma u251 cells to Cisplatin through concomitant inhibition of akt and autophagy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Anat Rec (Hoboken). 2013 Apr;296(4):595-603. doi: 10.1002/ar.22665. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ar.22665

AUTORES / AUTHORS:  - Su J; Xu Y; Zhou L; Yu HM; Kang JS; Liu N; Quan CS; Sun LK

INSTITUCIÓN / INSTITUTION:  - Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China.

RESUMEN / SUMMARY:  - Cisplatin resistance is a difficult problem in clinical chemotherapy, and the mechanisms involved in cisplatin resistance require further study. In this study, we investigated the role of chloride channel-3 (ClC-3) in cisplatin resistance. Autophagy was demonstrated by accumulation of LC3-II, beclin 1 and Atg12-Atg5. The ultrastructure changes were observed under electron microscope. Chemical staining with acridine orange or MDC was used to detect acidic vesicular organelles. Quantification of apoptosis was detected by PI and Annexin V staining. The mechanisms involved in the Akt pathway and autophagy were studied by western blot analysis. Our results showed that Akt phosphorylation and autophagy were induced by cisplatin in human glioma U251 cells. Specific inhibition of ClC-3 by ClC-3 siRNA sensitized the apoptosis-resistant U251 cells  to cisplatin-mediated cell death and downregulated phosphorylated Akt. Interestingly, ClC-3 suppression also inhibited induction of autophagy by cisplatin although the Akt/mTOR pathway was deregulated. Counteracting the autophagic process by 3-methylademine enhanced cytotoxicity of cisplatin, revealing that autophagy plays a key role in chemoresistance. Suppressing the Akt/mTOR pathway by the NADPH oxidase inhibitor diphenyl iodonium (DPI) indicated that cisplatin-induced activation of Akt/mTOR pathway requires generation of reactive oxygen species (ROS) through NADPH oxidase. Collectively, our results suggest that ClC-3 suppression causes the inhibition of Akt and autophagy, which  can enhance the therapeutic benefit of cisplatin in U251 cells. Anat Rec, 296:595-603, 2013. © 2013 Wiley Periodicals, Inc.

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[683]

TÍTULO / TITLE:  - Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(3):458-68. Epub 2013 Feb 15.

AUTORES / AUTHORS:  - del Pliego MG; Aguirre-Benitez E; Paisano-Ceron K; Valdovinos-Ramirez I; Rangel-Morales C; Rodriguez-Mata V; Solano-Agama C; Martin-Tapia D; de la Vega MT; Saldoval-Balanzario M; Camacho J; Mendoza-Garrido ME

INSTITUCIÓN / INSTITUTION:  - Department of Embryology, Autonomous National University of Mexico, Mexico, Mexico.

RESUMEN / SUMMARY:  - Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether a go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order  to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed.  ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

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[684]

TÍTULO / TITLE:  - Overexpression of the Notch3 receptor and its ligand Jagged1 in human clinically  non-functioning pituitary adenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Mar;5(3):845-851. Epub 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1113

AUTORES / AUTHORS:  - Lu R; Gao H; Wang H; Cao L; Bai J; Zhang Y

INSTITUCIÓN / INSTITUTION:  - Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Dongcheng, Beijing 100050, P.R. China ;

RESUMEN / SUMMARY:  - Human clinically non-functioning pituitary adenomas (NFPAs) primarily cause headaches, visual impairment and hypopituitarism due to the effect of the mass of the tumor. Surgery is the first-line treatment for these tumors. To date, no efficacious medical therapy exists for non-functioning adenomas. Previous studies have demonstrated that the Notch3 receptor is involved in the pathogenesis of various types of malignancies, including human NFPAs. The current study focused on the expression of the Notch3 receptor and its ligand Jagged1 in three types of pituitary adenomas and in the normal pituitary gland. Using quantitative real-time RT-PCR assays and western blot analyses, upregulated Notch3 and Jagged1 were observed in human NFPAs, but not in normal human pituitary glands or in hormone-secreting adenomas. Furthermore, Notch3 was positively correlated with Jagged1 at the mRNA and protein levels. These data indicate that Notch3 and Jagged1 may play an important role in the initiation and proliferation of human non-functioning adenomas, and there may be an interaction between Notch3 and Jagged1 in this process. Our study further elucidates the role of the Notch3 signaling pathway in the tumorigenesis of human NFPAs and provides a potential therapeutic target for the medical treatment of these tumors.

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[685]

TÍTULO / TITLE:  - Histopathological classification and location of consecutively operated meningiomas at a single institution in China from 2001 to 2010.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Feb;126(3):488-93.

AUTORES / AUTHORS:  - Wang DJ; Xie Q; Gong Y; Mao Y; Wang Y; Cheng HX; Zhong P; Che XM; Jiang CC; Huang FP; Zheng K; Li SQ; Gu YX; Bao WM; Yang BJ; Wu JS; Xie LQ; Zheng MZ; Tang HL; Zhu HD; Chen XC; Zhou LF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040,  China.

RESUMEN / SUMMARY:  - BACKGROUND: Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010. METHODS: This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized. RESULTS: The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was  significantly older than that of grade II or III meningiomas (P < 0.001, Fisher’s Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03  and 0.76, respectively; P < 0.001, chi(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series. CONCLUSIONS: Female predominance was found for  benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common  subtypes. The cerebral convexity was the most common meningioma location.

 

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[686]

TÍTULO / TITLE:  - Primary intraspinal ganglioneuroblastoma of the thoracic spine: A rare case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Pathol Microbiol. 2012 Oct;55(4):535-7. doi: 10.4103/0377-4929.107805.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0377-4929.107805

AUTORES / AUTHORS:  - Tripathy K; Misra A; Gouda AK; Das S; Das B

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, S.C.B. Medical College, Cuttack, Orissa, India.

RESUMEN / SUMMARY:  - Cerebral ganglioneuroblastoma is an embryonal tumor of the central nervous system, which has been rarely encountered into the spinal cord. The standard treatment for ganglioneuroblastoma is complete surgical excision. A 15-year old boy was presented with cord compression. Magnetic resonance imaging revealed an intradural and intramedullar enhancing lesion over T2 spine. A histomorphological diagnosis was made in the presence of immature small round cells admixed with a good number of ganglion cells. The morphological diagnosis was verified by immunohistochemistry. This is the first reported case of compressive myelopathy in the thoracic region of the spine.

 

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[687]

TÍTULO / TITLE:  - A case of lumbar myxopapillary ependymoma discovered due to headache.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Rinsho Shinkeigaku. 2013;53(2):136-42.

AUTORES / AUTHORS:  - Nozaki I; Matsumoto Y; Yamaguchi K; Shimizu Y; Kumahashi K; Munemoto S

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Ishikawa Prefectural Central Hospital.

RESUMEN / SUMMARY:  - A 23-year-old man was admitted to our hospital with lumbago about two weeks previously, and headache six days previously. Brain MR imaging revealed no remarkable findings except for left ethmoid sinusitis; both MR angiography and venography showed no vascular abnormalities. On the day after admission, lumbar puncture was performed because right homonymous hemianopsia and nuchal stiffness  developed. The cerebrospinal fluid appeared bloody, and the source of bleeding was searched for. MR images of the lumbar spine demonstrated an intradural tumor  with heterogenous contrast enhancement, and this tumor was considered to be the source of the bleeding. Tumor resection was performed, but some parts of the tumor could not be resected because of adhesion to the cauda equina. The pathological findings of the tumor demonstrated myxopapillary ependymoma. Radiation therapy was added to treat the residual tumor because myxopapillary ependymoma tended to recur in spite of the benign nature of the tumor. Spinal myxopapillary ependymoma is rare, but it causes subarachnoid hemorrhage. Subarachnoid hemorrhage from spinal tumor should be suspected when headache accompanied with severe low back pain are present even in the absence of spinal signs.

 

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[688]

TÍTULO / TITLE:  - Non-hodgkin lymphoma after treatment with extended dosing temozolomide and radiotherapy for a glioblastoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol. 2013 Jan;6(1):45-9. doi: 10.1159/000346614. Epub 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000346614

AUTORES / AUTHORS:  - Van Ginderachter L; Cox T; Drijkoningen R; Achten R; Joosens E; Maes A; Theunissen K; Mebis J

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, University of Hasselt, Diepenbeek, Belgium.

RESUMEN / SUMMARY:  - Temozolomide (TMZ) is an alkylating agent, used for the treatment of high-grade gliomas. This case report describes the development of a non-Hodgkin lymphoma in  a patient treated with extended-dose temozolomide and radiotherapy. In addition to the possible mutagenic effect of temozolomide - as described for all alkylating agents - there might have been an immunosuppressive effect of TMZ. The pathological appearance of the lymphoma as well as the presence of a grade 3 lymphopenia early in treatment supports this hypothesis. As the use of TMZ increases, the awareness that TMZ may induce secondary malignancies should increase as well.

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[689]

TÍTULO / TITLE:  - Venous Air Embolism during Elective Craniotomy for Parasagittal Meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Med J Malaysia. 2013 Feb;68(1):69-70.

AUTORES / AUTHORS:  - Mohd Nazaruddin WH; Asmah Z; Saedah A

INSTITUCIÓN / INSTITUTION:  - Universiti Sains Malaysia, School of Medical Sciences, Universiti Sains Malaysia, Anaesthesiology and Intensive Care, Jalan Sultanah Zainab II, Kota Bharu, Kelantan 16150, Malaysia. nazarudin@kb.usm.my.

RESUMEN / SUMMARY:  - We report a case of a 59 year old man who developed venous air embolism (VAE) during an elective craniotomy for parasagittal meningioma resection. The surgery  was done in the supine position with slightly elevated head position. VAE was provisionally diagnosed by sudden decreased in the end tidal carbon dioxide pressure from 34 to 18 mmHg, followed by marked hypotension and atrial fibrillation. Prompt central venous blood aspiration, aggressive resuscitation and inotropic support managed to stabilize the patient. Post operatively, he was  admitted in neuro intensive care unit and made a good recovery without serious complications.

 

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[690]

TÍTULO / TITLE:  - SMART Syndrome: A Reversible Complication after Radiation Therapy and Surgery for Brain Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 31. pii: S1878-8750(13)00200-3. doi: 10.1016/j.wneu.2013.01.101.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.101

AUTORES / AUTHORS:  - Sheehan J

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery, And Radiation Oncology, University of Virginia. Electronic address: jsheehan@virginia.edu.

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[691]

TÍTULO / TITLE:  - Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Apr;11(4):454-63. doi: 10.3171/2012.12.PEDS12336. Epub  2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.PEDS12336

AUTORES / AUTHORS:  - Jinguji S; Yoshimura J; Nishiyama K; Aoki H; Nagasaki K; Natsumeda M; Yoneoka Y; Fukuda M; Fujii Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brain Research Institute, and.

RESUMEN / SUMMARY:  - Object Radiation monotherapy-prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor-is the standard treatment for  intracranial germinomas at the authors’ institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them. Methods The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5-43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors’ institution. Thirty patients had germinomas in localized regions  and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months. Results The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and  the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest  visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma. Conclusions No tumor recurrence occurred in germinoma patients treated with the authors’ radiation monotherapy, which appears to be effective enough to cure the  tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems  to carry the risk of neurocognitive dysfunctions, which are attributable to late  adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient’s age and the extent of the tumor and with particular care to avoid surgical complications.

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[692]

TÍTULO / TITLE:  - Effects of Dual Targeting of Tumor Cells and Stroma in Human Glioblastoma Xenografts with a Tyrosine Kinase Inhibitor against c-MET and VEGFR2.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e58262. doi: 10.1371/journal.pone.0058262. Epub 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058262

AUTORES / AUTHORS:  - Navis AC; Bourgonje A; Wesseling P; Wright A; Hendriks W; Verrijp K; van der Laak JA; Heerschap A; Leenders WP

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

RESUMEN / SUMMARY:  - Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In in vitro cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, concomitant with inhibitory effects  on AKT and ERK1/2 phosphorylation, and cell proliferation and migration. VEGFR2 activation in endothelial cells was also effectively inhibited in vitro. Treatment of BALB/c nu/nu mice carrying orthotopic E98 xenografts resulted in a significant increase in overall survival. Cabozantinib effectively inhibited angiogenesis, resulting in increased hypoxia in angiogenesis-dependent tumor areas, and induced vessel normalization. Yet, tumors ultimately escaped cabozantinib therapy by diffuse infiltrative outgrowth via vessel co-option. Of importance, in contrast to the results from in vitro experiments, in vivo blockade of c-MET activation was incomplete, possibly due to multiple factors including restoration of the blood-brain barrier resulting from cabozantinib-induced VEGFR2 inhibition. In conclusion, cabozantinib is a promising therapy for c-MET positive glioma, but improving delivery of the drug to the tumor and/or the surrounding tissue may be needed for full activity.

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[693]

TÍTULO / TITLE:  - Myelopathy due to calcified meningiomas of the thoracic spine: minimum 3-year follow-up after surgical treatment.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Spine. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.2.SPINE12609

AUTORES / AUTHORS:  - Zhu Q; Qian M; Xiao J; Wu Z; Wang Y; Zhang J

INSTITUCIÓN / INSTITUTION:  - Spinal Tumor Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

RESUMEN / SUMMARY:  - Object Calcified meningiomas are an uncommon type of meningioma. This study details the clinical features, treatment, and follow-up of 11 calcified meningiomas treated from 2002 to 2009, for the purpose of providing general information, describing the skill required for the surgery, and detailing the imaging study of these tumors. Methods Between 2002 and 2009, 11 patients underwent surgery for the treatment of calcified meningiomas. All were treated by the same group of doctors at the same institution, including surgery and rehabilitation after surgery. The minimum 3-year (> 36 months) follow-up data from the 11 patients were detailed. Neurological function was evaluated twice, based on the Frankel scale and Japanese Orthopaedic Association scoring system. The first evaluation occurred before surgery and the second 3 years after surgery. Results In 3 cases, the Frankel score decreased by 1 level. In a comparison of the duration of preoperative symptoms, age, degree of canal stenosis, and intraoperative blood loss, it was found that the greater the degree of canal stenosis, the poorer the outcome of the patient. Calcified meningiomas were more likely to adhere to the nerves and dura, a finding that might explain the high incidence of neurological dysfunction and CSF leakage after surgery. Conclusions Calcified meningiomas are the most rare of all meningiomas. It appears that a greater degree of canal stenosis can lead to a poorer outcome. Computed tomography scans and MRI with contrast enhancement are recommended for intraspinal tumors before surgery to exclude the possibility of calcification. For calcified meningiomas, precise tumor resection, dura repair during surgery, and medical care after surgery are important for achieving an acceptable outcome.

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[694]

TÍTULO / TITLE:  - In Vivo Bioluminescence Imaging Validation of a Human Biopsy-derived Orthotopic Mouse Model of Glioblastoma Multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Imaging. 2013 May 1;12(3):161-72.

AUTORES / AUTHORS:  - Jarzabek MA; Huszthy PC; Skaftnesmo KO; McCormack E; Dicker P; Prehn JH; Bjerkvig R; Byrne AT

RESUMEN / SUMMARY:  - AbstractGlioblastoma multiforme (GBM), the most aggressive brain malignancy, is characterized by extensive cellular proliferation, angiogenesis, and single-cell  infiltration into the brain. We have previously shown that a xenograft model based on serial xenotransplantation of human biopsy spheroids in immunodeficient  rodents maintains the genotype and phenotype of the original patient tumor. The present work further extends this model for optical assessment of tumor engraftment and growth using bioluminescence imaging (BLI). A method for successful lentiviral transduction of the firefly luciferase gene into multicellular spheroids was developed and implemented to generate optically active patient tumor cells. Luciferase-expressing spheroids were injected into the brains of immunodeficient mice. BLI photon counts and tumor volumes from magnetic resonance imaging (MRI) were correlated. Luciferase-expressing tumors recapitulated the histopathologic hallmarks of human GBMs and showed proliferation rates and microvessel density counts similar to those of wild-type  xenografts. Moreover, we detected widespread invasion of luciferase-positive tumor cells in the mouse brains. Herein we describe a novel optically active model of GBM that closely mimics human pathology with respect to invasion, angiogenesis, and proliferation indices. The model may thus be routinely used for the assessment of novel anti-GBM therapeutic approaches implementing well-established and cost-effective optical imaging strategies.

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[695]

TÍTULO / TITLE:  - In Vivo Bioluminescence Imaging Validation of a Human Biopsy-derived Orthotopic Mouse Model of Glioblastoma Multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Imaging. 2013 Mar 1;12(2):1-12.

AUTORES / AUTHORS:  - Jarzabek MA; Huszthy PC; Skaftnesmo KO; McCormack E; Dicker P; Prehn JH; Bjerkvig R; Byrne AT

RESUMEN / SUMMARY:  - AbstractGlioblastoma multiforme (GBM), the most aggressive brain malignancy, is characterized by extensive cellular proliferation, angiogenesis, and single-cell  infiltration into the brain. We have previously shown that a xenograft model based on serial xenotransplantation of human biopsy spheroids in immunodeficient  rodents maintains the genotype and phenotype of the original patient tumor. The present work further extends this model for optical assessment of tumor engraftment and growth using bioluminescence imaging (BLI). A method for successful lentiviral transduction of the firefly luciferase gene into multicellular spheroids was developed and implemented to generate optically active patient tumor cells. Luciferase-expressing spheroids were injected into the brains of immunodeficient mice. BLI photon counts and tumor volumes from magnetic resonance imaging (MRI) were correlated. Luciferase-expressing tumors recapitulated the histopathologic hallmarks of human GBMs and showed proliferation rates and microvessel density counts similar to those of wild-type  xenografts. Moreover, we detected widespread invasion of luciferase-positive tumor cells in the mouse brains. Herein we describe a novel optically active model of GBM that closely mimics human pathology with respect to invasion, angiogenesis, and proliferation indices. The model may thus be routinely used for the assessment of novel anti-GBM therapeutic approaches implementing well-established and cost-effective optical imaging strategies.

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[696]

TÍTULO / TITLE:  - Radiation-induced spinal cord glioblastoma with cerebrospinal fluid dissemination subsequent to treatment of lymphoblastic lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2013;4:27. doi: 10.4103/2152-7806.107905. Epub 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.107905

AUTORES / AUTHORS:  - Kikkawa Y; Suzuki SO; Nakamizo A; Tsuchimochi R; Murakami N; Yoshitake T; Aishima S; Okubo F; Hata N; Amano T; Yoshimoto K; Mizoguchi M; Iwaki T; Sasaki T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Radiation-induced glioma arising in the spinal cord is extremely rare. We report a case of radiation-induced spinal cord glioblastoma with cerebrospinal fluid (CSF) dissemination 10 years after radiotherapy for T-cell lymphoblastic lymphoma. CASE DESCRIPTION: A 32-year-old male with a history of T-cell lymphoblastic lymphoma presented with progressive gait disturbance and sensory disturbance below the T4 dermatome 10 years after mediastinal irradiation. Gadolinium-enhanced magnetic resonance (MR) imaging revealed an intramedullary tumor extending from the C6 to the T6 level, corresponding to the  previous radiation site, and periventricular enhanced lesions. In this case, the  spinal lesion was not directly diagnosed because the patient refused any kind of  spinal surgery to avoid worsening of neurological deficits. However, based on a biopsy of an intracranial disseminated lesion and repeated immmunocytochemical examination of CSF cytology, we diagnosed the spinal tumor as a radiation-induced glioblastoma. The patient was treated with radiotherapy plus concomitant and adjuvant temozolomide. Then, the spinal tumor was markedly reduced in size, and the dissemination disappeared. CONCLUSION: We describe our detailed diagnostic process and emphasize the diagnostic importance of immunocytochemical analysis of CSF cytology.

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[697]

TÍTULO / TITLE:  - Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:28. doi: 10.3389/fonc.2013.00028. Epub 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00028

AUTORES / AUTHORS:  - Friedman GK; Raborn J; Kelly VM; Cassady KA; Markert JM; Gillespie GY

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Research Program, Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham Birmingham, AL, USA.

RESUMEN / SUMMARY:  - While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy  and radiotherapy resistant cells, termed “glioma stem cells” (GSCs), “glioma progenitor cells,” or “glioma-initiating cells,” which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able  to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV.

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[698]

TÍTULO / TITLE:  - Neuro-oncology: New therapeutic targets identified in meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Neurol. 2013 Mar;9(3):121. doi: 10.1038/nrneurol.2013.16. Epub 2013 Feb 12.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2013.16

AUTORES / AUTHORS:  - Bible E

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[699]

TÍTULO / TITLE:  - Embelin Induces Apoptosis in Human Glioma Cells Through Inactivating NF-kappaB.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pharmacol Sci. 2013;121(3):192-9.

AUTORES / AUTHORS:  - Park SY; Lim SL; Jang HJ; Lee JH; Um JY; Kim SH; Ahn KS; Lee SG

INSTITUCIÓN / INSTITUTION:  - Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Korea.

RESUMEN / SUMMARY:  - Aggressive tumor growth and diffuse tissue invasion are hallmarks of malignant glioma. Embelin is an active compound identified as a novel XIAP inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anti-cancer activities. In the present study, we investigated whether embelin could have a therapeutic effect in glioma. We found  that embelin suppressed proliferation of human glioma cells, but not in normal immortalized human astrocytes. In addition, embelin induced apoptosis in human glioma cells by inhibiting NF-kappaB, which is a crucial transcription factor associated with several human diseases including cancer and controls multiple genes involved in tumor progression such as cell proliferation and survival. Intriguingly, embelin had no inhibitory effect on XIAP in glioma cells even though discovered as an XIAP inhibitor, but instead inhibited NF-kappaB activity  by reducing nuclear translocation of p65 through decreasing phosphorylation and proteasomal degradation of IkappaBalpha in glioma cells. Furthermore, p65 overexpression decreased embelin-induced apoptosis in glioma cells. Taken together these results indicate that embelin could be a potent novel therapeutic  modality for glioma via blocking cancer cell proliferation and inducing apoptosis by inhibiting NF-kappaB activity.

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[700]

TÍTULO / TITLE:  - Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Molecules. 2013 Feb 21;18(2):2449-57. doi: 10.3390/molecules18022449.

            ●● Enlace al texto completo (gratuito o de pago) 3390/molecules18022449

AUTORES / AUTHORS:  - Lee DY; Lee MK; Kim GS; Noh HJ; Lee MH

INSTITUCIÓN / INSTITUTION:  - Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Korea.

RESUMEN / SUMMARY:  - Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of  exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of  apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7.

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[701]

TÍTULO / TITLE:  - World Neurosurgery Perspective: Nanotechnology-based Strategies for the Diagnosis and Treatment of Intracranial Neoplasms.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 14. pii: S1878-8750(13)00322-7. doi: 10.1016/j.wneu.2013.02.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.039

AUTORES / AUTHORS:  - Horowitz PM; Chiocca EA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brigham and Women’s Hospital, Boston MA; Dana-Farber  Cancer Institute, Boston MA; Broad Institute of MIT and Harvard, Boston MA; Harvard Medical School.

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[702]

TÍTULO / TITLE:  - Identification of non-canonical NF-kappaB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Mar 28;4:e564. doi: 10.1038/cddis.2013.70.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.70

AUTORES / AUTHORS:  - Tchoghandjian A; Jennewein C; Eckhardt I; Rajalingam K; Fulda S

INSTITUCIÓN / INSTITUTION:  - Institute for Experimental Cancer Research in Pediatrics, Goethe University, Frankfurt, Germany.

RESUMEN / SUMMARY:  - As inhibitor of apoptosis (IAP) proteins can regulate additional signaling pathways beyond apoptosis, we investigated the effect of the second mitochondrial activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non-apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical nuclear factor-kappaB (NF-kappaB) signaling and a tumor necrosis factor-alpha (TNFalpha)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators  of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell lines, BV6 triggers cell elongation, migration and invasion in primary, patient-derived GBM cells at non-toxic concentrations, which do not affect cell viability or proliferation, and also increases infiltrative tumor growth in vivo  underscoring the relevance of these findings. Molecular studies reveal that BV6 causes rapid degradation of cellular IAP proteins, accumulation of NIK, processing of p100 to p52, translocation of p52 into the nucleus, increased NF-kappaB DNA binding and enhanced NF-kappaB transcriptional activity. Electrophoretic mobility shift assay supershift shows that the NF-kappaB DNA-binding subunits consist of p50, p52 and RelB further confirming the activation of the non-canonical NF-kappaB pathway. BV6-stimulated NF-kappaB activation leads to elevated mRNA levels of TNFalpha and additional NF-kappaB target genes involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1, CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9). Importantly, inhibition of NF-kappaB by overexpression of dominant-negative IkappaBalpha superrepressor prevents the BV6-stimulated cell elongation, migration and invasion. Similarly, specific inhibition of non-canonical NF-kappaB signaling by RNA interference-mediated silencing of NIK suppresses the BV6-induced cell elongation, migration and invasion as well as upregulation of NF-kappaB target genes. Intriguingly, pharmacological or genetic  inhibition of the BV6-stimulated TNFalpha autocrine/paracrine loop by the TNFalpha-blocking antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced  cell elongation, migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic concentrations promotes migration and invasion of GBM cells via  non-canonical NF-kappaB signaling, our findings have important implications for the use of Smac mimetics as cancer therapeutics.

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[703]

TÍTULO / TITLE:  - Subtemporal transtentorial petrosalapex approach for giant petroclival meningiomas: analyzation and evaluation of the clinical application.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg B Skull Base. 2012 Feb;73(1):54-63. doi: 10.1055/s-0032-1304557.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1304557

AUTORES / AUTHORS:  - Yang J; Liu YH; Ma SC; Wei L; Lin RS; Qi JF; Hu YS; Yu CJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Fuxing Hospital, Capital University of Medical Sciences, The Third Neurosurgical Department of Capital University of Medical Science, Beijing;

RESUMEN / SUMMARY:  - With the advent of microsurgery and surgical techniques, along with the improvement in neuroimaging techniques and the microanatomy in cadaver study, improvement in terms of surgical morbidity and mortality has been remarkable; however, controversy still exists regarding the optimal surgical strategies for giant petroclival meningiomas (GPMs). We report a study of clinical and radiological features as well as the surgical findings and outcomes for patients  with GPM treated at our institution over the past 6 years. During a 6-year period (April 2004 to March 2010), 16 patients with GPM underwent surgery by subtemporal transtentorial petrosal apex approach during which electrophysiological monitoring of cranial nerves and brainstem function were reviewed. There were nine females and seven males with a mean age of 56.9 years (range from 32 to 78 years). The most frequent clinical manifestations were headache (93.7%) and dizziness (93.7%). Regions and directions of tumor extension include clivus, parasellar, and cavernous sinus, as well as compression of brainstem, and so on.  The trochlear nerve was totally wrapped in nine cases (56.2%). The postoperative  Karnofsky Performance Scale (KPS) score was 76.3 +/- 13.1. Mean maximum diameter  of the tumors on magnetic resonance imaging was 5.23 cm (range, 4.5 to 6.2 cm). Subtemporal transtentorial petrosalapex approach was performed in all 16 cases. Gross total resection was achieved in 14 cases (87.5%) and subtotal resection in  2 cases (12.5%) with no resultant mortality. Follow-up data were available for all 16 patients, with a mean follow-up period of 28.8 months (range from 4 to 69  months), of which 11 (68.75%) lived a normal life (KPS, 80-100). Our suggestion is that GPM could be completely resected by subtemporal transtentorial petrosalapex approach. The surgical strategy of GPM should be focused on survival and postoperative quality of life. Microneurosurgical technique plays a key role  in tumor resection and preservation of nerve function. Intraoperative electrophysiological monitoring also contributes dramatically to the preservation of the nerve function. Complete resection of the tumor should be attempted at the first operation. Any remnant is treated by radiosurgery.

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[704]

TÍTULO / TITLE:  - Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e58995. doi: 10.1371/journal.pone.0058995. Epub 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058995

AUTORES / AUTHORS:  - Wei KC; Chu PC; Wang HY; Huang CY; Chen PY; Tsai HC; Lu YJ; Lee PY; Tseng IC; Feng LY; Hsu PW; Yen TC; Liu HL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Chang-Gung University and Memorial Hospital, Taoyuan, Taiwan.

RESUMEN / SUMMARY:  - The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats  implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving  current brain tumor treatment.

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[705]

TÍTULO / TITLE:  - Genetic variants of AICDA/CASP14 associated with childhood brain tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genet Mol Res. 2013 Jan 30;12(AOP).

            ●● Enlace al texto completo (gratuito o de pago) 4238/2013.January.30.1

AUTORES / AUTHORS:  - Jeon S; Han S; Lee K; Choi J; Park SK; Park AK; Ahn HS; Shin HY; Kang HJ; Koo HH; Seo JJ; Choi JE; Kim H; Ahn Y; Kang D

INSTITUCIÓN / INSTITUTION:  - Graduate School of Convergence Science and Technology, College of Medicine or College of Pharmacy, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - We conducted a hospital-based case-control study in Korea to investigate whether  apoptosis and cell cycle control related genes are associated with childhood brain tumor. Incident brain tumor cases (N = 70) and non-cancer controls (N = 140) frequency-matched by age and gender were selected from three teaching hospitals in Seoul between 2003 and 2006. Tag single nucleotide polymorphism (SNPs) (N = 297) in 30 genes related to apoptosis and cell cycle control were selected using a pairwise linkage-disequilibrium-based algorithm. Five tag SNPs in two genes (AICDA and CASP14) remained significant after adjusted multiple tests. The most significant association with childhood brain tumor risk was for IVS1-401G>C in the AICDA gene [odds ratio (OR) = 2.8; 95% confidence interval (95%CI) = 1.25-6.46], the polymorphism *9276A>C of CASP14 was associated with decreased brain tumor risk (OR = 0.4; 95%CI = 0.19-0.95). We concluded that genetic polymorphisms in AICDA and CASP14 are associated with risk for brain tumor in Korean children.

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[706]

TÍTULO / TITLE:  - In vitro evaluation of the effects of graphene platelets on glioblastoma multiforme cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Nanomedicine. 2013;8:413-20. doi: 10.2147/IJN.S39456. Epub 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S39456

AUTORES / AUTHORS:  - Jaworski S; Sawosz E; Grodzik M; Winnicka A; Prasek M; Wierzbicki M; Chwalibog A

INSTITUCIÓN / INSTITUTION:  - Division of Biotechnology and Biochemistry of Nutrition, Warsaw University of Life Sciences, Warsaw, Poland.

RESUMEN / SUMMARY:  - Graphene is a single atom-thick material with exciting potential. It can be used  in many fields, from electronics to biomedicine. However, little is known about its toxicity and biocompatibility. Herein, we report a study on the toxicity of graphene platelets (GPs) by examining the influence of GPs on the morphology, mortality, viability, membrane integrity, and type of cell death of U87 and U118  glioma cells. It was found that graphene is toxic to glioma cells, but it activated apoptosis only in the U118 cell line, without inducing necrosis, indicating the potential applicability of GP in anticancer therapy.

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[707]

TÍTULO / TITLE:  - Expression of MMP-2 and MMP-9 in Benign Canine Rostrotentorial Meningiomas Is Not Correlated to the Extent of Peritumoral Edema.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Vet Pathol. 2013 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0300985813481610

AUTORES / AUTHORS:  - Beltran E; Matiasek K; Risio LD; Stefani AD; Feliu-Pascual AL; Matiasek LA

INSTITUCIÓN / INSTITUTION:  - Animal Health Trust, Newmarket, UK.

RESUMEN / SUMMARY:  - Matrix metalloproteinases (MMPs) are proteolytic enzymes involved with extracellular matrix degradation. They have been considered to be important for tumor growth and development of peritumoral edema. This retrospective study investigated the expression of MMP subtypes 9 and 2 in canine intracranial meningiomas and their association with peritumoral edema. Twenty-two cases of histologically confirmed grade I meningiomas based on human World Health Organization classification were enrolled. Tumor volume and peritumoral edema were measured by magnetic resonance imaging volumetry. The intratumoral MMP expression was semiquantitatively assessed by immunoreactivity scores and compared with the imaging data. MMP-9 was expressed in all the samples (22/22), whereas proMMP-2 was expressed in 21 of 22 meningiomas, and a/proMMP-2 was expressed in 9 of 22. The immunoreactivity scores were not statistically linked to the severity of peritumoral edema. None of the evaluated MMP expression parameters were statistically linked to the edema index. Although both edema index and MMP-9 expression were highest in meningiomas of the olfactory and frontal region, only the latter mounted up to statistical significance (P = .002) if compared with parafalx and convexity meningiomas of the parietal lobe. In summary, MMP-2 and MMP-9 expression by tumor cells, evaluated through immunohistochemistry, is not predictive of the formation of peritumoral edema in  canine rostrotentorial meningiomas.

 

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[708]

TÍTULO / TITLE:  - A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS Genet. 2013 Feb;9(2):e1003253. doi: 10.1371/journal.pgen.1003253. Epub 2013  Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pgen.1003253

AUTORES / AUTHORS:  - Read RD; Fenton TR; Gomez GG; Wykosky J; Vandenberg SR; Babic I; Iwanami A; Yang H; Cavenee WK; Mischel PS; Furnari FB; Thomas JB

INSTITUCIÓN / INSTITUTION:  - Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.

RESUMEN / SUMMARY:  - Glioblastoma, the most common primary malignant brain tumor, is incurable with current therapies. Genetic and molecular analyses demonstrate that glioblastomas  frequently display mutations that activate receptor tyrosine kinase (RTK) and Pi-3 kinase (PI3K) signaling pathways. In Drosophila melanogaster, activation of  RTK and PI3K pathways in glial progenitor cells creates malignant neoplastic glial tumors that display many features of human glioblastoma. In both human and  Drosophila, activation of the RTK and PI3K pathways stimulates Akt signaling along with other as-yet-unknown changes that drive oncogenesis. We used this Drosophila glioblastoma model to perform a kinome-wide genetic screen for new genes required for RTK- and PI3K-dependent neoplastic transformation. Human orthologs of novel kinases uncovered by these screens were functionally assessed  in mammalian glioblastoma models and human tumors. Our results revealed that the  atypical kinases RIOK1 and RIOK2 are overexpressed in glioblastoma cells in an Akt-dependent manner. Moreover, we found that overexpressed RIOK2 formed a complex with RIOK1, mTor, and mTor-complex-2 components, and that overexpressed RIOK2 upregulated Akt signaling and promoted tumorigenesis in murine astrocytes.  Conversely, reduced expression of RIOK1 or RIOK2 disrupted Akt signaling and caused cell cycle exit, apoptosis, and chemosensitivity in glioblastoma cells by  inducing p53 activity through the RpL11-dependent ribosomal stress checkpoint. These results imply that, in glioblastoma cells, constitutive Akt signaling drives RIO kinase overexpression, which creates a feedforward loop that promotes  and maintains oncogenic Akt activity through stimulation of mTor signaling. Further study of the RIO kinases as well as other kinases identified in our Drosophila screen may reveal new insights into defects underlying glioblastoma and related cancers and may reveal new therapeutic opportunities for these cancers.

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[709]

TÍTULO / TITLE:  - Onset of adreno-leukodystrophy after medulloblastoma therapy: causal connection or coincidence?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JIMD Rep. 2012;2:29-32. doi: 10.1007/8904_2011_39. Epub 2011 Sep 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/8904_2011_39

AUTORES / AUTHORS:  - Deib G; Poretti A; Meoded A; Cohen KJ; Raymond GV; Abromowitch M; Huisman TA

INSTITUCIÓN / INSTITUTION:  - Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

RESUMEN / SUMMARY:  - X-linked adreno-leukodystrophy (ALD) is a peroxisomal disorder affecting the white matter of the central nervous system and the adrenal cortex. It is caused by mutations in the ABCD1 gene encoding for a peroxisomal membrane protein. The absent genotype-phenotype correlation implies a contribution by environmental factors to explain the phenotypical heterogeneity. We report on a 4-year-old boy  with a biochemically confirmed diagnosis of ALD after birth. At the age of 32 months, the additional diagnosis of a medulloblastoma was made. After treatment of the medulloblastoma, he developed active areas of demyelination representing the characteristic neuroimaging features of ALD. The clinical history of our patient supports the hypothesis that external factors, like neurosurgical intervention as part of medulloblastoma treatment, may accelerate or initiate cerebral ALD-related demyelination. A postsurgical inflammatory reaction may facilitate the inclusion of abnormal fatty acids in myelin. The opening of the blood-brain barrier following neurosurgery may enhance the recognition of previously sequestered antigens considered to play a role in ALD onset. Consequently, neurosurgical disruption of the BBB can precipitate the immune-mediated inflammatory process, which progressively destroys myelin in ALD  patients. Tumor-related chemotherapy and/or radiotherapy may also play a contributing role. We suggest that X-ALD patients who undergo neurosurgical intervention need close follow-up imaging to identify active demyelination early.

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[710]

TÍTULO / TITLE:  - Hypoxia enhances stemness of cancer stem cells in glioblastoma: an in vitro study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Med Sci. 2013;10(4):399-407. doi: 10.7150/ijms.5407. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 7150/ijms.5407

AUTORES / AUTHORS:  - Li P; Zhou C; Xu L; Xiao H

INSTITUCIÓN / INSTITUTION:  - 1. Department of Neurosurgery, Research Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.

RESUMEN / SUMMARY:  - Objective: To investigate the relationship between hypoxia and in vitro “stemness” of cancer stem cells (CSCs). Methods: U87 cells, U251 cells and primary glioma cells (n=3) experienced hypoxia. Transmission electron microscopy  was done to detect the ultrastructure of these cancer cells; MTT assay to detect  the cell growth; flow cytometry to detect cell cycle and CD133 expression; Transwell chamber assay was carried out to detect the cell migration; colony-forming assay to detect the colony-forming efficiency; real-time quantitative PCR and Western blot were carried out to detect the mRNA and protein expression of markers of stem cells and their differentiation, respectively. Results: Hypoxia maintained the undifferentiated state of primary glioma cells, slowed down the growth of glioma cells which were in a relatively quiescent stage, increased the colony forming efficiency and migration of glioma cells, and elevated the expression of markers of stem cells, but the expression of markers for stem cell differentiation was reduced after hypoxia treatment. Conclusion: Hypoxia may induce the “dedifferentiation” of differentiated glioma cells which then acquire the stemness.

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[711]

TÍTULO / TITLE:  - MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54932. doi: 10.1371/journal.pone.0054932. Epub 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054932

AUTORES / AUTHORS:  - Hui W; Yuntao L; Lun L; WenSheng L; ChaoFeng L; HaiYong H; Yueyang B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

RESUMEN / SUMMARY:  - Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes  and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase  cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3’-untranslated regions (3’-UTR) of cyclin  D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an  important role to inhibit the proliferation of glioma cells, and present a novel  mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.

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[712]

TÍTULO / TITLE:  - Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Feb 22;13:83. doi: 10.1186/1471-2407-13-83.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-83

AUTORES / AUTHORS:  - Zitron IM; Thakur A; Norkina O; Barger GR; Lum LG; Mittal S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Wayne State University, Karmanos Cancer Institute, Detroit, MI, USA. smittal@med.wayne.edu.

RESUMEN / SUMMARY:  - BACKGROUND: Since most glioblastomas express both wild-type EGFR and EGFRvIII as  well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. METHODS: ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3xanti-HER2/neu (HER2Bi) and/or anti-CD3xanti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. RESULTS: EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50-80% cytotoxicity against four primary glioblastoma  lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133- and  CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi  simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. CONCLUSION: High-grade gliomas are suitable for specific targeting by armed ATC.  These data, together with additional animal studies, may provide the preclinical  support for the use of armed ATC as a valuable addition to current treatment regimens.

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[713]

TÍTULO / TITLE:  - Correlates of physiological and psychological stress among parents of childhood cancer and brain tumor survivors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acad Pediatr. 2013 Mar;13(2):105-12. doi: 10.1016/j.acap.2012.11.005. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.acap.2012.11.005

AUTORES / AUTHORS:  - Pollock EA; Litzelman K; Wisk LE; Witt WP

INSTITUCIÓN / INSTITUTION:  - Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison.

RESUMEN / SUMMARY:  - OBJECTIVE: First, we sought to determine if parents of children with cancer or a  brain tumor had greater stress compared to parents of healthy children and to evaluate the correlates of stress among parents of children with cancer or brain  tumors. Second, we sought to examine the relationship between perceived stress and symptoms of stress and how that relationship may differ for parents of children with cancer. METHODS: In-person, interviewer-assisted surveys were administered to 73 case dyads (children with cancer or a brain tumor and their parents) and 133 comparison dyads (children without health problems and their parents from a community sample). Descriptive analyses and multivariable logistic regressions were performed for case-comparison and case-only analyses to distinguish correlates of parental stress. RESULTS: Parents of children with cancer exhibited higher levels of physiological symptoms of stress than parents of healthy children. Poor sleep quality and greater social stress (negative social interactions) were significant correlates of increased levels of stress in parents of children with cancer (odds ratio 4.23, 95% confidence interval 1.15-15.60; and odds ratio 1.07, 95% confidence interval 1.00-1.14, respectively). A subset of parents reported symptoms of stress but not perceived  stress, and this discordance was more pronounced among cancer caregivers. CONCLUSIONS: Implementation of screening tools that include symptoms of stress may help clinicians to comprehensively identify parents of children with cancer who are in need of additional services. Targeted stress-reduction interventions that address sleep quality and negative social interactions may mitigate the deleterious effects of caregiving, improving the psychosocial well-being of both  parents and children with cancer.

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[714]

TÍTULO / TITLE:  - An MRI technique to evaluate tumor-brain adhesion in meningioma: Brain-surface motion imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 7. pii: S1878-8750(13)00280-5. doi: 10.1016/j.wneu.2013.02.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.015

AUTORES / AUTHORS:  - Yamada S; Taoka T; Nakagawa I; Nishimura F; Motoyama Y; Park YS; Nakase H; Kichikawa K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nara Medical University. Electronic address: syamada@naramed-u.ac.jp.

RESUMEN / SUMMARY:  - OBJECTIVE: We examined the effectiveness of a newly-developed magnetic resonance  imaging (MRI) technique, brain surface motion imaging (BSMI), in the preoperative evaluation of tumor-brain adhesion in meningioma surgery. METHODS: Cine phase-contrast MRI was used to measure cerebrospinal fluid (CSF) pulsations and heart rates at two different time points to create a subtraction image in meningioma patients who underwent BSMI. With no tumor-brain adhesion, a gap was observed in the tumor-brain movements resulting in an outline of the tumor in BSMI. If adhesion was evident, no outline was observed. Patients were evaluated as “exact” if the presence or absence of edema in T2-weighted MR images, BSMI findings, and intraoperative findings all matched, as “effected” when only BSMI findings and intraoperative images matched, and as “false” when BSMI findings and intraoperative findings did not match. RESULTS: BSMI judged 27 patients as “adhesion (+)” and 33 as “adhesion (-)”, while surgical findings evaluated 22 as  “adhesion (+)” and 38 as “adhesion (-)”. The sensitivity and specificity were both high, at 95.5% and 84.2%, respectively. Forty-one of 60 patients were evaluated as “exact,” 12 as “effected”, and seven as “false”. World Health Organization tumor grade assessment of “effected” subjects included 16.7% in grade 1 and 36.4% in grade 2. CONCLUSION: BSMI was shown to be effective in evaluating adhesion between the meningioma and the brain, allowing safe and effective removal planning to be carried out preoperatively.

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[715]

TÍTULO / TITLE:  - Intracranial arachnoid cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neurol India. 2013 Jan-Feb;61(1):1-2. doi: 10.4103/0028-3886.107911.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.107911

AUTORES / AUTHORS:  - Reddy RD

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Apollo Hospital, Jubilee Hills, Hyderabad, India.

 

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[716]

TÍTULO / TITLE:  - The role and clinical significance of DNA damage response and repair pathways in  primary brain tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Biosci. 2013 Feb 6;3(1):10. doi: 10.1186/2045-3701-3-10.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2045-3701-3-10

AUTORES / AUTHORS:  - Santivasi WL; Xia F

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The Ohio State University College of Medicine,  072A Starling Loving Hall, 300 W, 10th Avenue, Columbus, OH 43210, USA. fen.xia@osumc.edu.

RESUMEN / SUMMARY:  - Primary brain tumors, in particular, glioblastoma multiforme (GBM), continue to have dismal survivability despite advances in treating other neoplasms. The goal  of new anti-glioma therapy development is to increase their therapeutic ratios by enhancing tumor control and/or decreasing the severity and incidence of side effects. Because radiotherapy and most chemotherapy agents rely on DNA damage, the cell’s DNA damage repair and response (DRR) pathways may hold the key to new  therapeutic strategies. DNA double-strand breaks (DSBs) generated by ionizing radiation and chemotherapeutic agents are the most lethal form of damage, and are repaired via either homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Understanding and exploitation of the differences in the use of  these repair pathways between tumor and normal brain cells will allow for an increase in tumor cell killing and decreased normal tissue damage. A literature review and discussion on new strategies which can improve the anti-glioma therapeutic ratio by differentially targeting HR and NHEJ function in tumor and normal neuronal tissues is the focus of this article.

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[717]

TÍTULO / TITLE:  - Profiling pathway-specific novel therapeutics in preclinical assessment for central nervous system atypical teratoid rhabdoid tumors (CNS ATRT): Favorable activity of targeting EGFR- ErbB2 signaling with lapatinib.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Oncol. 2013 Jan 11. pii: S1574-7891(13)00012-4. doi: 10.1016/j.molonc.2013.01.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.01.001

AUTORES / AUTHORS:  - Singh A; Lun X; Jayanthan A; Obaid H; Ruan Y; Strother D; Chi SN; Smith A; Forsyth P; Narendran A

INSTITUCIÓN / INSTITUTION:  - Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC), Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada.

RESUMEN / SUMMARY:  - Despite intensifying multimodal treatments, children with central nervous system  atypical teratoid/rhabdoid tumor (CNS ATRT) continue to endure unacceptably high  mortality rates. At present, concerted efforts are focusing on understanding the  characteristic INI1 mutation and its implications for the growth and survival of  these tumors. Additionally, pharmaceutical pipeline libraries constitute a significant source of potential agents that can be taken to clinical trials in a  timely manner. However, this process requires efficient target validation and relevant preclinical studies. As an initial screening approach, a panel of 129 small molecule inhibitors from multiple pharmaceutical pipeline libraries was tested against three ATRT cell lines by in vitro cytotoxicity assays. Based on these data, agents that have strong activity and corresponding susceptible cellular pathways were identified. Target modulation, antibody array analysis, drug combination and in vivo xenograft studies were performed on one of the pathway inhibitors found in this screening. Approximately 20% of agents in the library showed activity with IC(50) values of 1 muM or less and many showed IC(50) values less than 0.05 muM. Intra cell line variability was also noted among some of the drugs. However, it was determined that agents capable of affecting pathways constituting ErbB2, mTOR, proteasomes, Hsp90, Polo like kinases and Aurora kinases were universally effective against the three ATRT cell lines. The first target selected for further analysis, the inhibition of ErbB2-EGFR pathway by the small molecule inhibitor lapatinib, indicated inhibition of cell migration properties and the initiation of apoptosis. Synergy  between lapatinib and IGF-IR inhibition was also demonstrated by combination index (CI) values. Xenograft studies showed effective antitumor activity of lapatinib in vivo. We present an experimental approach to identifying agents and  drug combinations for future clinical trials and provide evidence for the potential of lapatinib as an effective agent in the context of the biology and heterogeneity of its targets in ATRT.

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[718]

TÍTULO / TITLE:  - A Role for the Malignant Brain Tumour (MBT) Domain Protein LIN-61 in DNA Double-Strand Break Repair by Homologous Recombination.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS Genet. 2013 Mar;9(3):e1003339. doi: 10.1371/journal.pgen.1003339. Epub 2013  Mar 7.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pgen.1003339

AUTORES / AUTHORS:  - Johnson NM; Lemmens BB; Tijsterman M

INSTITUCIÓN / INSTITUTION:  - Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.

RESUMEN / SUMMARY:  - Malignant brain tumour (MBT) domain proteins are transcriptional repressors that  function within Polycomb complexes. Some MBT genes are tumour suppressors, but how they prevent tumourigenesis is unknown. The Caenorhabditis elegans MBT protein LIN-61 is a member of the synMuvB chromatin-remodelling proteins that control vulval development. Here we report a new role for LIN-61: it protects the genome by promoting homologous recombination (HR) for the repair of DNA double-strand breaks (DSBs). lin-61 mutants manifest numerous problems associated with defective HR in germ and somatic cells but remain proficient in meiotic recombination. They are hypersensitive to ionizing radiation and interstrand crosslinks but not UV light. Using a novel reporter system that monitors repair of a defined DSB in C. elegans somatic cells, we show that LIN-61 contributes to  HR. The involvement of this MBT protein in HR raises the possibility that MBT-deficient tumours may also have defective DSB repair.

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[719]

TÍTULO / TITLE:  - What is the clinical value of cancer stem cell markers in gliomas?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(3):334-48. Epub 2013 Feb 15.

AUTORES / AUTHORS:  - Dahlrot RH; Hermansen SK; Hansen S; Kristensen BW

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Odense University Hospital Odense, Denmark .

RESUMEN / SUMMARY:  - Recent data indicate that cancer stem cells (CSCs) are responsible for resistance of glioblastomas to radiotherapy and chemotherapy, thereby contributing to the poor survival of these patients. In order to identify novel prognostic markers in gliomas, several CSC markers have been investigated. This review summarizes current reports on putative glioma CSC markers and reviews the prognostic value of the individual immunohistochemical markers reported in the literature. Using the Pubmed database, twenty-seven CSC studies looking at membrane markers (CD133, podoplanin, CD15, and A2B5), filament markers (nestin), RNA-binding proteins (Musashi-1) and transcription factors (BMI1, SOX2, Id1 and Oct-4) qualified for this review. The level of CD133 and nestin increased with increasing malignancy grade, and for both markers a prognostic significance was identified in the majority of the studies. Moreover, the co-expression of CD133 and nestin was shown to have an even more powerful prognostic value than just single markers. Regarding podoplanin and Musashi-1, there was a trend towards a prognostic value  when summarizing all studies. Especially the co-expression of Musashi-1 and MIB1  seemed promising. For the remaining markers CD15, A2B5, BMI1, SOX2, Id1 and Oct4, no prognostic value was found regarding overall survival in this review. In conclusion we find that CD133, nestin, CD133/nestin, podoplanin, Musashi-1 and Musashi-1/MIB1 are the most promising markers for future investigation. Evaluation in larger cohorts with known clinical data and known status of important biomarkers like MGMT and IDH1 is necessary to reveal their full clinical potential.

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[720]

TÍTULO / TITLE:  - Mechanisms of neovascularization and resistance to anti-angiogenic therapies in glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Mol Med (Berl). 2013 Apr;91(4):439-48. doi: 10.1007/s00109-013-1019-z. Epub 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00109-013-1019-z

AUTORES / AUTHORS:  - Soda Y; Myskiw C; Rommel A; Verma IM

INSTITUCIÓN / INSTITUTION:  - Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most malignant brain tumor and highly resistant to intensive combination therapies. GBM is one of the most vascularized tumors and vascular endothelial growth factor (VEGF) produced by tumor cells is a major factor regulating angiogenesis. Successful results of preclinical studies of anti-angiogenic therapies using xenograft mouse models of human GBM cell lines encouraged clinical studies of anti-angiogenic drugs, such as bevacizumab (Avastin), an anti-VEGF antibody. However, these clinical studies have shown that most patients become resistant to anti-VEGF therapy after an initial response. Recent studies have revealed some resistance mechanisms against anti-VEGF therapies involved in several types of cancer. In this review, we address mechanisms of angiogenesis, including unique features in GBMs, and resistance to  anti-VEGF therapies frequently observed in GBM. Enhanced invasiveness is one such resistance mechanism and recent works report the contribution of activated MET signaling induced by inhibition of VEGF signaling. On the other hand, tumor cell-originated neovascularization including tumor-derived endothelial cell-induced angiogenesis and vasculogenic mimicry has been suggested to be involved in the resistance to anti-VEGF therapy. Therefore, these mechanisms should be targeted in addition to anti-angiogenic therapies to achieve better results for patients with GBM.

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[721]

TÍTULO / TITLE:  - Assessing current therapeutic approaches to decode potential resistance mechanisms in glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:59. doi: 10.3389/fonc.2013.00059. Epub 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00059

AUTORES / AUTHORS:  - Sze CI; Su WP; Chiang MF; Lu CY; Chen YA; Chang NS

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy and Cell Biology, College of Medicine, National Cheng Kung  University Tainan, Taiwan.

RESUMEN / SUMMARY:  - Unique astrocytic cell infiltrating growth and glial tumor growth in the confined skull make human glioblastoma (GBM) one of the most difficult cancers to treat in modern medicine. Prognosis for patients is very poor, as they die more or less within 12 months. Patients either die of the cancer itself, or secondary complications such as cerebral edema, herniations, or hemorrhages. GBMs rarely metastasize to other organs. However, GBM recurrence associated with resistance to therapeutic drugs is common. Patients die shortly after relapse. GBM is indeed an outstanding cancer model to search for potential mechanisms for drug resistance. Here, we reviewed the current cancer biology of gliomas and their pathophysiological events that contribute to the development of therapeutic resistance. We have addressed the potential roles of cancer stem cells, epigenetic modifications, and epithelial mesenchymal transition (EMT) in the development of resistance to inhibitor drugs in GBMs. The potential role of TIAF1 (TGF-beta-induced antiapoptotic factor) overexpression and generation of intratumor amyloid fibrils for conferring drug resistance in GBMs is discussed.

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[722]

TÍTULO / TITLE:  - Cervical metastatic glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Coll Physicians Surg Pak. 2013 Feb;23(2):160-1. doi: 02.2013/JCPSP.160161.

AUTORES / AUTHORS:  - Mujtaba SS; Haroon S; Faridi N

INSTITUCIÓN / INSTITUTION:  - Department of Histopathology, Liaquat National Postgraduate Medical Institute, Karachi.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour in adults. In spite of the hostile nature of glioblastoma multiforme (GBM), extracranial spread is not a common event. With improving management choices and survival times, reports of extracranial occurrence of GBM have increased. Most commonly these metastases are to the lungs, lymph nodes, neck, skull, scalp, liver, and bones; may be evident on routine follow-up images of the original lesion. Head and neck metastasis of GBM can be debilitating. We present  a case of cervical metastasis of GBM and discuss possible mechanisms of extraneural spread of this tumour.

 

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[723]

TÍTULO / TITLE:  - Primary intravascular large B-cell lymphoma of pituitary.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Pathol Microbiol. 2012 Oct;55(4):549-51. doi: 10.4103/0377-4929.107811.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0377-4929.107811

AUTORES / AUTHORS:  - Anila KR; Nair RA; Koshy SM; Jacob PM

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India.

RESUMEN / SUMMARY:  - A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence  of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done.  Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL) of pituitary was made. Our patient’s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

 

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[724]

TÍTULO / TITLE:  - Characterisation of Walker 256 breast carcinoma cells from two tumour cell banks  as assessed using two models of secondary brain tumours.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell Int. 2013 Feb 1;13(1):5. doi: 10.1186/1475-2867-13-5.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-5

AUTORES / AUTHORS:  - Lewis KM; Harford-Wright E; Vink R; Ghabriel MN

INSTITUCIÓN / INSTITUTION:  - Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia. mounir.ghabriel@adelaide.edu.au.

RESUMEN / SUMMARY:  - BACKGROUND: Metastatic brain tumours are a common end stage of breast cancer progression, with significant associated morbidity and high mortality. Walker 256 is a rat breast carcinoma cell line syngeneic to Wistar rats and commonly used to induce secondary brain tumours. Previously there has been the assumption that the same cancer cell line from different cell banks behave in a similar manner, although recent studies have suggested that cell lines may change their characteristics over time in vitro. METHODS: In this study internal carotid artery injection and direct cerebral inoculation models of secondary brain tumours were used to determine the tumorigenicity of Walker 256 cells obtained from two cell banks, the American Type Culture Collection (ATCC), and the Cell Resource Centre for Medical Research at Tohoku University (CRCTU). RESULTS: Tumour incidence and volume, plus immunoreactivity to albumin, IBA1 and GFAP, were used as indicators of tumorigenicity and tumour interaction with the host brain microenvironment. CRCTU Walker 256 cells showed greater incidence, larger tumour volume, pronounced blood-brain barrier disruption and prominent glial response when compared to ATCC cell line. CONCLUSIONS: These findings indicate that immortalised cancer cell lines obtained from different cell banks may have diverse characteristics and behaviour in vivo.

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[725]

TÍTULO / TITLE:  - Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced senescence in glioma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Mar 22;13(1):147.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-147

AUTORES / AUTHORS:  - Filippi-Chiela EC; Thome MP; Bueno E Silva MM; Pelegrini AL; Ledur PF; Garicochea B; Zamin LL; Lenz G

RESUMEN / SUMMARY:  - BACKGROUND: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months,  making the development of combined therapies to treat GBM fundamental. One candidate to GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects. METHODS: Glioma  cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics and protein expression and phosphorylation status were measured. We further evaluate senescence induction and clonogenic capacity at long term. RESULTS: As expected,  temozolomide caused a G2 cell cycle arrest and extensive DNA damage response. Rsv did not reduced this response, even increasing pATM, pChk2 and gammaH2Ax levels,  but abrogated the temozolomide-induced G2 arrest, increasing levels of cyclin B and pRb(S807/811) and reducing levels of pWee1(S642) and pCdk1(Y15). This suggests a cellular state of forced passage through G2 checkpoint despite large DNA damage, a scenario that may produce mitotic catastrophe. Indeed, the proportion of cells with high nuclear irregularity increased from 6 to 26% in 48  h after cotreatment. At a long term, a reduction in clonogenic capacity was observed, accompanied by a large induction of senescence. CONCLUSION: The presence of Rsv forces cells treated with TMZ through mitosis leading to mitotic  catastrophe and senescence, fully reducing the clonogenic capacity of glioma cells and increasing the chronic effects of temozolomide.

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[726]

TÍTULO / TITLE:  - Reversing chemoresistance of malignant glioma stem cells using gold nanoparticles.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Nanomedicine. 2013;8:689-702. doi: 10.2147/IJN.S37481. Epub 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S37481

AUTORES / AUTHORS:  - Orza A; Soritau O; Tomuleasa C; Olenic L; Florea A; Pana O; Bratu I; Pall E; Florian S; Casciano D; Biris AS

INSTITUCIÓN / INSTITUTION:  - Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University, Cluj-Napoca, Romania; ; Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, USA;

RESUMEN / SUMMARY:  - The low rate of survival for patients diagnosed with glioblastoma may be attributed to the existence of a subpopulation of cancer stem cells. These stem cells have certain properties that enable them to resist chemotherapeutic agents  and ionizing radiation. Herein, we show that temozolomide-loaded gold nanostructures are efficient in reducing chemoresistance and destroy 82.7% of cancer stem cells compared with a 42% destruction rate using temozolomide alone.  Measurements of in vitro cytotoxicity and apoptosis indicate that combination with gold facilitated the ability of temozolomide, an alkylating drug, to alter the resistance of these cancer stem cells, suggesting a new chemotherapy strategy for patients diagnosed with inoperable recurrent malignant glioma.

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[727]

TÍTULO / TITLE:  - Commentary on Monocyte-Derived Cells of the Brain and Malignant Gliomas: Translational Implications.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Mar 20. pii: S1878-8750(13)00486-5. doi: 10.1016/j.wneu.2013.03.037.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.03.037

AUTORES / AUTHORS:  - Bruce JN; Malone HR

INSTITUCIÓN / INSTITUTION:  - Columbia University, Department of Neurological Surgery, Director, Bartoli Brain  Tumor Research Laboratory, Neurological Institute, 710 West 168th Street, New York, NY 10032. Electronic address: jnb2@columbia.edu.

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[728]

TÍTULO / TITLE:  - Overexpression of CD99 Increases the Migration and Invasiveness of Human Malignant Glioma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Genes Cancer. 2012 Sep;3(9-10):535-49. doi: 10.1177/1947601912473603.

            ●● Enlace al texto completo (gratuito o de pago) 1177_1947601912473603 [pii

            ●● Enlace al texto completo (gratuito o de pago) 1177/1947601912473603

AUTORES / AUTHORS:  - Seol HJ; Chang JH; Yamamoto J; Romagnuolo R; Suh Y; Weeks A; Agnihotri S; Smith CA; Rutka JT

INSTITUCIÓN / INSTITUTION:  - Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada ; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (R.O.K.).

RESUMEN / SUMMARY:  - The malignant glioma is the most common primary human brain tumor, and its migration and invasiveness away from the primary tumor mass are considered a leading cause of tumor recurrence and treatment failure. Recently, gene expression profiling revealed that the transmembrane glycoprotein CD99 is more highly expressed in malignant glioma than in normal brain. Although its function  is not completely understood, CD99 is implicated in cell adhesion and migration in a variety of different cell types. CD99 has wild-type and splice variant isoforms. Previous studies have shown that wild-type CD99 may be an oncosuppressor in some tumors, distinct from the role of the splice variant isoform. In this study, our data reveal that only wild-type CD99 is expressed in  human glioma cells and tissues. Using a tissue microarray, we validated that gliomas demonstrate higher expression of CD99 compared with nonneoplastic brain.  To assess the role of CD99 in glioma migration and invasion, we inhibited CD99 expression by siRNA and demonstrated decreased glioma migration and invasion. In  contrast, when CD99 was overexpressed in glioma cells, we observed enhancement of cell migration and invasiveness. An orthotopic brain tumor model demonstrates that CD99 overexpression significantly increases invasiveness and decreases survival rate. Interestingly, Rac activity was decreased and Rho activity was increased in CD99 overexpressing glioma cells, and the proportion of amoeboid cells to mesenchymal cells was significantly increased. Taken together, our findings suggest that CD99 may play an important role in the migration and invasion of human gliomas independent of Akt, ERK, or JNK signaling pathways. Moreover, CD99 might be involved in amoeboid-mesenchymal transition in glioma migration. CD99 may be an important future target to inhibit migration and invasion, especially in CD99-expressing gliomas.

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[729]

TÍTULO / TITLE:  - The Effects of Progesterone on Glial Cell Line-derived Neurotrophic Factor Secretion from C6 Glioma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Basic Med Sci. 2012 Sep;15(5):1046-52.

AUTORES / AUTHORS:  - Hassanzadeh P; Arbabi E

INSTITUCIÓN / INSTITUTION:  - Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - OBJECTIVES: Progesterone is a steroid hormone whose biology has been greatly studied within the confines of reproductive function. In recent years, the neuroprotective effects of progesterone have attracted growing interest. Glial cell line-derived neurotrophic factor (GDNF), is a neurotrophic factor which plays a crucial role in the development and maintenance of distinct sets of central and peripheral neurons. In the present study, we investigated the potential implication of GDNF in the neuroprotective action of progesterone. MATERIALS AND METHODS: Cultured rat C6 glioma cells were treated with progesterone (100 nm, 1 microM, and 10 microM) or its vehicle. After 24, 36, 48 and 72 hr, GDNF protein levels were measured in the cell-conditioned media and cell lysates using a GDNF ELISA kit. Cell numbers were determined by a cell-counting assay kit. RESULTS: Forty-eight hr treatment with progesterone (10  microM) resulted in a significant elevation of GDNF secretion from C6 glioma cells that remained elevated up to 72 hr. The intracellular content of GDNF and cell numbers were not affected by progesterone treatment. CONCLUSION: Stimulation of GDNF release from glial cells appears as a potential mechanism through which progesterone exerts its neuroprotective effects.

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[730]

TÍTULO / TITLE:  - Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Mar 28;4:e561. doi: 10.1038/cddis.2013.85.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.85

AUTORES / AUTHORS:  - Bury M; Girault A; Megalizzi V; Spiegl-Kreinecker S; Mathieu V; Berger W; Evidente A; Kornienko A; Gailly P; Vandier C; Kiss R

INSTITUCIÓN / INSTITUTION:  - Laboratoire de Toxicologie, Faculte de Pharmacie, Universite Libre de Bruxelles (ULB), Brussels, Belgium.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells  exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely  by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell  death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of  caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer  a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.

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[731]

TÍTULO / TITLE:  - Stress response of glioblastoma cells mediated by miR-17-5p targeting PTEN and the passenger strand miR-17-3p targeting MDM2.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncotarget. 2012 Dec;3(12):1653-68.

AUTORES / AUTHORS:  - Li H; Yang BB

INSTITUCIÓN / INSTITUTION:  - Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto.

RESUMEN / SUMMARY:  - Tumor development not only destroys the homeostasis of local tissues but also the whole body, and thus the tumor cells have to face the body’s defense system, a shortage of nutrition and oxygen, and chemotherapeutic drug treatment. In response to these stresses, tumor cells often alter gene expression and microRNA  levels to facilitate survival. We have demonstrated that glioblastoma cells deprived of nutrition or treated with chemotherapeutics drugs expressed increased levels of miR-17. Ectopic transfection of miR-17 prolonged glioblastoma cell survival when the cells were deprived with nutrition or treated with chemotherapeutic drugs. Expression of miR-17 also promoted cell motility, invasion, and tube-like structure formation. We found that these phenotypes were  the results of miR-17 targeting PTEN. As a consequence, HIF1alpha and VEGF were up-regulated. Ectopic expression of miR-17 was found to facilitate enrichment of  stem-like tumor cells, since the cells became drug-resistant, showed increased capacity to form colonies and neurospheres, and expressed higher levels of CD133, a phenotype similar to ectopic expression of HIF1alpha. To further confirm the phenotypic property of stem cells, we demonstrated that glioblastoma cells transfected with miR-17 proliferated slower in different nutritional conditions by facilitating more cells staying in the G1 phase than the control cells. Finally, we demonstrated that miR-17 could repress MDM2 levels, resulting in decreased cell proliferation and drug-resistance. Our results added a new layer of functional mechanism for the well-studied miRNA miR-17.

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[732]

TÍTULO / TITLE:  - Activation of the NK-kappaB pathway by the STAT3 inhibitor JSI-124 in human glioblastoma cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Cancer Res. 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0528

AUTORES / AUTHORS:  - McFarland BC; Gray GK; Nozell SE; Hong SW; Benveniste EN

INSTITUCIÓN / INSTITUTION:  - Developmental and Integrative Biology, University of Alabama at Birmingham.

RESUMEN / SUMMARY:  - Glioblastoma tumors are characterized by their invasiveness and resistance to therapies. The transcription factor STAT3 was recently identified as a master transcriptional regulator in the mesenchymal subtype of GBM, which has generated  an increased interest in targeting STAT3. We have evaluated more closely the mechanism of action of one particular STAT3 inhibitor, JSI-124 (cucurbitacin I).  In this study, we confirmed that JSI-124 inhibits both constitutive and stimulus-induced JAK2 and STAT3 phosphorylation, and decreases cell proliferation while inducing apoptosis in cultured GBM cells. However, we discovered that prior to the inhibition of STAT3, JSI-124 activates the NF-kappaB pathway, via NF-kappaB p65 phosphorylation and nuclear translocation. In addition, JSI-124 treatment induces the expression of IL-6, IL-8 and SOCS3 mRNA, which leads to a corresponding increase in IL-6, IL-8 and SOCS3 protein expression. Moreover, the  NF-kappaB driven SOCS3 expression acts as a negative regulator of STAT3, abrogating any subsequent STAT3 activation and provides a mechanism of STAT3 inhibition following JSI-124 treatment. Chromatin immunoprecipitation analysis confirms that NF-kappaB p65 in addition to other activating co-factors are found  at the promoters of IL-6, IL-8 and SOCS3, following JSI-124 treatment. Using pharmacological inhibition of NF-kappaB and inducible knockdown of NF-kappaB p65, we found that JSI-124-induced expression of IL-6, IL-8 and SOCS3 was significantly inhibited, demonstrating an NF-kappaB dependent mechanism. Our data indicate that although JSI-124 may demonstrate potential anti-tumor effects through inhibition of STAT3, other off-target pro-inflammatory pathways are activated, emphasizing that more careful and thorough pre-clinical investigations must be implemented to prevent potential harmful effects.

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[733]

TÍTULO / TITLE:  - Inhibition of NF- kappa B by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide and gamma -Radiation Cytotoxicity in Glioblastoma Cells.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chemother Res Pract. 2013;2013:593020. doi: 10.1155/2013/593020. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/593020

AUTORES / AUTHORS:  - Brassesco MS; Roberto GM; Morales AG; Oliveira JC; Delsin LE; Pezuk JA; Valera ET; Carlotti CG Jr; Rego EM; de Oliveira HF; Scrideli CA; Umezawa K; Tone LG

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil ; Laboratorio de Pediatria, Hospital das Clinicas da Faculdade  de Medicina de Ribeirao Preto (USP), Bloco G, Avenida Bandeirantes, 3900 Bairro Monte Alegre, 14048-900 Ribeirao Preto, SP, Brazil.

RESUMEN / SUMMARY:  - Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF- kappa B is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF- kappa B inhibitor with antiproliferative properties in GBM. In the  present study, the ability of DHMEQ to surmount tumor’s invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O(6)-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.

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[734]

TÍTULO / TITLE:  - Optic nerve glioma treatment with fractionated stereotactic radiotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.2.PEDS11435

AUTORES / AUTHORS:  - Uslu N; Karakaya E; Dizman A; Yegen D; Guney Y

INSTITUCIÓN / INSTITUTION:  - Clinic of Radiation Oncology, Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital, Demetevler, Ankara, Turkey.

RESUMEN / SUMMARY:  - In the current report, the authors present a case of optic nerve glioma treated with fractionated stereotactic radiotherapy (FSRT). An 11-year-old girl was referred to our clinic with increasing proptosis over a 1-year period. At that time orbital MRI revealed a 20 x 17-mm mass in the right retroorbital lipomatous  tissue, and FSRT was delivered to the tumor using the CyberKnife. During the 1.5-year follow-up, ophthalmological examinations did not indicate any treatment-related severe toxicity, and posttreatment MRI demonstrated marked regression of the lesion to 13 x 10 mm. Given the scarcity of reports on this subject, the authors support more extended studies of the CyberKnife for the effective treatment of this relatively common childhood tumor.

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[735]

TÍTULO / TITLE:  - Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Feb 28;8(1):42. doi: 10.1186/1748-717X-8-42.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-42

AUTORES / AUTHORS:  - Milanovic D; Firat E; Grosu AL; Niedermann G

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University Hospital Freiburg, Freiburg 79106, Germany. dusan.milanovic@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: Heat shock Protein 90 (Hsp90) is a molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins involved in oncogenic signaling and in the regulation of radiosensitivity. It is  upregulated in response to stress such a heat. Hyperthermia is a potent radiosensitizer, but induction of Hsp90 may potentially limit its efficacy. Our aim was to investigate whether the new Hsp90 inhibitor NVP-HSP990 increases radiosensitivity, thermosensitivity and radiothermosensitivity of human tumor cell lines. MATERIAL AND METHODS: U251 glioblastoma and MIA PaCa-2 pancreatic carcinoma cells were used. To determine clonogenic survival, colony forming assays were performed. Cell viability and proliferation were assesed by Trypan blue staining. Cell cycle and apoptosis analyses were performed by flow cytometry. DAPI staining was used to detect mitotic catastrophe. RESULTS: NVP-HSP990 increased the thermosensitivity, radiosensitivity and radio-thermosensitivity of both cell lines in clonogenic assays. 72 hours after irradiation with 4 Gy, a significant reduction in cell number associated with considerable G2/M acumulation and mitotic catastrophe as well as cell death by apoptosis/necrosis was observed. CONCLUSIONS: Treatment with NVP-HSP990 strongly  sensitized U251 and MIA PaCa-2 cells to hyperthermia and ionizing radiation or combination thereof through augmentation of G2/M arrest, mitotic catastrophe and  associated apoptosis.

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[736]

TÍTULO / TITLE:  - Altered Expression of MGMT in High-Grade Gliomas Results from the Combined Effect of Epigenetic and Genetic Aberrations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e58206. doi: 10.1371/journal.pone.0058206. Epub 2013 Mar 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058206

AUTORES / AUTHORS:  - Ramalho-Carvalho J; Pires M; Lisboa S; Graca I; Rocha P; Barros-Silva JD; Savva-Bordalo J; Mauricio J; Resende M; Teixeira MR; Honavar M; Henrique R; Jeronimo C

INSTITUCIÓN / INSTITUTION:  - Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute-Porto, Porto, Portugal ; Department of Genetics, Portuguese Oncology Institute-Porto, Porto, Portugal.

RESUMEN / SUMMARY:  - MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect  its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were  determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases  polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion)  changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

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[737]

TÍTULO / TITLE:  - Oncolytic virotherapy for malignant glioma: translating laboratory insights into  clinical practice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:32. doi: 10.3389/fonc.2013.00032. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00032

AUTORES / AUTHORS:  - Auffinger B; Ahmed AU; Lesniak MS

INSTITUCIÓN / INSTITUTION:  - The Brain Tumor Center, The University of Chicago Chicago, IL, USA.

RESUMEN / SUMMARY:  - Glioblastoma multiforme, one of the most common and aggressive brain tumors in adults, is highly resistant to currently available therapies and often recurs. Due to its poor prognosis and difficult management, there is an urgent need for the development and translation of new anti-glioma therapeutic approaches into the clinic. In this context, oncolytic virotherapy arises as an exciting treatment option for glioma patients. These natural or genetically engineered viruses are able to effectively infect cancer cells, inducing a specific anti-tumor cytotoxic effect. In addition, some viruses have been redesigned to modulate glioma microenvironment, to express cytokines to boost a systemic anti-glioma immune response and to incorporate angiostatic genes to decrease glioma vasculature. Although recent clinical trials have confirmed the safety of  oncolytic virotherapies in the brain, their moderate clinical efficacy has not yet matched the encouraging preclinical laboratory results. In this review, we will discuss the leading anti-glioma virotherapy approaches that are presently under preclinical and clinical evaluation. We will also review different delivery methods, in vivo virus behavior, fate, replication, intratumoral spread, activation of anti-tumor immune response, and targeting of glioma stem cells. We  will focus on the advantages and limitations of each therapeutic approach and how to overcome these hurdles to effectively translate exciting laboratory results into promising clinical trials.

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[738]

TÍTULO / TITLE:  - Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onco Targets Ther. 2013;6:189-98. doi: 10.2147/OTT.S40992. Epub 2013 Mar 14.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S40992

AUTORES / AUTHORS:  - Duan Y; Zhao X; Ren W; Wang X; Yu KF; Li D; Zhang X; Zhang Q

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China.

RESUMEN / SUMMARY:  - Dichloroacetate (DCA), a small molecule mitochondria-targeting agent, can penetrate the blood-brain barrier, showing potential therapeutic effects on brain tumors. Considering the effects of DCA on tumor cellular metabolism, penetrating  across the blood-brain barrier, as well as having potential antitumor activity on brain tumors, the purpose of this study is to investigate the antitumor activity  of DCA on C6 glioma cells in vitro and in vivo. DCA inhibited C6 glioma cell proliferation, induced C6 cell apoptosis, and arrested C6 cells in S phase. DCA can inhibit the expression of heat shock proteins 70 (Hsp70) in a dose-dependent  and time-dependent manner (P < 0.01). Our in vivo antitumor effect results indicated that DCA markedly inhibited the growth of C6 glioma tumors in both C6 brain tumor-bearing rats and C6 tumor-bearing nude mice (P < 0.01). DCA significantly induced the ROS production and decreased the mitochondrial membrane potential in tumor tissues. Our in vivo antitumor effect results also indicated that DCA has potential antiangiogenic effects. In conclusion, DCA may be a viable therapeutic agent in the treatment of gliomas.

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[739]

TÍTULO / TITLE:  - Two case series reports: 8 cases of arachnoid Temporoparietal cysts (middle fossa & sylvian fissure) and 2 cases of chronic subdural hematoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Inj Violence Res. 2012 Nov;4(3 Suppl 1). pii: Paper No. 15.

AUTORES / AUTHORS:  - Meshkini A; Meshkini M

INSTITUCIÓN / INSTITUTION:  - Department of Medical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Arachnoid cysts are common intracranial space-occupying lesions which are often found in middle fossa and temporal regions of the skull. Many of these  lesions are asymptomatic but some might appear as space-occupying lesions. Almost arachnoid cyst rupture, either following a trauma or spontaneously can result in  intracystic hemorrhage, subdural hematoma and hygroma. The present study presents two case series including 8 cases of arachnoid cysts in temporal region and 2 cases of subdural hemorrhage. METHODS: Demographic data and clinical and neuroimaging features of 8 patients were evaluated. RESULTS: A total of 8 patients with arachnoid cysts in temporal region were assessed: age range 3 to 27 years old, 5 male and 3 female. The most important complains of the patients during their visit were seizure (3 cases), headache (4 cases), increased head circumference (1 case), parietotemporal arachnoid cyst in right (4 cases) and left hemisphere (4 cases). The conservative treatment and follow-up were performed in 6 out of 8 patients. In the other 2 patients, for craniotomy surgery with hematoma evacuation was performed. Furthermore, in the surgery the fenestration of arachnoid cyst wall into the basal cisterns as well as low pressure cysto-peritoneal shunt was performed. CONCLUSIONS: The risk of annual hemorrhage for patients with arachnoid cyst is very low. However, when the hemorrhage occurs it is treated by hematoma evacuation in most cases, but sometimes there is a need for fenestration of the cyst into basal cisterns under  endoscopy, microsurgical or cystoperitoneal shunt. KEYWORDS: Arachnoid cyst, Middle fossa, Chronic subdural hematoma.

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[740]

TÍTULO / TITLE:  - Regulation of cell proliferation and migration in glioblastoma: new therapeutic approach.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:53. doi: 10.3389/fonc.2013.00053. Epub 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00053

AUTORES / AUTHORS:  - Kim Y

INSTITUCIÓN / INSTITUTION:  - Department of Mathematics, Konkuk University Seoul, South Korea.

RESUMEN / SUMMARY:  - Glioblastoma is the most aggressive brain cancer with the poor survival rate. A microRNA, miR-451, and its downstream molecules, CAB39/LKB1/STRAD/AMPK, are known to play a critical role in regulating a biochemical balance between rapid proliferation and invasion in the presence of metabolic stress in microenvironment. We develop a novel multi-scale mathematical model where cell migration and proliferation are controlled through a core intracellular control system (miR-451-AMPK complex) in response to glucose availability and physical constraints in the microenvironment. Tumor cells are modeled individually and proliferation and migration of those cells are regulated by the intracellular dynamics and reaction-diffusion equations of concentrations of glucose, chemoattractant, extracellular matrix, and MMPs. The model predicts that invasion patterns and rapid growth of tumor cells after conventional surgery depend on biophysical properties of cells, dynamics of the core control system, and microenvironment as well as glucose injection methods. We developed a new type of therapeutic approach: effective injection of chemoattractant to bring invasive cells back to the surgical site after initial surgery, followed by glucose injection at the same location. The model suggests that a good combination of chemoattractant and glucose injection at appropriate time frames may lead to an effective therapeutic strategy of eradicating tumor cells.

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[741]

TÍTULO / TITLE:  - Successful management of unsuspected retroperitoneal paraganglioma via the use of combined epidural and general anesthesia: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Case Rep. 2013 Feb 28;7(1):58. doi: 10.1186/1752-1947-7-58.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-7-58

AUTORES / AUTHORS:  - Tomulic K; Saric JP; Kocman B; Skrtic A; Filipcic NV; Acan I

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology and Intensive Care, University Hospital Merkur, Zajceva 19, Zagreb, Croatia. ktomulic@gmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: Similar to pheochromocytomas, paragangliomas can secrete catecholamines, although they are usually non-functional and clinical presentation is non-specific. We present a case of accidental, intra-operatively  diagnosed neuroendocrine-active sympathetic paraganglioma, which was suspected and confirmed during elective retroperitoneal tumor removal. CASE PRESENTATION: A 25-year-old Caucasian Croatian man, American Society of Anesthesiologists status  1, underwent elective surgery for retroperitoneal tumor removal. The tumor had been discovered by chance during a routine examination and was suspected to be a  sarcoma. Our patient had no history of previous medical conditions nor did he have symptoms characteristic of a neuroendocrine secreting tumor. The results of  ultrasound and magnetic resonance imaging studies showed a large, well demarcated retroperitoneal tumor mass in his upper abdomen localized between the aorta and vena cava, measuring approximately 9x6x4.5cm. In the operating room an epidural catheter was inserted at the T7 to T8 level prior to induction of general anesthesia. Epidural analgesia was maintained by an infusion pump with local anesthetic and opiate mixture. During the surgical excision of the tumor, hemodynamic changes occurred, with hypertension (205/110mmHg) and tachycardia (up to 120 beats/minute). In spite of the fact that the surgical field of work did not include adrenal glands whose direct manipulation could explain this occurrence, there was a high degree of suspicion for the presence of a neurosecreting tumor. His clinical symptoms were relieved after administration of urapidil, esmolol and magnesium sulfate. After tumor excision, our patient developed severe hypotension. Hemodynamic stability was reinstated with aggressive volume replacement, with crystalloids and colloids, vasopressors and hydrocortisone. His post-operative course was unremarkable and on the eighth post-operative day our patient was discharged from hospital, with no consequences or symptoms on follow-up two years after surgery. CONCLUSIONS: Our patient’s case emphasizes the need to consider the presence of extra-adrenal paragangliomas in the differential diagnosis of retroperitoneal tumors, despite their rare occurrence. In our patient’s case, invasive hemodynamic monitoring during combined general anesthesia and epidural analgesia and early recognition of catechol-induced symptoms raised suspicion of the existence of a paraganglioma, and this led to an adequate therapeutic approach and favorable outcome of the surgery. Pre-operative recognition of paragangliomas could lead to better pre-operative preparation, but even high clinical suspicion in undiagnosed forms  during surgery and the availability of rapid and short-acting vasodilatators, alpha-blockers and beta-blockers might favor good outcome.

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[742]

TÍTULO / TITLE:  - Endoscopic Approach for the Treatment of Pineal Region Tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330958

AUTORES / AUTHORS:  - Herrada-Pineda T; Revilla-Pacheco F; Manrique-Guzman S

INSTITUCIÓN / INSTITUTION:  - Departmet of Pediatric Neurological Surgery, ABC Medical Center, Mexico City, Mexico.

RESUMEN / SUMMARY:  - Tumors of the pineal region account for 3 to 8% of the tumors involving the central nervous system. The most common are germ cell tumors (39%). Less common examples include teratomas, primitive neuroectodermic tumors, astrocytomas, and choriocarcinomas. Clinical presentation in pediatric patients is in direct relation to the anatomical structures surrounding the pineal region and to the associated hydrocephalus that is present in almost 90% of cases. The diagnosis of a tumor in the pineal region is based on radiological findings and the presence of tumor markers such as alpha-fetoprotein and human chorionic gonadotrophic hormone subfraction beta. Neuroendoscopy is considered to be one of the minimally invasive techniques useful for the management of such patients. This minimally invasive approach to pineal region tumors allows the treatment of hydrocephalus in a safe and effective way, avoiding the complications derived from other procedures such as external ventricular drainage or shunt surgery.

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[743]

TÍTULO / TITLE:  - Surgery of highly eloquent gliomas primarily assessed as non-resectable: risks and benefits in a cohort study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Feb 2;13:51. doi: 10.1186/1471-2407-13-51.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-51

AUTORES / AUTHORS:  - Krieg SM; Schnurbus L; Shiban E; Droese D; Obermueller T; Buchmann N; Gempt J; Meyer B; Ringel F

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str, 22, 81675, Munich, Germany. Sandro.Krieg@lrz.tum.de.

RESUMEN / SUMMARY:  - BACKGROUND: Today, the treatment of choice for high- and low-grade gliomas requires primarily surgical resection to achieve the best survival and quality of life. Nevertheless, many gliomas within highly eloquent cortical regions, e.g., insula, rolandic, and left perisylvian cortex, still do not undergo surgery because of the impending risk of surgery-related deficits at some centers. However, pre and intraoperative brain mapping, intraoperative neuromonitoring (IOM), and awake surgery increase safety, which allows resection of most of these tumors with a considerably low rate of postoperatively new deficits. METHODS: Between 2006 and 2012, we resected 47 out of 51 supratentorial gliomas (92%), which were primarily evaluated to be non-resectable during previous presentation  at another neurosurgical department. Out of these, 25 were glioblastomas WHO grade IV (53%), 14 were anaplastic astrocytomas WHO grade III (30%), 7 were diffuse astrocytomas WHO grade II (15%), and one was a pilocytic astrocytoma WHO  grade I (2%). All data, including pre and intraoperative brain mapping and monitoring (IOM) by motor evoked potentials (MEPs) were reviewed and related to the postoperative outcome. RESULTS: Awake surgery was performed in 8 cases (17%). IOM was required in 38 cases (81%) and was stable in 18 cases (47%), whereas MEPs changed the surgical strategy in 10 cases (26%). Thereby, gross total resection was achieved in 35 cases (74%). Postoperatively, 17 of 47 patients (36%) had a new motor or language deficit, which remained permanent in 8.5% (4 patients). Progression-free follow-up was 11.3 months (range: 2 weeks - 64.5 months) and median survival was 14.8 months (range: 4 weeks - 20.5 months). Median Karnofsky  Performance Scale was 85 before and 80 after surgery). CONCLUSIONS: In specialized centers, most highly eloquent gliomas are eligible for surgical resection with an acceptable rate of surgery-related deficits; therefore, they should be referred to specialized centers.

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[744]

TÍTULO / TITLE:  - Long-Term Results of stereotactic Brachytherapy (Temporary 125Iodine Seeds) for the Treatment of Low-Grade Astrocytoma (Grade II).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran Red Crescent Med J. 2013 Jan;15(1):49-57. doi: 10.5812/ircmj.4322. Epub 2013 Jan 5.

            ●● Enlace al texto completo (gratuito o de pago) 5812/ircmj.4322

AUTORES / AUTHORS:  - Shahzadi S; Azimi P; Parsa K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shahid-Beheshti University of Medical Science, Tehran, IR Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Treatment of low-grade astrocytoma (WHO grade II) (LGA II) remains a  challenge. There is limited information regarding the long-term effects of stereotactic brachytherapy (SBT) (temporary (125)Iodine seeds) on patients with LGA II. OBJECTIVES: The purpose of this study was to evaluate disease control and survival after stereotactic brachytherapy in patients with circumscribed and relatively small size tumors. MATERIALS AND METHODS: A retrospective review of 29 patients, treated between 1991 and 2011, was conducted to evaluate survival, complications, and local disease control after stereotactic brachytherapy. They belonged to a larger group of 48 cases with low-grade gliomas, treated with stereotactic brachytherapy. The demographic and clinical characteristics in patients including age, sex, and survival time were extracted from records. RESULTS: Thirteen patients were male and 16 were female, with the median age of 29 years (range, 2.5 - 64 years). The median follow-up was 95 (range, 6 - 240) months. Based on Pignatti classification, 10 patients were at low- and 19 patients at high-risk. The median overall as well as progression-free survivals for patients were 135 months (95% confidence interval: 76 - 194) and 96 months (95% confidence interval: 1 - 199), respectively. Five- and 10-year progression-free survivals were 41.4 % and 34.5 %, respectively, and the 5- and 10-year overall survivals were 65.5 % and 44.8%, respectively. Progression-free survival was not significantly higher in smaller size tumors (P = 0.224), nor for spherical versus non-spherical tumors (P = 0.307). There was no treatment-related morbidity after stereotactic brachytherapy, and no radiogenic complications occurred during the follow-up period. Mortality due to tumor progression occurred in 4 patients (14%), and 11 patients were alive at the last follow-up. CONCLUSIONS: The stereotactic brachytherapy for patients with circumscribed and relatively small size tumors appears to be a safe, feasible, and minimally-invasive treatment.

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[745]

TÍTULO / TITLE:  - Clinicopathological study of pineal parenchymal tumors of intermediate differentiation (PPTID).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 5. pii: S1878-8750(13)00272-6. doi: 10.1016/j.wneu.2013.02.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.007

AUTORES / AUTHORS:  - Ito T; Kanno H; Sato KI; Oikawa M; Ozaki Y; Nakamura H; Terasaka S; Kobayashi H; Houkin K; Hatanaka K; Murata JI; Tanaka S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brain Tumor Center, Nakamura Memorial Hospital. Electronic address: titoh@med.nmh.or.jp.

RESUMEN / SUMMARY:  - OBJECT: Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities and only limited data are available regarding their pathologic features and biologic behaviors. Because grading criteria of pineal parenchymal tumors (PPTs) has yet to be established, the treatment strategy and prognosis of PPTIDs remain controversial. We describe the clinicopathological study of six patients with PPTID and compare responses for the treatment and prognosis with cases of pineocytoma (PC) and pineoblastoma (PB). From this analysis, we attempt to clarify the treatment strategy for PPTIDs. METHODS: This  study included 15 patients with PPTs, consisting of 6 PCs, 6 PPTIDs, and 3 PBs. We focused on the six patients with PPTIDs. All PPTID cases were treated surgically and radiotherapy and chemotherapy were administered as adjuvant therapies in some cases. For histopathological study, we have already reported.(8) Briefly, we examined mitotic figures and necrosis by H&E staining and immunohistochemical markers such as neuronal markers (synaptophysin (SY), neurofilament (NF), and NeuN) and a MIB-1 labeling index (LI) was determined. RESULTS: In the PPTID cases, the extent of resection was variable and the recurrence rates among patients varied according to stage and treatment. All PC patients underwent total resection with no recurrence. All PB patients underwent  resection and adjuvant therapy with radiotherapy and chemotherapy. There were no  recurrences in patients with PC or PB. The results of histopathological findings  have been already reported.(8) Briefly, the results indicated no mitotic figure or necrosis in any of the six cases of PPTID, but those features were observed in PB cases. All cases even including PC and PB were immunopositive for neuronal markers. The MIB-1 LI of PPTID was 3.5%, whereas that was 0% in PC and 10.5% in PB. CONCLUSIONS: Good radiosensitivity of PPTIDs was observed in our series. Because there are cases with discrepancies between images and pathological findings, it is very difficult to determine the proper treatment strategy for PPTIDs. Proliferative potential was correlated with WHO grade, although the immunoreactivity of neuronal markers did not correlate with the histological grade.

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[746]

TÍTULO / TITLE:  - Thermally targeted delivery of a c-Myc inhibitory polypeptide inhibits tumor progression and extends survival in a rat glioma model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55104. doi: 10.1371/journal.pone.0055104. Epub 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055104

AUTORES / AUTHORS:  - Bidwell GL 3rd; Perkins E; Hughes J; Khan M; James JR; Raucher D

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.

RESUMEN / SUMMARY:  - Treatment of glioblastoma is complicated by the tumors’ high resistance to chemotherapy, poor penetration of drugs across the blood brain barrier, and damaging effects of chemotherapy and radiation to normal neural tissue. To overcome these limitations, a thermally responsive polypeptide was developed for  targeted delivery of therapeutic peptides to brain tumors using focused hyperthermia. The peptide carrier is based on elastin-like polypeptide (ELP), which is a thermally responsive biopolymer that forms aggregates above a characteristic transition temperature. ELP was modified with cell penetrating peptides (CPPs) to enhance delivery to brain tumors and mediate uptake across the tumor cells’ plasma membranes and with a peptide inhibitor of c-Myc (H1). In rats with intracerebral gliomas, brain tumor targeting of ELP following systemic administration was enhanced up to 5-fold by the use of CPPs. When the lead CPP-ELP-fused c-Myc inhibitor was combined with focused hyperthermia of the tumors, an additional 3 fold increase in tumor polypeptide levels was observed, and 80% reduction in tumor volume, delayed onset of tumor-associated neurological deficits, and at least doubled median survival time including complete regression in 80% of animals was achieved. This work demonstrates that a c-Myc inhibitory peptide can be effectively delivered to brain tumors.

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[747]

TÍTULO / TITLE:  - Mysterious meningioma: Surviving the odds.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2013;4:29. doi: 10.4103/2152-7806.107907. Epub 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.107907

AUTORES / AUTHORS:  - Bramhaprasad V; Rajesh A; Kumar A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India.

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[748]

TÍTULO / TITLE:  - Pyruvate kinase m2 expression, but not pyruvate kinase activity, is up-regulated  in a grade-specific manner in human glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e57610. doi: 10.1371/journal.pone.0057610. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057610

AUTORES / AUTHORS:  - Mukherjee J; Phillips JJ; Zheng S; Wiencke J; Ronen SM; Pieper RO

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America ; The Brain Tumor Research Center, University of California San Francisco, San Francisco, California, United States of America.

RESUMEN / SUMMARY:  - Normal tissues express the M1 isoform of pyruvate kinase (PK) that helps generate and funnel pyruvate into the mitochondria for ATP production. Tumors, in contrast, express the less active PKM2 isoform, which limits pyruvate production  and spares glycolytic intermediates for the generation of macromolecules needed for proliferation. Although high PKM2 expression and low PK activity are considered defining features of tumors, very little is known about how PKM expression and PK activity change along the continuum from low grade to high grade tumors, and how these changes relate to tumor growth. To address this issue, we measured PKM isoform expression and PK activity in normal brain, neural progenitor cells, and in a series of over 100 astrocytomas ranging from benign grade I pilocytic astrocytomas to highly aggressive grade IV glioblastoma multiforme (GBM). All glioma exhibited comparably reduced levels of PKM1 expression and PK activity relative to normal brain. In contrast, while grade I-III gliomas all had modestly increased levels of PKM2 RNA and protein expression relative to normal brain, GBM, regardless of whether they arose de novo or progressed from lower grade tumors, showed a 3-5 fold further increase in PKM2 RNA and protein expression. Low levels of PKM1 expression and PK activity were important for cell growth as PKM1 over-expression and the accompanying increases in PK activity slowed the growth of GBM cells. The increased expression of PKM2, however, was also important, because shRNA-mediated PKM2 knockdown decreased total PKM2 and the already low levels of PK activity, but paradoxically also limited cell growth in vitro and in vivo. These results show that pyruvate kinase M expression, but not pyruvate kinase activity, is regulated in a grade-specific manner in glioma, but that changes in both PK activity and PKM2 expression contribute to growth of GBM.

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[749]

TÍTULO / TITLE:  - Clinical implications of microRNAs in human glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:19. doi: 10.3389/fonc.2013.00019. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00019

AUTORES / AUTHORS:  - Mizoguchi M; Guan Y; Yoshimoto K; Hata N; Amano T; Nakamizo A; Sasaki T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve  the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA), appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ) resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC) properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Here in, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.

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[750]

TÍTULO / TITLE:  - Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e56077. doi: 10.1371/journal.pone.0056077. Epub 2013 Feb 13.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056077

AUTORES / AUTHORS:  - Niesen CE; Xu J; Fan X; Li X; Wheeler CJ; Mamelak AN; Wang C

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

RESUMEN / SUMMARY:  - The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play  a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis. To identify the genes possibly involved in tumor-induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from formalin-fixed paraffin embedded (FFPE) peritumoral cortex tissue slides from 5-seizure vs. 5-non-seizure low grade brain tumor patients. We identified many differentially expressed genes (DEGs). Seven dysregulated genes (i.e., C1QB, CALCRL, CCR1, KAL1, SLC1A2, SSTR1 and TYRO3) were validated by qRT-PCR, which showed a high concordance. Principal Component Analysis (PCA) showed that epilepsy subjects were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy subjects. Molecular functional categorization showed that significant portions of the DEGs functioned as receptor activity, molecular binding including enzyme binding and transcription factor binding. Pathway analysis showed these DEGs were mainly enriched in focal  adhesion, ECM-receptor interaction, and cell adhesion molecules pathways. In conclusion, our study showed that dysregulation of gene expression in the peritumoral tissues may be one of the major mechanisms of brain tumor induced-epilepsy. However, due to the small sample size of the present study, further validation study is needed. A deeper characterization on the dysregulated genes involved in brain tumor-induced epilepsy may shed some light on the management of epilepsy due to brain tumors.

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[751]

TÍTULO / TITLE:  - Sleep characteristics of family caregivers of individuals with a primary malignant brain tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Nurs Forum. 2013 Mar 1;40(2):171-9. doi: 10.1188/13.ONF.171-179.

            ●● Enlace al texto completo (gratuito o de pago) 1188/13.ONF.171-179

AUTORES / AUTHORS:  - Pawl JD; Lee SY; Clark PC; Sherwood PR

INSTITUCIÓN / INSTITUTION:  - School of Nursing, Georgia Regents University in Augusta.

RESUMEN / SUMMARY:  - Purpose/Objectives: To describe the sleep characteristics of family caregivers of individuals with a primary malignant brain tumor (PMBT).Design: Cross-sectional,  correlational design using baseline data from a longitudinal study.Setting: Neuro-oncology and neurosurgery clinics at an urban tertiary medical center in the United States.Sample: 133 family caregivers recruited one to two months following diagnosis of family member’s PMBT.Methods: Subjective and objective measures of sleep were obtained via self-report and the use of accelerometers (three nights).Main Research Variables: Sleep characteristics including sleep latency, total sleep time, wake after sleep onset, number of naps, number of arousals, sleep-wake cycle, and sleep quality.Findings: Sleep latency in caregivers was, on average, 35 minutes (SD = 34.5)-more than twice as long as the norm of 15 minutes (t[113]) = 6.18, p < 0.01). Caregivers averaged a total sleep  time of 5 hours and 57 minutes (SD = 84.6), significantly less than the recommended 7 hours (t[113] = -8, p < 0.01), and were awake in the night 15% of the time, significantly more than the norm of 10% (t[111] = 5.84, p < 0.01). Caregivers aroused an average of 8.3 times during nocturnal sleep (SD = 3.5, range = 2-21), with about 32% reporting poor or very poor sleep quality.Conclusions: Caregivers experienced sleep impairments that placed them at risk for poor mental and physical health, and may compromise their ability to continue in the caregiving role.Implications for Nursing: Nurses need to assess sleep in caregivers of individuals with PMBT and implement interventions to improve sleep.Knowledge Translation: Sleep deprivation is common in family caregivers during the early stages of care for individuals with a PMBT. A single-item sleep quality question could be an easy but valuable tool in assessing sleep disturbances in family caregivers of individuals with a PMBT. The health trajectory of family caregivers warrants further longitudinal study, in addition to the examination of the bidirectional relationship of health status of care recipients and their family caregiver.

 

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[752]

TÍTULO / TITLE:  - CT cisternography for presurgical evaluation of arachnoid cyst: case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - B-ENT. 2012;8(4):289-94.

AUTORES / AUTHORS:  - Verhoeven S; De Ridder D; Venstermans C; Van de Heyning P

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Antwerp, University of Antwerp, Belgium. verhoeven.sarah@gmail.com

RESUMEN / SUMMARY:  - A 62-year-old man complaining of vertigo and progressive hearing loss was diagnosed with an arachnoid cyst at the right cerebellopontine angle based on magnetic resonance imaging (MRI). In this case-report, we used computed tomography (CT) cisternography to determine whether the arachnoid cyst communicated with the cerebrospinal fluid (CSF) space. Differentiating between a  noncommunicating and communicating arachnoid cyst is required for presurgical evaluation. CT cisternography is a less used but reliable radiological technique  for determining the presence of communication, and could therefore be included in the diagnostic work-up of arachnoid cysts. The patient underwent surgery with fenestration of the arachnoid cyst; his vertigo improved and his hearing was preserved.

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[753]

TÍTULO / TITLE:  - Spinal Meningeal Oligodendrogliomatosis in Two Boxer Dogs.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Vet Pathol. 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0300985813476056

AUTORES / AUTHORS:  - Kovi RC; Wunschmann A; Armien AG; Hall K; Carlson T; Shivers J; Oglesbee MJ

INSTITUCIÓN / INSTITUTION:  - Minnesota Veterinary Diagnostic Laboratory, University of Minnesota, St. Paul, MN.

RESUMEN / SUMMARY:  - Two Boxer dogs developed progressive ataxia in association with a neoplastic infiltration of the spinal leptomeninges. In the first dog, the leptomeningeal neoplasm encompassed the entire cord and the ventral aspect of the brainstem and  extended bilaterally into the piriform lobes. In the second, the neoplasm surrounded the C1-C3 segments of the spinal cord and the brainstem without involvement of the brain or spinal cord parenchyma. In both dogs, the neoplastic  cells had variably distinct cell borders, clear to eosinophilic cytoplasm, and a  round to ovoid hyperchromatic nucleus. Neoplastic cells were immunopositive for Olig2 and doublecortin in both dogs and for vimentin in one dog but were immunonegative for glial fibrillary acidic protein, S-100, CD34, E-cadherin, cytokeratin, CD3, and CD20. The morphological and immunohistochemical features of the neoplastic cells were consistent with an oligodendrocyte lineage. This hitherto poorly recognized neoplasm in dogs is analogous to human leptomeningeal  oligodendrogliomatosis.

 

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[754]

TÍTULO / TITLE:  - Convection-enhanced delivery for targeted delivery of antiglioma agents: the translational experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Drug Deliv. 2013;2013:107573. doi: 10.1155/2013/107573. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/107573

AUTORES / AUTHORS:  - Yun J; Rothrock RJ; Canoll P; Bruce JN

INSTITUCIÓN / INSTITUTION:  - Gabriele Bartoli Brain Tumor Laboratory, Departments of Neurosurgery, Columbia University Medical Center, 1130 St. Nicholas Avenue Room 1001, New York, NY 10032, USA.

RESUMEN / SUMMARY:  - Recent improvements in the understanding of glioblastoma (GBM) have allowed for increased ability to develop specific, targeted therapies. In parallel, however,  there is a need for effective methods of delivery to circumvent the therapeutic obstacles presented by the blood-brain barrier and systemic side effects. The ideal delivery system should allow for adequate targeting of the tumor while minimizing systemic exposure, applicability across a wide range of potential therapies, and have existing safe and efficacious systems that allow for widespread application. Though many alternatives to systemic delivery have been developed, this paper will focus on our experience with convection-enhanced delivery (CED) and our focus on translating this technology from pre-clinical studies to the treatment of human GBM.

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[755]

TÍTULO / TITLE:  - Stereotactically-guided craniotomy for resection of cerebral cavernous hemangioma: a series case report of 8 cases in Rasoul-e-Akram hospital (Tehran, Iran).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Inj Violence Res. 2012 Nov;4(3 Suppl 1). pii: Paper No. 23.

AUTORES / AUTHORS:  - Parvaresh M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: In line with recent advances in magnetic resonance imaging (MRI), cavernous hemangioma (cavernoma) can be detected efficiently and reliably in patients with intractable epilepsy that surgical resection is a common treatment  for them. Because these lesions are usually small and may be located near the eloquent areas, stereotactically-guided resection should be considered. This study aims to report the surgical features and outcomes of 6 patients underwent the stereotactically-guided craniotomy for excision of cavernoma. METHODS: A total of six patients (1 male and 5 female, aged 10-42 years, mean age of 29 years) with cavernoma underwent stereotactically-guided craniotomy surgery in the Rasoul-e-Akram Hospital, affiliated to Tehran University of Medical Sciences (Tehran, Iran) for resection of cerebral cavernous hemangioma during September 2007 to May 2012. Clinical presentations were seizures, headache and hemorrhage.  Two patients had a previous history of intracranial hemorrhage. Diagnosis was made using MRI and digital subtraction angiography. Locations of the lesions were parietal, frontal and temporoparietal. Size of lesion ranged from 0.7 to 3.1 cm (mean 1.7 cm). All those lesions were deep-seated or located near or within eloquent areas. Stereotactically-guided craniotomy was performed for excision of  lesion. Clinical follow-up period ranged 5-48 months (mean 28 months). In all patients, complete surgical resection was achieved as demonstrated by postoperative image studies. RESULTS: There was no associated morbidity or mortality. Histological diagnosis was consistent with cavernoma in all cases. Clinical follow-up revealed that all patients had complete recovery from preoperative symptoms and patients with seizures showed marked improvement. CONCLUSIONS: In conclusion, stereotactic guided craniotomy in surgery of eloquent or deep-seated cerebral cavernous malformations represents a very accurate and safe approach. KEYWORDS: Stereotactically-guided craniotomy, Cavernous hemangioma, Magnetic resonance imaging.

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[756]

TÍTULO / TITLE:  - Case Report: Primary pituitary non-Hodgkin’s lymphoma developed following surgery and radiation of a pituitary macroadenoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hormones (Athens). 2012 Oct;11(4):488-94.

AUTORES / AUTHORS:  - Papanastasiou L; Pappa T; Dasou A; Kyrodimou E; Kontogeorgos G; Samara C; Bacaracos P; Galanopoulos A; Piaditis G

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Diabetes Center, “G. Genimatas” General Hospital, Athens, Greece.

RESUMEN / SUMMARY:  - OBJECTIVE: Primary central nervous system (CNS) non-Hodgkin’s lymphoma is a rarely encountered clinical entity. Here we present a case of a primary CNS diffuse large B-cell non-Hodgkin’s lymphoma developed on a previously operated and irradiated pituitary macroadenoma. DESIGN-RESULTS: A 60-year-old woman presented with muscle weakness and eye lid ptosis. Thirty years ago, she was diagnosed with a non-functioning pituitary macroadenoma requiring repeated incomplete operations and conventional radiotherapy and accompanied by partial anterior pituitary deficiency. On admission, the magnetic resonance imaging (MRI) identified a pituitary sellar mass extending into the suprasellar region, compressing the optic chiasm and invading the left cavernous sinus. Following transsphenoidal surgery, the histological investigation revealed the presence of  a diffuse large B-cell non-Hodgkin’s lymphoma without other loci from the systemic staging. Following chemotherapy and despite a marked resolution of the neoplastic pituitary mass in the post-chemotherapy MRI scan, the patient’s course was complicated with consciousness deterioration attributed to epileptic seizures and she died of a hospital acquired infection. CONCLUSIONS: Clinicians should include primary CNS lymphoma in the differential diagnosis of an isolated invasive sellar mass. The possible association of primary CNS lymphoma development with the history of operated and irradiated pituitary adenoma is herein discussed.

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[757]

TÍTULO / TITLE:  - The NF-kappaB RelB Protein Is an Oncogenic Driver of Mesenchymal Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e57489. doi: 10.1371/journal.pone.0057489. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057489

AUTORES / AUTHORS:  - Lee DW; Ramakrishnan D; Valenta J; Parney IF; Bayless KJ; Sitcheran R

INSTITUCIÓN / INSTITUTION:  - Department of Molecular & Cellular Medicine, Texas A&M University Health Science  Center, College Station, Texas, United States of America.

RESUMEN / SUMMARY:  - High-grade gliomas, such as glioblastomas (GBMs), are very aggressive, invasive brain tumors with low patient survival rates. The recent identification of distinct glioma tumor subtypes offers the potential for understanding disease pathogenesis, responses to treatment and identification of molecular targets for  personalized cancer therapies. However, the key alterations that drive tumorigenesis within each subtype are still poorly understood. Although aberrant  NF-kappaB activity has been implicated in glioma, the roles of specific members of this protein family in tumorigenesis and pathogenesis have not been elucidated. In this study, we show that the NF-kappaB protein RelB is expressed in a particularly aggressive mesenchymal subtype of glioma, and loss of RelB significantly attenuated glioma cell survival, motility and invasion. We find that RelB promotes the expression of mesenchymal genes including YKL-40, a marker of the MES glioma subtype. Additionally, RelB regulates expression of Olig2, a regulator of cancer stem cell proliferation and a candidate marker for the cell of origin in glioma. Furthermore, loss of RelB in glioma cells significantly diminished tumor growth in orthotopic mouse xenografts. The relevance of our studies for human disease was confirmed by analysis of a human GBM genome database, which revealed that high RelB expression strongly correlates with rapid tumor progression and poor patient survival rates. Thus, our findings demonstrate that RelB is an oncogenic driver of mesenchymal glioma tumor growth and invasion, highlighting the therapeutic potential of inhibiting the noncanonical NF-kappaB (RelB-mediated) pathway to treat these deadly tumors.

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[758]

TÍTULO / TITLE:  - Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Open. 2013 Mar 15;3(3). pii: e002262. doi: 10.1136/bmjopen-2012-002262. Print 2013.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bmjopen-2012-002262

AUTORES / AUTHORS:  - Archavlis E; Tselis N; Birn G; Ulrich P; Baltas D; Zamboglou N

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Klinikum Offenbach, Akademisches Lehrkrankenhaus der  Universitat Frankfurt, Offenbach, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: Tumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy. DESIGN: Retropective cohort study. SETTING: Primary level of care with two participating centres. The geographical location was central Germany. PARTICIPANTS: From January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression. INTERVENTIONS: This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. PRIMARY AND SECONDARY OUTCOME MEASURES: Median survival, progression free survival and complication rate. RESULTS: Median survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively. CONCLUSIONS: CT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with  concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.

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[759]

TÍTULO / TITLE:  - Osseous metaplastic meningioma in the thoracic spine mimicking osteosarcoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Spine (Phila Pa 1976). 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/BRS.0b013e31828a34e3

AUTORES / AUTHORS:  - Mannoji C; Koda M; Murakami M; Kubosawa H; Yamazaki M; Okawa A; Furuya T; Takahashi K

INSTITUCIÓN / INSTITUTION:  - Affiliations: *Department of Orthopaedic Surgery, Chiba Aoba Municipal Hospital,  Aobacho 1273-2, Chuo-ku, Chiba 260-0852, Japan daggerDepartment of Pathology, Chiba Aoba Municipal Hospital, Aobacho 1273-2, Chuo-ku, Chiba 260-0852, Japan double daggerDepartment of Orthopaedic Surgery, Chiba University Graduate School  of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan section signDepartment of Orthopaedic Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

RESUMEN / SUMMARY:  - Study Design: Case reportObjective: We describe a case of osseous metaplastic meningioma in the thoracic spine that pathologically mimicked osteosarcoma.Summary of background data: As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically.Methods: The patient’s medical records, imaging results, and pathological findings were reviewed, as was the relevant literature.Results: A 20-year-old woman with a 6-month history of lumbago and right sciatica was referred to our hospital because magnetic resonance imaging (MRI) showed a tumor  compressing her spinal cord at the T11 vertebra level. Computed tomography (CT) showed calcification of the tumor, and the preoperative diagnosis was meningioma. Surgery was performed and the tumor was entirely removed. The tumor was very hard, and pathological findings suggested atypical meningioma with massive ossification. Some parts of the tumor appeared malignant, as spindle cells with a high nucleo-cytoplasmic ratio were highly concentrated, which led to the possibility of osteosarcoma. The tumor was conclusively diagnosed as osseous metaplastic meningioma based not only on the pathology, but also on CT and MRI findings and the postoperative course.Conclusions: As meningioma presents in many pathological forms, it is sometimes difficult to diagnose it pathologically. Results of imaging studies including CT and MRI, as well as patients’ postoperative course, should be considered when making a final diagnosis of meningioma.

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[760]

TÍTULO / TITLE:  - Intramedullary Thoracic Spinal Cord Meningioma: A Rare Case Report and Review of  the Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330959

AUTORES / AUTHORS:  - Yuan D; Liu D; Yuan XR; Xi J; Ding XP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xiangya Hospital, Central South University; The Institute of Skull Base and Neurooncology at Hunan, Changsha, China.

RESUMEN / SUMMARY:  - A 33-year-old male presented with a thoracic spinal intramedullary meningioma manifesting as bilateral asymmetric progressive weakness in the lower extremities. Preoperative magnetic resonance imaging (MRI) showed an intramedullary mass at the T1-T3 level. Intraoperative inspection found that the  spinal cord was markedly swollen with a normal surface while dural attachment was not confirmed. Gross total removal of the tumor was achieved. The morphologic and immunohistochemical findings were compatible with the diagnosis of meningioma. Postoperatively, the patient recovered from preoperative paraplegia. Although extremely rare, meningiomas should be considered when diagnosing intramedullary tumors.

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[761]

TÍTULO / TITLE:  - Infratentorial benign cystic meningioma mimicking a hemangioblastoma radiologically and a pilocytic astrocytoma intraoperatively: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Case Rep. 2013 Mar 28;7(1):87.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-7-87

AUTORES / AUTHORS:  - Guan TK; Pancharatnam D; Chandran H; Hooi TK; Kumar G; Ganesan D

RESUMEN / SUMMARY:  - INTRODUCTION: Cystic meningiomas are rare variants of meningiomas; they can pose  a radiological diagnostic dilemma. CASE PRESENTATION: We present a rare case of a 30-year-old Chinese woman with a histopathological diagnosis of infratentorial cystic meningioma (World Health Organization Grade 1) in which the features in imaging modalities were suggestive of a hemangioblastoma. Intraoperatively, however, the gross macroscopic features were more in keeping with a pilocytic astrocytoma. CONCLUSION: In benign cystic meningiomas, particularly the infratentorial variety, radiological findings utilizing the various imaging modalities and intraoperative impressions may not be reflective of or in keeping  with the final histopathological diagnosis.

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[762]

TÍTULO / TITLE:  - Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-alpha.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Neurosci. 2013 Mar 15;14(1):33.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2202-14-33

AUTORES / AUTHORS:  - Chio CC; Chang CH; Wang CC; Cheong CU; Chao CM; Cheng BC; Yang CZ; Chang CP

RESUMEN / SUMMARY:  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is elevated early in injured  brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-alpha antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of  TNF-alpha. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-alpha expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-alpha was measured by Immunofluorescence staining. In addition, TNFalpha contents of ischemic cerebral homogenates was measured using commercial  enzyme-linked immunosorbent assay kits. RESULTS: In addition to inducing brain ischemia as well as neurological and motor deficits, TBI caused significantly higher numbers of microglia-TNF-alpha double positive cells, but not neurons-TNF-alpha or astrocytes-TNF-alpha double positive cells in the injured brain areas than did the sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral ischemia, neurological motor deficits, and increased numbers of microglia-TNF-alpha double positive cells and increased TNF-alpha levels in the injured brain were all significantly attenuated by etanercept therapy. CONCLUSION: This finding indicates that early microglia overproduction of TNF-alpha in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.

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[763]

TÍTULO / TITLE:  - CT and MR Studies of Giant Dermoid Cyst Associated to Fat Dissemination at the Cortical and Cisternal Cerebral Spaces.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Radiol. 2013;2013:239258. doi: 10.1155/2013/239258. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/239258

AUTORES / AUTHORS:  - D’Amore A; Borderi A; Chiaramonte R; Conte G; Chiaramonte I; Albanese V

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University Hospital of Catania, 95100 Catania, Italy.

RESUMEN / SUMMARY:  - This study focuses on CT and MR studies of adult patient with giant lesion of the posterior cranial fossa associated with micro- and macroaccumulations with density and signal like “fat” at the level of the cortical and cisternal cerebral spaces. This condition is compatible with previous asymptomatic ruptured dermoid  cyst. Histological findings confirm the hypothesis formulated using the imaging.  We also integrate elements of differential diagnosis by another giant lesion of the posterior cranial fossa.

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[764]

TÍTULO / TITLE:  - Carbenoxolone Enhances TRAIL-Induced Apoptosis Through the Upregulation of Death  Receptor 5 and Inhibition of Gap Junction Intercellular Communication in Human Glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cells. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Dev. 2013 Mar 26.

            ●● Enlace al texto completo (gratuito o de pago) 1089/scd.2012.0529

AUTORES / AUTHORS:  - Yulyana Y; Endaya BB; Ng WH; Guo CM; Hui KM; Lam PY; Ho IA

INSTITUCIÓN / INSTITUTION:  - 1 Laboratory of Cancer Gene Therapy, Cellular and Molecular Research Division, Humphrey Oei Institute of Cancer Research , National Cancer Centre of Singapore,  Singapore, Singapore .

RESUMEN / SUMMARY:  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In this study, we combined the tumor selectivity of TRAIL and tumor-homing properties of mesenchymal stem cells (MSC) with gap junction (GJ) inhibitory effect of carbenoxolone (CBX) to target orthotopic glioma. MSC were engineered to express TRAIL (MSC-TRAIL) by incorporating the secretable trimeric form of TRAIL  into a Herpes Simplex Virus (HSV) type I amplicon vector. Our results showed that combined treatment of MSC-TRAIL and CBX enhanced glioma cell death, especially in three primary human glioma isolates, of which two of those are marginally sensitive to TRAIL. CBX enhanced TRAIL-induced apoptosis through upregulation of  death receptor 5, blockade of GJ intercellular communication, and downregulation  of connexin 43. Dual arm therapy using TRAIL and CBX prolonged the survival of treated mice by approximately 27% when compared with the controls in an intracranial glioma model. The enhanced efficacy of TRAIL in combination with CBX coupled with the minimal cytotoxic nature of CBX suggested a favorable clinical usage of this treatment regimen.

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[765]

TÍTULO / TITLE:  - Vertebral column metastases from an esthesioneuroblastoma: chemotherapy, radiation, and resection for recurrence with 15-year followup.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Surg. 2013;2013:107315. doi: 10.1155/2013/107315. Epub 2013 Feb 19.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/107315

AUTORES / AUTHORS:  - Shirzadi AS; Drazin DG; Strickland AS; Bannykh SI; Johnson JP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

RESUMEN / SUMMARY:  - Esthesioneuroblastoma (ENB) is an uncommon aggressive malignant intranasal neoplasm that originates from neural crest cells of the olfactory epithelium. Although local invasion to the sinuses is common, spinal metastasis of ENB is rare with only 28 documented cases involving the spine spinal cord, or leptomeninges. We report a case of ENB with multiple drop metastases to the cervical and thoracic spine, and review the patient’s disease, medical history, and multiple interventions during a span of 15 years following the initial cranial resection. Despite aggressive multiple surgical resections, radiation, and chemotherapy, the tumor had significant progression and recurrence. The literature is reviewed, followed by a discussion of the natural progression of the disease and various reported interventions. Although a combination of surgery with chemotherapy and radiation therapy has been recommended, no definitive management has been established for ENB. Further research is needed to determine  decisive treatment for metastatic ENB to the spine.

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[766]

TÍTULO / TITLE:  - Epidemiology of primary brain tumors in childhood and adolescence in Kuwait.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Springerplus. 2013 Dec;2(1):58. Epub 2013 Feb 18.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2193-1801-2-58

AUTORES / AUTHORS:  - Katchy KC; Alexander S; Al-Nashmi NM; Al-Ramadan A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Al-Sabah Hospital, Safat, Kuwait ; FRCPath, FRCPC, Department of Pathology, Al-Sabah Hospital, P.O.Box 4078, 13041 Safat, Kuwait.

RESUMEN / SUMMARY:  - The relatively high frequency of primary brain tumors (PBT) observed in childhood and adolescence in Kuwait has necessitated this epidemiological study. It is based on the records of the Department of Pathology, Al-Sabah Hospital, which examined all brain tumor biopsies done in this age group in Kuwait between 1995 and 2011. During this period, 75 boys (49%) boys and 77 (51%) girls had histologically confirmed PBT. They comprised 122 children (0-14 years) and 30 adolescents (15-19 years). The boys/girls ratio was 1.03 in childhood and 0.76 in adolescence. The age-adjusted incidence rate was 11.2/ million person-years. Early childhood (0-4 years) had the peak frequency of tumors (33%), highest adjusted age-specific incidence rate (3.8/million person-years) of all tumors and the least boys/girls rates ratio (0.38) for astrocytic tumors. Low grade and high grade tumors peaked in 5-9 and 0-4 years respectively. Risk factors (hereditary syndromes or previous radio-therapy) were identified in three patients. Three (2%) tumors were congenital. High grade tumors comprised 47% of childhood and 23% of adolescence PBT. The most common tumors in childhood were astrocytoma (37%), embryonal tumors (31%), ependymoma (8%), and in adolescence astrocytoma (27%), pituitary adenoma (23%) and glioblastoma (13%). Embryonal tumors formed 44% of PBT in early childhood. Gliomas constituted 54% and 43% of all PBT, but 25% and 57% of high grade tumors in childhood and adolescence respectively. Most common tumor locations were cerebellum (47%), ventricles (19%) and cerebral lobes (17%)  in childhood and pituitary (30%), cerebellum (27%) and 13% each for cerebral lobes and ventricles in adolescence. Approximately 57% of childhood and 23% of adolescence PBT were infratentorial. In conclusion, despite the high relative frequency of PBT before the age of 20 years in Kuwait, its incidence rate is apparently low. Compared with Western countries, Kuwait has a lower incidence of  malignant gliomas, but a higher frequency of cerebellar and intraventricular tumors. Embryonal tumors are remarkably common in early childhood.

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[767]

TÍTULO / TITLE:  - Echography in the diagnosis and follow-up of retinal astrocytoma: case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Acta Clin Croat. 2012 Dec;51 Suppl 1:127-9.

AUTORES / AUTHORS:  - Henc-Petrinovic L; Petrinovid-Doresic J; Kuzmanovic-Elabjer B

INSTITUCIÓN / INSTITUTION:  - University Department of Ophthalmology, Sveti Duh University Hospital, Zagreb, Croatia.

RESUMEN / SUMMARY:  - The purpose is to show echographic presentation of retinal astrocytoma in Bourneville’s disease and the possibilities of clinical and echographic diagnosis and follow-up. In our patient, partial and generalized seizures were the first sign of the disease at the age of 3.5 years. Computed tomography showed hyperdense cerebral lesions and Sabryl medication was efficient in controlling the seizures. At the age of 7, typical retinal mulberry lesions were seen on the  fundus bilaterally. Echography revealed solid epiretinal masses of high surface and internal echogenicity casting a shadow on distal structures. There were two parapapillary lesions and one lesion in the periphery on the left eye. Due to permanent Sabryl therapy, perimetry and visual evoked potentials were monitored to show reduced retinal sensitivity in the periphery of both eyes. Facial angiofibrosis developed at the age of 8 years. Regular yearly controls up to the  age of 12 were without significant changes in clinical and echographic characteristics. In conclusion, typical echographic presentation of retinal astrocytoma is of great help in differential diagnosis to other intrabulbar massive lesions in childhood, such as retinoblastoma.

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[768]

TÍTULO / TITLE:  - Automatic brain tumor extraction from T1-weighted coronal MRI using fast bounding box and dynamic snake.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:444-7. doi: 10.1109/EMBC.2012.6345963.

            ●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6345963

AUTORES / AUTHORS:  - Xu T; Mandal M

INSTITUCIÓN / INSTITUTION:  - Department of Electrical and Computer Engineering, University of Alberta, Edmonton, AB, T6G 2V4, Canada. txl@ualberta.ca

RESUMEN / SUMMARY:  - Brain tumor segmentation from MRI data is an important but challenging task. This paper presents an efficient and fully automatic brain tumor segmentation technique. The proposed technique includes a fuzzy C-means (FCM) based preprocessing to enhance the quality of T1-weighted coronal MR images, a fast bounding box (FBB) detection algorithm to locate a rectangle around tumor, and a  new dynamic snake using modified Hausdorff distance (MHD) for the final tumor extraction.

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[769]

TÍTULO / TITLE:  - IDH1-Associated Primary Glioblastoma in Young Adults Displays Differential Patterns of Tumour and Vascular Morphology.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e56328. doi: 10.1371/journal.pone.0056328. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056328

AUTORES / AUTHORS:  - Popov S; Jury A; Laxton R; Doey L; Kandasamy N; Al-Sarraj S; Jurgensmeier JM; Jones C

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom ; Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom.

RESUMEN / SUMMARY:  - Glioblastoma is a highly aggressive tumour with marked heterogeneity at the morphological level in both the tumour cells and the associated highly prominent  vasculature. As we begin to develop an increased biological insight into the underlying processes driving the disease, fewer attempts have thus far been made  to understand these phenotypic differences. We sought to address this by carefully assessing the morphological characteristics of both the tumour cells and the associated vasculature, relating these observations to the IDH1/MGMT status, with a particular focus on the early onset population of young adults who develop primary glioblastoma. 276 primary glioblastoma specimens were classified  into their predominant cell morphological type (fibrillary, gemistocytic, giant cell, small cell, oligodendroglial, sarcomatous), and assessed for specific tumour (cellularity, necrosis, palisades) and vascular features (glomeruloid structures, arcades, pericyte proliferation). IDH1 positive glioblastomas were associated with a younger age at diagnosis, better clinical outcome, prominent oligodendroglial and small cell tumour cell morphology, pallisading necrosis and  glomeruloid vascular proliferation in the absence of arcade-like structures. These features widen the phenotype of IDH1 mutation-positive primary glioblastoma in young adults and provide correlative evidence for a functional role of mutant  IDH1 in the differential nature of neo-angiogenesis in different subtypes of glioblastoma.

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[770]

TÍTULO / TITLE:  - Brain tumor imaging: imaging brain metastasis using a brain-metastasizing breast  adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cold Spring Harb Protoc. 2013 Mar 1;2013(3). pii: pdb.prot073676. doi: 10.1101/pdb.prot073676.

            ●● Enlace al texto completo (gratuito o de pago) 1101/pdb.prot073676

AUTORES / AUTHORS:  - Madden KS; Zettel ML; Majewska AK; Brown EB

RESUMEN / SUMMARY:  - Brain metastases from primary or secondary breast tumors are difficult to model in the mouse. When metastatic breast cancer cell lines are injected directly into the arterial circulation, only a small fraction of cells enter the brain to form  metastatic foci. To study the molecular and cellular mechanisms of brain metastasis, we have transfected MB-231BR, a brain-homing derivative of a human breast adenocarcinoma line MDA-MB-231, with the yellow fluorescent protein (YFP)  variant Venus. MB-231BR selectively enters the brain after intracardiac injection into the arterial circulation, resulting in accumulation of fluorescent foci of cells in the brain that can be viewed by standard fluorescence imaging procedures. We describe how to perform the intracardiac injection and the parameters used to quantify brain metastasis in brain sections by standard one-photon fluorescence imaging. The disadvantage of this model is that the kinetics of growth over time cannot be determined in the same animal. In addition, the injection technique does not permit precise placement of tumor cells within the brain. This model is useful for determining the molecular determinants of brain tumor metastasis.

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[771]

TÍTULO / TITLE:  - Brain tumor imaging: live imaging of glioma by two-photon microscopy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cold Spring Harb Protoc. 2013 Mar 1;2013(3). pii: pdb.prot073668. doi: 10.1101/pdb.prot073668.

            ●● Enlace al texto completo (gratuito o de pago) 1101/pdb.prot073668

AUTORES / AUTHORS:  - Madden KS; Zettel ML; Majewska AK; Brown EB

RESUMEN / SUMMARY:  - Glioblastoma is a highly invasive and aggressive brain tumor that is very difficult to treat. The rat glioma cell line CNS-1 is a widely used, well-characterized model of infiltrative glioma. We have used CNS-1 to study tumors that initiate within the brain parenchyma. The CNS-1 cells were stably transfected with the yellow fluorescent protein (YFP) variant Venus to enable standard one-photon and two-photon imaging. In this protocol, we describe how to  prepare a cranial window and how to inject the tumor cells into the cerebral cortex at a depth suitable for two-photon imaging. Imaging can begin 24 h after implantation of the cells. Two-photon imaging uses a long excitation wavelength (920 nm); the emission spectrum is the same for the fluorophore as for standard one-photon imaging (emission maximum = 528 nm). Two-photon microscopy permits tissue imaging to depths of 500 mum with three-dimensional (3D) high resolution and minimal photodamage to surrounding tissues. Multiple imaging sessions can be  conducted over weeks in the same animal, depending on how long the cranial window remains clear and how quickly the tumor grows. Using this technique, the kinetics of tumor growth and invasion into the surrounding brain parenchyma can be measured in the same animal. This model can be used for determining the molecular and cellular players in brain tumor growth and invasion and for testing potential drug therapies to prevent brain metastasis.

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[772]

TÍTULO / TITLE:  - SMO and AKT1 Mutations Occur in Non-NF2 Meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Mar;3(3):OF13. doi: 10.1158/2159-8290.CD-RW2013-028. Epub 2013 Feb 7.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2013-028

RESUMEN / SUMMARY:  - Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma.

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[773]

TÍTULO / TITLE:  - Management of Low-Grade Gliomas in Childhood.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 31. pii: S1878-8750(13)00203-9. doi: 10.1016/j.wneu.2013.01.104.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.104

AUTORES / AUTHORS:  - Pollack IF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: ian.pollack@chp.edu.

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[774]

TÍTULO / TITLE:  - Subtle Changes to Polymer Structure and Degradation Mechanism Enable Highly Effective Nanoparticles for siRNA and DNA Delivery to Human Brain Cancer (Adv. Healthcare Mater. 3/2013).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Adv Healthc Mater. 2013 Mar;2(3):467. doi: 10.1002/adhm.201370017.

            ●● Enlace al texto completo (gratuito o de pago) 1002/adhm.201370017

AUTORES / AUTHORS:  - Tzeng SY; Green JJ

INSTITUCIÓN / INSTITUTION:  - Johns Hopkins University School of Medicine Department of Biomedical Engineering, the Wilmer Eye Institute, the Institute for Nanobiotechnology, and the Translational Tissue Engineering Center, 400 N. Broadway, Smith 5017, Baltimore,  MD, 21231, USA.

RESUMEN / SUMMARY:  - Polymeric nanoparticles are engineered to deliver siRNA and DNA to human brain cancer cells, as reported by Jordan J. Green and Stephany Y. Tzeng on page 468. Changes to polymer structure, such as to molecular weight, hydrophobicity, polymer endgroup, and degradable linkages, tune delivery in a manner that is often dependent on the type of nucleic acid cargo being delivered. Hydrolytically degradable polymers effectively deliver DNA whereas bioreducible degrading polymers effectively deliver siRNA.

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[775]

TÍTULO / TITLE:  - CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clinics (Sao Paulo). 2013;68(2):167-72.

AUTORES / AUTHORS:  - Silva Rd; Marie SK; Uno M; Matushita H; Wakamatsu A; Rosemberg S; Oba-Shinjo SM

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade  de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric  brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for beta-catenin gene (CTNNB1) mutations, beta-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS:  CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3beta phosphorylation sites, which participate in beta-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear beta-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of beta-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity  medulloblastoma variants but not in large-cell medulloblastomas.

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[776]

TÍTULO / TITLE:  - Sellar repair in endoscopic endonasal transsphenoidal surgery for pituitary adenoma: a report of 240 cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Inj Violence Res. 2012 Nov;4(3 Suppl 1). pii: Paper No. 68.

AUTORES / AUTHORS:  - Jalessi M; Sharifi G

INSTITUCIÓN / INSTITUTION:  - Endoscopic Pituitary and Skull Base Surgery Center, ENT-Head & Neck Research Center and Department, Hazrat Rasoul Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Cerebrospinal fluid (CSF) leak is a devastating complication after transsphenoidal surgical approach to pituitary adenoma and sellar repair has been postulated as crucial step in this approach. In this study, we describe our experience regarding sellar repair in pure endoscopic endonasal approach in 240 patients with pituitary adenoma. METHODS: During April 2005 to April 2011, a total of 240 patients with pituitary adenomas underwent endoscopic endonasal approaches for tumor removal. The degree of intra-operative CFS leak was graded as followed: Grade 0: no leakage was observed; grade 1: leakage in form of drops; and grade 3: flow of CSF was observed. Repair was done according to degree of leak e.g. surgicel for grade 0, fat and fascia for grade 1, with adding synthetic sealant and/or lumbar drain for grade 2. The method of repair is discussed in each group and exceptions were also bolded. No sphenoid sinus obliteration was needed. RESULTS: There were 208 macroadenomas and 32 microadenomas. One hundred and thirteen patients (55.4%) had grade 0 CSF leaks, 78 patients (32.5%) grade 1  CSF leaks, and 29 patients (12%) showed grade 2 leaks. There were 2 documented post operative CSF leak (0.8%) one of them was treated by lumbar drainage and the other with revision endoscopic repair. There was also one case of pneumocephalus  (0.4%) with no obvious leak in nasal endoscopic exam which managed medically. There were also 2 cases of post-operation meningitis (0.8%) with no leak that one of them was due to outbreak of acinetobacter in ICU. CONCLUSIONS: Findings of this study showed that intra-operative CSF leak is an important factor determining the need and extend of sellar repair in endoscopic endonasal approach for pituitary adenoma. The low rate of post-operative CSF leak is in favor of the applicability of grading system and method chosen for repair. KEYWORDS: Sellar repair, Endoscopic endonasal transsphenoidal surgery, Pituitary adenoma,Intra-operative Cerebrospinal fluid leak.

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[777]

TÍTULO / TITLE:  - Retroperitoneal paraganglioma presenting as a chest pain: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol Med. 2013;2013:329472. doi: 10.1155/2013/329472. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/329472

AUTORES / AUTHORS:  - Brahmbhatt P; Patel P; Saleem A; Narayan R; Young M

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, East Tennessee State University, P.O. Box 70622, Johnson City, TN 37614, USA.

RESUMEN / SUMMARY:  - Paragangliomas are very rare tumors derived from neuroendocrine cells of autonomic nervous system. Extra-adrenal paragangliomas account for only 10 to 15% of all paragangliomas and may present incidentally as a mass. Typical triad of fluctuating hypertension, headache, and sweating is not always present which makes the diagnosis difficult sometimes. Definitive diagnosis is usually made with histologic findings and surgery is the treatment of choice. We report a case of a 53-year-old male who presented with chest pain and vomiting.

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[778]

TÍTULO / TITLE:  - Admission criteria to the Danish Brain Cancer Program are moderately associated with magnetic resonance imaging findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Dan Med J. 2013 Mar;60(3):A4580.

AUTORES / AUTHORS:  - Hill TW; Nielsen MK; Nepper-Rasmussen J

INSTITUCIÓN / INSTITUTION:  - Klovervaenget 22, 5000 Odense C, Denmark. thomaswintherhill@hotmail.com.

RESUMEN / SUMMARY:  - INTRODUCTION: The objective of this study was to evaluate the Danish Brain Cancer Program by examining the criteria for admission to the program and the results of magnetic resonance imaging (MRI) of the brain in 359 patients referred to the program at the Odense University Hospital during one year. The admission criteria given by the Danish Health and Medicines Authority are as follows: 1. Prior computed tomography or MRI indicating tumour. 2. Progressive focal neurological deficits. 3. Epileptic seizure in adults. 4. Change in behaviour or cognition showing progression. 5. Headache with progression over 3-4 weeks. MATERIAL AND METHODS: This was a retrospective analysis of the cerebral MRI of 359 patients. The patients were categorized by admission criteria and MRI outcome. The findings were grouped into four main outcomes: 1. Primary malignant intracerebral tumour.  2. Intracranial tumour -(including meningeoma and metastasis). 3. Acute pathology in total (including tumours and other acute pathologies). 4. Findings of no consequence. RESULTS: We found 46 acute/subacute pathologies including 21 tumours of which eight were primary intracerebral malignant tumours and 313 scans did not have findings of any consequence. In the group with monosymptomatic headache, we  found significantly fewer tumours (p = 0.0066, Fisher’s exact test) and acute pathologies (p = 0.0008) than in the remaining groups. In the group with change in behaviour or cognition, we found significantly more primary intracerebral malignant tumours (p = 0.0002), tumours in all (p = 0.0001) and acute pathologies (p = 0.0002) than in the other groups. CONCLUSION: Fewer tumours than expected were found. Significantly fewer pathologies were found in the group with monosymptomatic headache than in the remaining groups. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

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[779]

TÍTULO / TITLE:  - Anterior interhemispheric calcified lipoma together with subcutaneous lipoma and  agenesis of corpus callosum: a rare manifestation of midline craniofacial dysraphism.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Radiol. 2013 Mar 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11604-013-0200-1

AUTORES / AUTHORS:  - Karakas O; Karakas E; Boyaci FN; Celik B; Cullu N

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Faculty of Medicine, Harran University, 63300, Sanliurfa, Turkey, dromerkarakas@hotmail.com.

RESUMEN / SUMMARY:  - Frontonasal dysplasia (FND) or craniofacial dysraphism includes a variety of craniofacial defects. FNDs are rarely associated with intracranial lipoma. The majority of intracranial lipomas are incidentally identified on radiological examinations. They are commonly accompanied by other congenital intracranial malformations. Moreover, they are rarely associated with subcutaneous lipoma. We  present a rare case of midline craniofacial dysraphism with interhemispheric calcified lipoma together with subcutaneous lipoma and agenesis of the corpus callosum.

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[780]

TÍTULO / TITLE:  - The Potential for Substance P Antagonists as Anti-Cancer Agents in Brain Tumours.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Recent Pat CNS Drug Discov. 2013 Mar 8.

AUTORES / AUTHORS:  - Harford-Wright E; Lewis KM; Vink R

INSTITUCIÓN / INSTITUTION:  - Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, South Australia, 5005, Australia. Robert.Vink@adelaide.edu.au.

RESUMEN / SUMMARY:  - Despite recent advances in cancer treatment and diagnosis, the prognosis for patients with CNS tumours remains extremely poor. This is, in part, due to the difficulty in completely removing tumours surgically, and also because of the presence of the blood brain barrier, which can prevent the entry of chemotherapeutic agents typically used in cancer treatment. Despite the presence  of the blood brain barrier, tumour cells are capable of entering and colonising the brain to form secondary brain tumours. Additionally, tumour related disruption of the blood brain barrier is associated with the clinical presentation of many patients, with accompanying increases in intracranial pressure due, in part, to the development of vasogenic oedema. Vasogenic oedema results because the newly formed angiogenic vessels within brain tumours do not retain the highly selective properties of the blood brain barrier, and thus allow for the extravasation of plasma proteins and water into the brain parenchyma. Tachykinins, and in particular substance P, have been implicated in blood brain barrier disruption and the genesis of cerebral oedema in other CNS insults via a  process known as neurogenic inflammation. Recent evidence suggests that substance P may play a similar role in CNS tumours. It has been well established that an upregulation of substance P and its receptors occurs in a number of different cancer types, including CNS neoplasms. In addition to disrupting blood brain barrier permeability, substance P and the NK1 receptors facilitate promotion of tumour growth and the development of cerebral oedema. Accordingly, recent patents describe the potential of NK1 receptor antagonists as anti-cancer agents suggesting that substance P may provide a novel cancer treatment target. This review will examine the role of substance P in the development of CNS tumours.

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[781]

TÍTULO / TITLE:  - Surgical resection of thalamic tumors: a report of four cases.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Inj Violence Res. 2012 Nov;4(3 Suppl 1). pii: Paper No. 5.

AUTORES / AUTHORS:  - Mohammadi HR; Azimi P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - Thalamic tumors (TTs) are rare which represent about 4% of all brain tumors. CASE: The present study reports four cases of TTs Of which 3 cases were male and  1 female, aged 10 to 20 years (mean age= 14.2 years). Symptoms of raised intracranial pressure (75%), and hemiparesis (50%) were the most frequent manifestations in our TTs patients. All patients had a low-grade glioma. All cases were operated through transcortical or transsylvian-transinsular approaches. Gross-total resection was accomplished in 3 patients and subtotal resection (STR) in 1. Although hydrocephalus was frequent, only 2 patients required a ventriculoperitoneal shunt placement. After the follow-up period (average time of 12 months, range 3-24 months), adjuvant therapy was not administered for our patients. At the last clinical visit, 4 patients were alive, of which 3 cases showed the normal neurological examination results. The outcomes for the remaining patients were classified as mild (n=3) and moderate disability  (n=1). KEYWORDS: Brain tumors, Thalamic Tumors, Surgery.

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[782]

TÍTULO / TITLE:  - Infra-diaphragmatic Craniopharyngioma in the Adult.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Mar 20. pii: S1878-8750(13)00488-9. doi: 10.1016/j.wneu.2013.03.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.03.039

AUTORES / AUTHORS:  - Loyo-Varela M; Herrada-Pineda T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, American British Cowdray Medical Center, Mexico City, Mexico. Electronic address: neuro_mloyov@yahoo.com.

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[783]

TÍTULO / TITLE:  - Correlation between contrast enhancement on intraoperative magnetic resonance imaging and histopathology in glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3:158. doi: 10.4103/2152-7806.105097. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.105097

AUTORES / AUTHORS:  - Kubben PL; Wesseling P; Lammens M; Schijns OE; Ter Laak-Poort MP; van Overbeeke JJ; van Santbrink H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Maastricht University Medical Center, Maastricht, Netherlands.

RESUMEN / SUMMARY:  - OBJECT: Glioblastoma is a highly malignant brain tumor, for which standard treatment consists of surgery, radiotherapy, and chemotherapy. Increasing extent  of tumor resection (EOTR) is associated with prolonged survival. Intraoperative magnetic resonance imaging (iMRI) is used to increase EOTR, based on contrast enhanced MR images. The correlation between intraoperative contrast enhancement and tumor has not been studied systematically. METHODS: For this prospective cohort study, we recruited 10 patients with a supratentorial brain tumor suspect  for a glioblastoma. After initial resection, a 0.15 Tesla iMRI scan was made and  neuronavigation-guided biopsies were taken from the border of the resection cavity. Scores for gadolinium-based contrast enhancement on iMRI and for tissue characteristics in histological slides of the biopsies were used to calculate correlations (expressed in Kendall’s tau). RESULTS: A total of 39 biopsy samples  was available for further analysis. Contrast enhancement was significantly correlated with World Health Organization (WHO) grade (tau 0.50), vascular changes (tau 0.53), necrosis (tau 0.49), and increased cellularity (tau 0.26). Specificity of enhancement patterns scored as “thick linear” and “tumor-like” for detection of (high grade) tumor was 1, but decreased to circa 0.75 if “thin linear” enhancement was included. Sensitivity for both enhancement patterns varied around 0.39-0.48 and 0.61-0.70, respectively. CONCLUSIONS: Presence of intraoperative contrast enhancement is a good predictor for presence of tumor, but absence of contrast enhancement is a bad predictor for absence of tumor. The  use of gadolinium-based contrast enhancement on iMRI to maximize glioblastoma resection should be evaluated against other methods to increase resection, like new contrast agents, other imaging modalities, and “functional neurooncology” - an approach to achieve surgical resection guided by functional rather than oncological-anatomical boundaries.

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[784]

TÍTULO / TITLE:  - The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Cancer. 2013 Mar 8;13:106. doi: 10.1186/1471-2407-13-106.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-106

AUTORES / AUTHORS:  - Yasui H; Asanuma T; Kino J; Yamamori T; Meike S; Nagane M; Kubota N; Kuwabara M; Inanami O

INSTITUCIÓN / INSTITUTION:  - Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, Japan. inanami@vetmed.hokudai.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUND: Glioblastoma is one of the intractable cancers and is highly resistant to ionizing radiation. This radioresistance is partly due to the presence of a hypoxic region which is widely found in advanced malignant gliomas. In the present study, we evaluated the effectiveness of the hypoxic cell sensitizer doranidazole (PR-350) using the C6 rat glioblastoma model, focusing on the status of blood brain barrier (BBB). METHODS: Reproductive cell death in the  rat C6 glioma cell line was determined by means of clonogenic assay. An intracranial C6 glioma model was established for the in vivo experiments. To investigate the status of the BBB in C6 glioma bearing brain, we performed the Evans blue extravasation test. Autoradiography with [14C]-doranidazole was performed to examine the distribution of doranidazole in the glioma tumor. T2-weighted MRI was employed to examine the effects of X-irradiation and/or doranidazole on tumor growth. RESULTS: Doranidazole significantly enhanced radiation-induced reproductive cell death in vitro under hypoxia, but not under normoxia. The BBB in C6-bearing brain was completely disrupted and [14C]-doranidazole specifically penetrated the tumor regions. Combined treatment  with X-irradiation and doranidazole significantly inhibited the growth of C6 gliomas. CONCLUSIONS: Our results revealed that BBB disruption in glioma enables  BBB-impermeable radiosensitizers to penetrate and distribute in the target region. This study is the first to propose that in malignant glioma the administration of hydrophilic hypoxic radiosensitizers could be a potent strategy for improving the clinical outcome of radiotherapy without side effects.

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[785]

TÍTULO / TITLE:  - The effects of voxel localization and time of echo on the diagnostic accuracy of  cystic brain tumors in 3 tesla magnetic resonance spectroscopy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Nov;9(4):195-201. doi: 10.5812/iranjradiol.7510. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.7510

AUTORES / AUTHORS:  - Rezvanizadeh A; Firouznia K; Salehi-Sadaghiani M; Mohseni M; Gharaei D; Ghanaati H; Saligheh Rad H; Masoudnia M

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Although magnetic resonance spectroscopy (MRS) has been shown as an effective diagnostic tool in distinguishing inflammation from neoplasm in cystic  brain lesions, the optimum approach in selecting the portions of lesions in MRS and the possible effects of different times of echoes (TEs) remains unknown. OBJECTIVES: To determine the most effective TE in diagnosing neoplastic lesions based on detecting choline (Cho), N acetyl aspartate (NAA) and creatinine (Cr). Moreover, the role of voxel localization on the diagnosis of the neoplastic nature of the lesions is assessed through comparing the abovementioned metabolite ratios in the rim and center of each lesion with the same TE. PATIENTS AND METHODS: In 16 patients with brain cystic tumors, MRS was performed at TEs of 30, 135 and 270 ms for detection of Cho, NAA and Cr metabolites using a 3 tesla MRI unit. The percentage of analyzed ratios greater than a cut-off point of 1.3 for Cho/Cr and 1.6 for Cho/NAA were calculated. RESULTS: Cho/Cr and Cho/NAA ratio means at all TEs were more at the central area in comparison with the periphery,  although none of the differences were statistically significant. There was no statistically significant difference among the compared TEs. The percentages of ratios above the cut-off point at all TEs were more in the rim compared to the center and in the union of both compared to the rim or center. All the patients had at least one voxel with a Cho/Cr ratio of more than 1.3 when the voxel was chosen according to the hotspots shown in the chemical shift imaging map, regardless of their location at all examined TEs. CONCLUSIONS: Selection of voxels with the guide of chemical shift imaging map yields to 100% diagnostic sensitivity. If not accessible, the use of the union of peripheral and central voxels enhances the sensitivity when compared to usage of peripheral or central voxels solely.

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[786]

TÍTULO / TITLE:  - Expression and biological role of CIP2A in human astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Med Rep. 2013 Mar 5. doi: 10.3892/mmr.2013.1357.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1357

AUTORES / AUTHORS:  - Yi F; Ni W; Liu W; Bai J; Li W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121000, P.R. China.

RESUMEN / SUMMARY:  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized oncoprotein involved in the progression of several human malignancies. The present study aimed to investigate the clinical significance and biological function of CIP2A in astrocytoma. CIP2A expression was analyzed in 135 archived astrocytoma specimens using immunohistochemistry. Of these specimens, 75 cases (55.6%) overexpressed CIP2A. The CIP2A overexpression was observed to be positively correlated with advanced tumor grade (P<0.001). siRNA-mediated knockdown of CIP2A was performed in A172 and U87 cell lines. MTT, colony formation and soft agar colony formation assays and Annexin V/propidium iodide analysis were performed to assess the role of CIP2A in cell proliferation and apoptosis. CIP2A depletion in the astrocytoma cell lines inhibited cell growth, reduced anchorageindependent cell growth and increased apoptosis. In addition, CIP2A depletion increased caspase3 cleavage and downregulated cMyc, Bcl2 and phosphoAkt expression. These results validate the role of CIP2A as a clinically relevant oncoprotein and establish CIP2A as a promising therapeutic target of astrocytoma.

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[787]

TÍTULO / TITLE:  - Definition of miRNAs expression profile in glioblastoma samples: the relevance of non-neoplastic brain reference.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55314. doi: 10.1371/journal.pone.0055314. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055314

AUTORES / AUTHORS:  - Visani M; de Biase D; Marucci G; Taccioli C; Baruzzi A; Pession A

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Pathology, University of Bologna, Bologna, Italy.

RESUMEN / SUMMARY:  - Glioblastoma is the most aggressive brain tumor that may occur in adults. Regardless of the huge improvements in surgery and molecular therapy, the outcome of neoplasia remains poor. MicroRNAs are small molecules involved in several cellular processes, and their expression is altered in the vast majority of tumors. Several studies reported the expression of different miRNAs in glioblastoma, but one of the most critical point in understanding glioblastoma miRNAs profile is the comparison of these studies. In this paper, we focused our  attention on the non-neoplastic references used for determining miRNAs expression. The aim of this study was to investigate if using three different non-neoplastic brain references (normal adjacent the tumor, commercial total RNA, and epileptic specimens) could provide discrepant results. The analysis of 19 miRNAs was performed using Real-Time PCR, starting from the set of samples described above and the expression values compared. Moreover, the three different normal RNAs were used to determine the miRNAs profile in 30 glioblastomas. The data showed that different non-neoplastic controls could lead to different results and emphasize the importance of comparing miRNAs profiles obtained using  the same experimental condition.

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[788]

TÍTULO / TITLE:  - Association of morbidity with extent of resection and cavernous sinus invasion in sphenoid wing meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg B Skull Base. 2012 Feb;73(1):76-83. doi: 10.1055/s-0032-1304562.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1304562

AUTORES / AUTHORS:  - Ivan ME; Cheng JS; Kaur G; Sughrue ME; Clark A; Kane AJ; Aranda D; McDermott M; Barani IJ; Parsa AT

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of California, San Francisco, California.

RESUMEN / SUMMARY:  - Sphenoid wing meningiomas (SWMs) typically are histologically benign, insidious lesions, but the propensity of these tumors for local invasion makes disease control very challenging. In this review, we assess whether the degree of resection and extent of cavernous sinus invasion affects morbidity, mortality, and recurrence in patients with SWM. A comprehensive search of the English-language literature was performed. Patients were stratified according to  extent of resection and extent of cavernous sinus invasion, and tumor recurrence  rate, morbidity, and mortality were analyzed. A total of 23 studies and 131 patients were included. Overall recurrence and surgical mortality rate were 11% and 2%, respectively (average follow-up = 65 months). Cranial nerve III palsy was significantly associated with incompletely versus completely resected SWMs (7 to  0%) as well as meningiomas with cavernous sinus invasion versus no sinus invasion (14 vs. 0%). No significant difference in tumor recurrence rate was noted between these groups. In conclusion, complete excision of SWMs is always recommended whenever possible, but surgeons should acknowledge that there is nonetheless a chance of recurrence and should weigh this against the risk of causing cranial nerve injuries.

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[789]

TÍTULO / TITLE:  - Efficacy and safety of higher dose stereotactic radiosurgery for functional pituitary adenomas: A preliminary report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 2. pii: S1878-8750(13)00264-7. doi: 10.1016/j.wneu.2013.01.127.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.127

AUTORES / AUTHORS:  - Grant RA; Whicker M; Lleva R; Knisely JP; Inzucchi SE; Chiang VL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Yale University School of Medicine and Yale-New Haven Medical Center, New Haven, Connecticut, USA.

RESUMEN / SUMMARY:  - OBJECTIVE: Single fraction stereotactic radiosurgery (SRS) is a common adjuvant therapy for hormonally active pituitary adenomas when surgical resection fails to control tumor growth or normalize hypersecretory activity. Marginal doses of 20-24 Gy are used at many centers and here we report our outcome data in patients treated with a higher marginal dose of 35 Gy. METHODS: 31 patients with secretory pituitary adenomas (ACTH: n = 15, GH: n = 13, PRL: n = 2, TSH: n = 1) were treated with 35 Gy to the 50% isodose line, and had a mean follow-up time of 40.2 months (range 12 - 96). All patients were evaluated post-SRS for time to hormonal normalization, time to relapse, as well as incidence and time course of radiation-induced hypopituitarism and cranial neuropathies. RESULTS: Initial normalization of hypersecretion was achieved in 22 patients (70%) with a median time to remission of 17.7 months. After initial hormonal remission, 7 patients (32%) experienced an endocrine relapse, with a mean time to relapse of 21 months. New endocrine deficiency within any of the 5 major hormonal axes occurred in 10 patients (32%). One patient (3%) developed new onset unilateral optic nerve pallor within the temporal field 3 years after SRS. Three patients (10%) reported transient new or increasing frontal headaches of unclear etiology following their procedures. CONCLUSION: Time to endocrine remission was more rapid in patients treated with 35 Gy, as compared to previously reported literature using marginal  doses of 20-24 Gy. Rates of endocrine remission and relapse, post-SRS hypopituitarism, and radiation-induced sequelae were not increased following higher dose treatment.

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[790]

TÍTULO / TITLE:  - Increased co-expression of macrophage migration inhibitory factor and matrix metalloproteinase 9 is associated with tumor recurrence of meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Med Sci. 2013;10(3):276-85. doi: 10.7150/ijms.5185. Epub 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 7150/ijms.5185

AUTORES / AUTHORS:  - Huang Q; Zhao SL; Tian XY; Li B; Li Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-sen University. 58 Zhongshan Road II, Guangzhou 510080, China.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE: We detected the expression of MIF and matrix metalloproteinase 9 (MMP9) in meningiomas to determine whether they are valuable  recurrence predictor for meningioma. METHODS: 67 cases of meningiomas, including  57 benign tumors (WHO grade I) and 10 non-benign tumors (WHO grade II and III), were collected, and expression of MIF and MMP9 in tissue microarray was evaluated immunohistochemically. The correlations between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, were analyzed statistically. RESULTS: Increased expressions of both MIF (58.2%, 39/67) and MMP9 (55.2%, 37/67) were significantly associated with microvessel density (MVD) of tumor, but only dual high-expression of MIF and MMP9 was in relation to  tumor invasion (P=0.016) and tumor recurrence (P=0.001). Based on univariate analysis, histological grade, tumor invasion and co-expression of MIF and MMP9 were significant predictors for recurrence. However, only histological grade and  co-expression of MIF and MMP9 in tumor were independent recurrence factors with a hazard ratio of 49.033 (P=0.002) and 37.766 (P=0.002) in multivariate analysis. CONCLUSIONS: Together with histological grade, increased co-expression of MIF and MMP9 in tumor might be a valuable predictor for recurrence, especially for benign meningiomas.

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[791]

TÍTULO / TITLE:  - An attempt toward objective assessment of brain tumor vascularization using susceptibility weighted imaging and dedicated computer program - a preliminary study.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pol J Radiol. 2013 Jan;78(1):50-6. doi: 10.12659/PJR.883767.

            ●● Enlace al texto completo (gratuito o de pago) 12659/PJR.883767

AUTORES / AUTHORS:  - Wieczorek-Pastusiak J; Kocinski M; Razniewski M; Strzelecki M; Stefanczyk L; Majos A

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Diagnostic Imaging, Medical University of Lodz, Barlicki University Hospital No. 1, Lodz, Poland.

RESUMEN / SUMMARY:  - BACKGROUND: Susceptibility weighted imaging (SWI) is a novel MRI sequence which demonstrates the susceptibility differences between adjacent tissues and it is promising to be a sequence useful in the assessment of brain tumors vascularity.  The aim of our study was to demonstrate usefulness of SWI in evaluation of intratumoral vessels in comparison to CET1 sequence in a standardized, objective  manner. MATERIALMETHODS: 10 patients with supratentorial brain tumors were included in the study. All of them underwent conventional MRI examination with a  1,5 T scanner. SWI sequence was additionally performed using the following parameters: TR 49 ms,TE 40 ms. We used authors’ personal computer software - Vessels View, to assess the vessels number. RESULTS: Comparison of SWI and CET1 sequences was performed using our program. Analysis of all 26 ROIs demonstrated predominance of SWI in the amount of white pixels (vessel cross-sectional) and a  similar number of elongated structures (blood vessels). CONCLUSIONS: To conclude, the results of this study are encouraging; they confirm the added value of SWI as an appropriate and useful sequence in the process of evaluation of intratumoral vascularity. Using our program significantly improved visualization of blood vessels in cerebral tumors. The Vessel View application assists radiologists in demonstrating the vessels and facilitates distinguishing them from adjacent tissues in the image.

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[792]

TÍTULO / TITLE:  - Something old and something new about molecular diagnostics in gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Pathol Clin. 2012 Dec 1;5(4):919-939.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.path.2012.09.001

AUTORES / AUTHORS:  - Horbinski C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Kentucky.

RESUMEN / SUMMARY:  - Progress in our understanding of the molecular biology of neoplasms has been driven by remarkable improvements in molecular biology techniques. This has created a rapidly moving field in which even subspecialists struggle to keep abreast of the current literature. Nowhere is this more clearly demonstrated than in neuro-oncology, wherein molecular diagnostics can now wring more clinically useful information out of very small biopsies than ever before. Herein the biologic and practical aspects of four key molecular biomarkers in gliomas are discussed, including two that have been known for some time (1p/19q codeletion and EGFR amplification) as well as two whose relevance was discovered via advanced whole-genome assays (IDH1/2 mutations and BRAF alterations).

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[793]

TÍTULO / TITLE:  - Current and evolving knowledge of prognostic factors for pediatric ependymomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Future Oncol. 2013 Feb;9(2):183-91. doi: 10.2217/fon.12.174.

            ●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.174

AUTORES / AUTHORS:  - Andreiuolo F; Ferreira C; Puget S; Grill J

INSTITUCIÓN / INSTITUTION:  - Centre National de la Recherche Scientifique Unite Mixte de Recherche 8203 Vectorology & Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris-Sud University, Villejuif, France.

RESUMEN / SUMMARY:  - Ependymomas are one of the most common pediatric malignant brain tumors. Prognosis, especially in young children, remains poor due to their inherent chemo- and radio-resistance and effective treatment remains one of the more difficult tasks in pediatric oncology: up to half of the patients may die from the disease. The only reproducible prognostic factor is the extent of surgery; neither histological grading nor other biomarkers can be used to reliably make treatment decisions in clinical practice. None of the studies identifying new biomarkers have been conducted prospectively, only few have been undertaken within the context of a clinical trial and most have been conducted with limited  samples (often including adults and childhood samples). International collaboration is needed to improve ependymoma prognostication.

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[794]

TÍTULO / TITLE:  - Retroperitoneal paraganglioma with metastasis to the abdominal vertebra: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Pathol. 2013 Mar 28;8(1):52.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-52

AUTORES / AUTHORS:  - He J; Wang X; Zheng W; Zhao Y

RESUMEN / SUMMARY:  - BACKGROUND: Extra-adrenal paraganglioma of the retroperitoneum with metastasis to the vertebra is very rare. To our knowledge this is the first report of this kind of disease in the literature. CASE PRESENTATION: Here, we present an oroginal case of paraganglioma of the retroperitoneum with metastasis to the abdominal vertebra in a 42-year-old female patient who was successfully treated by complete removal of the tumor and its metastasis. The patient was followed up for four years and remained disease-free. CONCLUSION: Our case demonstrated the need to consider paraganglioma of the retroperitoneum in the differential diagnosis of retroperitoneal mass, metastatic tumors to the vertebra, and the importance of radical surgery for a successful management of the disease.Virtual Slides: The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/1956611954880197.

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[795]

TÍTULO / TITLE:  - Multifocal Glioblastoma Multiforme in the Posterior Fossa Mimicking Cerebral Metastases: Case Presentation and Review of the Current Literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330113

AUTORES / AUTHORS:  - Walter J; Koch A; Herbold C; Schiffler S; Reichart R; Waschke A; Kalff R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Friedrich-Schiller-University, Jena, Germany.

RESUMEN / SUMMARY:  - Objective In general, glioblastomas multiforme (GBM) arise in the supratentorial  region, but in less than 4% of cases they also occur in the posterior fossa, particularly in the cerebellum. Furthermore, a minority of malignant gliomas are  multifocal. We report on an unusual case with infratentorial multifocal lesions,  suspicious for metastases, which turned out to be a multifocal GBM of the posterior fossa.Patient and Method A 69-year-old woman presented with recurring episodes of vertigo, headache, and progressive weight loss. Three multifocal cerebellar and brainstem lesions highly suspicious for metastases were identified by magnetic resonance imaging (MRI). Workup for malignancy elsewhere in the body  was negative.Results The patient underwent craniotomy with successful resection of the tumor in the cerebellar vermis with an excellent outcome and uneventful postsurgical course. Histopathology of the tumor revealed features consistent with the diagnosis of GBM and ruled out metastatic lesions. Workup for molecular  genetics characterized this tumor as a primary GBM. The patient initially responded to treatment with radiation therapy and temozolomide but died after 10  months with a tumor relapse.Conclusion We discuss the unusual aspects of multifocal primary GBMs in the posterior fossa. Although rare, they should be considered in the differential diagnosis of cerebellar tumors, which stresses the importance of a surgical treatment to establish a histological diagnosis because  there are no reliable radiographic criteria for distinguishing multifocal infratentorial gliomas from multiple metastases and other tumor entities. The differentiation between a primary and secondary cerebellar GBM did not lead to any change of the treatment strategy in this case.

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[796]

TÍTULO / TITLE:  - Bilateral Ptosis as Initial Presentation of Gliomatosis Cerebri: Case Report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Feb 20.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1333417

AUTORES / AUTHORS:  - Kovanda T; Braca J; Prabhu V

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Loyola University Medical Center, Maywood, Illinois, United States.

RESUMEN / SUMMARY:  - Gliomatosis cerebri is a rare, diffuse glioma of neuroepithelial origin involving more than two cerebral lobes. Clinical presentation of gliomatosis cerebri is variable and depends on the degree, extent, and location of cortical involvement. Signs and symptoms related to supratentorial cortical involvement predominate and the diagnosis is reached through a combination of clinical, radiographic, and histopathological evaluations. This is a report of a young man who presented with visual problems and bilateral ptosis, which were eventually attributed to gliomatosis cerebri. Standard radiation and chemotherapy were administered but the patient eventually succumbed to the disease. The unique clinical presentation is discussed in light of this rare neoplasm of the central nervous system.

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[797]

TÍTULO / TITLE:  - The Evangelismos hospital central nervous system tumor registry: Analysis of 1414 cases (1998-2009).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2013;4:23. doi: 10.4103/2152-7806.107893. Epub 2013 Feb 27.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.107893

AUTORES / AUTHORS:  - Stranjalis G; Kalamatianos T; Stavrinou LC; Mathios D; Koutsarnakis C; Tzavara C; Loufardaki M; Protopappa D; Argyrakos T; Rontogianni DP; Sakas DE

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Athens, Evangelismos Hospital, Athens,  Greece ; Hellenic Center of Neurosurgical Research (HCNR), “Professor Petros S. Kokkalis”, Athens, Greece.

RESUMEN / SUMMARY:  - BACKGROUND: The Evangelismos Hospital central nervous system (CNS) Tumor Registry represents the current effort of the Departments of Neurosurgery and Pathology to collect data for primary and metastatic CNS tumor patients. In the present study, 12-year hospital data (1998-2009) were reviewed and analyzed. METHODS: Patients that underwent surgery for CNS tumors for the first time were identified. Histologically confirmed tumor rates by age and gender were compared. Time trends in annual rates for specific tumor types were investigated. In-hospital mortality rates and length of hospital stay were analyzed by age and gender and their putative variations across the study period investigated. RESULTS: A total of 1414 patients (age 15-89 years) were identified. The most frequently encountered  histologies were gliomas and meningiomas, accounting for, respectively, 32.8% and 29.1% of the total sample. A greater proportion of meningiomas was found in women; the proportion of glioblastomas and metastatic tumors, as well as of mixed gliomas, were greater in men. Increased rates of glioblastoma and meningioma with advancing age at diagnosis were also apparent. There were no significant variations in time trends for specific tumor types. In-hospital mortality was significantly higher for older patients (>/=70 years). An increase in the length  of hospital stay was apparent between the first and middle third of the study period. CONCLUSIONS: Analysis of tumor rates in relation to age at diagnosis and  gender showed significant bias in accordance with salient literature. Available data indicated no significant variations in time trends for specific tumor types  across the study period, while an adverse effect of advanced age on in-hospital mortality was shown. The present findings can guide the formulation of future treatment programs and preventive strategies and provide the basis for further intra- and/or interdepartmental research.

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[798]

TÍTULO / TITLE:  - Remote Cerebellar Hemorrhage after Removal of a Supratentorial Glioma without Perioperative CSF Loss: A Case Report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Surg. 2013;2013:305039. doi: 10.1155/2013/305039. Epub 2013 Feb 21.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/305039

AUTORES / AUTHORS:  - Hara T; Matsuda M; Watanabe S; Nakai K; Yamamoto T; Matsumura A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba,  Ibaraki 305-8575, Japan.

RESUMEN / SUMMARY:  - A 44-year-old man presented with the rare complication of remote cerebellar hemorrhage (RCH) after removal of a supratentorial glioma without the loss of a large volume of cerebrospinal fluid (CSF). He presented with severe headache, nausea, and vomiting for a few days, then he developed neurological deterioration including progressive disturbance of consciousness and left hemiparesis. Magnetic resonance imaging revealed a large tumor with intratumoral hemorrhage in the right frontal lobe that led to subfalcial and transtentorial herniation. The tumor was removed en bloc without excessive loss of CSF throughout the perioperative period. Although the level of consciousness remained unchanged from the preoperative level and no new neurological deficit was detected, routine postoperative computed tomography showed a bilateral RCH. Careful conservative therapy was provided and follow-up computed tomography demonstrated no further progression of hemorrhage. Compensatory acute engorgement of venous sinuses derived from the rapid decrease in intracranial pressure that occurred due to removal of the huge tumor might have caused cerebellar hemorrhagic venous infarction.

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[799]

TÍTULO / TITLE:  - Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol. 2013 Jan;6(1):25-30. doi: 10.1159/000346340. Epub 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000346340

AUTORES / AUTHORS:  - Nishino K; Niwa Y; Mizutani T; Shimizu K; Hayashi K; Chaya J; Kato N; Yamamuro O

INSTITUCIÓN / INSTITUTION:  - Department of Obstetrics and Gynecology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.

RESUMEN / SUMMARY:  - We present the case of a 44-year-old nulliparous woman who experienced irregular  menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders  ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

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[800]

TÍTULO / TITLE:  - Histone H3.3 Mutations Drive Pediatric Glioblastoma through Upregulation of MYCN.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0426

AUTORES / AUTHORS:  - Bjerke L; Mackay A; Nandhabalan M; Burford A; Jury A; Popov S; Bax DA; Carvalho D; Taylor KR; Vinci M; Bajrami I; McGonnell IM; Lord CJ; Reis RM; Hargrave D; Ashworth A; Workman P; Jones C

INSTITUCIÓN / INSTITUTION:  - 1Divisions of Molecular Pathology and 2Cancer Therapeutics, and 3Breakthrough Breast Cancer Research Centre and CRUK Gene Function Laboratory, Division of Breast Cancer Research, The Institute of Cancer Research; 4Royal Veterinary College; 5Great Ormond Street Hospital, London, United Kingdom; 6University of Coimbra, Coimbra; 7ICVS, University of Minho, Braga, Portugal; and 8Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos SP, Brazil.

RESUMEN / SUMMARY:  - Children and young adults with glioblastoma (GBM) have a median survival rate of  only 12 to 15 months, and these GBMs are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A, occurring either at or close to key residues marked by methylation for regulation of transcription-K27 and G34. Here, we show that the cerebral hemisphere-specific G34 mutation drives a distinct expression signature through differential genomic  binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem-cell maintenance, cell-fate decisions, and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene that is causative of GBMs when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population through inhibiting kinases responsible for stabilization of the protein.

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[801]

TÍTULO / TITLE:  - Meningiomas engaging major venous sinuses.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 30. pii: S1878-8750(13)00194-0. doi: 10.1016/j.wneu.2013.01.095.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.095

AUTORES / AUTHORS:  - Mathiesen T; Pettersson-Segerlind J; Kihlstrom L; Ulfarsson E

INSTITUCIÓN / INSTITUTION:  - Dept of Neurosurgery, Karolinska Hospital, Stockholm, Sweden. Electronic address: Tiit.Mathiesen@karolinska.se.

RESUMEN / SUMMARY:  - BACKGROUND: Meningiomas with growth onto or into the major venous sinuses, “venous meningiomas”, provide management problems regarding radical removal and preservation of venous drainage. The relationship to venous structures often precludes radical surgery; the risk of recurrence and aggressive histology is higher for parasagittal meningiomas than in other locations. Older series reflect the conflict between radical surgery and subtotal removal followed by “wait and scan” for the residual. This review summarizes our experience of a more contemporary series of venous meningiomas with access to gamma-knife radiosurgery for residual tumors and a long follow-up of ten years. MATERIAL AND METHODS: Treatment, histopathology and follow-up data of 100 consecutive patients undergoing surgery for venous meningiomas were prospectively collected. Gamma-knife surgery was considered as a direct post-surgical adjunct or as an adjunct following a period of radiological follow-up. The proliferaton marker MIB-1 was prospectively analysed. Two patients were lost to follow-up after five  years and 98 were followed until the patients death or a minimum of ten years. RESULTS: The six-month outcome was god-excellent in 94 patients; one patient died. Eighteen patients died within ten years. Ten of them had aggressive or anaplastic meningiomas. In ten years, umor recurrence/progression was noted in 23 patients. One important reason was that only 42% of patients undergoing Simpson grade 1 removal had free resection margins at microscopic examination. Patients with Simpson grade 1 surgery had a recurrence rate of ten%. Patients with deliberate non-radical surgery (Simpson grade 4) had a tumor recurrence rate of 72% while a combined treatment of direct gamma-knife radiosurgery following a tailored microsurgical resection (“Simpson4 gamma”) allowed return to a low recurrence rate of 10%. The tumor proliferation indices (MIB-1/Ki-67) were prognostically relevant for recurrence following either microsurgery or gamma-knife radiosurgery. CONCLUSION: Surgical microscopic radicality was unexpectedly difficult to achieve. Gamma-knife radiosurgery was a useful adjunct, but only in patients with tumors of low proliferative index. It should probably be employed as part of the initial surgical management. As expected, treatment results for these patients seem to have improved over the last decades but recurrence and malignification remained a problem which is not always solved by repeated radiosurgery.

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[802]

TÍTULO / TITLE:  - IgG4-related inflammatory pseudotumors mimicking multiple meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Jpn J Radiol. 2013 Mar 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11604-013-0191-y

AUTORES / AUTHORS:  - Nishino T; Toda J; Nakatsuka T; Kimura T; Inaoka T; Terada H

INSTITUCIÓN / INSTITUTION:  - Department of Gastroenterology, Tokyo Women’s Medical University Yachiyo Medical  Center, Yachiyo, Japan.

RESUMEN / SUMMARY:  - IgG4-related disease is an emerging clinicopathologic entity. Hypophysitis, diffuse thickening of dura, and enlargement of the trigeminal nerve are well-known intracranial involvements of IgG4-related disease. This report of a case of systemic IgG4-related disease is the first to present neuroimaging of apparent supratentorial meningioma-like lesions and thickening and contrast enhancement of the walls of the intracranial internal carotid arteries. It is important to recognize IgG4-related intracranial pseudotumors so that patients do not undergo unnecessary surgical procedures.

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[803]

TÍTULO / TITLE:  - Intracranial Meningiomas in French West Indies and French Guiana.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Feb 26.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1333128

AUTORES / AUTHORS:  - Mostofi K

INSTITUCIÓN / INSTITUTION:  - Department of Neurology/Neurosurgery, General Hospital of Cayenne, Cayenne, French Guiana.

RESUMEN / SUMMARY:  - Background Studies toward the end of the 20th century and in the first decade of  the millennium show that meningioma represents the most common brain tumor of all types. There are no data available regarding meningiomas in the French West Indies and French Guiana. The author aimed to determine clinical and epidemiological features and provide data of meningiomas in French West Indies and French Guiana.Material and Methods I reviewed the files of 358 patients who underwent surgery between January 2000 and December 2008.Results I found a sex ratio of 2.5 to 1-256 (71.5%) female to 102 (28.5%) male. Meningiomas were encountered mostly in the sixth decade of life and the most common anatomical location was cerebral convexities (29.32% of patients) followed by parasagittal and parafalcine (20.11%). The third most common was sphenoid wing meningioma. The incidence of meningiomas was 6.31 per 100,000 inhabitants.Conclusion The current  study attempts to estimate frequency and peculiarities of meningiomas in the French West Indies and French Guiana and is the first of its kind.

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[804]

TÍTULO / TITLE:  - Non small cell carcinoma metastasis to meningioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2013 Jan;53(1):43-5. doi: 10.3340/jkns.2013.53.1.43. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2013.53.1.43

AUTORES / AUTHORS:  - Kim KH; Hong EK; Lee SH; Yoo H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - “Tumor-to-tumor” metastasis is a rare event; meningioma has been reported as the  most common primary intracranial tumor to harbor cancer metastases. Several hypotheses have been previously proposed to explain this occurrence, but the exact mechanism by which these metastases develop into meningiomas is not yet understood. Magnetic resonance imaging and spectroscopy have been valuable diagnostic tools, but preoperative diagnosis of metastasis to meningioma remains  highly difficult. We present a case report of a metastasis of non-small cell lung cancer into an intracranial meningioma.

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[805]

TÍTULO / TITLE:  - Posterior cranial fossa meningiomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg B Skull Base. 2012 Feb;73(1):1-10. doi: 10.1055/s-0032-1304835.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1304835

AUTORES / AUTHORS:  - Javalkar V; Banerjee AD; Nanda A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana.

RESUMEN / SUMMARY:  - This study evaluated the outcomes, complications, and recurrence rates of posterior cranial fossa meningiomas. We retrospectively reviewed our surgical experience with 64 posterior cranial fossa meningiomas. Mean age was 56 years with a female preponderance (67.2%). Headache was the most common symptom. Retrosigmoid approach was the commonest surgical procedure (23.4%). The incidence of cranial nerve related complications was 28%. Postoperatively facial nerve weakness was observed in 11%. The incidence of cerebrospinal fluid leak was 4.6%. Gross total resection was achieved in 37 patients (58%). Sixteen patients (25%) with residual tumors underwent Gamma knife radiosurgery. Recurrence or tumor progression was observed in 12 patients (18.7%). Operative mortality was 3.1%. At their last follow-up, 93% of the cases achieved Glasgow Outcome Scale scores 4 or 5. Total excision is the ideal goal which can be achieved with meningiomas located in certain location, such as lateral convexity, but for other posterior fossa meningiomas the close proximity of critical structures is a major obstacle  in achieving this goal. In practicality, a balance between good functional outcome and extent of resection is important for posterior cranial fossa meningiomas in proximity to critical structures.

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[806]

TÍTULO / TITLE:  - Extracranial Intraluminal Extension of Atypical Meningioma within the Internal Jugular Vein.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Otolaryngol. 2013;2013:875607. doi: 10.1155/2013/875607. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/875607

AUTORES / AUTHORS:  - Taki N; Wein RO; Bedi H; Heilman CB

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-HNS, Tufts Medical Center, 800 Washington Street, Box 850, Boston, MA 02111, USA.

RESUMEN / SUMMARY:  - Meningiomas represent the most common benign intracranial neoplasms, and may spread by direct extension into nearby venous sinuses, but gross spread to the extracranial venous system is uncommon. We report the case of a patient with extracranial intraluminal spread of meningioma within the internal jugular vein to level III of the neck. Review of the preoperative assessment and management is also presented.

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[807]

TÍTULO / TITLE:  - Stereotactic Radiosurgery for Functioning Pituitary Adenomas - A Higher Dose Is Better but only Up to a Point.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 28. pii: S1878-8750(13)00390-2. doi: 10.1016/j.wneu.2013.02.080.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.080

AUTORES / AUTHORS:  - Sheehan J

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery University of Virginia. Electronic address: jsheehan@virginia.edu.

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[808]

TÍTULO / TITLE:  - Radiosurgical Dose Selection for Secreting Pituitary Adenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 28. pii: S1878-8750(13)00389-6. doi: 10.1016/j.wneu.2013.02.079.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.079

AUTORES / AUTHORS:  - Pollock BE

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery,(1) and Radiation Oncology,(2) Mayo Clinic College of Medicine, Rochester, Minnesota. Electronic address: pollock.bruce@mayo.edu.

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[809]

TÍTULO / TITLE:  - Connective tissue growth factor (CTGF/CCN2) is negatively regulated during neuron-glioblastoma interaction.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55605. doi: 10.1371/journal.pone.0055605. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055605

AUTORES / AUTHORS:  - Romao LF; Mendes FA; Feitosa NM; Faria JC; Coelho-Aguiar JM; de Souza JM; Moura Neto V; Abreu JG

INSTITUCIÓN / INSTITUTION:  - Universidade Federal do Rio de Janeiro, Campus Macae, Rio de Janeiro, Brazil.

RESUMEN / SUMMARY:  - Connective-tissue growth factor (CTGF/CCN2) is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular  matrix remodeling. Glioblastoma (GBM) is the major malignant primary brain tumor  and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGFbeta luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out  an interesting view in the understanding of the tumor and cerebral microenvironment interactions and could open up new strategies as well as suggest a new target in GBM control.

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[810]

TÍTULO / TITLE:  - Unusual Imaging Appearance of a Huge Intracranial Dermoid Cyst Located Across the Anterior and Middle Skull Base.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0033-1337610

AUTORES / AUTHORS:  - Wang X; Yu Y; Zhang X; Hu F; Gu Y; Xie T; Yu H; Cai Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Nantong No.1 People Hospital, Jiangsu, China.

RESUMEN / SUMMARY:  - Intracranial dermoid cysts are rare congenital neoplasms. Typical dermoid cysts are well-circumscribed fat-density masses with no associated contrast enhancement. We report a woman with a dermoid cyst across the anterior and middle skull base of unusual imaging appearance. This report highlights the challenge facing the diagnosis and management of intracranial dermoid cysts with unusual primary imaging findings.

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[811]

TÍTULO / TITLE:  - Recursive feature elimination for brain tumor classification using desorption electrospray ionization mass spectrometry imaging.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5258-61. doi: 10.1109/EMBC.2012.6347180.

            ●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6347180

AUTORES / AUTHORS:  - Gholami B; Norton I; Tannenbaum AR; Agar NY

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. bgholami@bwh.harvard.edu

RESUMEN / SUMMARY:  - The metabolism and composition of lipids is of increasing interest for understanding and detecting disease processes. Lipid signatures of tumor type and grade have been demonstrated using magnetic resonance spectroscopy. Clinical management and ultimate prognosis of brain tumors depend largely on the tumor type, subtype, and grade. Mass spectrometry, a well-known analytical technique used to identify molecules in a given sample based on their mass, can significantly improve the problem of tumor type classification. This work focuses on the problem of identifying lipid features to use as input for classification.  Feature selection could result in improvements in classifier performance, discovery of biomarkers, improved data interpretation, and patient treatment.

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[812]

TÍTULO / TITLE:  - Neuro-oncology: Optimizing the potential of MGMT as a prognostic biomarker in glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Neurol. 2013 Mar;9(3):121. doi: 10.1038/nrneurol.2013.20. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2013.20

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[813]

TÍTULO / TITLE:  - Spontaneous high-grade glial intramedullary tumor of the spine in a rhesus macaque (Macaca mulatta).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Med Primatol. 2013 Mar 28. doi: 10.1111/jmp.12045.

            ●● Enlace al texto completo (gratuito o de pago) 1111/jmp.12045

AUTORES / AUTHORS:  - Hanley PW; Wilkerson GK; Bernacky BJ; Barnhart KF; Baze WB; McArthur MJ

INSTITUCIÓN / INSTITUTION:  - Department of Veterinary Sciences, UT MD Anderson Cancer Center, Bastrop, TX, USA.

RESUMEN / SUMMARY:  - BACKGROUND: A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities. METHODS: A complete blood count, serum biochemical analysis,  neurologic exam and necropsy were performed. RESULTS: The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma. CONCLUSIONS: We describe a case of a naturally occurring spontaneous  spinal cord neoplasia in a non-human primate.

 

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[814]

TÍTULO / TITLE:  - Targeting SRC family kinases inhibits bevacizumab-induced glioma cell invasion.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e56505. doi: 10.1371/journal.pone.0056505. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056505

AUTORES / AUTHORS:  - Huveldt D; Lewis-Tuffin LJ; Carlson BL; Schroeder MA; Rodriguez F; Giannini C; Galanis E; Sarkaria JN; Anastasiadis PZ

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.

RESUMEN / SUMMARY:  - Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM). Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab’s influence on glioma biology and block it’s actions towards cell invasion.To explore the mechanism(s) of GBM cell  invasion we have examined a panel of serially transplanted human GBM lines grown  either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits  increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1) activation of Src family kinases (SFKs) is common in GBM, 2) the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3) SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive  tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support  testing the combination of dasatinib with bevacizumab in the clinic.

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[815]

TÍTULO / TITLE:  - Wnt activation promotes neuronal differentiation of glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Feb 21;4:e500. doi: 10.1038/cddis.2013.32.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.32

AUTORES / AUTHORS:  - Rampazzo E; Persano L; Pistollato F; Moro E; Frasson C; Porazzi P; Della Puppa A; Bresolin S; Battilana G; Indraccolo S; Te Kronnie G; Argenton F; Tiso N; Basso G

INSTITUCIÓN / INSTITUTION:  - Department of Woman and Child Health, University of Padova, Padova, Italy.

RESUMEN / SUMMARY:  - One of the biggest challenges in tumour research is the possibility to reprogram  cancer cells towards less aggressive phenotypes. In this study, we reprogrammed primary Glioblastoma multiforme (GBM)-derived cells towards a more differentiated and less oncogenic phenotype by activating the Wnt pathway in a hypoxic microenvironment. Hypoxia usually correlates with malignant behaviours in cancer  cells, but it has been recently involved, together with Wnt signalling, in the differentiation of embryonic and neural stem cells. Here, we demonstrate that treatment with Wnt ligands, or overexpression of beta-catenin, mediate neuronal differentiation and halt proliferation in primary GBM cells. An hypoxic environment cooperates with Wnt-induced differentiation, in line with our finding that hypoxia inducible factor-1alpha (HIF-1alpha) is instrumental and required to sustain the expression of beta-catenin transcriptional partners TCF-1 and LEF-1.  In addition, we also found that Wnt-induced GBM cell differentiation inhibits Notch signalling, and thus gain of Wnt and loss of Notch cooperate in the activation of a pro-neuronal differentiation program. Intriguingly, the GBM sub-population enriched of cancer stem cells (CD133(+) fraction) is the primary target of the pro-differentiating effects mediated by the crosstalk between HIF-1alpha, Wnt, and Notch signalling. By using zebrafish transgenics and mutants as model systems to visualize and manipulate in vivo the Wnt pathway, we confirm  that Wnt pathway activation is able to promote neuronal differentiation and inhibit Notch signalling of primary human GBM cells also in this in vivo set-up.  In conclusion, these findings shed light on an unsuspected crosstalk between hypoxia, Wnt and Notch signalling in GBM, and suggest the potential to manipulate these microenvironmental signals to blunt GBM malignancy.

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[816]

TÍTULO / TITLE:  - Inflammation and Gliomagenesis: Bi-Directional Communication at Early and Late Stages of Tumor Progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Pathobiol Rep. 2013 Mar 1;1(1):19-28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s40139-012-0006-3

AUTORES / AUTHORS:  - Galvao RP; Zong H

INSTITUCIÓN / INSTITUTION:  - Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.

RESUMEN / SUMMARY:  - Inflammation has been closely linked to various forms of cancer. Less is known about the role of inflammation in glioma, especially at the initiation stage. In  this review, we first describe the unique features of the immune system in the brain. We then discuss the current understanding of the mechanisms by which glioma cells modulate the immune system, especially how bi-directional communications between immune cells and glioma cells create an immunosuppressed microenvironment that promotes tumor survival and growth. We also address the potential tumor-initiating roles of inflammation in glioma. Finally, we describe  several immunotherapy approaches currently being developed to reverse these interactions and stimulate the immune system to eliminate glioma cells.

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[817]

TÍTULO / TITLE:  - Myeloablative Temozolomide Enhances CD8(+) T-Cell Responses to Vaccine and Is Required for Efficacy against Brain Tumors in Mice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e59082. doi: 10.1371/journal.pone.0059082. Epub 2013 Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059082

AUTORES / AUTHORS:  - Sanchez-Perez LA; Choi BD; Archer GE; Cui X; Flores C; Johnson LA; Schmittling RJ; Snyder D; Herndon JE 2nd; Bigner DD; Mitchell DA; Sampson JH

INSTITUCIÓN / INSTITUTION:  - Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.

RESUMEN / SUMMARY:  - Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases.  A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed  that recovery from chemotherapy-induced lymphopenia may actually be exploited to  potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA) TMZ resulted in markedly reduced CD4(+), CD8(+) T-cell and CD4(+)Foxp3(+) TReg counts. Adoptive transfer of naive CD8(+) T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8(+) T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA) dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell  expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ-but not lymphodepletive, NMA TMZ-led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain  tumors.

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[818]

TÍTULO / TITLE:  - Clearance and Toxicity of Recombinant Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (r-metHu GDNF) Following Acute Convection-Enhanced Delivery into the Striatum.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e56186. doi: 10.1371/journal.pone.0056186. Epub 2013 Mar 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056186

AUTORES / AUTHORS:  - Taylor H; Barua N; Bienemann A; Wyatt M; Castrique E; Foster R; Luz M; Fibiger C; Mohr E; Gill S

INSTITUCIÓN / INSTITUTION:  - School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.

RESUMEN / SUMMARY:  - BACKGROUND: Despite promising early results, clinical trials involving the continuous delivery of recombinant methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF) into the putamen for the treatment of Parkinson’s disease have shown evidence of poor distribution and toxicity due to  point-source accumulation. Convection-enhanced delivery (CED) has the potential to facilitate more widespread and clinically effective drug distribution. AIMS: We investigated acute CED of r-metHuGDNF into the striatum of normal rats in order to assess tissue clearance, toxicity (neuron loss, gliosis, microglial activation, and decreases in synaptophysin), synaptogenesis and neurite-outgrowth. We investigated a range of clinically relevant infused concentrations (0.1, 0.2, 0.6 and 1.0 microg/microL) and time points (2 and 4 weeks) in order to rationalise a dosing regimen suitable for clinical translation. RESULTS: Two weeks after single dose CED, r-metHuGDNF was below the  limit of detection by ELISA but detectable by immunohistochemistry when infused at low concentrations (0.1 and 0.2 microg/microL). At these concentrations, there was no associated neuronal loss (neuronal nuclei, NeuN, immunohistochemistry) or  synaptic toxicity (synaptophysin ELISA). CED at an infused concentration of 0.2 microg/microL was associated with a significant increase in synaptogenesis (p<0.01). In contrast, high concentrations of r-metHuGDNF (above 0.6 microg/microL) were associated with neuronal and synaptic toxicity (p<0.01). Markers for gliosis (glial fibrillary acidic protein, GFAP) and microglia (ionized calcium-binding adapter molecule 1, Iba1) were restricted to the needle  track and the presence of microglia had diminished by 4 weeks post-infusion. No change in neurite outgrowth (Growth associated protein 43, GAP43, mRNA) compared  to artificial cerebral spinal fluid (aCSF) control was observed with any infused  concentration. CONCLUSION: The results of this study suggest that acute CED of low concentrations of GDNF, with dosing intervals determined by tissue clearance, has most potential for effective clinical translation by optimising distribution  and minimising the risk of toxic accumulation.

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[819]

TÍTULO / TITLE:  - What is your diagnosis? Impression smears of a cerebral mass from a dog.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Vet Clin Pathol. 2013 Feb 21. doi: 10.1111/vcp.12026.

            ●● Enlace al texto completo (gratuito o de pago) 1111/vcp.12026

AUTORES / AUTHORS:  - Spoor MS; Kim DY; Kanazono S; Wininger FA; Whitney MS

INSTITUCIÓN / INSTITUTION:  - Department of Pathobiology, Veterinary Medical Diagnostic Laboratory, University  of Missouri, Columbia, MO, USA.

 

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[820]

TÍTULO / TITLE:  - Tanycytic ependymoma: a challenging histological diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Neurol Med. 2013;2013:170791. doi: 10.1155/2013/170791. Epub 2013 Feb 14.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/170791

AUTORES / AUTHORS:  - Krisht KM; Schmidt MH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT 84132, USA.

RESUMEN / SUMMARY:  - Tanycytic ependymoma is a rare form of ependymoma that usually arises in the intramedullary spine. It has a unique histology emphasized by the inconspicuous ependymal pattern of cells and close resemblance to schwannoma and astrocytoma. The authors report a 50-year-old man with a cervical tanycytic ependymoma that was initially thought to be a schwannoma. The frozen histology section showed spindle cells with oval and elongated nuclei with occasional hemosiderin deposits present suggesting a preliminary diagnosis of schwannoma. Immunohistochemical staining of the permanent section revealed strong immunoreactivity for glial fibrillary acidic protein with intermittent S-100 positivity, confirming that the tumor was a tanycytic ependymoma. This underlines the challenges involved in making an accurate diagnosis and demonstrates that careful and detailed histological inspection with immunohistochemical stains and ultrastructural microscopy may be necessary to distinguish tanycytic ependymoma from other neoplasms.

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[821]

TÍTULO / TITLE:  - A Decision Support System for the assisted diagnosis of brain tumors: a feasibility study for (1)(8)F-FDG PET preclinical studies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:6255-8. doi: 10.1109/EMBC.2012.6347424.

            ●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6347424

AUTORES / AUTHORS:  - Grosso E; Lopez M; Salvatore C; Gallivanone F; Di Grigoli G; Valtorta S; Moresco R; Gilardi MC; Ramirez J; Gorriz JM; Castiglioni I

INSTITUCIÓN / INSTITUTION:  - University of Milan-Bicocca, Milan, Italy. grosso.eleonora@ hsr.it

RESUMEN / SUMMARY:  - Decision support systems for the assisted medical diagnosis offer the main feature of giving assessments which are poorly affected from arbitrary clinical reasoning. Aim of this work was to assess the feasibility of a decision support system for the assisted diagnosis of brain cancer, such approach presenting potential for early diagnosis of tumors and for the classification of the degree  of the disease progression. For this purpose, a supervised learning algorithm combined with a pattern recognition method was developed and cross-validated in (1)(8)F-FDG PET studies of a model of a brain tumour implantation.

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[822]

TÍTULO / TITLE:  - Vascular distribution of glioblastoma multiforme at diagnosis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Interv Neuroradiol. 2013 Mar;19(1):127-31. Epub 2013 Mar 4.

AUTORES / AUTHORS:  - Yohay K; Wolf DS; Aronson LJ; Duus M; Melhem ER; Cohen KJ

INSTITUCIÓN / INSTITUTION:  - Departments of Neurology (DSW) and The Sidney Kidney Kimmel Comprehensive Cancer  Center at Johns Hopkins (LJA, MD, KJC); Baltimore, USA; Department of Pediatrics  (KY), Weill Cornell Medical College; New York, NY, USA; epartment of Radiology (ERM), University of Pennsylvania; Philadelphia, PA, USA - E-mail: kcohen@jhmi.edu.

RESUMEN / SUMMARY:  - Treatment of high-grade gliomas with selective intra-arterial (IA) administration of chemotherapies has been proposed, and utilized as a therapeutic modality. This approach offers the conceptual benefit of providing maximal delivery of the agent to the tumor bed, while potentially reducing systemic exposure to the agent. This retrospective study was designed to determine the vascular distribution of glioblastoma multiforme (GBM) at the time of diagnosis in an effort to determine  what proportion of patients would likely be candidates for this approach. The preoperative MRI scans of 50 patients with GBM were analyzed and compared to published normative data of intracranial vascular distribution. Vascular distribution was determined by analyzing post-gadolinium axial and coronal T1 images, axial T2 images, and axial T2 images with an additional 1 cm margin (T2 + 1 cm) added in all dimensions. T1 analysis demonstrated 60% of tumors in a single vascular distribution. T2 analysis of these tumors reduced that number to 34%. When the T2 + 1 cm margin was utilized, only 6% of tumors were in a single vascular distribution. 66% of tumors were limited to the anterior circulation on  T1 imaging but only 34% on T2 + 1 cm imaging. 30% of tumors were also within the  distribution of the anterior choroidal artery. These findings suggest that the use of selective IA administration of agents is necessarily limited to a fraction of presenting patients or will require administration via multiple cerebral arteries.

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[823]

TÍTULO / TITLE:  - A Novel, Diffusely Infiltrative Xenograft Model of Human Anaplastic Oligodendroglioma with Mutations in FUBP1, CIC, and IDH1.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(3):e59773. doi: 10.1371/journal.pone.0059773. Epub 2013 Mar 19.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059773

AUTORES / AUTHORS:  - Klink B; Miletic H; Stieber D; Huszthy PC; Valenzuela JA; Balss J; Wang J; Schubert M; Sakariassen PO; Sundstrom T; Torsvik A; Aarhus M; Mahesparan R; von Deimling A; Kaderali L; Niclou SP; Schrock E; Bjerkvig R; Nigro JM

INSTITUCIÓN / INSTITUTION:  - Institut fur Klinische Genetik, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany.

RESUMEN / SUMMARY:  - OLIGODENDROGLIOMA POSES A BIOLOGICAL CONUNDRUM FOR MALIGNANT ADULT HUMAN GLIOMAS: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as  intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma  in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in  the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

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[824]

TÍTULO / TITLE:  - Neuronavigation used for the transsphenoidal resection of a pituitary adenoma accompanied by a concha sphenoid sinus.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Endocrinol Lett. 2012;33(8):765-8.

AUTORES / AUTHORS:  - Sun L; Gao Y; Fu C; Li F; Zhao C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Jilin University, Changchun, Jilin Province, China.

RESUMEN / SUMMARY:  - A concha non-pneumatized sphenoid is considered to be a contraindication for the  transsphenoidal resection of a pituitary adenoma. Specifically, this anatomical variation makes it difficult to approach the sella turcica. However, in this report, an intra-operative navigational system was used as a guide to access the  sella through the sphenoid sinus. This procedure was found to be both reasonable  and safe.

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[825]

TÍTULO / TITLE:  - Immunoexcitatory mechanisms in glioma proliferation, invasion and occasional metastasis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2013;4:15. doi: 10.4103/2152-7806.106577. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.106577

AUTORES / AUTHORS:  - Blaylock RL

INSTITUCIÓN / INSTITUTION:  - Theoretical Neurosciences LLC, Visiting Professor of Biology, Department of Biology, Belhaven University, Jackson, MS 39157, USA.

RESUMEN / SUMMARY:  - There is increasing evidence of an interaction between inflammatory cytokines and glutamate receptors among a number of neurological diseases including traumatic brain injuries, neurodegenerative diseases and central nervous system (CNS) infections. A number of recent studies have now suggested a strong relation between inflammatory mechanisms and excitatory cascades and these may play a role in glioma invasiveness and proliferation. Chronic inflammation appears to be a major initiating mechanism in most human cancers, involving cell-signaling pathways, which are responsible for cell cycling, cancer cell migration, invasion, tumor aggressiveness, and angiogenesis. It is less well appreciated that glutamate receptors also play a significant role in both proliferation and especially glioma invasion. There is some evidence that sustained elevations in glutamate may play a role in initiating certain cancers and new studies demonstrate an interaction between inflammation and glutamate receptors that may  enhance tumor invasion and metastasis by affecting a number of cell-signaling mechanisms. These mechanisms are discussed in this paper as well as novel treatment options for reducing immune-glutamate promotion of cancer growth and invasion.

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[826]

TÍTULO / TITLE:  - MAGNETIC RESONANCE IMAGING FEATURES OF INTRACRANIAL GRANULAR CELL TUMORS IN SIX DOGS.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Vet Radiol Ultrasound. 2013 Mar 25. doi: 10.1111/vru.12027.

            ●● Enlace al texto completo (gratuito o de pago) 1111/vru.12027

AUTORES / AUTHORS:  - Anwer CC; Vernau KM; Higgins RJ; Dickinson PJ; Sturges BK; Lecouteur RA; Bentley RT; Wisner ER

INSTITUCIÓN / INSTITUTION:  - Department of Surgical and Radiological Sciences, University of California - Davis, Davis, CA.

RESUMEN / SUMMARY:  - Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether  distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.

 

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[827]

TÍTULO / TITLE:  - Intraneural OX7-saporin for neuroma-in-continuity in a rat model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Orthop Surg Traumatol. 2013 Apr;23(3):263-72. doi: 10.1007/s00590-012-0996-x. Epub 2012 Apr 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00590-012-0996-x

AUTORES / AUTHORS:  - Mavrogenis AF; Pavlakis K; Stamatoukou A; Papagelopoulos PJ; Theoharis S; Zetahang Z; Soucacos PN; Zoubos AB

INSTITUCIÓN / INSTITUTION:  - First Department of Orthopaedics, Athens University Medical School, 41 Ventouri Street, 15562, Holargos, Athens, Greece, afm@otenet.gr.

RESUMEN / SUMMARY:  - We employed 54 rats to devise a model of neuroma-in-continuity and explore the effect of the immunotoxin OX7-saporin on the neuroma. The left common peroneal, tibial or sciatic nerves were crushed by one 10-s application of a micro-artery forceps. At 3 and 6 weeks, the nerve was cut distal to the site of nerve crush, and retrograde fluorescent labeling was done. Pressure microinjection of 2 mul of natural saline or 2 mul of the immunotoxin conjugate OX7-saporin was done at the  nerve stump 2 days later. Sacrifice was done after 3 weeks. In all control and saline-injection nerve specimens, gross observation and histology showed a neuroma-in-continuity. In 19 of the 24 OX7-saporin nerve specimens, gross observation showed a narrowed area at the site of nerve crush. Histology showed inhibition of neuroma-in-continuity formation. Fluorescent microscopy showed ablation of the labeled neurons in the dorsal root ganglia corresponding to the OX7-saporin subgroups.

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[828]

TÍTULO / TITLE:  - Prevalence of primary and metastatic brain tumors: a five-year single-center survey in Zahedan (Iran).

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Inj Violence Res. 2012 Nov;4(3 Suppl 1). pii: Paper No. 3.

AUTORES / AUTHORS:  - Salehi M; Shahlaee A; Rahimi-Movaghar V

INSTITUCIÓN / INSTITUTION:  - Sina Trauma and Surgery Research Center, Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: There are a few well documented reports about epidemiologic features  of brain tumors (BTs) in Iran. The present study was aimed to epidemiologically review the prevalence and trends of brain tumors, treated in a neurosurgical center in Zahedan over five years. METHODS: We analyzed the data compiled from 112 patients with brain tumors operated on in Khatam-ol-Anbia Hospital (Zahedan,  Iran) during 1992 to 1996. Data related to the age, gender, tumor site, tumor pathology, symptoms, signs, and first clinical manifestation were collected and analyzed. The prevalence of different histological types of brain tumors was analyzed from the data of operative biopsies/ surgeries/ resections. RESULTS: The male to female occurrence ratio was 1.07 (51.8% males, 48.2% females). Brain tumors were most commonly diagnosed in the 31-40 year age group (23.2%) followed  by the 11-20 year (17.9%) and 51-60 year (15.2%) age groups. And finally, the 41-50 year age group showed the lowest percent (3.6%) of BTs. The five most common histological types of BTs were astrocytoma (25.9%) followed by meningioma  (17.9%), pituitary adenoma (8.9%), oligodendroglioma (8.9%), and ependymoma (7.1%). 6.3% of tumors were of metastasis stage. We found that 26% of brain tumors were located in cerebellum, 26% in the parietal lobe, 13% in frontal lobe, and 10% in the temporal lobe. The most common primary symptoms were headache (40%), vomiting (13%), and seizure (10%). The most common overall signs/symptoms  were headache (98%), vomiting (40%), hemiparesis (37%), papilledema (22%), and visual loss (20%). CONCLUSIONS: Findings of our study present an epidemiological  basis for understanding the brain tumor burden in Iran. Moe comprehensice epidemiological studies of a prospective nature are further required in this respect. KEYWORDS: Central Nervous System Tumors, Epidemiology, Brain tumors.

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[829]

TÍTULO / TITLE:  - Selective use of peri-operative steroids in pituitary tumor surgery: escape from  dogma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Endocrinol (Lausanne). 2013;4:30. doi: 10.3389/fendo.2013.00030. Epub 2013  Mar 18.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fendo.2013.00030

AUTORES / AUTHORS:  - Regan J; Watson J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosciences, Inova Health Systems Falls Church, VA, USA.

RESUMEN / SUMMARY:  - Objective: Traditional neurosurgical practice calls for administration of peri-operative stress-dose steroids for sellar-suprasellar masses undergoing operative treatment. This practice is considered critical to prevent peri-operative complications associated with hypoadrenalism, such as hypotension  and circulatory collapse. However, stress-dose steroids complicate the management of these patients. It has been our routine practice to use stress steroids during surgery only if the patient has clinical or biochemical evidence of hypocortisolism pre-operatively. We wanted to be certain that this practice was safe. Methods: We present our retrospective analysis from a consecutive series of 114 operations in 109 patients with sellar and/or suprasellar tumors, the majority of whom were managed without empirical stress-dose steroid coverage. Only patients who were hypoadrenal pre-operatively or who had suffered apoplexy were given stress-dose coverage during surgery. We screened for biochemical evidence of hypoadrenalism as a result of surgery by measuring immediate post-operative AM serum cortisol levels. Results: There were no adverse events related to the selective use of cortisol replacement in this patient population.  Conclusion: Our experience demonstrates that selective use of corticosteroid replacement is safe; it simplifies the management of the patients, and has advantages over empiric “dogmatic” steroid coverage.

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[830]

TÍTULO / TITLE:  - Surface-modified polymeric nanoparticles for targeted delivery to glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nanomedicine (Lond). 2013 Feb;8(2):170-1.

AUTORES / AUTHORS:  - Joshi M

INSTITUCIÓN / INSTITUTION:  - Midwestern University, Chicago College of Pharmacy, Downers Grove, IL 60515, USA. mjoshi@midwestern.edu

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[831]

TÍTULO / TITLE:  - Genome-wide associations of signaling pathways in glioblastoma multiforme.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Med Genomics. 2013 Mar 28;6:11. doi: 10.1186/1755-8794-6-11.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1755-8794-6-11

AUTORES / AUTHORS:  - Wuchty S; Vazquez A; Bozdag S; Bauer PO

INSTITUCIÓN / INSTITUTION:  - National Center of Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA. wuchtys@ncbi.nlm.nih.gov.

RESUMEN / SUMMARY:  - BACKGROUND: eQTL analysis is a powerful method that allows the identification of  causal genomic alterations, providing an explanation of expression changes of single genes. However, genes mediate their biological roles in groups rather than in isolation, prompting us to extend the concept of eQTLs to whole gene pathways. METHODS: We combined matched genomic alteration and gene expression data of glioblastoma patients and determined associations between the expression of signaling pathways and genomic copy number alterations with a non-linear machine  learning approach. RESULTS: Expectedly, over-expressed pathways were largely associated to tag-loci on chromosomes with signature alterations. Surprisingly, tag-loci that were associated to under-expressed pathways were largely placed on  other chromosomes, an observation that held for composite effects between chromosomes as well. Indicating their biological relevance, identified genomic regions were highly enriched with genes having a reported driving role in gliomas. Furthermore, we found pathways that were significantly enriched with such driver genes. CONCLUSIONS: Driver genes and their associated pathways may represent a functional core that drive the tumor emergence and govern the signaling apparatus in GBMs. In addition, such associations may be indicative of  drug combinations for the treatment of brain tumors that follow similar patterns  of common and diverging alterations.

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[832]

TÍTULO / TITLE:  - Bmi-1 promotes glioma angiogenesis by activating NF-kappaB signaling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55527. doi: 10.1371/journal.pone.0055527. Epub 2013 Jan 31.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055527

AUTORES / AUTHORS:  - Jiang L; Song L; Wu J; Yang Y; Zhu X; Hu B; Cheng SY; Li M

INSTITUCIÓN / INSTITUTION:  - Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, China.

RESUMEN / SUMMARY:  - Angiogenesis in glioma is associated with the poor prognosis of the disease and closely correlates with the highly invasive phenotype of glioma cells, which represents the most challenging impediment against the currently glioma treatments. Bmi-1, an onco-protein, has been implicated in the progression of various human cancers, including gliomas, whereas its role in glioma angiogenesis remains unclear. Our current study examined the effects of Bmi-1 on glioma angiogenesis in vitro as well as in vivo. We found that overexpression of Bmi-1 enhanced, whereas knockdown of Bmi-1 diminished, the capability of glioma cells to induce tubule formation and migration of endothelial cells and neovascularization in chicken chorioallantoic membrane. In vivo, Bmi-1 overexpression and knockdown, respectively, promoted and inhibited angiogenesis in orthotopically transplanted human gliomas. Furthermore, NF-kappaB activity and VEGF-C expression was induced by Bmi-1 overexpression, whereas Bmi-1 knockdown attenuated NF-kappaB signaling and decreased VEGF-C expression. Additionally suppression of NF-kappaB activity using a specific chemical inhibitor abrogated the NF-kappaB activation and the pro-angiogenic activities of glioma cells. Together, our data suggest that Bmi-1 plays an important role in glioma angiogenesis and therefore could represent a potential target for anti-angiogenic therapy against the disease.

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[833]

TÍTULO / TITLE:  - MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e54652. doi: 10.1371/journal.pone.0054652. Epub 2013 Feb 4.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054652

AUTORES / AUTHORS:  - Lee HK; Bier A; Cazacu S; Finniss S; Xiang C; Twito H; Poisson LM; Mikkelsen T; Slavin S; Jacoby E; Yalon M; Toren A; Rempel SA; Brodie C

INSTITUCIÓN / INSTITUTION:  - Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan, USA.

RESUMEN / SUMMARY:  - Glioblastomas (GBM), the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis  and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs) compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF) as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3’-UTR fused to  luciferase. Overexpression of a CTGF plasmid lacking the 3’-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression  in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors.

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[834]

TÍTULO / TITLE:  - Intradural lipoma: timely intervention is what matters.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Mar 14;2013. pii: bcr2013008820. doi: 10.1136/bcr-2013-008820.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2013-008820

AUTORES / AUTHORS:  - Kumar N; Kumar G; Dembla G; Trisal D

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, PGIMER & Dr Ram Manohar Lohia Hospital, New Delhi, India.

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[835]

TÍTULO / TITLE:  - Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Mar 19;8(1):65.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-65

AUTORES / AUTHORS:  - Barazzuol L; Jena R; Burnet NG; Meira LB; Jeynes JC; Kirkby KJ; Kirkby NF

RESUMEN / SUMMARY:  - BACKGROUND: The cytotoxicity of radiotherapy and chemotherapy can be enhanced by  modulating DNA repair. PARP is a family of enzymes required for an efficient base-excision repair of DNA single-strand breaks and inhibition of PARP can prevent the repair of these lesions. The current study investigates the trimodal  combination of ABT-888, a potent inhibitor of PARP1-2, ionizing radiation and temozolomide(TMZ)-based chemotherapy in glioblastoma (GBM) cells. METHODS: Four human GBM cell lines were treated for 5 h with 5 muM ABT-888 before being exposed to X-rays concurrently with TMZ at doses of 5 or 10 muM for 2 h. ABT-888[prime]s  PARP inhibition was measured using immunodetection of poly(ADP-ribose) (pADPr). Cell survival and the different cell death pathways were examined via clonogenic  assay and morphological characterization of the cell and cell nucleus. RESULTS: Combining ABT-888 with radiation yielded enhanced cell killing in all four cell lines, as demonstrated by a sensitizer enhancement ratio at 50% survival (SER50)  ranging between 1.12 and 1.37. Radio- and chemo-sensitization was further enhanced when ABT-888 was combined with both X-rays and TMZ in the O6-methylguanine-DNA-methyltransferase (MGMT)-methylated cell lines with a SER50  up to 1.44. This effect was also measured in one of the MGMT-unmethylated cell lines with a SER50 value of 1.30. Apoptosis induction by ABT-888, TMZ and X-rays  was also considered and the effect of ABT-888 on the number of apoptotic cells was noticeable at later time points. In addition, this work showed that ABT-888 mediated sensitization is replication dependent, thus demonstrating that this effect might be more pronounced in tumour cells in which endogenous replication lesions are present in a larger proportion than in normal cells. CONCLUSIONS: This study suggests that ABT-888 has the clinical potential to enhance the current standard treatment for GBM, in combination with conventional chemo-radiotherapy. Interestingly, our results suggest that the use of PARP inhibitors might be clinically significant in those patients whose tumour is MGMT-unmethylated and currently derive less benefit from TMZ.

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[836]

TÍTULO / TITLE:  - ARID1A is a tumour suppressor and inhibits glioma cell proliferation via the PI3K pathwa.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Head Neck Oncol. 2013 Jan 14;5(1):6.

AUTORES / AUTHORS:  - Zeng Y; Liu Z; Yang J; Liu Y; Huo L; Li Z; Lan S; Wu J; Chen X; Yang K; Li C; Li M; Liu J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, USA Corresponding authors Email: xylancet@yahoo.com.cn; min.li@uth.tmc.edu.

RESUMEN / SUMMARY:  - The AT-rich interactive domain 1A gene (ARID1A) plays an important role in malignant tumorigenesis, but its role in gliomas remains unclear. This study aims to identify a possible biomarker that could be used in the diagnosis and tumour grade assessment of gliomas. Additionally, the biological role of ARID1A was further characterized in glioma cells. Data were collected from sporadic glioma specimens (n = 55) and normal brain tissues (n = 5), and ARID1A expression was examined by quantitative RT-PCR and Western blot. We verified the differential expression of ARID1A and evaluated the associations of ARID1A expression with the pathological characteristics of gliomas. An ARID1A overexpression plasmid was constructed and transfected into the human glioblastoma cell line U87, and cell proliferation and apoptosis were examined. Our results showed that the ARID1A mRNA in gliomas was significantly down-regulated compared with that in normal brain tissues. As the pathological grade (World Health Organization classification 2007) increased, the expression of ARID1A decreased. Overexpression of ARID1A was able to inhibit cell proliferation and arrest cell cycle progression in the G1/S phase as well as induce cell apoptosis in glioma cells. Furthermore, ARID1A overexpression was accompanied by the suppression of glioma cell proliferation via the phosphatidylinositol 3-kinase pathway and decreased expression of pAKT and pS6K. Therefore, ARID1A may be a useful target for the diagnosis and therapy of gliomas.

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[837]

TÍTULO / TITLE:  - A computational multiscale model of glioblastoma growth: regulation of cell migration and proliferation via microRNA-451, LKB1 and AMPK.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:6620-3. doi: 10.1109/EMBC.2012.6347512.

            ●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6347512

AUTORES / AUTHORS:  - Schuetz TA; Becker S; Mang A; Toma A; Buzug TM

INSTITUCIÓN / INSTITUTION:  - Institute of Medical Engineering, University of Luebeck, 23562 Luebeck, Germany.  fschuetz@imt.uni-luebeck.de

RESUMEN / SUMMARY:  - A new computational multiscale model of glioblastoma growth is introduced. This model combines an agent-based model for representing processes on the cellular level with a molecular interaction network for each cell on the subcellular scale. The network is based on recently published work on the interaction of microRNA-451, LKB1 and AMPK in the regulation of glioblastoma cell migration and  proliferation. We translated this network into a mathematical description by the  use of 17 ordinary differential equations. In our model, we furthermore establish a link from the molecular interaction network of a single cell to cellular actions (e.g. chemotactic movement) on the microscopic level. First results demonstrate that the computational model reproduces a tumor cell development comparable to that observed in in vitro experiments.

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[838]

TÍTULO / TITLE:  - Combined open microsurgical and endoscopic resection of hypothalamic hamartomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.2.PEDS12275

AUTORES / AUTHORS:  - Roth J; Bercu MM; Constantini S

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Neurosurgery, Dana Children’s Hospital, Tel Aviv Sourasky Medical Center, and Tel Aviv University, Tel Aviv, Israel.

RESUMEN / SUMMARY:  - Hypothalamic hamartomas (HHs) are typically located within the vicinity of the third ventricle. They can be attached to the walls of the third ventricle, within the interpeduncular cistern (third ventricle floor), and/or attached to the mammillary bodies and hypothalamus. Depending on their location, resection is performed either through the third ventricle, approaching from above, or via a frontotemporal craniotomy (pterional or frontoorbital), approaching from below. “Above” approaches typically include the transcallosal-anterior interforniceal approach, and recently, purely endoscopic approaches performed transforaminally.  The authors present a combined open and endoscopic approach for resection of HHs  located within the third ventricle. They used this approach in 2 young girls with relatively small lateral and third ventricles. Following an interhemispheric, transcallosal approach and exposure of the right foramen of Monro, an endoscope was inserted through the foramen, which enabled safe resection of the HH. The main advantage of the combined approach is when the lateral and third ventricles  are relatively small, making a purely endoscopic approach more challenging and possibly riskier.

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[839]

TÍTULO / TITLE:  - Endoscopic Assisted Resection of Prepontine Epidermoid Cysts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1328956

AUTORES / AUTHORS:  - Krass J; Hahn Y; Karami K; Babu S; Pieper DR

INSTITUCIÓN / INSTITUTION:  - Section of Neurosurgery, St. John Providence Hospital & Medical Centers, Michigan State University, Southfield, Michigan, United States.

RESUMEN / SUMMARY:  - Objective/Background To describe an innovative endoscopic technique to treat prepontine epidermoid cysts. These cysts are typically resected in a microsurgical fashion and can be associated with significant risks and complications. This report is the first description of an endoscopic-assisted removal of an epidermoid cyst without the use of the operative microscope and evaluates the operative findings, technique, and postoperative course.Study Design Retrospective review at tertiary referral center.Methods Two patients, one with rapidly progressive headache and ataxia, and another with trigeminal neuralgia were found to have mixed-intensity cystic lesions of the prepontine region consistent with an epidermoid cyst. A detailed description of the preoperative preparation, surgical approach, intraoperative technique, pre- and post-operative imaging findings and monitoring outcomes are emphasized.Results Both patients underwent resection of the epidermoid cyst using an endoscope-assisted technique. The procedures were 3 and 4 hours in duration with  an estimated blood loss of 50 cc in both operations. No intraoperative complications occurred. The patients were discharged from the hospital on postoperative days 2 and 3, respectively. Postoperative imaging revealed no edema of the cerebellum and complete resolution of the cyst. Neurological examination revealed improvement of preoperative symptoms with complete resolution of headache and ataxia of case 1, with resolution of trigeminal neuralgia in case 2. Case 2 did develop an ipsilateral cranial nerve (CN) VI paresis postoperatively that resolved over a 3-week period. The patient from case 1 remains symptom free  after 24-months with magnetic resonance imaging (MRI) consistent with gross-total resection of the epidermoid cyst. Case 2 has continued resolution of trigeminal neuralgia and CN VI palsy with 12-month follow-up MRI consistent with gross total resection.Conclusions The use of the endoscope as the sole means to access the posterior fossa to treat prepontine cystic lesions affords the surgeon excellent  visualization with minimal cerebellar retraction and can be done in a safe and effective manner with little to no morbidity.

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[840]

TÍTULO / TITLE:  - Cancer as the Main Aging Factor for Humans: The Fundamental Role of 5-Methoxy-Tryptamine in Reversal of Cancer-Induced Aging Processes in Metabolic and Immune Reactions by Non-melatonin Pineal Hormones.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Aging Sci. 2012 Dec 1;5(3):231-5.

AUTORES / AUTHORS:  - Lissoni P; Messina G; Rovelli F

INSTITUCIÓN / INSTITUTION:  - Psychiatric Division, Policlinico Hospital, Milan, Italy. giusy.messina@libero.it.

RESUMEN / SUMMARY:  - Aging and advanced cancer are characterized by similar neuroendocrine and immune  deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in  human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients  receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.

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[841]

TÍTULO / TITLE:  - Transzygomatic approach with intraoperative neuromonitoring for resection of middle cranial fossa tumors.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg B Skull Base. 2012 Feb;73(1):28-35. doi: 10.1055/s-0032-1304561.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1304561

AUTORES / AUTHORS:  - Son BC; Lee SW; Kim S; Hong JT; Sung JH; Yang SH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea.

RESUMEN / SUMMARY:  - The authors reviewed the surgical experience and operative technique in a series  of 11 patients with middle fossa tumors who underwent surgery using the transzygomatic approach and intraoperative neuromonitoring (IOM) at a single institution. This approach was applied to trigeminal schwannomas (n = 3), cavernous angiomas (n = 3), sphenoid wing meningiomas (n = 3), a petroclival meningioma (n = 1), and a hemangiopericytoma (n = 1). An osteotomy of the zygoma, a low-positioned frontotemporal craniotomy, removal of the remaining squamous temporal bone, and extradural drilling of the sphenoid wing made a flat trajectory to the skull base. Total resection was achieved in 9 of 11 patients. Significant motor pathway damage can be avoided using a change in motor-evoked potentials as an early warning sign. Four patients experienced cranial nerve palsies postoperatively, even though free-running electromyography of cranial nerves showed normal responses during the surgical procedure. A simple transzygomatic approach provides a wide surgical corridor for accessing the cavernous sinus, petrous apex, and subtemporal regions. Knowledge of the middle fossa structures is essential for anatomic orientation and avoiding injuries to neurovascular structures, although a neuronavigation system and IOM helps orient  neurosurgeons.

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[842]

TÍTULO / TITLE:  - Image-guided resection of malignant gliomas using fl uorescent nanoparticles.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013 Feb 1. doi: 10.1002/wnan.1212.

            ●● Enlace al texto completo (gratuito o de pago) 1002/wnan.1212

AUTORES / AUTHORS:  - Su X; Cheng K; Wang C; Xing L; Wu H; Cheng Z

INSTITUCIÓN / INSTITUTION:  - Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Bio-X Program and Stanford Cancer Center, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Stanford, CA, USA; Department  of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen  University, Xiamen, P.R. China.

RESUMEN / SUMMARY:  - Intraoperative fluorescence imaging especially near-infrared fluorescence (NIRF)  imaging has the potential to revolutionize neurosurgery by providing high sensitivity and real-time image guidance to surgeons for defining gliomas margins. Fluorescence probes including targeted nanoprobes are expected to improve the specificity and selectivity for intraoperative fluorescence or NIRF tumor imaging. The main focus of this article is to provide a brief overview of intraoperative fluorescence imaging systems and probes including fluorescein sodium, 5-aminolevulinic acid, dye-containing nanoparticles, and targeted NIRF nanoprobes for their applications in image-guided resection of malignant gliomas. Moreover, photoacoustic imaging is a promising molecular imaging modality, and its potential applications for brain tumor imaging are also briefly discussed. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1212 For further resources related to this article, please visit the WIREs website.

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[843]

TÍTULO / TITLE:  - Four-year follow-up study in a NF1 boy with a focal pontine hamartoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ital J Pediatr. 2013 Feb 11;39:10. doi: 10.1186/1824-7288-39-10.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1824-7288-39-10

AUTORES / AUTHORS:  - Parisi P; Persechino S; Paolino MC; Nicita F; Torrente I; Bozzao A; Villa MP

INSTITUCIÓN / INSTITUTION:  - Child Neurology, Chair of Paediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University c/o St Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy. pasquale.parisi@uniroma1.it

RESUMEN / SUMMARY:  - Neurofibromatosis is a collective name for a group of genetic conditions in which benign tumours affect the nervous system. Type 1 is caused by a genetic mutation  in the NF1 gene (OMIM 613113) and symptoms can vary dramatically between individuals, even within the same family. Some people have very mild skin changes, whereas others suffer severe medical complications. The condition usually appears in childhood and is diagnosed if two of the following are present: six or more cafe-au-lait patches larger than 1.5 cm in diameter, axillary or groin freckling, 2 or more Lisch nodules (small pigmented areas in the iris of the eye), 2 or more neurofibromas, optic pathway gliomas, bone dysplasia, and a first-degree family relative with Neurofibromatosis type 1. The  pattern of inheritance is autosomal dominant, however, half of all NF1 cases are  ‘sporadic’ and there is no family history. Neurofibromatosis type 1 is an extremely variable condition whose morbidity and mortality is largely dictated by the occurrence of the many complications that may involve any of the body systems. We describe a family affected by NF1 in whom genetic molecular analysis  identified the same mutation in the son and father. Routine MRI showed pontine focal lesions in the eight-year-old son, though not in the father. We performed a four years follow-up study and at follow-up pontine hamartoma size remained unchanged in the son, and the father showed still no brain lesions, confirming thus an intra-familial phenotype variability.

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[844]

TÍTULO / TITLE:  - Coincidence of spinal tumor (astrocytoma) and non-specific encephalomyelitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Endocrinol Lett. 2012 Dec 1;33(7).

AUTORES / AUTHORS:  - Burgetova A; Vaneckova M; Nytrova P; Matej R; Seidl Z

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, General Teaching Hospital, First Faculty of Medicine, Charles University in Prague, Czech Republic.

RESUMEN / SUMMARY:  - The aim of this paper is to demonstrate that differential diagnostics of intra-medullary spinal lesions can sometimes be very difficult, even when the latest complement examinations are used, including magnetic resonance imaging. The particular case dealt with here was complicated by the presence of two different pathological processes. We present the case report, where the case history, clinical course and results of the paraclinical examinations, including  the magnetic resonance imaging, suggested an intra-medullary inflammatory/demyelinating process. The post-mortem histological finding was a surprise, because besides signs of non-specific encephalomyelitis, it also displayed signs of a spinal tumor (histological character of diffuse astrocytoma  grade II-III). We would like to emphasize some important facts in our discussion, especially from the perspective of the magnetic resonance imaging. Finally, we would like to ask if the presence of both pathologies (astrocytoma and nonspecific myelitis) was coincidental, or if the myelitis had an iatrogenic etiology (by therapy, by infection during the lumbar punctions).

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[845]

TÍTULO / TITLE:  - Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Radiol. 2013 Jan 28;5(1):20-4. doi: 10.4329/wjr.v5.i1.20.

            ●● Enlace al texto completo (gratuito o de pago) 4329/wjr.v5.i1.20

AUTORES / AUTHORS:  - Kanza RE; Gagnon S; Villeneuve H; Laverdiere D; Rousseau I; Bordeleau E; Berube M

INSTITUCIÓN / INSTITUTION:  - Rene Epunza Kanza, Isabelle Rousseau, Edith Bordeleau, Michel Berube, Department  of Radiology, Chicoutimi Hospital, Saguenay, Quebec G7H5H6, Canada.

RESUMEN / SUMMARY:  - We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult, non-pregnant woman. Her condition was triggered by unrecognized primary hypothyroidism, which regressed after thyroid hormone replacement therapy. This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism, which are not well known in the medical and radiological profession. Such improved knowledge will help avoid delays in diagnosis, progression to life-threatening complications, and unnecessary surgery.

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[846]

TÍTULO / TITLE:  - Intracranial phosphaturic mesenchymal tumor, mixed connective tissue variant presenting without oncogenic osteomalacia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3:151. doi: 10.4103/2152-7806.104745. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.104745

AUTORES / AUTHORS:  - Bower RS; Daugherty WP; Giannini C; Parney IF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Mayo Clinic College of Medicine, 200, 1 St. SW, Rochester, MN, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia. CASE DESCRIPTION: A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection  of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia. CONCLUSION: This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia.

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[847]

TÍTULO / TITLE:  - Disseminated glioneuronal tumor with neuropil-like islands of the spinal cord: A  distinctive entity.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 8. pii: S1878-8750(13)00294-5. doi: 10.1016/j.wneu.2013.02.029.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.029

AUTORES / AUTHORS:  - Serra SM; Dabdoub CB; da Cunha AH; Salazar B; Lima TP; Azevedo-Filho HC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Restauracao Hospital, Recife, Pernambuco, Brazil.

RESUMEN / SUMMARY:  - BACKGROUND: Glioneuronal tumors with neuropil-like islands (GTNI) was recently added as a novel lesion in the most recent update of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) in 2007. Since this tumor’s initial description, approximately 28 cases of GTNI have been published. In this report, we describe the ninth case of a spinal GTNI  in the world literature. CASE DESCRIPTION: We report here a case arising in a 2-year-old female patient who presented headaches associated with intermittent vomiting due to a tetraventricular hydrocephalus. After ventricularperitoneal shunt placement, the patient presented lower extremity motor weakness and sensory disturbance. A dorso-lumbar spine magnetic resonance imaging (MRI) scan revealed  an intramedullary spinal neoplasm involving T12 through L2 in association with the thick linear enhancement of the spinal cord surfaces. A brain MRI demonstrated focal leptomeningeal enhancement in the Sylvian fissures, the basal  cistern, tentorium and multiple small cystic-like lesions extending on the cerebellar surface, brain stem, and temporal lobes. The patient underwent a T11-L2 laminectomy for a gross-total tumor resection. Histology revealed a WHO grade II GTNI. CONCLUSION: GTNI is a rare type of glioneuronal tumor recently described in the literature. The outcome of these tumors seems to have an unfavorable clinical course despite their low-grade morphology. However, the combination of gross-total resection and adjuvant chemo-radiotherapy can enhance  chances for longer survival among children with spinal GTNI associated with meningeal dissemination, and a clinical follow-up of a large series will be necessary to evaluate the long-term prognosis.

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[848]

TÍTULO / TITLE:  - Letter to the Editor: Pilomyxoid astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2011.10.PEDS11420

AUTORES / AUTHORS:  - Amirjamshidi A; Alimohammadi M

INSTITUCIÓN / INSTITUTION:  - Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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[849]

TÍTULO / TITLE:  - A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54916. doi: 10.1371/journal.pone.0054916. Epub 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054916

AUTORES / AUTHORS:  - Curtis VF; Wang H; Yang P; McLendon RE; Li X; Zhou QY; Wang XF

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.

RESUMEN / SUMMARY:  - Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in  many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate myeloid cell mobilization from the bone marrow, leading to activation of the angiogenic process, as well as accumulation of macrophages and neutrophils in the tumor site. Neutralizing antibodies against PK2 were shown to display potent anti-tumor efficacy, illustrating the potential of PK2-antagonists as therapeutic agents for the treatment of cancer. In this study we demonstrate the  anti-tumor activity of a small molecule PK2 antagonist, PKRA7, in the context of  glioblastoma and pancreatic cancer xenograft tumor models. For the highly vascularized glioblastoma, PKRA7 was associated with decreased blood vessel density and increased necrotic areas in the tumor mass. Consistent with the anti-angiogenic activity of PKRA7 in vivo, this compound effectively reduced PK2-induced microvascular endothelial cell branching in vitro. For the poorly vascularized pancreatic cancer, the primary anti-tumor effect of PKRA7 appears to be mediated by the blockage of myeloid cell migration/infiltration. At the molecular level, PKRA7 inhibits PK2-induced expression of certain pro-migratory chemokines and chemokine receptors in macrophages. Combining PKRA7 treatment with standard chemotherapeutic agents resulted in enhanced effects in xenograft models for both types of tumor. Taken together, our results indicate that the anti-tumor activity of PKRA7 can be mediated by two distinct mechanisms that are relevant to the pathological features of the specific type of cancer. This small molecule PK2 antagonist holds the promise to be further developed as an effective agent for combinational cancer therapy.

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[850]

TÍTULO / TITLE:  - Anaplastic medullary ependymoma presenting as subarachnoid hemorrhage.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Neurol Med. 2013;2013:701820. doi: 10.1155/2013/701820. Epub 2013 Mar 6.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2013/701820

AUTORES / AUTHORS:  - Nicastro N; Schnider A; Leemann B

INSTITUCIÓN / INSTITUTION:  - Neurorehabilitation Service, Department of Clinical Neurosciences, Geneva University Hospital, Avenue de Beau-Sejour 26, 1206 Geneva, Switzerland.

RESUMEN / SUMMARY:  - A-41-year old man presented with violent thunderclap headache and a bilateral proprioceptive sensibility deficit of the upper limbs. Cerebral CT scan and MRI were negative. Lumbar puncture confirmed subarachnoid hemorrhage (SAH), but cerebral angiography was negative. Three months later, the patient presented with paraparesis, and a thorough work-up revealed a diffuse, anaplastic extramedullary C7-D10 ependymoma with meningeal carcinomatosis considered the source of hemorrhage. The patient went through a D5-D8 laminectomy, temozolomide chemotherapy, and radiotherapy. The situation remained stable for a few months. In this paper, we would like to emphasize that spinal masses should be considered in cases of SAH with negative diagnostic findings for aneurysms or arteriovenous  malformation.

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[851]

TÍTULO / TITLE:  - Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Infect Agent Cancer. 2013 Feb 8;8(1):8. doi: 10.1186/1750-9378-8-8.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1750-9378-8-8

AUTORES / AUTHORS:  - Thirugnanam S; Rout N; Gnanasekar M

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Sciences, University of Illinois, College of Medicine, 1601 Parkview Ave, Rockford, IL, 61107, USA. mgnanas@uic.edu.

RESUMEN / SUMMARY:  - BACKGROUND: The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. PRESENTATION OF THE HYPOTHESIS: Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs), which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. TESTING THE HYPOTHESIS: The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as  brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. EXPECTED OUTCOME: The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. IMPLICATIONS OF THE HYPOTHESIS: Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and therapeutic tools against Toxoplasma driven brain cancers.

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[852]

TÍTULO / TITLE:  - Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - BMC Complement Altern Med. 2013 Feb 27;13:50. doi: 10.1186/1472-6882-13-50.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1472-6882-13-50

AUTORES / AUTHORS:  - Markiewicz-Zukowska R; Borawska MH; Fiedorowicz A; Naliwajko SK; Sawicka D; Car H

INSTITUCIÓN / INSTITUTION:  - The Department of Bromatology, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland. bromatos@umb.edu.pl.

RESUMEN / SUMMARY:  - BACKGROUND: Propolis is a honey bee product which contains many active compounds, such as CAPE or chrysin, and has many beneficial activities. Recently, its anti-tumor properties have been discussed. We have tested whether the ethanolic extract of propolis (EEP) interferes with temozolomide (TMZ) to inhibit U87MG cell line growth. METHODS: The U87MG glioblastoma cell line was exposed to TMZ (10-100 muM), EEP (10-100 mug/ml) or a mixture of TMZ and EEP during 24, 48 or 72 hours. The cell division was examined by the H3-thymidine incorporation, while the western blot method was used for detection of p65 subunit of NF-kappaB and ELISA test to measure the concentration of its p50 subunit in the nucleus. RESULTS: We have found that both, TMZ and EEP administrated alone, had a dose- and time-dependent inhibitory effect on the U87MG cell line growth, which was manifested by gradual reduction of cell viability and alterations in proliferation rate. The anti-tumor effect of TMZ (20 muM) was enhanced by EEP, which was especially well observed after a short time of exposition, where simultaneous usage of TMZ and EEP resulted in a higher degree of growth inhibition than each biological factor used separately. In addition, cells treated with TMZ presented no changes in NF-kappaB activity in prolonged time of  treatment and EEP only slightly reduced the nuclear translocation of this transcription factor. In turn, the combined incubation with TMZ and EEP led to an approximately double reduction of NF-kappaB nuclear localization. CONCLUSIONS: We conclude that EEP presents cytotoxic properties and may cooperate with TMZ synergistically enhancing its growth inhibiting activity against glioblastoma U87MG cell line. This phenomenon may be at least partially mediated by a reduced  activity of NF-kappaB.

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[853]

TÍTULO / TITLE:  - Neurenteric Cysts of the Cerebellopontine Angle.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Feb 8.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330860

AUTORES / AUTHORS:  - Roder C; Ebner FH; Schuhmann MU

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany.

RESUMEN / SUMMARY:  - Neurenteric cysts in the central nervous system are rare developmental malformations. Usually the cysts are located ventral to the high thoracic or low  cervical spinal cord. Only a few cases of intracranial neurenteric cysts have been reported in the literature to date. We report two cases of intracranial neurenteric cysts in the cerebellopontine angle with totally different radiographic, macroscopic, and microscopic appearance. As seen in these cases, the imaging spectrum of neurenteric cysts can be diverse, including malignancy-suspecting partial rim-enhancement or low-grade glioma features. Microsurgical therapy should include endoscopic assistance to ensure complete removal of cyst content.

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[854]

TÍTULO / TITLE:  - Inhibition of U-87 MG glioblastoma by AN-152 (AEZS-108), a targeted cytotoxic analog of luteinizing hormone-releasing hormone.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncotarget. 2013 Mar 7.

AUTORES / AUTHORS:  - Jaszberenyi M; Schally AV; Block NL; Nadji M; Vidaurre I; Szalontay L; Rick FG

INSTITUCIÓN / INSTITUTION:  - Veterans Affairs Medical Center, Miami, FL.

RESUMEN / SUMMARY:  - Glioblastoma multiforme is the most frequent tumor of the central nervous system  in adults and has a dismal clinical outcome, which necessitates the development of new therapeutic approaches. We investigated in vivo the action of the targeted cytotoxic analog of luteinizing hormone releasing hormone, AN-152 (AEZS-108) in nude mice (Ncr nu/nu strain) bearing xenotransplanted U-87 MG glioblastoma tumors. We evaluated in vitro the expression of LHRH receptors, proliferation, apoptosis and the release of oncogenic and tumor suppressor cytokines. Clinical and U-87 MG samples of glioblastoma tumors expressed LHRH receptors. Treatment of nude mice with AN-152, once a week at an intravenous dose of 413 nmol/20g, for six weeks resulted in 76 % reduction in tumor growth. AN-152 nearly completely abolished tumor progression and elicited remarkable apoptosis in vitro. Genomic (RT-PCR) and proteomic (ELISA, Western blot) studies revealed that AN-152 activated apoptosis, as reflected by the changes in p53 and its regulators and substrates, inhibited cell growth, and elicited changes in intermediary filament  pattern. AN-152 similarly reestablished contact regulation as demonstrated by expression of adhesion molecules and inhibited vascularization, as reflected by the transcription of angiogenic factors. Our findings suggest that targeted cytotoxic analog AN-152 (AEZS-108) should be considered for a treatment of glioblastomas.

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[855]

TÍTULO / TITLE:  - Hypothalamic hamartoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Feb 7;2013. pii: bcr2012008273. doi: 10.1136/bcr-2012-008273.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008273

AUTORES / AUTHORS:  - Grech R; Looby S; Thornton J; Brennan P

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, Beaumont Hospital, Dublin, Ireland. reubengrech@yahoo.com

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[856]

TÍTULO / TITLE:  - Incidental paraganglioma of the urinary bladder in a 66-year-old woman.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Mar 15;2013. pii: bcr2013008771. doi: 10.1136/bcr-2013-008771.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2013-008771

AUTORES / AUTHORS:  - Christodoulidou M; Lucky M; Mansour P; Gammal M

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Southport and Ormskirk Hospital NHS Trust, Southport, Merseyside, UK.

RESUMEN / SUMMARY:  - A 66-year-old female patient was referred to drology department when a bladder mass was incidentally found on a transvaginal ultrasound scan. Cystoscopy revealed a small, smooth mass just above the trigone which appeared to be covered with normal urothelium. The histology from this growth after transurethral resection revealed a paraganglioma of the bladder. We will discuss the management of this case and literature review of this finding in this study.

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[857]

TÍTULO / TITLE:  - Midbrain encephalitis associated with neoplasia.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pract Neurol. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1136/practneurol-2012-000395

AUTORES / AUTHORS:  - Nitkunan A; Lunn MP; Plant GT; Schon F

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Atkinson Morley Wing, St George’s Hospital, , London, UK.

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[858]

TÍTULO / TITLE:  - Adrenal ganglioneuroma: a rare incidental finding.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 30;2013. pii: bcr2012008067. doi: 10.1136/bcr-2012-008067.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008067

AUTORES / AUTHORS:  - Leao RR; Pereira BJ; Borges R; Grenha V

INSTITUCIÓN / INSTITUTION:  - Department of Urology and Renal Transplantation, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal. romaoleao@gmail.com

RESUMEN / SUMMARY:  - The widespread use of imaging technology as a diagnostic tool has resulted in the identification of many previously unknown, clinically benign lesions. The current era of easy access to imaging studies places physicians in a difficult position,  since many lesions are not precisely diagnosed by imaging. For example, the accurate diagnosis of non-functioning adrenal lesions remains a clinical challenge. This report describes a patient with the incidental CT finding of an uncommon adrenal ganglioneuroma. Clinical and radiological findings can guide suspicion towards this rare lesion; however, the actual diagnosis is based on histological findings. Specific characteristics of adrenal ganglioneuromas that would allow their diagnosis without invasive procedures have not been established. This case report is an attempt to add more data that will help to establish diagnostic criteria for this rare disease.

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[859]

TÍTULO / TITLE:  - Editorial: Hypothalamic hamartomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Mar 22.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.10.PEDS12413

AUTORES / AUTHORS:  - Rekate HL

INSTITUCIÓN / INSTITUTION:  - The Chiari Institute, Great Neck, New York.

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[860]

TÍTULO / TITLE:  - What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hormones (Athens). 2012 Oct;11(4):477-82.

AUTORES / AUTHORS:  - Phillips J; East HE; French SE; Melcescu E; Hamilton RD; Nicholas WC; Fratkin JF; Parent AD; Luzardo G; Koch CA

INSTITUCIÓN / INSTITUTION:  - Division of Endocrinology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT: A 25-year-old white man developed  severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of  the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient  then underwent proton beam radiation to the area of concern involving the sella.  Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION: Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

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[861]

TÍTULO / TITLE:  - Mifepristone improves chemo-radiation response in glioblastoma xenografts.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Cell Int. 2013 Mar 25;13(1):29.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-29

AUTORES / AUTHORS:  - Llaguno-Munive M; Medina LA; Jurado R; Romero-Pina M; Garcia-Lopez P

RESUMEN / SUMMARY:  - BACKGROUND: We have investigated the ability of Mifepristone, an anti-progestin and anti-glucocorticoid drug, to modulate the antitumor effect of current standard clinical treatment in glioblastoma xenografts. METHODS: The effect of radiation alone or combined with Mifepristone and Temozolamide was evaluated on tumor growth in glioblastoma xenografts, both in terms of preferentially triggering tumor cell death and inhibiting angiogenesis. Tumor size was measured  once a week using a caliper and tumor metabolic-activity was carried out by molecular imaging using a microPET/CT scanner. The effect of Mifepristone on the  expression of angiogenic factors after concomitant radio-chemotherapy was determined using a quantitative real-time PCR analysis of VEGF gene expression. RESULTS: The analysis of the data shows a significant antitumoral effect by the simultaneous administration of radiation-Mifepristone-Temozolamide in comparison  with radiation alone or radiation-Temozolamide. CONCLUSION: Our results suggest that Mifepristone could improve the efficacy of chemo-radiotherapy in Glioblastoma. The addition of Mifepristone to standard radiation-Temozolamide therapy represents a potential approach as a chemo-radio-sensitizer in treating GBMs, which have very limited treatment options.

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[862]

TÍTULO / TITLE:  - MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e55008. doi: 10.1371/journal.pone.0055008. Epub 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055008

AUTORES / AUTHORS:  - Jia Z; Wang K; Wang G; Zhang A; Pu P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Neurolgical Institute, Laboratory of Neuro-Oncology, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of  Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, People’s Republic of China.

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of hundreds of human genes. Variations in miRNA expression levels were shown to be associated with glioma. We have previously found miR-30a-5p overexpression in glioma cell lines and specimens. Bioinformatics analyses predict that several miRNAs, including miR-30a-5p, are involved in the post-transcriptional regulation of SEPT7. SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. In the present study, we knocked down miR-30a-5p with antisense oligonucleotide (miR-30a-5p AS)  in LN229 and SNB19 glioblastoma(GBM) cells, and found that cell growth and invasion were inhibited, while apoptosis was induced. miR-30a-5p AS treated cells showed upregulation of SEPT7 and downregulation of PCNA, cyclin D1, Bcl2, MMP2 and MMP9. In contrast, when miR-30a-5p mimics were transfected into LN229 and SNB19 GBM cells, cell growth and invasion were promoted and the expression of relevant proteins increased. Meanwhile, the effect of miR-30a-5p mimics on glioma cells can be reversed by transfection of SEPT7 construct. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. Our study demonstrates,for the first time, that miR-30a-5p is a bona fide negative regulator of SEPT7 and the oncogenic activity of miR-30a-5p in human gliomas is at least in part through the repression of SEPT7.

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[863]

TÍTULO / TITLE:  - Secretome analysis of Glioblastoma cell line - HNGC-2.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Biosyst. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1039/c3mb25383j

AUTORES / AUTHORS:  - Gupta MK; Polisetty RV; Ramamoorthy K; Tiwary S; Kaur N; Uppin MS; Shiras A; Sirdeshmukh R

INSTITUCIÓN / INSTITUTION:  - Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, 500007, India.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common and aggressive type of primary malignant tumor of the central nervous system. We have carried out a deep analysis of the secretome of a rapidly proliferating and tumorigenic cell line HNGC-2, representing GBM, in an effort to identify proteins, which may be targeted in the plasma of GBM patients as markers for diagnosis and disease surveillance. Prefractionation of the proteins from the conditioned medium of HNGC-2 cells in SDS gels followed by LC-MS/MS analysis using an ESI-IT mass spectrometer (LTQ) led to a total of 996 protein identifications with >/=2 peptides each. Of them, 664 proteins were observed in the transcriptome of HNGC-2 cells. The dataset of 996 proteins was mapped to important functional groups, such as cellular assembly and organisation, DNA recombination and repair, and other classes. Actin cytoskeleton signalling, phosphatidyl inositol 3 kinase (PI3K/AKT) and integrin linked kinase (ILK) signalling pathways were seen as enriched pathways. Comparisons with the published secretome of cell lines from 12 different cancers, including GBM, revealed that 348 proteins shared a commonality with a secretome of at least one other cell line, 321 of which were found to contain signal sequences or transmembrane domains and 335 could be linked to a plasma membrane or extracellular localization. Through intergration of this data  we arrived at a non-redundant list of 597 protein identifications with the potential for secretion either by classical secretory pathways or by non-secretory processes; 233 of them have been detected in cerebrospinal fluid or plasma as per the published literature, and 172 have been implicated in GBM or other cancers. The HNGC-2 secretome dataset could serve as a useful resource for  designing a targeted investigation of GBM biomarkers in plasma.

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[864]

TÍTULO / TITLE:  - Fourth ventricular subependymoma presenting as worsening headache.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc (Bayl Univ Med Cent). 2013 Jan;26(1):52-4.

AUTORES / AUTHORS:  - Saad AF; Bidiwala SB; Layton KF; Snipes GJ; Opatowsky MJ

INSTITUCIÓN / INSTITUTION:  - Departments of Radiology (Saad, Layton, Opatowsky), Neurological Surgery (Bidiwala), and Pathology (Snipes), Baylor University Medical Center at Dallas.

RESUMEN / SUMMARY:  - Subependymomas are rare, slow-growing benign neoplasms. Although most are asymptomatic, they can present with symptoms related to increased intracranial pressure and hydrocephalus. We describe a 47-year-old man with worsening headaches who was found to have a subependymoma, with a focus on the imaging findings, differential diagnoses, pathology, and treatment.

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[865]

TÍTULO / TITLE:  - High-throughput screening for growth inhibitors using a yeast model of familial paraganglioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e56827. doi: 10.1371/journal.pone.0056827. Epub 2013 Feb 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056827

AUTORES / AUTHORS:  - Bancos I; Bida JP; Tian D; Bundrick M; John K; Holte MN; Her YF; Evans D; Saenz DT; Poeschla EM; Hook D; Georg G; Maher LJ 3rd

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.

RESUMEN / SUMMARY:  - Classical tumor suppressor genes block neoplasia by regulating cell growth and death. A remarkable puzzle is therefore presented by familial paraganglioma (PGL), a neuroendocrine cancer where the tumor suppressor genes encode subunits of succinate dehydrogenase (SDH), an enzyme of the tricarboxylic acid (TCA) cycle of central metabolism. Loss of SDH initiates PGL through mechanisms that remain unclear. Could this metabolic defect provide a novel opportunity for chemotherapy of PGL? We report the results of high throughput screening to identify compounds  differentially toxic to SDH mutant cells using a powerful S. cerevisiae (yeast) model of PGL. Screening more than 200,000 compounds identifies 12 compounds that  are differentially toxic to SDH-mutant yeast. Interestingly, two of the agents, dequalinium and tetraethylthiuram disulfide (disulfiram), are anti-malarials with the latter reported to be a glycolysis inhibitor. We show that four of the additional hits are potent inhibitors of yeast alcohol dehydrogenase. Because alcohol dehydrogenase regenerates NAD(+) in glycolytic cells that lack TCA cycle  function, this result raises the possibility that lactate dehydrogenase, which plays the equivalent role in human cells, might be a target of interest for PGL therapy. We confirm that human cells deficient in SDH are differentially sensitive to a lactate dehydrogenase inhibitor.

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[866]

TÍTULO / TITLE:  - Optic Pathway Gliomas: Neoplasms, Not Hamartomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Ophthalmol. 2013 Mar 21:1-5. doi: 10.1001/jamaophthalmol.2013.1652.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamaophthalmol.2013.1652

AUTORES / AUTHORS:  - Liu GT; Katowitz JA; Rorke-Adams LB; Fisher MJ

RESUMEN / SUMMARY:  - IMPORTANCE Optic pathway gliomas are an important neuro-ophthalmic cause of vision loss in children. Their management depends on whether they are considered  neoplasms or hamartomas. OBJECTIVE To outline the evidence that optic pathway gliomas are slowly growing neoplasms and not hamartomas. DESIGN Review of relevant studies in the literature. SETTING The authors are from a pediatric tertiary referral center. RESULTS The growth patterns and histopathology of optic pathway gliomas are more consistent with those of neoplasms. Spontaneous regression, thought to be a characteristic of hamartomas, can be seen in neoplasms of other types as well as in optic pathway gliomas. Chemotherapy used in low-grade gliomas has been shown to halt or improve vision loss in optic pathway gliomas in many cases. CONCLUSIONS AND RELEVANCE Optic pathway gliomas are not hamartomas but truly are neoplasms. Thus, patients should be followed up  closely, and chemotherapies should be used when clinical progression occurs. Other more directed therapies will certainly be used in the future.

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[867]

TÍTULO / TITLE:  - Stereotactic radiosurgery for functioning pituitary adenomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Mar 13. pii: S1878-8750(13)00462-2. doi: 10.1016/j.wneu.2013.03.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.03.015

AUTORES / AUTHORS:  - Kim JW; Kim DG

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

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[868]

TÍTULO / TITLE:  - Photoclinic. Cerebellar liponeurocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Iran Med. 2013 Mar;16(3):199-200. doi: 013163/AIM.0018.

AUTORES / AUTHORS:  - Dey S; Chaudhury MK; Basu SK; Chaudhury K; Chatterjee A; Manna AK; Dutta SK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology (Histopathology), Scientific Clinical Research Laboratory, West Bengal, India. drsoumitdey@gmail.com

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[869]

TÍTULO / TITLE:  - Stereotactic Radiosurgery for High Grade Gliomas: Available Evidence And the Need for Further Investigation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Feb 14. pii: S1878-8750(13)00321-5. doi: 10.1016/j.wneu.2013.02.038.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.02.038

AUTORES / AUTHORS:  - Sheehan J

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of Virginia. Electronic address: jsheehan@virginia.edu.

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[870]

- CASTELLANO -

TÍTULO / TITLE:Germinativne nadory pinealnej oblasti: prehlad.

TÍTULO / TITLE:  - Pineal Germ Cell Tumors: Review.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Klin Onkol. 2013 Winter;26(1):19-24.

AUTORES / AUTHORS:  - Miskovska V; Usakova V; Vertakova-Krakovska B; Mrinakova B; Lehotska V; Chorvath M; Rychly B; Steno J; Ondrus D

RESUMEN / SUMMARY:  - Background: Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor  markers (AFP and beta-HCG) measured in the serum and cere-brospinal fluid. Case:  A pineal germ cell tumor was observed in a 26-year-old male with pre-sentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemothe-rapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease. Conclusion: The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients  after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated  area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial. Key words: pinealoma - germinoma - brain neoplasms - diagnosis - treatment.

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[871]

TÍTULO / TITLE:  - The Bmi-1/NF-kappaB/VEGF story: another hint for proteasome involvement in glioma angiogenesis?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cell Commun Signal. 2013 Mar 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12079-013-0198-2

AUTORES / AUTHORS:  - Vlachostergios PJ; Papandreou CN

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, Biopolis, 41110, Larissa, Greece, pvlacho@med.uth.gr.

RESUMEN / SUMMARY:  - Angiogenesis is an essential process for sustaining tumor growth, particularly in cancer cell types with rapid proliferation, including malignant glioma. Bmi-1 is  a transcriptional regulator of the polycomb group involved in repression of gene  expression by altering the state of chromatin at specific promoters. Bmi-1 overexpression was previously implicated in glioma tumorigenesis, proliferation,  self-renewal, apoptotic resistance and invasiveness. In a recent study, Jiang et  al. (PLoS One 8:e55527, 2013) have revealed the involvement of Bmi-1/NF-kappaB/VEGF pathway in promoting glioma cell-mediated tubule formation and migration of endothelial cells and neovascularization both in vitro and in vivo. NF-kappaB inhibition reversed these effects, supporting a role for Bmi-1 in glioma angiogenesis. Given the intimate association of Bmi-1 and NF-kappaB with the ubiquitin-proteasome system, a better understanding of protein turnover in angiogenic signaling, discussed here, provides novel implications for anti-angiogenic treatment strategies in gliomas.

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[872]

TÍTULO / TITLE:  - Delineating the cytogenomic and epigenomic landscapes of glioma stem cell lines.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(2):e57462. doi: 10.1371/journal.pone.0057462. Epub 2013 Feb 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057462

AUTORES / AUTHORS:  - Baronchelli S; Bentivegna A; Redaelli S; Riva G; Butta V; Paoletta L; Isimbaldi G; Miozzo M; Tabano S; Daga A; Marubbi D; Cattaneo M; Biunno I; Dalpra L

INSTITUCIÓN / INSTITUTION:  - Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, Italy ; Science and Technology Park, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, Italy.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM), the most common and malignant type of glioma, is characterized by a poor prognosis and the lack of an effective treatment, which are due to a small sub-population of cells with stem-like properties, termed glioma stem cells (GSCs). The term “multiforme” describes the histological features of this tumor, that is, the cellular and morphological heterogeneity. At the molecular level multiple layers of alterations may reflect this heterogeneity providing together the driving force for tumor initiation and development. In order to decipher the common “signature” of the ancestral GSC population, we examined six already characterized GSC lines evaluating their cytogenomic and epigenomic profiles through a multilevel approach (conventional cytogenetic, FISH, aCGH, MeDIP-Chip and functional bioinformatic analysis). We found several canonical cytogenetic alterations associated with GBM and a common minimal deleted region (MDR) at 1p36.31, including CAMTA1 gene, a putative tumor suppressor gene, specific for the GSC population. Therefore, on one hand our data confirm a role of driver mutations for copy number alterations (CNAs) included in the GBM genomic-signature (gain of chromosome 7- EGFR gene, loss of chromosome 13- RB1 gene, loss of chromosome 10-PTEN gene); on the other, it is not obvious that the new identified CNAs are passenger mutations, as they may be necessary for tumor progression specific for the individual patient. Through our approach,  we were able to demonstrate that not only individual genes into a pathway can be  perturbed through multiple mechanisms and at different levels, but also that different combinations of perturbed genes can incapacitate functional modules within a cellular networks. Therefore, beyond the differences that can create apparent heterogeneity of alterations among GSC lines, there’s a sort of selective force acting on them in order to converge towards the impairment of cell development and differentiation processes. This new overview could have a huge importance in therapy.

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[873]

TÍTULO / TITLE:  - Hes3 regulates cell number in cultures from glioblastoma multiforme with stem cell characteristics.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Sci Rep. 2013;3:1095. doi: 10.1038/srep01095. Epub 2013 Feb 5.

            ●● Enlace al texto completo (gratuito o de pago) 1038/srep01095

AUTORES / AUTHORS:  - Park DM; Jung J; Masjkur J; Makrogkikas S; Ebermann D; Saha S; Rogliano R; Paolillo N; Pacioni S; McKay RD; Poser S; Androutsellis-Theotokis A

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of Virginia, Virginia, USA.

RESUMEN / SUMMARY:  - Tumors exhibit complex organization and contain a variety of cell populations. The realization that the regenerative properties of a tumor may be largely confined to a cell subpopulation (cancer stem cell) is driving a new era of anti-cancer research. Cancer stem cells from Glioblastoma Multiforme tumors express markers that are also expressed in non-cancerous neural stem cells, including nestin and Sox2. We previously showed that the transcription factor Hes3 is a marker of neural stem cells, and that its expression is inhibited by JAK activity. Here we show that Hes3 is also expressed in cultures from glioblastoma multiforme which express neural stem cell markers, can differentiate into neurons and glia, and can recapitulate the tumor of origin when transplanted into immunocompromised mice. Similar to observations in neural stem cells, JAK inhibits Hes3 expression. Hes3 RNA interference reduces the number of cultured glioblastoma cells suggesting a novel therapeutic strategy.

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[874]

TÍTULO / TITLE:  - Cancer stem cell contribution to glioblastoma invasiveness.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Stem Cell Res Ther. 2013 Feb 28;4(1):18.

            ●● Enlace al texto completo (gratuito o de pago) 1186/scrt166

AUTORES / AUTHORS:  - Ortensi B; Setti M; Osti D; Pelicci G

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy. giuliana.pelicci@ieo.eu.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. Its invasive nature currently represents the most challenging hurdle to surgical resection. The mechanism adopted by GBM cells to carry out their invasive strategy is an intricate program that recalls what takes place in embryonic cells during development and in carcinoma cells during metastasis formation, the so-called epithelial-to-mesenchymal transition. GBM cells undergo a series of molecular and conformational changes shifting the tumor toward mesenchymal traits, including extracellular matrix remodeling, cytoskeletal re-patterning, and stem-like trait acquisition. A deeper understanding of the mechanisms driving the whole infiltrative process represents the first step toward successful treatment of this pathology. Here, we review recent findings demonstrating the invasive nature of GBM cancer stem cells, together with novel candidate molecules associated with both cancer stem cell biology and GBM invasion, like doublecortin and microRNAs. These findings may affect the design of effective therapies currently not considered for GBM invasive progression.

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[875]

TÍTULO / TITLE:  - Image-defined resolution following radiosurgery for hypothalamic hamartoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Apr;11(4):464-8. doi: 10.3171/2013.1.PEDS12290. Epub 2013 Feb 1.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.PEDS12290

AUTORES / AUTHORS:  - O’Connor L; Curl-Roper T; Reeves N; Kemeny AA; Josan VA

INSTITUCIÓN / INSTITUTION:  - Manchester Medical School, University of Manchester;

RESUMEN / SUMMARY:  - The authors present the rare case of complete image-defined resolution of a hypothalamic hamartoma (HH) following Gamma Knife surgery (GKS). A 9-month-old girl presented with an episode of generalized tonic-clonic seizures. Magnetic resonance imaging revealed a left-sided HH, which remained radiologically stable. By 3 years of age the patient had a development delay of 12 months, and experienced 8 gelastic seizures per day while on 2 antiepileptic medications. Thirty-one months after presentation, the patient underwent elective GKS to treat the HH. She has since been seizure free for 22 months, while receiving 3 antiepileptic medications. Twelve months after radiosurgery, MRI revealed complete radiological resolution of the lesion. The authors discuss alternative management options for HH, including microsurgical resection, endoscopic disconnection, stereotactic radiofrequency thermocoagulation, and interstitial radiosurgery. Gamma Knife surgery is a minimally invasive procedure associated with a lower morbidity rate than that of published surgical results. The present  case demonstrates the potential for complete image-defined resolution of an HH post-GKS, without long-term neurological sequelae, emphasizing the safety and efficacy of this therapeutic option for the control of epileptic seizures produced by small-volume, surgically inaccessible HHs.

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[876]

TÍTULO / TITLE:  - Choroidal paraganglioma with metastases to the fellow eye.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Ophthalmol. 2013 Jan;4(1):17-22. doi: 10.1159/000347169. Epub 2013 Feb 25.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000347169

AUTORES / AUTHORS:  - Ginderdeuren RV; Missotten GS; van den Oord J

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium ; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.

RESUMEN / SUMMARY:  - PURPOSE: To report a case of a paraganglioma in the right eye with metastatic disease in the fellow eye 3 years later. METHODS: A 70-year-old man presented with a painful amblyopic right eye; rubeosis iridis and a large choroidal tumor were found. The tumor was treated by enucleation. Pathology diagnosed the tumor as a paraganglioma. Screening for other tumors or metastatic disease was negative at that moment. After 3 years, a paraganglioma skin metastasis was detected, and  screening revealed metastatic disease in the liver. Another 6 months later he was referred for tumors in the left eye, which were treated by radiotherapy. He succumbed 6 months later. RESULTS: Histopathology of the right eye revealed the typical image of a paraganglioma, with expression of synaptophysin, neuron-specific enolase and chromogranin. S-100 staining was positive in the sustentacular cells; staining for HMB-45, SME, EMA and pan-keratin was negative.  Microscopy of the tumors in the skin and liver 3 years later showed a dedifferentiated tumor with the same immunological characteristics, but with higher Ki67 expression and more mitoses. CONCLUSIONS: This report documents a very rare choroidal paraganglioma which presented clinically as a melanoma. The patient succumbed 4 years later to generalized metastatic disease. No other primary paraganglioma was found; however, paraganglion cells in the eye have never been described.

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[877]

TÍTULO / TITLE:  - A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Clin Pharm. 2013 Mar 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11096-013-9765-0

AUTORES / AUTHORS:  - Cecchi M; Vaiani M; Ceroti M; Banfi R

INSTITUCIÓN / INSTITUTION:  - Pharmacy Department, Careggi Hospital, Florence, Italy, cecchim@aou-careggi.toscana.it.

RESUMEN / SUMMARY:  - Background Recurrent glioblastoma is nearly always fatal, with median survival rates of approximately 12-14 months. Previous phase II clinical trials showed promising results with bevacizumab, alone or in combination with irinotecan, in patients with recurrent glioblastoma. Objective To assess whether the survival of patients with recurrent glioblastoma receiving bevacizumab alone or with irinotecan in everyday practice is comparable to that reported in clinical trials. Setting This was a retrospective observational study conducted at a single hospital in Italy. Method Patients with recurrent glioblastoma who had received bevacizumab alone or with irinotecan from January 2009 to September 2011 were included in our study. Main outcome measure Progression-free survival (PFS)  and overall survival (OS), and rates of PFS and OS at 6 months. Results Median PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69 %, respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for  bevacizumab + irinotecan, with 6-month OS rates of 100 and 90 %, respectively. Conclusion Although the number of patients included is not sufficient to allow a  conclusive statement about the place of bevacizumab in the treatment of recurrent glioblastoma, the data appear promising, and are consistent with the results of clinical trials.

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[878]

TÍTULO / TITLE:  - Cranial Dural Cavernous Angioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuroradiol. 2013 Mar 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-013-0210-5

AUTORES / AUTHORS:  - Tsutsumi S; Yasumoto Y; Saeki H; Ito M

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, 279-0021, Urayasu, Chiba, Japan, shotaro@juntendo-urayasu.jp.

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[879]

TÍTULO / TITLE:  - Midbrain encephalitis associated with neoplasia: commentary.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Pract Neurol. 2013 Mar 13.

            ●● Enlace al texto completo (gratuito o de pago) 1136/practneurol-2013-000527

AUTORES / AUTHORS:  - Rees J

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[880]

TÍTULO / TITLE:  - Subependymal giant cell astrocytoma with intratumoral hemorrhage.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Apr;11(4):469-72. doi: 10.3171/2013.1.PEDS12403. Epub 2013 Feb 15.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.1.PEDS12403

AUTORES / AUTHORS:  - Ogiwara H; Morota N

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, National Center for Child Health and Development, Tokyo, Japan.

RESUMEN / SUMMARY:  - The authors report on 2 cases of subependymal giant cell astrocytoma (SEGA) with  intratumoral hemorrhage causing acute hydrocephalus, necessitating emergent resection of the tumor. They review the literature and present their insights on  the management of SEGA showing growth on serial imaging. Intratumoral hemorrhage  causing acute hydrocephalus can occur not only in the pediatric ages but also in  the early 20s in patients with SEGA. Awareness of this sequela is considered to be important in addressing surgical timing. The authors suggest early resection of the lesions when the evidence of growth has been confirmed, to prevent possible morbidity and mortality.

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[881]

TÍTULO / TITLE:  - Vaccine strategies for glioblastoma: progress and future directions.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Immunotherapy. 2013 Feb;5(2):155-67. doi: 10.2217/imt.12.155.

            ●● Enlace al texto completo (gratuito o de pago) 2217/imt.12.155

AUTORES / AUTHORS:  - Jackson C; Ruzevick J; Brem H; Lim M

INSTITUCIÓN / INSTITUTION:  - The Johns Hopkins Hospital, Department of Neurosurgery, Baltimore, MD 21287, USA.

RESUMEN / SUMMARY:  - Recent advances in glioblastoma therapy have led to optimism that more effective  therapies will improve outcomes. Immunotherapy is a promising approach that has demonstrated the potential to eradicate cancer cells with cellular-level accuracy while minimizing damage to surrounding healthy tissue. Several vaccination strategies have been evaluated for activity against glioblastoma in clinical trials. These include peptide vaccines, polyvalent dendritic cell vaccines, heat  shock protein vaccines and adoptive immunotherapy. In this review, we highlight clinical trials representative of each of these approaches and discuss strategies for integrating these therapies into routine patient care.

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[882]

TÍTULO / TITLE:  - Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2013;3:43. doi: 10.3389/fonc.2013.00043. Epub 2013 Mar 4.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00043

AUTORES / AUTHORS:  - Chiang MF; Chou PY; Wang WJ; Sze CI; Chang NS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Mackay Memorial Hospital Taipei, Taiwan ; Graduate Institute of Injury Prevention and Control, Taipei Medical University Taipei, Taiwan.

RESUMEN / SUMMARY:  - Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide (TMZ) and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is  frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and  postulate potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.

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[883]

TÍTULO / TITLE:  - Cluster headache and arachnoid cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Springerplus. 2013 Dec;2(1):4. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2193-1801-2-4

AUTORES / AUTHORS:  - Edvardsson B; Persson S

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Faculty of Medicine, Skane University Hospital, S-221 85 Lund, Sweden.

RESUMEN / SUMMARY:  - BACKGROUND: Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. However, symptomatic cases have been described, e.g. tumours, particularly pituitary adenomas, malformations, and infections/inflammations. The evaluation of cluster headache is an issue unresolved. CASE DESCRIPTION: We present a case of a 43-year-old patient who presented with a 2-month history of side-locked attacks of pain located in the left orbit. He satisfied the revised International Classification of Headache Disorders criteria for cluster headache. His medical and family histories were unremarkable. There was no history of headache. A diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Computer tomography and enhanced magnetic resonance imaging after 1 month displayed a supra- and intrasellar arachnoid cyst with mass effect on adjacent structures. After operation, the headache attacks resolved completely. DISCUSSION AND EVALUATION: Although we cannot exclude an unintentional comorbidity, in our opinion, the co-occurrence of an arachnoid cyst with mass effect with unilateral headache, in  a hitherto headache-free man, points toward the fact that in this case the CH was caused or triggered by the AC. The headache attacks resolved completely after the operation and the patient also remained headache free at the follow-up. The response of the headache to sumatriptan and other typical CH medications does not exclude a secondary form. Symptomatic CHs responsive to this therapy have been described. Associated cranial lesions such as tumours have been reported in CH patients and the attacks may be clinically indistinguishable from the primary form. CONCLUSIONS: Neuroimaging, preferably contrast-enhanced magnetic resonance  imaging should always be considered in patients with cluster headache despite normal neurological examination. Late-onset cluster headache represents a condition that requires careful evaluation. Supra- and intrasellar arachnoid cyst can present as cluster headache.

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[884]

TÍTULO / TITLE:  - Error in Text in: Visual Function and Optic Pathway Glioma: A Critical Response.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Ophthalmol. 2013 Mar 1;131(3):369. doi: 10.1001/jamaophthalmol.2013.251.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamaophthalmol.2013.251

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[885]

TÍTULO / TITLE:  - Coincidence of spinal tumor (astrocytoma) and non-specific encephalomyelitis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Neuro Endocrinol Lett. 2012;33(8):769-72.

AUTORES / AUTHORS:  - Burgetova A; Vaneckova M; Nytrova P; Matej R; Seidl Z

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Charles University Prague, Czech Republic. andrea.burgetova@vfn.cz

RESUMEN / SUMMARY:  - The aim of this paper is to demonstrate that differential diagnostics of intra-medullary spinal lesions can sometimes be very difficult, even when the latest complement examinations are used, including magnetic resonance imaging. The particular case dealt with here was complicated by the presence of two different pathological processes. We present the case report, where the case history, clinical course and results of the paraclinical examinations, including  the magnetic resonance imaging, suggested an intra-medullary inflammatory/demyelinating process. The post-mortem histological finding was a surprise, because besides signs of non-specific encephalomyelitis, it also displayed signs of a spinal tumor (histological character of diffuse astrocytoma  grade II-III). We would like to emphasize some important facts in our discussion, especially from the perspective of the magnetic resonance imaging. Finally, we would like to ask if the presence of both pathologies (astrocytoma and nonspecific myelitis) was coincidental, or if the myelitis had an iatrogenic etiology (by therapy, by infection during the lumbar punctions).

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[886]

TÍTULO / TITLE:  - Extramedullary plasmacytoma presenting as a solitary mass in the intracranial posterior fossa.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Nov;9(4):223-6. doi: 10.5812/iranjradiol.8759. Epub 2012 Nov  20.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.8759

AUTORES / AUTHORS:  - Daghighi MH; Poureisa M; Shimia M; Mazaheri-Khamene R; Daghighi S

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Radiotherapy and Nuclear Medicine, Tabriz University of  Medical Sciences, Tabriz, Iran.

RESUMEN / SUMMARY:  - A patient with a 3-month history of headache refractory to pain medication was admitted. The CT scan and MRI showed evidence of a posterior fossa mass. This was pathologically confirmed as an extra medullary plasmacytoma (EMP). He had a pathologic fracture of the left humerus 7 years ago while the radiologist was unaware at the time of diagnosis. A solitary bone plasmacytoma (SBP) was the cause of the pathologic fracture. This report includes the first description of MRI findings in a patient with a rare-incidence intracranial solitary extra medullary plasmacytoma (SEP) in Iran. There is a striking similarity between the  features of intracranial SEP and meningiomas. Intracranial SEP, although rare, should be included in the differential diagnosis of brain tumors in areas where meningiomas commonly arise. The MRI findings and differential diagnosis of plasmacytoma are reviewed. Before this case report, only few cases have been reported in the literature. Nonetheless, this is the first report of posterior fossa EMP from Iran.

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[887]

TÍTULO / TITLE:  - Pituitary macroadenoma: a rare cause of thyrotoxic hypokalaemic periodic paralysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - British Medical J (BMJ). Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Feb 6;2013. pii: bcr2012008411. doi: 10.1136/bcr-2012-008411.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008411

AUTORES / AUTHORS:  - Ghosh S; Sahoo R; Rao S; Rath D

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, PGIMER & Dr Ram Manohar Lohia Hospital, New Delhi, India. soumik13joy@gmail.com

RESUMEN / SUMMARY:  - Thyrotoxic hypokalaemic periodic palsy (THPP) is a well-recognised but under-diagnosed complication of hyperthyroidism and is commonly seen in Asian males. Patients usually present fully conscious with acute onset of severe motor  weakness. Baseline investigation reveals severe hypokalaemia due to Na(+)/K(+) ATPase overactivity causing a massive influx of intracellular potassium ions. The most common cause of THPP identified in the medical literature is Graves’ disease. We report an interesting and unusual case of THPP due to previously undiagnosed hyperthyroidism secondary to a pituitary macroadenoma. The patient was consequently found to have a tumour secreting gonadotropin and thyrotropin.

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