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[1]

TÍTULO / TITLE:  - Images in clinical medicine. The hairy eyeball—limbal dermoid.

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

REVISTA / JOURNAL:  - N Engl J Med. 2013 Jan 3;368(1):64. doi: 10.1056/NEJMicm1208993.

            ●● Enlace al texto completo (gratuito o de pago) 1056/NEJMicm1208993

AUTORES / AUTHORS:  - Mahdavi Fard A; Pourafkari L

INSTITUCIÓN / INSTITUTION:  - Tabriz University of Medical Sciences, Tabriz, Iran.

 

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[2]

TÍTULO / TITLE:  - Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.

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

REVISTA / JOURNAL:  - Nat Genet. 2013 Jan 20. doi: 10.1038/ng.2526.

            ●● Enlace al texto completo (gratuito o de pago) 1038/ng.2526

AUTORES / AUTHORS:  - Brastianos PK; Horowitz PM; Santagata S; Jones RT; McKenna A; Getz G; Ligon KL; Palescandolo E; Van Hummelen P; Ducar MD; Raza A; Sunkavalli A; Macconaill LE; Stemmer-Rachamimov AO; Louis DN; Hahn WC; Dunn IF; Beroukhim R

INSTITUCIÓN / INSTITUTION:  - 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Hematology/Oncology, Massachusetts General  Hospital, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Broad Institute of MIT and Harvard, Boston, Massachusetts, USA. [5].

RESUMEN / SUMMARY:  - Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of all meningiomas, but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers in an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets.

 

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[3]

TÍTULO / TITLE:  - Multicenter phase I trial of intraventricular immuno-chemotherapy in recurrent CNS lymphoma.

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

REVISTA / JOURNAL:  - Blood. 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1182/blood-2012-07-440974

AUTORES / AUTHORS:  - Rubenstein JL; Li J; Chen L; Advani R; Drappatz J; Gerstner E; Batchelor T; Krouwer H; Hwang J; Auerback G; Kadoch C; Lowell C; Munster P; Cha S; Shuman MA; Damon LE

INSTITUCIÓN / INSTITUTION:  - Division of Hematology/Oncology, University of California, San Francisco, CA, United States;

RESUMEN / SUMMARY:  - Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although intravenous administration of rituximab mediates superior disease control of systemic non-Hodgkin’s lymphoma (NHL), it fails to completely  eliminate the risk of meningeal recurrence, likely because of minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy in systemic lymphoma, we conducted the first phase I study of intraventricular immuno-chemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg (N=3) or 25 mg (N=11) intraventricular rituximab twice-weekly over four weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (12 mg) during the second treatment each week. Greater than 150 doses were administered without serious toxicity. In a population with NHL refractory to a median of five prior therapies, 75% of patients achieved complete cytologic cerebrospinal fluid  (CSF) responses and 43% of patients achieved an overall complete response (CR) in CSF and/or brain parenchyma. Two patients achieved a first CR of CNS NHL with intraventricular rituximab/methotrexate, including one with CNS lymphoma refractory to high-dose systemic and intrathecal methotrexate plus intravenous rituximab. Intraventricular rituximab in combination with methotrexate is feasible and highly active in the treatment of drug-resistant CNS NHL, refractory or non-responsive to intravenous rituximab. Registered at clinicaltrials.gov: NCT00221325.

 

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[4]

TÍTULO / TITLE:  - Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO.

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

REVISTA / JOURNAL:  - Science. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1126/science.1233009

AUTORES / AUTHORS:  - Clark VE; Erson-Omay EZ; Serin A; Yin J; Cotney J; Ozduman K; Avsar T; Li J; Murray PB; Henegariu O; Yilmaz S; Gunel JM; Carrion-Grant G; Yilmaz B; Grady C; Tanrikulu B; Bakircioglu M; Kaymakcalan H; Caglayan AO; Sencar L; Ceyhun E; Atik AF; Bayri Y; Bai H; Kolb LE; Hebert R; Omay SB; Mishra-Gorur K; Choi M; Overton JD; Holland EC; Mane S; State MW; Bilguvar K; Baehring JM; Gutin PH; Piepmeier JM; Vortmeyer A; Brennan CW; Pamir MN; Kilic T; Lifton RP; Noonan JP; Yasuno K; Gunel M

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and Genetics, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT 06510, USA.

RESUMEN / SUMMARY:  - We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the skull base. In contrast, the vast majority of atypical meningiomas were NF2-mutant, showing genomic instability and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting novel avenues for targeted therapeutics.

 

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[5]

TÍTULO / TITLE:  - Enhancing quality of life and mastery of informal caregivers of high-grade glioma patients: a randomized controlled trial.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 2.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1012-3

AUTORES / AUTHORS:  - Boele FW; Hoeben W; Hilverda K; Lenting J; Calis AL; Sizoo EM; Collette EH; Heimans JJ; Taphoorn MJ; Reijneveld JC; Klein M

INSTITUCIÓN / INSTITUTION:  - Department of Medical Psychology, VU University Medical Center, Van der Boechorststraat 7, D-345, 1081 BT, PO Box 7057, 1007 MB, Amsterdam, The Netherlands, f.boele@vumc.nl.

RESUMEN / SUMMARY:  - High-grade gliomas (HGG) are serious primary brain tumors that may prevent the patient from functioning normally in social, emotional and cognitive respect. Often the partner’s role will convert to that of informal caregiver. Consequently, they may experience significant stress and reductions in caregiver  mastery, negatively affecting their health-related quality of life (HRQOL). We aimed at (1) determining factors that impact HRQOL and mastery of caregivers of HGG patients, and (2) investigate if a structured intervention consisting of psychoeducation and cognitive behavioral therapy leads to improvements in the mental component of HRQOL and mastery of caregivers. Fifty-six patient-caregiver  dyads were randomly assigned to the intervention group or the care as usual group. The intervention program consisted of six one-hour sessions with a psychologist. Participants completed questionnaires concerning their perceptions  of the patients’ HRQOL (SF-36), neurological functioning (BN20), and cognitive functioning (MOS), and concerning their own HRQOL (SF-36) and feelings of caregiver mastery (CMS) both at baseline (i.e. before randomization) and every 2  months thereafter until 8 months later, five times in total. Patients’ HRQOL and  neurological functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an 8 month period. Our findings suggest that informal caregivers can benefit from a psychological intervention as it is a helpful tool in maintaining a stable level  of mental functioning and caregiver mastery.

 

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[6]

TÍTULO / TITLE:  - Progress from clinical trials and emerging non-conventional therapies for the treatment of Medulloblastomas.

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

REVISTA / JOURNAL:  - Cancer Lett. 2012 Dec 2. pii: S0304-3835(12)00701-X. doi: 10.1016/j.canlet.2012.11.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.039

AUTORES / AUTHORS:  - Ajeawung NF; Wang HY; Kamnasaran D

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Laval University, Quebec, Canada.

RESUMEN / SUMMARY:  - Medulloblastomas are highly aggressive tumors of the cerebellum with an embryonal origin. Despite current treatment modalities which include a combination of surgery, chemotherapy and/or radiation, challenges still exist to effectively treat some patients, especially those within the younger age group. In an effort  to find improved therapies, ongoing research led by world-wide teams have explored non-conventional therapeutic strategies, as well as examined the efficacy of several drugs in clinical trials among patients with Medulloblastomas. We outline in this article, recent advances on the efficacy and toxicity of numerous therapeutic agents including those that are DNA damaging agents, microtubules binding compounds, and those that are inhibitors of Topoisomerase and of the Notch and Hedgehog signaling pathway, which were assessed in recent Phase I and II clinical trials. Among these clinical trials, it is unfortunate that the outcomes were dismal with the majority of the patients with Medulloblastomas still succumbing to relapse after conventional therapies. Furthermore, it is yet to be established clearly the clinical efficacy of non-conventional therapies such as immunotherapy and gene therapy. Moreover, there is growing interest in proton therapy as a potential replacement for photon therapy, while high dose chemotherapy and autologous stem cell rescue may improve therapeutic efficacies. However, further research is needed to resolve the inherent toxicity from these novel therapeutic methods. In conclusion, novel therapies based on a better understanding of the biology of Medulloblastomas are  pivotal in improving non-conventional therapies in the treatment of this deadly disease.

 

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[7]

TÍTULO / TITLE:  - Piece of my mind. Warning shot.

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

REVISTA / JOURNAL:  - JAMA. 2012 Dec 26;308(24):2575-6. doi: 10.1001/jama.2012.128365.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jama.2012.128365

AUTORES / AUTHORS:  - Maldonado M

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Stamford Hospital, Stamford, Connecticut, USA. memaldonado@msn.com

 

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[8]

TÍTULO / TITLE:  - The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.

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

REVISTA / JOURNAL:  - J Clin Invest. 2013 Jan 9. pii: 67144. doi: 10.1172/JCI67144.

            ●● Enlace al texto completo (gratuito o de pago) 1172/JCI67144

AUTORES / AUTHORS:  - Parker BC; Annala MJ; Cogdell DE; Granberg KJ; Sun Y; Ji P; Li X; Gumin J; Zheng H; Hu L; Yli-Harja O; Haapasalo H; Visakorpi T; Liu X; Liu CG; Sawaya R; Fuller GN; Chen K; Lang FL; Nykter M; Zhang W

RESUMEN / SUMMARY:  - Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can  lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3’-untranslated region (3’-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered  FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3’-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.

 

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[9]

TÍTULO / TITLE:  - Systemic administration of a bispecific antibody targeting EGFRvIII successfully  treats intracerebral glioma.

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

REVISTA / JOURNAL:  - Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):270-5. doi: 10.1073/pnas.1219817110.  Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219817110

AUTORES / AUTHORS:  - Choi BD; Kuan CT; Cai M; Archer GE; Mitchell DA; Gedeon PC; Sanchez-Perez L; Pastan I; Bigner DD; Sampson JH

INSTITUCIÓN / INSTITUTION:  - Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Department of Pathology, and Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710.

RESUMEN / SUMMARY:  - Bispecific antibodies (bscAbs), particularly those of the bispecific T-cell engager (BiTE) subclass, have been shown to effectively redirect T cells against  cancer. Previous efforts to target antigens expressed in both tumors and normal tissues have produced significant toxicity, however. Moreover, like other large molecules, bscAbs may be restricted from entry into the “immunologically privileged” CNS. A tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, is a constitutively activated tyrosine kinase not found in normal tissues but frequently expressed in glioblastomas and many other neoplasms. Because it is localized solely to tumor tissue, EGFRvIII presents an ideal target for immunotherapy. Here we report the preclinical evaluation of an EGFRvIII-targeted BiTE, bscEGFRvIIIxCD3. Our results show that bscEGFRvIIIxCD3 activates T cells to mediate potent and antigen-specific lysis of EGFRvIII-expressing gliomas in vitro (P < 0.001) at exceedingly low concentrations (10 ng/mL) and effector-to-target ratios (2.5:1). Treatment with i.v. bscEGFRvIIIxCD3 yielded extended survival in mice with well-established intracerebral tumors (P < 0.05) and achieved durable complete cure at rates up to 75%. Antitumor efficacy was significantly abrogated on blockade of EGFRvIII binding, demonstrating the need for target antigen specificity both in vitro and  in vivo. These results demonstrate that BiTEs can be used to elicit functional antitumor immunity in the CNS, and that peptide blockade of BiTE-mediated activity may greatly enhance the safety profile for antibody-redirected T-cell therapies. Finally, bscEGFRvIIIxCD3 represents a unique advancement in BiTE technology given its exquisite tumor specificity, which enables precise elimination of cancer without the risk of autoimmune toxicity.

 

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[10]

TÍTULO / TITLE:  - Human Leukocyte Antigen-G Is Frequently Expressed in Glioblastoma and May Be Induced in Vitro by Combined 5-Aza-2’-Deoxycytidine and Interferon-gamma Treatments: Results from a Multicentric Study.

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

REVISTA / JOURNAL:  - Am J Pathol. 2013 Feb;182(2):540-52. doi: 10.1016/j.ajpath.2012.10.021. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.10.021

AUTORES / AUTHORS:  - Wastowski IJ; Simoes RT; Yaghi L; Donadi EA; Pancoto JT; Poras I; Lechapt-Zalcman E; Bernaudin M; Valable S; Carlotti CG Jr; Flajollet S; Jensen SS; Ferrone S; Carosella ED; Kristensen BW; Moreau P

INSTITUCIÓN / INSTITUTION:  - Commissariat a l’Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Therapies Innovantes, Service de Recherches en Hemato-Immunologie, Hopital Saint-Louis, Paris, France; Universite Paris-Diderot, Sorbonne Paris-Cite, UMR E5, Institut Universitaire d’Hematologie, Hopital Saint-Louis, Paris, France.

RESUMEN / SUMMARY:  - Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) class I molecule involved in immune tolerance processes, playing an important role in the maintenance of the semi-allogeneic fetus. Although HLA-G expression is restricted in normal tissues, it is broadly expressed in malignant  tumors and may favor tumor immune escape. We analyzed HLA-G protein and mRNA expression in tumor samples from patients with glioblastoma collected in France,  Denmark, and Brazil. We found HLA-G protein expression in 65 of 108 samples and mRNA in 20 of 21 samples. The absence of HLA-G protein expression was associated  with a better long-term survival rate. The mechanisms underlying HLA-G gene expression were investigated in glioma cell lines U251MG, D247MG, and U138MG. Induction of HLA-G transcriptional activity was dependent of 5-aza-2’-deoxycytidine treatment and enhanced by interferon-gamma. HLA-G protein  expression was observed in U251MG cells only. These cells exhibited a permissive  chromatin state at the HLA-G gene promoter and the highest levels of induced HLA-G transcriptional activity following 5-aza-2’-deoxycytidine treatment. Several antigen-presenting machinery components were up-regulated in U251MG cells after demethylating and IFN-gamma treatments, suggesting an effect on the up-regulation of HLA-G cell surface expression. Therefore, because of its role in tumor tolerance, HLA-G found to be expressed in glioblastoma samples should be taken into consideration in clinical studies on the pathology and in the design of therapeutic strategies to prevent its expression in HLA-G-negative tumors.

 

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[11]

TÍTULO / TITLE:  - Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine (ACNU) versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma (JCOG0305).

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Feb;71(2):511-21. doi: 10.1007/s00280-012-2041-5. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2041-5

AUTORES / AUTHORS:  - Shibui S; Narita Y; Mizusawa J; Beppu T; Ogasawara K; Sawamura Y; Kobayashi H; Nishikawa R; Mishima K; Muragaki Y; Maruyama T; Kuratsu J; Nakamura H; Kochi M; Minamida Y; Yamaki T; Kumabe T; Tominaga T; Kayama T; Sakurada K; Nagane M; Kobayashi K; Nakamura H; Ito T; Yazaki T; Sasaki H; Tanaka K; Takahashi H; Asai A; Todo T; Wakabayashi T; Takahashi J; Takano S; Fujimaki T; Sumi M; Miyakita Y; Nakazato Y; Sato A; Fukuda H; Nomura K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, sshibui@ncc.go.jp.

RESUMEN / SUMMARY:  - PURPOSE: Glioblastoma (GBM) is one of the worst cancers in terms of prognosis. Standard therapy consists of resection with concomitant chemoradiotherapy. Resistance to nimustine hydrochloride (ACNU), an alkylating agent, has been linked to methylguanine DNA methyltransferase (MGMT). Daily administration of procarbazine (PCZ) has been reported to decrease MGMT activity. This study investigated the efficacy of ACNU + PCZ compared to ACNU alone for GBM and anaplastic astrocytoma (AA). METHODS: Patients (20-69 years) who had newly diagnosed AA and GBM were randomly assigned to receive radiotherapy with ACNU alone or with ACNU + PCZ. The primary endpoint was overall survival (OS). This was designed as a phase II/III trial with a total sample size of 310 patients and was registered as UMIN-CTR C000000108. RESULTS: After 111 patients from 19 centers in Japan were enrolled, this study was terminated early because temozolomide was newly approved in Japan. The median OS and median progression-free survival (PFS) with ACNU alone (n = 55) or ACNU + PCZ (n = 56) in the intention-to-treat population were 27.4 and 22.4 months (p = 0.75), and 8.6 and 6.9 months, respectively. The median OS and median PFS of the GBM subgroup treated with ACNU alone (n = 40) or ACNU + PCZ (n = 41) were 19.0 and 19.5 months, and 6.2 and 6.3 months, respectively. Grade ¾ hematologic adverse  events occurred in more than 40 % of patients in both arms, and 27 % of patients  discontinued treatment because of adverse events. CONCLUSIONS: The addition of PCZ to ACNU was not beneficial, in comparison with ACNU alone, for patients with  newly diagnosed AA and GBM.

 

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[12]

TÍTULO / TITLE:  - A Comparison of Two Doses of Mannitol on Brain Relaxation During Supratentorial Brain Tumor Craniotomy: A Randomized Trial.

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

REVISTA / JOURNAL:  - Anesth Analg. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 1213/ANE.0b013e318282dc70

AUTORES / AUTHORS:  - Quentin C; Charbonneau S; Moumdjian R; Lallo A; Bouthilier A; Fournier-Gosselin MP; Bojanowski M; Ruel M; Sylvestre MP; Girard F

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Anesthesiology and daggerSurgery, Montreal University Medical Center; and double daggerResearch Center, Montreal University Medical Centre, Montreal, Quebec, Canada.

RESUMEN / SUMMARY:  - BACKGROUND:Twenty percent mannitol is widely used to reduce brain bulk and facilitate the surgical approach in intracranial surgery. However, a dose-response relationship has not yet been established. In this study, we compared the effects of 0.7 and 1.4 g.kg(-1) mannitol on brain relaxation during  elective supratentorial brain tumor surgery.METHODS:In this prospective, randomized, double-blind study, we enrolled 80 patients undergoing supratentorial craniotomy for tumor resection. Patients were assigned to receive 0.7 g.kg(-1) (group L) or 1.4 g.kg(-1) (group H) of 20% mannitol at surgical incision. Brain relaxation was assessed immediately after opening of the dura on a scale ranging  from 1 to 4 (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain).RESULTS:There was no significant difference between the 2 groups regarding age, sex, body mass index, and brain tumor localization or size. In group L 52.5% of patients and in group H 77.5% of patients presented a midline shift (P = 0.03). The median scores of brain relaxation (interquantile range) were 2.0 (1.75-3) and 2.0 (1-3) (P = 0.16 for patients in group L and H, respectively). We then used a proportional odds model to adjust for this unbalanced distribution and to assess the group effect (low-dose versus high-dose mannitol) on brain relaxation scores. When adjusted for the presence of midline shift, the use of a higher dose of mannitol resulted in an odds ratio of 2.5 (P = 0.03). This indicates that, considering the effect of a midline shift, the odds of having a 1-level improvement in relaxation score in patients who received a higher dose of mannitol (group H) was 2.5 times as large as the odds for the low-dose group. The odds ratio of 0.29 (P = 0.007) for the midline shift indicates that its occurrence was associated with a higher probability of a lower relaxation score, on average.CONCLUSION:In this study, we show that 1.4 g.kg(-1)  of 20% mannitol results in equivalent brain relaxation scores as 0.7 g.kg(-1) in  patients undergoing craniotomy for supratentorial brain tumor. When corrected for the presence of midline shift, this study reveals that patients in the high-dose  group had significantly more chances of obtaining a better relaxation score compared with the lower-dose group.

 

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[13]

TÍTULO / TITLE:  - Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation  Therapy for Childhood Craniopharyngioma.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 11. pii: S0360-3016(12)03729-7. doi: 10.1016/j.ijrobp.2012.10.030.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.030

AUTORES / AUTHORS:  - Merchant TE; Kun LE; Hua CH; Wu S; Xiong X; Sanford RA; Boop FA

INSTITUCIÓN / INSTITUTION:  - St Jude Children’s Research Hospital, Radiological Sciences, Memphis, Tennessee.  Electronic address: thomas.merchant@stjude.org.

RESUMEN / SUMMARY:  - PURPOSE: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. METHODS AND MATERIALS: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive  the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. RESULTS: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs </=5 mm) at 5 years (88.1% +/- 6.3% vs 96.2% +/- 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. CONCLUSIONS: These results suggest that targeted volume reductions for radiation  therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating the differences in outcome based on host factors to explain the results.

 

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[14]

TÍTULO / TITLE:  - Urinary tract infections in meningioma patients: analysis of risk factors and outcomes.

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

REVISTA / JOURNAL:  - J Hosp Infect. 2012 Dec 27. pii: S0195-6701(12)00376-3. doi: 10.1016/j.jhin.2012.10.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jhin.2012.10.011

AUTORES / AUTHORS:  - Nosova K; Nuno M; Mukherjee D; Lad SP; Boakye M; Black KL; Patil CG

INSTITUCIÓN / INSTITUTION:  - Center for Neurosurgical Outcomes Research, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Cedars - Sinai Medical Center, Los Angeles, California, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Urinary tract infections (UTIs) account for about 35% of all nosocomial infections and 75% are associated with the use of urethral catheters.  AIM: The goal of this study was to evaluate preoperative factors associated with  the risk of UTI and to estimate the impact of UTIs on patient outcome and resource utilization. METHODS: Adult meningioma patients treated with craniotomy  in US hospitals between 2002 and 2007 were queried from the Nationwide Inpatient  Sample (NIS) database. Univariate and multivariate analyses that correct for sample survey design data were used to study the association of perioperative UTIs and outcomes. FINDINGS: In all, 46,344 patients were included. Women comprised the majority (70.0%), had lower mortality (1.2% vs 2.0%), shorter in-hospital stay (6.7 vs 7.5 days), lower hospital charges (US$76,682 vs 87,220)  and higher UTI rates (6.3% vs 3.9%) than men. In multivariate analysis, female gender (odds ratio: 2.2; P < 0.0001), older age (1.4; P < 0.001), emergency room  admissions (1.8; P < 0.0001), total length of stay (1.08; P < 0.0001), comorbidity score (1.04; P = 0.0147), postoperative fluid abnormalities (1.96; P  < 0.0001) and pulmonary complications (1.3; P < 0.0011) were associated with UTI. UTI was associated with an additional 2.3 days of hospital stay and an incremental US$18,920 in hospital charges. CONCLUSIONS: Perioperative UTIs are associated with specific comorbidities and postoperative complications. They significantly increase in-hospital length of stay and costs. Our data emphasize the need to support national efforts that are underway to reduce hospital-acquired UTIs within the neurosurgical population.

 

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[15]

TÍTULO / TITLE:  - Isolated central nervous system relapse in patient with blast-crisis chronic myeloid leukemia in durable complete cytogenetic remission on dasatinib treatment: pharmacokinetics and ABL mutation analysis in cerebrospinal fluid.

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

REVISTA / JOURNAL:  - Leuk Lymphoma. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2012.745933

AUTORES / AUTHORS:  - Zhou HS; Dai M; Wei Y; Wang Q; Xu N; Yin C; Meng F

INSTITUCIÓN / INSTITUTION:  - Department of Hematology, Nanfang Hospital, Southern Medical University , Guangzhou , China.

 

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[16]

TÍTULO / TITLE:  - Multiple functions of a glioblastoma fusion oncogene.

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

REVISTA / JOURNAL:  - J Clin Invest. 2013 Jan 9. pii: 67658. doi: 10.1172/JCI67658.

            ●● Enlace al texto completo (gratuito o de pago) 1172/JCI67658

AUTORES / AUTHORS:  - Babic I; Mischel PS

RESUMEN / SUMMARY:  - RNA sequencing facilitates the discovery of novel gene fusions in cancer. In this issue of the JCI, Parker et al. identify an FGFR3-TACC3 fusion oncogene in glioblastoma and demonstrate a novel mechanism of pathogenicity. A miR-99a binding site within the 3’-untranslated region (3’-UTR) of FGFR3 is lost, releasing FGFR3 signaling from miR-99a-dependent inhibition and greatly enhancing tumor progression relative to WT FGFR3. These results provide compelling insight  into the pathogenicity of a novel fusion oncogene and suggest new therapeutic approaches for a subset of glioblastomas.

 

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[17]

TÍTULO / TITLE:  - Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis.

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

REVISTA / JOURNAL:  - J Clin Invest. 2013 Jan 2;123(1):405-17. doi: 10.1172/JCI63811. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1172/JCI63811

AUTORES / AUTHORS:  - Niola F; Zhao X; Singh D; Sullivan R; Castano A; Verrico A; Zoppoli P; Friedmann-Morvinski D; Sulman E; Barrett L; Zhuang Y; Verma I; Benezra R; Aldape K; Iavarone A; Lasorella A

RESUMEN / SUMMARY:  - High-grade gliomas (HGGs) are incurable brain tumors that are characterized by the presence of glioma-initiating cells (GICs). GICs are essential to tumor aggressiveness and retain the capacity for self-renewal and multilineage differentiation as long as they reside in the perivascular niche. ID proteins are master regulators of stemness and anchorage to the extracellular niche microenvironment, suggesting that they may play a role in maintaining GICs. Here, we modeled the probable therapeutic impact of ID inactivation in HGG by selective ablation of Id in tumor cells and after tumor initiation in a new mouse model of  human mesenchymal HGG. Deletion of 3 Id genes induced rapid release of GICs from  the perivascular niche, followed by tumor regression. GIC displacement was mediated by derepression of Rap1gap and subsequent inhibition of RAP1, a master regulator of cell adhesion. We identified a signature module of 5 genes in the ID pathway, including RAP1GAP, which segregated 2 subgroups of glioma patients with  markedly different clinical outcomes. The model-informed survival analysis together with genetic and functional studies establish that ID activity is required for the maintenance of mesenchymal HGG and suggest that pharmacological  inactivation of ID proteins could serve as a therapeutic strategy.

 

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[18]

TÍTULO / TITLE:  - Glioblastoma: Microvesicles as major biomarkers?

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

REVISTA / JOURNAL:  - Nat Rev Cancer. 2013 Jan;13(1):8. doi: 10.1038/nrc3424. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrc3424

AUTORES / AUTHORS:  - Burgess DJ

 

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[19]

TÍTULO / TITLE:  - A comparison between intensive and conventional cabergoline treatment of newly diagnosed patients with macroprolactinomas.

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

REVISTA / JOURNAL:  - Clin Endocrinol (Oxf). 2013 Jan 24. doi: 10.1111/cen.12149.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cen.12149

AUTORES / AUTHORS:  - Rastogi A; Bhansali A; Dutta P; Singh P; Vijaivergiya R; Gupta V; Sachdeva N; Bhadada SK; Walia R

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Post Graduate of Medical Education and Research (PGIMER), Chandigarh, 160012.

RESUMEN / SUMMARY:  - CONTEXT: Intensive treatment with cabergoline may lead to earlier reduction in prolactin and tumor volume in comparison to conventional schedule. OBJECTIVE: To  compare the efficacy and safety of two different dosing schedules of cabergoline  in patients with macroprolactinoma DESIGN: Prospective, randomized trial in drug  naive patients assigned to conventional (4 weekly escalation by 0.5 mg per week,  group A) or intensive (weekly increase by 1 mg per week followed by 4 weekly escalation, group B) treatment with cabergoline OUTCOME MEASURE: The duration required to achieve normoprolactinemia and tumor shrinkage of greater than 50% as a composite end-point RESULTS: 38 patients (19 in each group) completed the study with a mean follow-up of 64.3+/-24.9 weeks. More (22%) achieved the composite end-point in group B (18/19) as compared to the group A (14/19) (p=0.18). The duration of cabergoline treatment required to achieve the composite end-point was 13.1+/-9.5 weeks versus 19.3+/-15.7 weeks (p=0.34) in the group A and B, respectively. A reduction in prolactin of >/=90% by the 4(th) week of cabergoline therapy predicted subsequent normalization of prolactin (AUC 0.78; p=0.04). A further increase in cabergoline dosage after normalization of prolactin in patients with tumor reduction of <50%, led to further tumor shrinkage by 31.2% in an additional 26.3% of patients. CONCLUSIONS: Intensive treatment with cabergoline is not superior to the conventional recommended dosage schedule in respect to the time necessary to achieve normoprolactinemia and >/= 50% tumor shrinkage. © 2013 Blackwell Publishing Ltd.

 

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[20]

TÍTULO / TITLE:  - Longitudinal Linear Growth and Final Height is Impaired in Childhood Acute Lymphoblastic Leukemia Survivors after Treatment without Cranial Irradiation.

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

REVISTA / JOURNAL:  - J Pediatr. 2013 Jan 23. pii: S0022-3476(12)01526-0. doi: 10.1016/j.jpeds.2012.12.037.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jpeds.2012.12.037

AUTORES / AUTHORS:  - Vandecruys E; Dhooge C; Craen M; Benoit Y; De Schepper J

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Hemato-Oncology, Ghent University Hospital, Ghent, Belgium. Electronic address: els.vandecruys@ugent.be.

RESUMEN / SUMMARY:  - OBJECTIVE: To evaluate long-term growth and final height (FH) in survivors of childhood acute lymphoblastic leukemia (ALL) who were treated without cranial radiation therapy and underwent evaluation of growth hormone (GH) status at the end of treatment. STUDY DESIGN: Data on longitudinal growth (collected at the start of treatment, end of treatment, and 1 year thereafter) and FH of 67 adult survivors of childhood ALL who had been treated according to European Organisation for Research and Treatment of Cancer 58831/2 protocols with chemotherapy as the only treatment modality were reviewed retrospectively. Height data were expressed as SDS for national references. The relative role of sex, age at diagnosis, intensity of chemotherapeutic regimen, and GH status at the end of  treatment as contributing factors were analyzed. RESULTS: A modest but significant loss in FH (change in SDS [DeltaSDS] = -0.59 +/- 0.86; P < .001) was  found. Two-thirds of the height deficit observed from diagnosis until FH occurred during treatment. The height deficit was more severe in the male patients (P = .036). The DeltaSDS for height from diagnosis to FH was not correlated with age at diagnosis or intensity of treatment. No correlation was found between the results of the GH stimulation test and DeltaSDS for height from diagnosis or the  end of treatment to FH. CONCLUSION: Adult survivors of childhood ALL treated with chemotherapeutic regimens of moderate intensity without cranial radiation therapy exhibit a modest loss in SDS for height at FH irrespective of GH status at the cessation of treatment.

 

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[21]

TÍTULO / TITLE:  - Pseudoprogression of Glioblastoma after Chemo- and Radiation Therapy: Diagnosis by Using Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging with Ferumoxytol versus Gadoteridol and Correlation with Survival.

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

REVISTA / JOURNAL:  - Radiology. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12111472

AUTORES / AUTHORS:  - Gahramanov S; Muldoon LL; Varallyay CG; Li X; Kraemer DF; Fu R; Hamilton BE; Rooney WD; Neuwelt EA

INSTITUCIÓN / INSTITUTION:  - Departments of Neurology, Neurosurgery, Public Health and Preventative Medicine,  Emergency Medicine, Radiology, and the Advanced Imaging Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L603, Portland, OR 97239-3098; Office of Research and Development, Department of Veterans Affairs Medical Center, Portland, Ore.

RESUMEN / SUMMARY:  - Purpose:To compare gadoteridol and ferumoxytol for measurement of relative cerebral blood volume (rCBV) in patients with glioblastoma multiforme (GBM) who showed progressive disease at conventional magnetic resonance (MR) imaging after  chemo- and radiation therapy (hereafter, chemoradiotherapy) and to correlate rCBV with survival.Materials and Methods:Informed consent was obtained from all participants before enrollment in one of four institutional review board-approved protocols. Contrast agent leakage maps and rCBV were derived from perfusion MR imaging with gadoteridol and ferumoxytol in 19 patients with apparently progressive GBM on conventional MR images after chemoradiotherapy. Patients were  classified as having high rCBV (>1.75), indicating tumor, and low rCBV (</=1.75), indicating pseudoprogression, for each contrast agent separately, and with or without contrast agent leakage correction for imaging with gadoteridol. Statistical analysis was performed by using Kaplan-Meier survival plots with the  log-rank test and Cox proportional hazards models.Results:With ferumoxytol, rCBV  was low in nine (47%) patients, with median overall survival (mOS) of 591 days, and high rCBV in 10 (53%) patients, with mOS of 163 days. A hazard ratio of 0.098 (P = .004) indicated significantly improved survival. With gadoteridol, rCBV was  low in 14 (74%) patients, with mOS of 474 days, and high in five (26%), with mOS  of 156 days and a nonsignificant hazard ratio of 0.339 (P = .093). Five patients  with mismatched high rCBV with ferumoxytol and low rCBV with gadoteridol had an mOS of 171 days. When leakage correction was applied, rCBV with gadoteridol was significantly associated with survival (hazard ratio, 0.12; P = .003).Conclusion:Ferumoxytol as a blood pool agent facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic  biomarker, and unlike gadoteridol, does not require contrast agent leakage correction.© RSNA, 2012.

 

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[22]

TÍTULO / TITLE:  - Erratum: Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS10377a

AUTORES / AUTHORS:  - Muragaki Y

INSTITUCIÓN / INSTITUTION:  - Tokyo Women’s Medical University, Tokyo, Japan.

 

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[23]

TÍTULO / TITLE:  - Migration of mesenchymal stem cells towards glioblastoma cells depends on hepatocyte-growth factor and is enhanced by aminolaevulinic acid-mediated photodynamic treatment.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Jan 16. pii: S0006-291X(13)00098-3. doi: 10.1016/j.bbrc.2012.12.153.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.12.153

AUTORES / AUTHORS:  - Vogel S; Peters C; Etminan N; Borger V; Schimanski A; Sabel MC; Sorg RV

INSTITUCIÓN / INSTITUTION:  - Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine University Hospital, Moorenstrasse 5, 40225 Dusseldorf, Germany.

RESUMEN / SUMMARY:  - Hepatocyte-growth factor (HGF) is expressed by glioblastomas and contributes to their growth, migration and invasion. HGF also mediates migration of mesenchymal  stem cells (MSC) to sites of apoptotic cell death. Moreover, MSC show tropism for glioblastomas, which is exploited in gene therapy to deliver the therapeutics to  the tumor cells. Here, we have studied whether HGF contributes to the recruitment of MSC by glioblastoma cells and whether aminolaevulinic acid-mediated photodynamic therapy (ALA/PDT), a novel therapeutic approach that induces apoptosis in glioblastoma cells, affects HGF release and this migratory response. MSC expressed the HGF receptor MET and migrated towards U87 and U251 glioblastoma spheroids. Migration increased significantly when spheroids were subjected to ALA/PDT, which was associated with induction of apoptosis and up-regulation of HGF. Neutralizing HGF resulted in significant inhibition of MSC migration towards untreated as well as ALA/PDT-treated spheroids. Thus, glioblastoma cells express  HGF, which contributes to the attraction of MSC. ALA/PDT induces apoptosis and augments HGF release causing enhanced MSC migration towards the tumor cells. ALA/PDT may therefore be exploited to improve targeting of MSC delivered gene therapy, but it may also constitute a risk in terms of beneficial effects for the tumor.

 

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[24]

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:  - Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1611-6. doi: 10.1073/pnas.1215687110. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1215687110

AUTORES / AUTHORS:  - Eberlin LS; Norton I; Orringer D; Dunn IF; Liu X; Ide JL; Jarmusch AK; Ligon KL; Jolesz FA; Golby AJ; Santagata S; Agar NY; Cooks RG

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry and Center for Analytical Instrumentation Development, Purdue University, West Lafayette, IN 47907.

RESUMEN / SUMMARY:  - The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few  exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over  segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing  rapid diagnosis, and tumor margin assessment in near-real time.

 

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[25]

TÍTULO / TITLE:  - A phase II trial of oral gimatecan for recurrent glioblastoma.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1023-0

AUTORES / AUTHORS:  - Hu J; Wen PY; Abrey LE; Fadul CE; Drappatz J; Salem N; Supko JG; Hochberg F

INSTITUCIÓN / INSTITUTION:  - Johnnie L. Cochran Jr. Brain Tumor Center, 8631 West Third St, Suite 410E, Los Angeles, CA, 90048, USA, jethro.hu@gmail.com.

RESUMEN / SUMMARY:  - Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included </=1 prior treatment for recurrent disease, age >/=18, Eastern Cooperative Oncology Group performance status 0-1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m(2) was given orally once daily for 5 consecutive days during each 28-day cycle. The  primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if >4 patients in stage 1 achieved PFS at  6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25-77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m(2) after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade ¾ toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of  the 19 patients treated at 1.0 mg/m(2)/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m(2)/day for 5 days, repeated every 28-days showed minimal efficacy.

 

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[26]

TÍTULO / TITLE:  - Toxicity and survival in primary glioblastoma patients treated with concomitant plus adjuvant temozolomide versus adjuvant temozolomide: results of a single-institution, retrospective, matched-pair analysis.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1583-y

AUTORES / AUTHORS:  - Gutenberg A; Bock HC; Reifenberger G; Bruck W; Giese A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany, agutenberg@uni-mainz.de.

RESUMEN / SUMMARY:  - BACKGROUND: To compare survival and hematological toxicity rates between two postoperative therapy regimens in patients with primary glioblastoma (GBM), namely temozolomide (TMZ) concomitant to radiation, followed by adjuvant TMZ, versus adjuvant TMZ after radiation only. PATIENTS AND METHODS: A total of 191 patients with primary GBM were postoperatively treated with either radiation and  concomitant TMZ, followed by adjuvant TMZ (Stupp protocol) (n = 154), or radiation followed by adjuvant TMZ (n = 37). The incidence of hematological adverse effects (AE) was recorded for all patients. From both treatment groups, 26 patients were matched according to age, Karnofsky performance scale (KPS) score, and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. RESULTS: Hematological AEs were mild in both unmatched groups, but were significantly more frequent in the concomitant plus adjuvant TMZ group (p < 0.001). Matched-pair analysis confirmed significantly more frequent hematological AEs in the concomitant and adjuvant group compared to the sequential (adjuvant) TMZ group (p = 0,012). Patients treated with concomitant plus adjuvant TMZ showed significantly longer progression-free survival (PFS) (10.6 versus 6.6 months; p = 0.014), but no prolonged overall survival (OS) (16.9 vs. 15.6 months; p = 0.717)  compared to patients who received the sequential treatment regimen. CONCLUSION: In this retrospective study, the OS in patients with primary GBM treated with sequential TMZ following radiation appeared to be similar to that in patients treated with concomitant plus adjuvant TMZ. Given the significantly higher risk of hematological AE for concomitant treatment, the role of concomitant plus adjuvant TMZ use compared to sequential administration of TMZ, especially for patients with MGMT-unmethylated tumors, should be further evaluated.

 

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[27]

TÍTULO / TITLE:  - Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

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

REVISTA / JOURNAL:  - Ann Oncol. 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds621

AUTORES / AUTHORS:  - Holte H; Leppa S; Bjorkholm M; Fluge O; Jyrkkio S; Delabie J; Sundstrom C; Karjalainen-Lindsberg ML; Erlanson M; Kolstad A; Fossa A; Ostenstad B; Lofvenberg E; Nordstrom M; Janes R; Pedersen LM; Anderson H; Jerkeman M; Eriksson M

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Oslo University Hospital, Oslo, Norway.

RESUMEN / SUMMARY:  - BackgroundMany patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events.Patients and methodsInclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years.ResultsA total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months.ConclusionsThe results are  promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis.CinicalTrials.gov. identifierNCT01502982.

 

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[28]

TÍTULO / TITLE:  - Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation.

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

REVISTA / JOURNAL:  - Haematologica. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 3324/haematol.2012.076075

AUTORES / AUTHORS:  - Schorb E; Kasenda B; Atta J; Kaun S; Morgner A; Hess G; Elter T; von Bubnoff N; Dreyling M; Ringhoffer M; Krause S; Derigs G; Klimm B; Niemann D; Fritsch K; Finke J; Illerhaus G

INSTITUCIÓN / INSTITUTION:  - Germany;

RESUMEN / SUMMARY:  - Background. High-dose chemotherapy followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed primary central nervous system lymphoma. In this retrospective multicenter study we investigated prognosis and baseline risk factors in patients with primary central nervous system lymphoma who underwent this treatment approach. Design and Methods. We retrospectively analyzed 105 immunocompetent patients with primary central nervous system lymphoma who underwent high-dose chemotherapy followed by autologous stem cell transplantation with or without whole brain radiotherapy as first line consolidation treated at 12 German centers between 1997 and 2011. We estimated survival rates and investigated the impact of age, performance status, serum lactate dehydrogenase level, and deep brain involvement on overall and progression-free survival. Patients were additionally  categorized into three prognostic groups according to the Memorial Sloan Kettering Cancer Center prognostic model. Results. After a median follow-up of 47 months, median progression free survival and overall survival was reached after 85 and 121 months; 2 and 5-years overall survival rates were 82% and 79%, respectively. The Memorial Sloan Kettering Cancer Center prognostic model did not predict survival. Only age revealed some evidence of prognostic relevance. Overall response rate was 95%; of those patients with progressive disease before  high-dose chemotherapy, 7/20 achieved ongoing complete remission after therapy without whole brain radiation therapy. Transplantation-associated mortality was 2.8%. Conclusions. High-dose chemotherapy followed by autologous stem cell transplantation is a highly effective and safe treatment modality for selected primary central nervous system lymphoma patients. Superiority compared to standard chemotherapy still warrants further investigation.

 

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[29]

TÍTULO / TITLE:  - Brainstem Ganglioglioma Successfully Treated With Vemurafenib.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.1568

AUTORES / AUTHORS:  - Rush S; Foreman N; Liu A

INSTITUCIÓN / INSTITUTION:  - University of Colorado Denver, Denver, CO.

 

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[30]

TÍTULO / TITLE:  - A pilot study of glioblastoma multiforme in elderly patients: Treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 17. pii: S0303-8467(12)00644-0. doi: 10.1016/j.clineuro.2012.12.023.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.023

AUTORES / AUTHORS:  - Abhinav K; Aquilina K; Gbejuade H; La M; Hopkins K; Iyer V

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE, UK. Electronic address: kumar.abhinav@doctors.org.uk.

RESUMEN / SUMMARY:  - OBJECTIVES: Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients. PATIENTS AND METHODS: Patients >/=65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (STR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p<0.05 was considered  significant. RESULTS: 59 patients were identified with median age at diagnosis being 72.68 years (65.72-85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall  survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p=0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME  patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p=0.007). MOS in UN group was 308 days vs. 167 days in ME group (p=0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated  with a reduced risk for death (HR 0.443, 95% CI 0.200-0.982, p=0.045). CONCLUSIONS: In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective  of MGMT status in this population with future large prospective studies needed to elucidate this further.

 

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[31]

TÍTULO / TITLE:  - Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 20;31(3):328-36. doi: 10.1200/JCO.2012.44.1444. Epub 2012  Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.1444

AUTORES / AUTHORS:  - Erdem-Eraslan L; Gravendeel LA; de Rooi J; Eilers PH; Idbaih A; Spliet WG; den Dunnen WF; Teepen JL; Wesseling P; Sillevis Smitt PA; Kros JM; Gorlia T; van den Bent MJ; French PJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Be 438, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the  Netherlands; p.french@erasmusmc.nl.

RESUMEN / SUMMARY:  - PURPOSE Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can  be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples. PATIENTS AND METHODS Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133_Plus_2.0 and HuEx_1.0_st arrays, respectively. Results All previously identified six IGSs are  present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMT methylation), and histologic parameters. Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (proportion of explained variation, 30% v 23% for each individual group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P = .0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50). CONCLUSION Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV.

 

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[32]

TÍTULO / TITLE:  - Id-1 is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target.

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

REVISTA / JOURNAL:  - Cancer Res. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1943

AUTORES / AUTHORS:  - Soroceanu L; Murase R; Limbad C; Singer EL; Allison J; Adrados I; Kawamura R; Pakdel A; Fukuyo Y; Nguyen D; Khan S; Arauz R; Yount GL; Moore D; Desprez PY; McAllister SD

INSTITUCIÓN / INSTITUTION:  - Neuroscience, CPMC Research Institute.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is the most common form of primary adult brain tumors. A majority of GBMs grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically. We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathological grades in patient biopsies. Id-1 knockdown dramatically reduces GBM cell invasion that is accompanied by profound morphological changes and robust reduction in expression levels of “mesenchymal” markers, as well as inhibition of self-renewal potential and down-regulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human  GBM. Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. Additionally, cannabidiol significantly inhibits the invasion of GBM cells through an organotypic brain slice and glioma progression in vivo. Our  results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving  the therapy and outcome of GBM patients.

 

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[33]

TÍTULO / TITLE:  - Focused Ultrasound Delivers Targeted Immune Cells To Metastatic Brain Tumors.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2609

AUTORES / AUTHORS:  - Alkins RD; Burgess A; Ganguly M; Francia G; Kerbel RS; Wels WS; Hynynen K

INSTITUCIÓN / INSTITUTION:  - Medical Biophysics, University of Toronto.

RESUMEN / SUMMARY:  - Natural killer (NK) cells are cytotoxic lymphocytes involved in innate immunity.  NK-92, a human NK cell line, may be targeted to tumor-associated antigens in solid malignancies where it exhibits antitumor efficacy, but its clinical utility for treating brain tumors is limited by an inability to cross the blood-brain barrier (BBB). We investigated the potential for focused ultrasound (FUS) to deliver targeted NK-92 cells to the brain using a model of metastatic breast cancer. HER-2-expressing human breast tumor cells were implanted into the brain of nude rats. The NK-92-scFv(FRP5)-zeta cell line expressing a chimeric HER-2 antigen receptor was transfected with super-paramagnetic iron oxide nanoparticles before intravenous injection, before and following BBB-disruption using focused ultrasound (551.5 kHz focused transducer, 0.33 MPa average peak rarefaction pressure) in the presence of a microbubble contrast agent. Baseline and post-treatment 1.5T and 7T MR imaging was performed, and histology used to identify NK-92 cells post-mortem. Contrast-enhanced MRI showed reproducible and consistent BBB-disruption. 7T MR images obtained at 16 hours post-treatment revealed a significant reduction in signal indicating the presence of iron-loaded NK-92 cells at the tumor site. The average ratio of NK-92 to tumor cells was 1:100 when NK cells were present in the vasculature at the time of sonication, versus 2:1000 and 1:1000 when delivered after sonication and without BBB-disruption, respectively. Our results offer a preclinical proof-of-concept that FUS can improve the targeting of immune cell therapy of brain metastases.

 

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[34]

TÍTULO / TITLE:  - Temozolomide use in adult patients with gliosarcoma: an evolving clinical practice.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 25.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1029-7

AUTORES / AUTHORS:  - Walker GV; Gilbert MR; Prabhu SS; Brown PD; McAleer MF

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 97, Houston, TX, 77030, USA.

RESUMEN / SUMMARY:  - The purpose of this study is to determine the factors that impact overall survival (OS) in adult patients with gliosarcoma in the modern era treated at a single institution compared with a cohort from the SEER registry. A total of 46 adult patients with pathologically confirmed gliosarcoma at MD Anderson Cancer Center from 2000 to 2010 were retrospectively analyzed. Demographic and treatment were obtained. For comparison, a total of 218 patients with gliosarcoma in the SEER database from 1991 to 2008 were analyzed. Survival analysis was conducted using the Kaplan-Meier log rank test. At MD Anderson, the overall incidence of gliosarcoma over the specified time interval was 1.5 %. Gliosarcoma was more common in males (n = 31, 67.4 %) with a median age of 56 years (range 24-92 years). Median survival in all patients was 12.5 months. A total of 17 patients (37 %) received temozolomide (TMZ) concurrently with RT and adjuvantly, with a 24 month OS of 20.0 %, compared with 10.2 % among those not treated with this regimen (p = 0.68). In contrast, the 2 year OS rate in the SEER database was 24.2 % during 2006-2008, compared to 12.1 % among those diagnosed in 2000-2003 (p = 0.03), presumably related to the widespread adoption of the chemoradiation regimen. Patients with gliosarcoma treated with TMZ at a single institution improved OS although this finding did not reach statistical significance. Patients diagnosed in the TMZ era in the SEER database display an improved OS, although the explanation for this finding requires further elucidation.

 

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[35]

TÍTULO / TITLE:  - Implanted Carmustine Wafers Followed by Concomitant Radiochemotherapy to Treat Newly Diagnosed Malignant Gliomas: Prospective, Observational, Multicenter Study  on 92 Cases.

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

REVISTA / JOURNAL:  - Ann Surg Oncol. 2012 Dec 2.

            ●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2764-x

AUTORES / AUTHORS:  - Duntze J; Litre CF; Eap C; Theret E; Debreuve A; Jovenin N; Lechapt-Zalcman E; Metellus P; Colin P; Guillamo JS; Emery E; Menei P; Rousseaux P; Peruzzi P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Hopital Maison Blanche, Reims University Hospital, Reims, France, jduntze@chu-reims.fr.

RESUMEN / SUMMARY:  - OBJECTIVES: Study the feasibility and effectiveness of a treatment associated surgery, intraoperative chemotherapy (carmustine wafers), and concomitant radiochemotherapy (temozolomide) for the management of newly diagnosed, high-grade gliomas. METHODS: Prospective multicenter study conducted in 17 French centers with a total of 92 patients with newly diagnosed malignant glioma treated by surgery, implanted Carmustine wafers (Gliadel(®)) followed by concomitant radiochemotherapy by temozolomide (Temodar(®)). Clinical, imaging, and survival data were collected to study toxicity-induced adverse events and efficacy. RESULTS: A total of 20.6 % presented with adverse events during surgery, potentially attributable to carmustine, including 5 severe infections. Afterwards, 37.2 % of patients showed adverse events during radiochemotherapy and 40 % during adjuvant chemotherapy by temozolomide. We report a 10.5-month, median, progression-free survival and an 18.8-month median overall survival. No significant statistical difference was observed according to age, Karnofsky Performance Scale, or grade of the tumor. A prognostic difference at the limit of the significance threshold was observed according to the extent of the resection. CONCLUSIONS: Multimodal treatment associating implanted carmustine chemotherapy and concomitant radiochemotherapy with temozolomide seems to yield better survival rates than those usually described when carmustine or temozolomide are used alone independently from one another. These interesting results were obtained without increased adverse events and would need to be validated during a phase 3 study.

 

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[36]

TÍTULO / TITLE:  - Early relapses in patients with primary CNS lymphoma treated with methotrexate-based chemotherapy without consolidating whole brain irradiation.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1052-3

AUTORES / AUTHORS:  - Birnbaum T; Bochmann K; von Baumgarten L; Straube A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany, tobias.birnbaum@gmx.de.

RESUMEN / SUMMARY:  - Methotrexate (MTX)-based chemotherapy is used as upfront treatment for most patients with primary CNS lymphoma. Whether consolidating whole brain irradiation (WBI) should be recommended for patients who achieve complete remission (CR) is still a matter of debate. Patients who are predicted to experience an early relapse (ER, </=12 months from diagnosis) might especially benefit from consolidating treatment. We therefore evaluated the incidence and prognostic impact of ER in patients with CR following chemotherapy without WBI. We identified 40 patients between 2000 and 2010 who had achieved CR following MTX-based chemotherapy. Of 36 evaluable patients 11 (31 %) experienced an ER. These patients had significantly impaired overall survival (46.0 vs. 79.0 months, p = 0.001). Normal cerebrospinal fluid cell count (11.0 vs. 76.0 months, p = 0.001) and frequent reduction of MTX dose due to impaired creatinine clearance (10.0 vs. 48.0 months, p = 0.005) had a significantly negative impact on relapse-free survival. Patients with CR following MTX-based induction chemotherapy represent a heterogeneous population. In these patients, ER is an independent risk factor for impaired overall survival. Therefore, these patients  might especially benefit from consolidating treatment. These results have to be validated by prospective trials.

 

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[37]

TÍTULO / TITLE:  - Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient.

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

REVISTA / JOURNAL:  - Phys Med Biol. 2013 Jan 16;58(4):807-823.

            ●● Enlace al texto completo (gratuito o de pago) 1088/0031-9155/58/4/807

AUTORES / AUTHORS:  - Zhang R; Howell RM; Giebeler A; Taddei PJ; Mahajan A; Newhauser WD

INSTITUCIÓN / INSTITUTION:  - Graduate School of Biomedical Sciences, The University of Texas at Houston, Houston, TX, USA. Department of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

RESUMEN / SUMMARY:  - Pediatric patients who received radiation therapy are at risk of developing side  effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations,  and stray radiation doses for photon therapy were determined from measured data.  Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation  weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

 

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[38]

TÍTULO / TITLE:  - Intratumoral, not circulating, endothelial progenitor cells share genetic aberrations with glial tumor cells.

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

REVISTA / JOURNAL:  - J Cell Physiol. 2012 Dec 18. doi: 10.1002/jcp.24309.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcp.24309

AUTORES / AUTHORS:  - Zheng PP; van der Weiden M; van der Spek PJ; Vincent AJ; Kros JM

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands. p.zheng.1@erasmusmc.nl.

RESUMEN / SUMMARY:  - Literature data indicate that glioma stem cells may give rise to both tumor cells and EPCs. Malignant glioma patients usually have increased levels of circulating  endothelial progenitor cells (EPCs) and these cells are known to contribute to the glioma neovasculature. In this study we compared the intratumoral and circulating EPCs of glioma patients for a set of common glioma genotypical aberrations (amplification of EGFR; deletion of PTEN and aneusomy of chromosomes  7 and 10). We found that the EPCs present in the tumor tissues, not the circulating EPCs, share genetic aberrations with the tumor cells. EPCs with EGFR  amplification were found in 46% and with PTEN deletion in 36% of the cases. EPCs  with polysomy 7 and monosomy 10 were detected in 56% and 38% of the cases while centrosomal abnormalities in EPCs were found in 68% of the cases. The presence of genetic aberrations of glioma cells in intratumoral EPCs may point to transdifferentiation of glioma stem cells into EPCs. However, the tissue specific CD133 splice variant of blood EPCs was detected in the glioma tissues but not in  control brains, suggestive of a blood origin of at least part of the intratumoral EPCs. The findings highlight the complexity of the cellular constituents of glioma neovascularization which should be taken into account when developing anti-angiogenic strategies for gliomas. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.

 

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[39]

TÍTULO / TITLE:  - SP600125, a JNK inhibitor, suppresses growth of JNK-inactive glioblastoma cells through cell-cycle G2/M phase arrest.

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

REVISTA / JOURNAL:  - Pharmazie. 2012 Nov;67(11):942-6.

AUTORES / AUTHORS:  - Li JY; Huang JY; Xing B; Ren KW; Li M; Wei D; Gu PY; Chen G; Gu B; Zhang GF; Hu WX

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, Nanjing, China.

RESUMEN / SUMMARY:  - SP600125 is a well studied inhibitor of c-Jun N-terminal kinase (JNK). Its direct biochemical effects on JNK-inactive tumor cells are usually ignored. In this study, we investigated the effects of SP600125 on JNK-inactive U251 human glioblastoma cells. Our results demonstrate that, 20 microM or more SP600125 can  induce significant cell growth inhibition and cell-cycle G2/M phase arrest in U251 cells. Interestingly, we also found that SP600125 can stop the duplicated chromosomes from separating into two cells and the karyokinesis progression. Our  study opened up a new perspective for further studies involved in JNK inhibitors  or anti-glioma therapy.

 

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[40]

TÍTULO / TITLE:  - GPU-accelerated nonparametric kinetic analysis of DCE-MRI data from glioblastoma  patients treated with bevacizumab.

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

REVISTA / JOURNAL:  - Magn Reson Imaging. 2012 Nov 29. pii: S0730-725X(12)00362-1. doi: 10.1016/j.mri.2012.09.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mri.2012.09.007

AUTORES / AUTHORS:  - Hsu YH; Ferl GZ; Ng CM

INSTITUCIÓN / INSTITUTION:  - Division of Clinical Pharmacology and Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA.

RESUMEN / SUMMARY:  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is often used to examine vascular function in malignant tumors and noninvasively monitor drug efficacy of antivascular therapies in clinical studies. However, complex numerical methods used to derive tumor physiological properties from DCE-MRI images can be time-consuming and computationally challenging. Recent advancement  of computing technology in graphics processing unit (GPU) makes it possible to build an energy-efficient and high-power parallel computing platform for solving  complex numerical problems. This study develops the first reported fast GPU-based method for nonparametric kinetic analysis of DCE-MRI data using clinical scans of glioblastoma patients treated with bevacizumab (Avastin®). In the method, contrast agent concentration-time profiles in arterial blood and tumor tissue are smoothed using a robust kernel-based regression algorithm in order to remove artifacts due to patient motion and then deconvolved to produce the impulse response function (IRF). The area under the curve (AUC) and mean residence time (MRT) of the IRF are calculated using statistical moment analysis, and two tumor  physiological properties that relate to vascular permeability, volume transfer constant between blood plasma and extravascular extracellular space (K(trans)) and fractional interstitial volume (v(e)) are estimated using the approximations  AUC/MRT and AUC. The most significant feature in this method is the use of GPU-computing to analyze data from more than 60,000 voxels in each DCE-MRI image  in parallel fashion. All analysis steps have been automated in a single program script that requires only blood and tumor data as the sole input. The GPU-accelerated method produces K(trans) and v(e) estimates that are comparable to results from previous studies but reduces computational time by more than 80-fold compared to a previously reported central processing unit-based nonparametric method. Furthermore, it is at least several orders of magnitudes faster than standard parametric methods that perform compartmental modeling. This finding indicates that the GPU-based method can significantly shorten the computational times required to assess tumor physiology from DCE-MRI data in preclinical and clinical development of antivascular therapies.

 

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[41]

TÍTULO / TITLE:  - Prediction of response to chemotherapy in anaplastic glioma: how many markers does it take?

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 20;31(3):297-8. doi: 10.1200/JCO.2012.46.9627. Epub 2012 Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.46.9627

AUTORES / AUTHORS:  - de Groot JF

INSTITUCIÓN / INSTITUTION:  - The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 431,  Houston, TX 77030; jdegroot@mdanderson.org.

 

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[42]

TÍTULO / TITLE:  - Exclusion of Histiocytes/Endothelial Cells and Using Endothelial Cells as Internal Reference Are Crucial for Interpretation of MGMT Immunohistochemistry in Glioblastoma.

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

REVISTA / JOURNAL:  - Am J Surg Pathol. 2013 Feb;37(2):264-71. doi: 10.1097/PAS.0b013e318267b061.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e318267b061

AUTORES / AUTHORS:  - Hsu CY; Lin SC; Ho HL; Chang-Chien YC; Hsu SP; Yen YS; Chen MH; Guo WY; Ho DM

INSTITUCIÓN / INSTITUTION:  - *Department of Pathology and Laboratory Medicine double daggerNeurology section signRadiology, Taipei Veterans General Hospital daggerSchool of Medicine, National Yang-Ming University, Taipei, Taiwan.

RESUMEN / SUMMARY:  - We evaluated the predictive value of O6-methylguanine-DNA methyltransferase (MGMT) protein expression and MGMT promoter methylation status in glioblastomas (GBM) treated with temozolomide (TMZ) in a Taiwan medical center. Protein expression by immunohistochemical analysis (IHC) and MGMT promoter methylation detected by methylation-specific polymerase chain reaction (MSP) were performed in a series of 107 newly diagnosed GBMs. We used endothelial cells as an internal reference for IHC staining because the staining intensities of the MGMT-expressing cells in different specimens varied considerably; a positive result was defined as the staining intensity of the majority of tumor cells similar to that of the adjacent endothelial cells. Immunostainings for microglial/endothelial markers were included as part of the MGMT IHC evaluation,  and in cases that were difficult to interpret, double-labeling helped to clarify  the nature of reactive cells. The MGMT protein expression was reversely associated with MGMT promoter methylation status in 83.7% of cases (MSP/IHC and MSP/IHC; Pearson r=-0.644, P<0.001). Twenty-two of 24 (91.7%) IHC tumors did not  respond to TMZ treatment. Combining MSP and IHC results, all the 15 MSP/IHC GBMs  were TMZ resistant. The MGMT status detected by either IHC or MSP was significantly correlated with the TMZ treatment response (both P<0.001) and survival of GBM patients (both P<0.05).

 

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[43]

TÍTULO / TITLE:  - Impairment of Glioma Stem Cell Survival and Growth by a Novel Inhibitor for Survivin-Ran Protein Complex.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-0647

AUTORES / AUTHORS:  - Guvenc H; Pavlyukov MS; Joshi K; Kurt H; Banasavadi-Siddegowda YK; Mao P; Hong C; Yamada R; Kwon CH; Bhasin D; Chettiar S; Kitange G; Park IH; Sarkaria JN; Li C; Shakhparonov MI; Nakano I

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Department of Neurological Surgery; Division of Medicinal  Chemistry and Pharmacognosy, College of Pharmacy; James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota; Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; and Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Xi’an, Jiaotong University, Xi’an, China.

RESUMEN / SUMMARY:  - PURPOSE: Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to the development of therapy resistance.EXPERIMENTAL DESIGN: The expression of Survivin and Ran was evaluated by immunohistochemistry with GBM tissues, and quantitative reverse transcriptase (qRT)-PCR and immunocytochemistry with patient-derived GBM sphere cultures. With a computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, and evaluated as inhibitor candidates for the molecular interaction of Survivin protein. The molecular mechanism of the lead compound, LLP-3, was determined by Western blot, ELISA, in situ proximity ligation assay, and immunocytochemistry. The effects of LLP-3 treatment on GSCs were evaluated both in vitro and in vivo. Quantitative immunohistochemistry was carried out to compare Survivin expression in tissues from 44 newly diagnosed and 31 recurrent post-chemoradiation GBM patients. Lastly, the sensitivities of temozolomide-resistant GBM spheres to LLP-3 were evaluated in vitro.RESULTS: Survivin and Ran were strongly expressed in GBM tissues, particularly in the perivasculature, and also in patient-derived GSC cultures. LLP-3 treatment disrupted the Survivin-Ran protein complex in cancer cells and abolished the growth of patient-derived GBM spheres in vitro and in vivo. This inhibition was dependent on caspase activity and associated with p53 status of cells. Immunohistochemistry showed that Survivin expression is significantly increased in recurrent GBM compared with newly diagnosed tumors, and temozolomide-resistant GBM spheres exhibited high sensitivities to LLP-3 treatment.CONCLUSIONS: Disruption of the Survivin-Ran complex by LLP-3 abolishes survival and growth of  GSCs both in vitro and in vivo, indicating an attractive novel therapeutic approach for GBM. Clin Cancer Res; 19(3); 1-12. ©2012 AACR.

 

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[44]

TÍTULO / TITLE:  - Vaccine injection site matters: qualitative and quantitative defects in CD8 T cells primed as a function of proximity to the tumor in a murine glioma model.

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

REVISTA / JOURNAL:  - J Immunol. 2013 Jan 15;190(2):613-20. doi: 10.4049/jimmunol.1201557. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1201557

AUTORES / AUTHORS:  - Ohlfest JR; Andersen BM; Litterman AJ; Xia J; Pennell CA; Swier LE; Salazar AM; Olin MR

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455;

RESUMEN / SUMMARY:  - Malignant gliomas are lethal brain tumors for which novel therapies are urgently  needed. In animal models, vaccination with tumor-associated Ags efficiently primes T cells to clear gliomas. In clinical trials, cancer vaccines have been less effective at priming T cells and extending survival. Generalized immune suppression in the tumor draining lymph nodes has been documented in multiple cancers. However, a systematic analysis of how vaccination at various distances from the tumor (closest to farthest) has not been reported. We investigated how the injection site chosen for vaccination dictates CD8 T cell priming and survival in an OVA-transfected murine glioma model. Glioma-bearing mice were vaccinated with Poly:ICLC plus OVA protein in the neck, hind leg, or foreleg for  drainage into the cervical, inguinal, or axillary lymph nodes, respectively. OVA-specific CD8 T cell number, TCR affinity, effector function, and infiltration into the brain decreased as the vaccination site approached the tumor. These effects were dependent on the presence of the tumor, because injection site did not appreciably affect CD8 T cell priming in tumor-free mice. Our data suggest the site of vaccination can greatly impact the effectiveness of cancer vaccines.  Considering that previous and ongoing clinical trials have used a variety of injection sites, vaccination site is potentially a critical aspect of study design that is being overlooked.

 

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[45]

TÍTULO / TITLE:  - Supratentorial Ependymoma: Disease Control, Complications, and Functional Outcomes After Irradiation.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 11. pii: S0360-3016(12)03733-9. doi: 10.1016/j.ijrobp.2012.10.033.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.033

AUTORES / AUTHORS:  - Landau E; Boop FA; Conklin HM; Wu S; Xiong X; Merchant TE

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Sheba Medical Center, Ramat Gan, Israel.

RESUMEN / SUMMARY:  - PURPOSE: Ependymoma is less commonly found in the supratentorial brain and has known clinical and molecular features that are unique. Our single-institution series provides valuable information about disease control for supratentorial ependymoma and the complications of supratentorial irradiation in children. METHODS AND MATERIALS: A total of 50 children with newly diagnosed supratentorial ependymoma were treated with adjuvant radiation therapy (RT); conformal methods were used in 36 after 1996. The median age at RT was 6.5 years (range, 1-18.9 years). The entire group was characterized according to sex (girls 27), race (white 43), extent of resection (gross-total 46), and tumor grade (anaplastic 28). The conformal RT group was prospectively evaluated for neurologic, endocrine, and cognitive effects. RESULTS: With a median follow-up time of 9.1 years from the start of RT for survivors (range, 0.2-23.2 years), the 10-year progression-free and overall survival were 73% + 7% and 76% + 6%, respectively. None of the evaluated factors was prognostic for disease control. Local and distant failures were evenly divided among the 16 patients who experienced progression. Eleven patients died of disease, and 1 of central nervous system necrosis. Seizure disorders were present in 17 patients, and 4 were considered to be clinically disabled. Clinically significant cognitive effects were limited to  children with difficult-to-control seizures. The average values for intelligence  quotient and academic achievement (reading, spelling, and math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy. CONCLUSION: RT may be administered with acceptable risks for complications in children with supratentorial ependymoma. These results suggest that outcomes for these children are improving and that complications may be limited by use of focal irradiation methods.

 

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[46]

TÍTULO / TITLE:  - Development of anxiety and depression in patients with benign intracranial meningiomas: a prospective long-term study.

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

REVISTA / JOURNAL:  - Support Care Cancer. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00520-012-1675-5

AUTORES / AUTHORS:  - Goebel S; Mehdorn HM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital Schleswig-Holstein, Schittenhelmstr 10, 24105, Kiel, Germany, goebels@nch.uni-kiel.de.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this study was to provide the first prospective longitudinal  assessment of anxiety and depression in patients with a benign intracranial meningioma (WHO degrees I). METHODS: The Hospital Anxiety and Depression Scale was applied prior to (t1) and directly after (t2) neurosurgery as well as 6 months after surgery (t3). The research was conducted in a single treatment centre in Germany. Numerous sociodemographic, medical, psychological and cognitive accompanying measures were assessed. The study population consisted of  52 meningioma patients. Additionally, a control group of 24 patients with malignant brain tumours (astrocytoma WHO degrees III) was assessed. RESULTS: In meningioma patients, anxiety was high prior to surgery but declined significantly after successful neurosurgical treatment. Low levels of depression were observed  at all times. In contrast, astrocytoma patients showed constantly high levels of  anxiety whilst depression increased over the course of the disease. Numerous medical, psychosocial and psychological factors were associated with psychiatric  morbidity in meningioma patients. CONCLUSIONS: In conclusion, psychiatric morbidity of patients with benign intracranial meningiomas was comparable to that of the general population after successful neurosurgical treatment. Numerous associated factors suggest complex relationships within a biopsychosocial model.  However, due to the small sample size and recruitment in a single institution, our results are of limited generalisability and need cross-validation in future studies.

 

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[47]

TÍTULO / TITLE:  - The SDF-1 3’A Genetic Variation Is Correlated with Elevated Intra-tumor Tissue and Circulating Concentration of CXCL12 in Glial Tumors : A Study on Iranian Anaplastic Astrocytoma and Glioblastoma Multiforme Patients.

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

REVISTA / JOURNAL:  - J Mol Neurosci. 2013 Jan 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12031-013-9954-2

AUTORES / AUTHORS:  - Moosavi SR; Khorramdelazad H; Amin M; Fatahpoor S; Moogooei M; Karimabad MN; Paghale MJ; Vakilian A; Hassanshahi G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kerman University of Medical Sciences, Kerman, Iran.

RESUMEN / SUMMARY:  - Immunological factors are important in pathogenesis of various malignancies, including neural cancers. The CXC chemokine CXCL12 is involved in the immune responses. Therefore, the aim of the present study was to investigate the association between tumor tissue and circulating concentrations of CXCL12 as well as its genetic variation at position +801 known as(the SDF-1 3’A), in Iranian patients suffering from malignant glial tumors. In this study, stereotactic tumor biopsy specimens in parallel with peripheral blood samples were collected from 123 patients and 189 healthy controls. The serum level of CXCL12 was measured by  ELISA and tumor tissues were subjected to Western blotting for intra-tumor CXCL12 detection; we also employed PCR-RFLP to detect the SDF-1 3’A polymorphism. Demographic data were collected by a researcher-designed questionnaire. These results demonstrated a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of CXCL12. We also indicated elevated levels of CXCL12 in circulation and tumor tissue obtained from in patients suffering from malignant glial tumors. Based upon the results of this investigation, we propose that CXCL12 and its SDF-1 3’A polymorphism play a fundamental part in the pathogenesis of malignant glial tumors. It is also noteworthy that CXCL12 could probably be utilized as a beneficial biological marker in the diagnosis of these tumors.

 

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[48]

TÍTULO / TITLE:  - Glioblastoma with Oligodendroglioma Component (GBM-O): Molecular Genetic and Clinical Characteristics.

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

REVISTA / JOURNAL:  - Brain Pathol. 2013 Jan 4:0. doi: 10.1111/bpa.12018.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12018

AUTORES / AUTHORS:  - Appin CL; Gao J; Chisolm C; Torian M; Alexis D; Vincentelli C; Schniederjan MJ; Hadjipanayis C; Olson JJ; Hunter S; Hao C; Brat DJ

INSTITUCIÓN / INSTITUTION:  - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival  of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were  used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of  GBMs with distinctive morphologic, clinical and molecular characteristics.

 

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[49]

TÍTULO / TITLE:  - Thrombin-cleaved fragments of osteopontin are overexpressed in malignant glial tumors and provide a molecular niche with survival advantage.

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

REVISTA / JOURNAL:  - J Biol Chem. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.362954

AUTORES / AUTHORS:  - Yamaguchi Y; Shao Z; Sharif S; Du XY; Myles T; Merchant M; Harsh G; Glantz M; Recht L; Morser J; Leung LL

INSTITUCIÓN / INSTITUTION:  - Stanford University School of Medicine, United States;

RESUMEN / SUMMARY:  - Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity that is modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples  from all cancer patients compared to non-cancer patients. However thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double cleaved OPN (OPN-L) levels  were markedly increased in GBM and non-GBM gliomas compared to systemic cancer and non-cancer patients. Cleaved OPN constituted ~23% and ~31% of the total OPN in the GBM and non-GBM CSF samples respectively. OPN-R was also elevated in GBM tissues. Thrombin-antithrombin levels were highly correlated with cleaved OPN, but not OPN-FL, suggesting that the cleaved OPN fragments resulted from increased thrombin and CPB2 in this extracellular compartment. Levels of VEGF and CCL4 were increased in CSF of GBM and significantly correlated with the levels of cleaved OPN. GBM cell lines were significantly more adherent to OPN-R and OPN-L than OPN-FL. Adhesion to OPN altered gene expression, in particular genes involved with cellular processes, cell cycle regulation, death and inflammation. OPN promoted motility of U-87 MG cells and conferred resistance to apoptosis. While functional mutation of the RGD motif in OPN largely abolished these functions, OPN(RAA)-R regained significant cell binding and signaling function, suggesting that the SVVYGLR motif in OPN-R may substitute for the RGD-motif if the latter becomes inaccessible. OPN cleavage contributes to GBM development by allowing more cells to bind in niches in which they acquire anti-apoptotic properties.

 

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[50]

TÍTULO / TITLE:  - Long-term survival of patients with glioblastoma multiforme (GBM).

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 23. pii: S0967-5868(12)00495-X. doi: 10.1016/j.jocn.2012.05.040.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.05.040

AUTORES / AUTHORS:  - Smoll NR; Schaller K; Gautschi OP

INSTITUCIÓN / INSTITUTION:  - Gippsland Medical School, Monash University, Churchill, Victoria, Australia; Department of Neurosurgery, Geneva University Medical Center, Faculty of Medicine, University of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. Electronic address: nrsmoll@me.com.

RESUMEN / SUMMARY:  - Long-term survival is an often used, yet poorly defined, concept in the study of  glioblastoma multiforme (GBM). This study suggests a method to define a time-point for long-term survival in patients with GBM. Data for this study were  obtained from the Surveillance, Epidemiology and End-Results database, which was  limited to the most recent data using the period approach. Relative survival measures were used and modelled using piecewise constant hazards to describe the  survival profile of long-term survivors of GBM. For patients with GBM, the first  quarter of the second year (5th quarter) post-diagnosis is considered to be the peak incidence of mortality with an excess hazard ratio of 7.58 (95% confidence interval=6.54, 8.78) and the risk of death due to GBM decreases to half of its rate at 2.5years post-diagnosis. The 2.5-year cumulative relative survival (CRS)  for all patients is approximately 8%, with a CRS of approximately 2% at 10years.  Using the definition of long-term survival suggested here, the results indicate that long-term survivors are patients who survive at least 2.5years post-diagnosis. The most likely time period for patients with GBM to die is the 5th quarter post-diagnosis.

 

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[51]

TÍTULO / TITLE:  - Does RTOG 9802 Change Practice With Respect to Newly Diagnosed Low-Grade Glioma?

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.46.7969

AUTORES / AUTHORS:  - Chamberlain MC

INSTITUCIÓN / INSTITUTION:  - University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer  Care Alliance, Seattle, WA.

 

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[52]

TÍTULO / TITLE:  - Netrin-1 Promotes Glioblastoma Cell Invasiveness and Angiogenesis by Multiple Pathways Including Activation of RhoA, Cathepsin B, and cAMP-response Element-binding Protein.

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

REVISTA / JOURNAL:  - J Biol Chem. 2013 Jan 25;288(4):2210-22. doi: 10.1074/jbc.M112.397398. Epub 2012  Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.397398

AUTORES / AUTHORS:  - Shimizu A; Nakayama H; Wang P; Konig C; Akino T; Sandlund J; Coma S; Italiano JE Jr; Mammoto A; Bielenberg DR; Klagsbrun M

INSTITUCIÓN / INSTITUTION:  - From the Vascular Biology Program and.

RESUMEN / SUMMARY:  - Glioblastomas are very difficult tumors to treat because they are highly invasive and disseminate within the normal brain, resulting in newly growing tumors. We have identified netrin-1 as a molecule that promotes glioblastoma invasiveness. As evidence, netrin-1 stimulates glioblastoma cell invasion directly through Matrigel-coated transwells, promotes tumor cell sprouting and enhances metastasis to lymph nodes in vivo. Furthermore, netrin-1 regulates angiogenesis as shown in  specific angiogenesis assays such as enhanced capillary endothelial cells (EC) sprouting and by increased EC infiltration into Matrigel plugs in vivo, as does VEGF-A. This netrin-1 signaling pathway in glioblastoma cells includes activation of RhoA and cyclic AMP response element-binding protein (CREB). A novel finding is that netrin-1-induced glioblastoma invasiveness and angiogenesis are mediated  by activated cathepsin B (CatB), a cysteine protease that translocates to the cell surface as an active enzyme and co-localizes with cell surface annexin A2 (ANXA2). The specific CatB inhibitor CA-074Me inhibits netrin-1-induced cell invasion, sprouting, and Matrigel plug angiogenesis. Silencing of CREB suppresses netrin-1-induced glioblastoma cell invasion, sprouting, and CatB expression. It is concluded that netrin-1 plays an important dual role in glioblastoma progression by promoting both glioblastoma cell invasiveness and angiogenesis in  a RhoA-, CREB-, and CatB-dependent manner. Targeting netrin-1 pathways may be a promising strategy for brain cancer therapy.

 

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[53]

TÍTULO / TITLE:  - MicroRNA 218 Acts as a Tumor Suppressor by Targeting Multiple Cancer Phenotype-associated Genes in Medulloblastoma.

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

REVISTA / JOURNAL:  - J Biol Chem. 2013 Jan 18;288(3):1918-28. doi: 10.1074/jbc.M112.396762. Epub 2012  Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.396762

AUTORES / AUTHORS:  - Venkataraman S; Birks DK; Balakrishnan I; Alimova I; Harris PS; Patel PR; Handler MH; Dubuc A; Taylor MD; Foreman NK; Vibhakar R

INSTITUCIÓN / INSTITUTION:  - From the Department of Pediatrics.

RESUMEN / SUMMARY:  - Aberrant expression of microRNAs has been implicated in many cancers. We recently demonstrated differential expression of several microRNAs in medulloblastoma. In  this study, the regulation and function of microRNA 218 (miR-218), which is significantly underexpressed in medulloblastoma, was evaluated. Re-expression of  miR-218 resulted in a significant decrease in medulloblastoma cell growth, cell colony formation, cell migration, invasion, and tumor sphere size. We used C17.2  neural stem cells as a model to show that increased miR-218 expression results in increased cell differentiation and also decreased malignant transformation when transfected with the oncogene REST. These results suggest that miR-218 acts as a  tumor suppressor in medulloblastoma. MicroRNAs function by down-regulating translation of target mRNAs. Targets are determined by imperfect base pairing of  the microRNA to the 3’-UTR of the mRNA. To comprehensively identify actual miR-218 targets, medulloblastoma cells overexpressing miR-218 and control cells were subjected to high throughput sequencing of RNA isolated by cross-linking immunoprecipitation, a technique that identifies the mRNAs bound to the RNA-induced silencing complex component protein Argonaute 2. High throughput sequencing of mRNAs identified 618 genes as targets of miR-218 and included both  previously validated targets and many targets not predicted computationally. Additional work further confirmed CDK6, RICTOR, and CTSB (cathepsin B) as targets of miR-218 and examined the functional role of one of these targets, CDK6, in medulloblastoma.

 

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[54]

TÍTULO / TITLE:  - Loss of miR-204 Expression Enhances Glioma Migration and Stem Cell-like Phenotype.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 15;73(2):990-9. doi: 10.1158/0008-5472.CAN-12-2895. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2895

AUTORES / AUTHORS:  - Ying Z; Li Y; Wu J; Zhu X; Yang Y; Tian H; Li W; Hu B; Cheng SY; Li M

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Departments of Microbiology and Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China; and Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine & The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

RESUMEN / SUMMARY:  - Phenotypic similarities have long been recognized between subpopulations of glioma and neural stem cells. Many of these similar properties, including the robust abilities to self-renew, migrate, and invade, are hallmarks of glioma cells that render them extremely aggressive. However, the molecular mechanisms underlying this character, particularly in glioma stem-like cells that drive this disease, remain poorly understood. Here, we report the results of a differential  miRNA expression screen that compared glioma and neural stem cells, where we found that miR-204 was markedly downregulated in both types of cells. Mechanistic investigations revealed that miR-204 simultaneously suppressed self-renewal, stem cell-associated phenotype, and migration of glioma cells by targeting the stemness-governing transcriptional factor SOX4 and the migration-promoting receptor EphB2. Restoring miR-204 expression in glioma cells suppressed tumorigenesis and invasiveness in vivo and increased overall host survival. Further evaluation revealed that the miR-204 promoter was hypermethylated and that attenuating promoter methylation was sufficient to upregulate miR-204 in glioma cells. Together, our findings reveal miR-204 as a pivotal regulator of the development of stem cell-like phenotypes and cell motility in malignant glioma cells. Cancer Res; 73(2); 990-9. ©2012 AACR.

 

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[55]

TÍTULO / TITLE:  - Multimodal Elucidation of Choline Metabolism in a Murine Glioma Model using Magnetic Resonance Spectroscopy and 11C-choline Positron Emission Tomography.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2532

AUTORES / AUTHORS:  - Wehrl HF; Schwab J; Hasenbach K; Reischl G; Tabatabai G; Quintanilla-Martinez L; Jiru F; Chughtai K; Kiss A; Cay F; Bukala D; Heeren RM; Pichler BJ; Sauter AW

INSTITUCIÓN / INSTITUTION:  - Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University.

RESUMEN / SUMMARY:  - The metabolites, transporters and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both MR Spectroscopy (MRS using CSI tCho) and 11C-choline PET can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially injected into syngeneic VM/Dk mice, analyzing animals at  various post-implantation time points using dynamic microPET imaging and chemical shift imaging MR spectroscopy. We observed an increase in tumor volume and 11C-choline uptake between days 5-18. Similarly, tCho levels decreased at days 5-18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and 11C-choline PET data,  while a negative correlation occurred when CSI was not referenced. Thus, 11C-choline PET and MRS methods appeared to be complementary in strengths. While  advancing tumor proliferation caused an increasing 11C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry (SIMS) imaging. Our findings provide definitive evidence of the utility of MRS, CSI and PET for imaging tumors in vivo.

 

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[56]

TÍTULO / TITLE:  - MicroRNA-21 silencing enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma.

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

REVISTA / JOURNAL:  - Hum Mol Genet. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1093/hmg/dds496

AUTORES / AUTHORS:  - Costa PM; Cardoso AL; Nobrega C; Pereira de Almeida LF; Bruce JN; Canoll P; Pedroso de Lima MC

INSTITUCIÓN / INSTITUTION:  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.

RESUMEN / SUMMARY:  - Highly malignant glioblastoma (GBM) is characterized by high genetic heterogeneity and infiltrative brain invasion patterns, and aberrant miRNA expression has been associated with hallmark malignant properties of GBM. The lack of effective GBM treatment options prompted us to investigate whether miRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. Here, we show that  microRNA-21 (miR-21) is upregulated and microRNA-128 (miR-128) is downregulated in mouse and human GBM samples, a finding that is corroborated by analysis of a large set of human GBM data from The Cancer Genome Atlas. Moreover, we demonstrate that oligonucleotide-mediated miR-21 silencing in U87 human GBM cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Cell exposure to pifithrin, an inhibitor of p53 transcriptional activity, reduced the caspase activity associated with decreased miR-21 expression. Finally, we demonstrate for the first time that miR-21 silencing enhances the antitumoral effect of the tyrosine  kinase inhibitor sunitinib, whereas no therapeutic benefit is observed when coupling miR-21 silencing with the first-line drug temozolomide. Overall, our results provide evidence that miR-21 is uniformly overexpressed in GBM and constitutes a highly promising target for multimodal therapeutic approaches toward GBM.

 

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[57]

TÍTULO / TITLE:  - Laminin alpha 2 enables glioblastoma stem cell growth.

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

REVISTA / JOURNAL:  - Ann Neurol. 2012 Nov;72(5):766-78. doi: 10.1002/ana.23674.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ana.23674

AUTORES / AUTHORS:  - Lathia JD; Li M; Hall PE; Gallagher J; Hale JS; Wu Q; Venere M; Levy E; Rani MR; Huang P; Bae E; Selfridge J; Cheng L; Guvenc H; McLendon RE; Nakano I; Sloan AE; Phillips HS; Lai A; Gladson CL; Bredel M; Bao S; Hjelmeland AB; Rich JN

INSTITUCIÓN / INSTITUTION:  - Departments of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; Department of Molecular Medicine, University Hospital-Case Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH. lathiaj@ccf.org.

RESUMEN / SUMMARY:  - OBJECTIVE: Glioblastomas (GBMs) are lethal cancers that display cellular hierarchies parallel to normal brain. At the apex are GBM stem cells (GSCs), which are relatively resistant to conventional therapy. Interactions with the adjacent perivascular niche are an important driver of malignancy and self-renewal in GSCs. Extracellular matrix (ECM) cues instruct neural stem/progenitor cell-niche interactions, and the objective of our study was to elucidate its composition and contribution to GSC maintenance in the perivascular niche. METHODS: We interrogated human tumor tissue for immunofluorescence analysis and derived GSCs from tumor tissues for functional studies. Bioinformatics analyses were conducted by mining publicly available databases. RESULTS: We find that laminin ECM proteins are localized to the perivascular GBM  niche and inform negative patient prognosis. To identify the source of laminins,  we characterized cellular elements within the niche and found that laminin alpha  chains were expressed by nonstem tumor cells and tumor-associated endothelial cells (ECs). RNA interference targeting laminin alpha2 inhibited GSC growth and self-renewal. In co-culture studies of GSCs and ECs, laminin alpha2 knockdown in  ECs resulted in decreased tumor growth. INTERPRETATION: Our studies highlight the contribution of nonstem tumor cell-derived laminin juxtracrine signaling. As laminin alpha2 has recently been identified as a molecular marker of aggressive ependymoma, we propose that the brain vascular ECM promotes tumor malignancy through maintenance of the GSC compartment, providing not only a molecular fingerprint but also a possible therapeutic target. ANN NEUROL 2012;72:766-778.

 

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[58]

TÍTULO / TITLE:  - Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 11. pii: S0360-3016(12)03732-7. doi: 10.1016/j.ijrobp.2012.10.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.032

AUTORES / AUTHORS:  - Maclean J; Fersht N; Bremner F; Stacey C; Sivabalasingham S; Short S

INSTITUCIÓN / INSTITUTION:  - Radiotherapy Department, University College London Hospital, , London, UK. Electronic address: jillian.maclean@uclh.nhs.uk.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate ophthalmologic outcomes and toxicity of intensity modulated  radiation therapy (IMRT) in patients with meningiomas causing visual deficits. METHODS AND MATERIALS: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy  to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3  optic nerve sheath meningiomas); 4 were posterior to the chiasm. RESULTS: Vision  improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions  in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2  keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. CONCLUSION: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of  radiological change.

 

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[59]

TÍTULO / TITLE:  - beta-defensin-3 negatively regulates TLR4-HMGB1 axis mediated HLA-G expression in IL-1beta treated glioma cells.

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

REVISTA / JOURNAL:  - Cell Signal. 2013 Mar;25(3):682-9. doi: 10.1016/j.cellsig.2012.12.001. Epub 2012  Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cellsig.2012.12.001

AUTORES / AUTHORS:  - Gupta P; Ghosh S; Nagarajan A; Mehta VS; Sen E

INSTITUCIÓN / INSTITUTION:  - National Brain Research Centre, Manesar, Haryana 122 050, India.

RESUMEN / SUMMARY:  - The non-classical HLA class I antigen HLA-G contributes to immune escape mechanisms in glioblastoma multiforme (GBM). We have previously shown that IL-1beta-HIF-1alpha axis connects inflammatory and oncogenic pathways in GBM. In  this study, we investigated the role of IL-1beta induced inflammation in regulating HLA-G expression. IL-1beta increased HLA-G and Toll like receptor 4 (TLR4) expression in a HIF-1alpha dependent manner. Inhibition of TLR4 signaling  abrogated IL-1beta induced HLA-G. IL-1beta increased HMGB1 expression and its interaction with TLR4. Inhibition of HMGB1 inhibited TLR4 and vice versa suggesting the existence of HMGB1-TLR4 axis in glioma cells. Interestingly, HMGB1 inhibition prevented IL-1beta induced HLA-G expression. Elevated levels of HMGB1  and beta-defensin 3 were observed in GBM tumors. Importantly, beta-defensin-3 prevented IL-1beta induced HLA-G, TLR4, HMGB1 expression and release of pro-inflammatory mediators. Our studies indicate that beta-defensin-3 abrogates IL-1beta induced HLA-G expression by negatively affecting key molecules associated with its regulation.

 

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[60]

TÍTULO / TITLE:  - Moesin Is a Glioma Progression Marker That Induces Proliferation and Wnt/beta-Catenin Pathway Activation via Interaction with CD44.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1040

AUTORES / AUTHORS:  - Zhu X; Morales FC; Agarwal NK; Dogruluk T; Gagea M; Georgescu MM

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: Department of Neuro-Oncology and Veterinary Medicine, University of Texas MD Anderson Cancer Center, Houston; and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.

RESUMEN / SUMMARY:  - Moesin is an ERM family protein that connects the actin cytoskeleton to transmembrane receptors. With the identification of the ERM family protein NF2 as a tumor suppressor in glioblastoma, we investigated roles for other ERM proteins  in this malignancy. Here, we report that overexpression of moesin occurs generally in high-grade glioblastoma in a pattern correlated with the stem cell marker CD44. Unlike NF2, moesin acts as an oncogene by increasing cell proliferation and stem cell neurosphere formation, with its ectopic overexpression sufficient to shorten survival in an orthotopic mouse model of glioblastoma. Moesin was the major ERM member activated by phosphorylation in glioblastoma cells, where it interacted and colocalized with CD44 in membrane protrusions. Increasing the levels of moesin competitively displaced NF2 from CD44, increasing CD44 expression in a positive feedback loop driven by the Wnt/beta-catenin signaling pathway. Therapeutic targeting of the moesin-CD44 interaction with the small-molecule inhibitor 7-cyanoquinocarcinol (DX-52-1) or with a CD44-mimetic peptide specifically reduced the proliferation of glioblastoma cells overexpressing moesin, where the Wnt/beta-catenin pathway was  activated. Our findings establish moesin and CD44 as progression markers and drugable targets in glioblastoma, relating their oncogenic effects to activation  of the Wnt/beta-catenin pathway. Cancer Res; 73(3); 1-14. ©2012 AACR.

 

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[61]

TÍTULO / TITLE:  - Dopamine Agonist-Induced Impulse Control Disorders in a Patient with Prolactinoma.

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

REVISTA / JOURNAL:  - Psychosomatics. 2012 Dec 19. pii: S0033-3182(12)00184-3. doi: 10.1016/j.psym.2012.10.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.psym.2012.10.002

AUTORES / AUTHORS:  - Almanzar S; Zapata-Vega MI; Raya JA

INSTITUCIÓN / INSTITUTION:  - Department of Psychiatry, Mount Sinai School of Medicine at Elmhurst Hospital Center, Elmhurst, NY. Electronic address: ALMANZAS@nychhc.org.

 

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[62]

TÍTULO / TITLE:  - Description of selected characteristics of familial glioma patients - Results from the Gliogene Consortium.

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

REVISTA / JOURNAL:  - Eur J Cancer. 2013 Jan 4. pii: S0959-8049(12)00894-5. doi: 10.1016/j.ejca.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.11.009

AUTORES / AUTHORS:  - Sadetzki S; Bruchim R; Oberman B; Armstrong GN; Lau CC; Claus EB; Barnholtz-Sloan JS; Il’yasova D; Schildkraut J; Johansen C; Houlston RS; Shete S; Amos CI; Bernstein JL; Olson SH; Jenkins RB; Lachance D; Vick NA; Merrell R; Wrensch M; Davis FG; McCarthy BJ; Lai R; Melin BS; Bondy ML

INSTITUCIÓN / INSTITUTION:  - Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: siegals@gertner.health.gov.il.

RESUMEN / SUMMARY:  - BACKGROUND: While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part  of the Gliogene Consortium. METHODS: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. FINDINGS: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a  male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (+/-standard deviation [SD]) diagnosis age was 49.4  (+/-18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40y, and in 12% both were diagnosed under 40y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals  with grades I-II were on average 17y younger than those with grades III-IV. INTERPRETATION: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in  the counselling and clinical management of individuals with a family history of glioma.

 

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[63]

TÍTULO / TITLE:  - Primary Cerebral Angioimmunoblastic T-Cell Lymphoma.

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

REVISTA / JOURNAL:  - J Clin Oncol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.8226

AUTORES / AUTHORS:  - Lachenal F; Berger F; Cimarelli S; Formaglio M; Ghesquieres H

INSTITUCIÓN / INSTITUTION:  - Hopital Pierre Oudot, Bourgoin-Jallieu, France.

 

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[64]

TÍTULO / TITLE:  - Parental alcohol consumption and risk of childhood acute lymphoblastic leukemia and brain tumors.

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

REVISTA / JOURNAL:  - Cancer Causes Control. 2013 Feb;24(2):391-402. doi: 10.1007/s10552-012-0125-5. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10552-012-0125-5

AUTORES / AUTHORS:  - Milne E; Greenop KR; Scott RJ; de Klerk NH; Bower C; Ashton LJ; Heath JA; Armstrong BK

INSTITUCIÓN / INSTITUTION:  - Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia, lizm@ichr.uwa.edu.au.

RESUMEN / SUMMARY:  - PURPOSE: Childhood acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and brain tumors (CBTs) are the leading cause of cancer death in children. In our Australian case-control studies of these cancers, we investigated whether parental alcohol consumption before or during pregnancy was  associated with risk. METHODS: Cases were identified through the ten Australian pediatric oncology centers, and controls were recruited through national random-digit dialling. Detailed information on alcohol consumption, including beverage type, amount, and timing, was collected from 690 case families (388 ALL  and 302 CBT) and 1,396 control families. Data were analyzed using unconditional logistic regression. RESULTS: We found no evidence that maternal alcohol use before or during pregnancy was associated with an increased risk of either cancer; rather, there was evidence of inverse associations, particularly with wine. For both cancers, we observed U-shaped associations with paternal alcohol consumption in the year before the pregnancy, possibly driven by reduced risk at  moderate levels of beer and wine intake and increased risk associated with high levels of beer intake. Moderate intake of spirits by fathers was associated with  an increased risk of CBT but not ALL. These findings would be strengthened by corroboration in other studies. While the inverse associations with wine may be interesting mechanistically, the public health message remains that maternal alcohol use during pregnancy causes serious disorders in the offspring and should be avoided. CONCLUSIONS: Our findings suggest that men, as well as women, should  limit their alcohol intake when planning a pregnancy.

 

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[65]

TÍTULO / TITLE:  - A new prognostic scoring scale for patients with primary WHO grade III gliomas based on molecular predictors.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1026-x

AUTORES / AUTHORS:  - Jiang H; Ren X; Zhang W; Ma J; Sui D; Jiang Z; Cui X; Lin S

INSTITUCIÓN / INSTITUTION:  - Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

RESUMEN / SUMMARY:  - This study was designed to select molecular markers associated with prognosis, and to propose a prognostic scoring scale for patients with primary WHO grade III gliomas based on these molecular predictors. A series of 83 grade III glioma patients surgically treated and pathologically confirmed in Beijing Tiantan Hospital between May 2009 and December 2010 were retrospectively reviewed in the  study. Log-rank analysis was used to identify molecular markers associated with progression-free survival (PFS) and overall survival (OS), which were further assessed using Cox regression analysis. Based on the prognostic molecular markers, a scoring scale was proposed and Kaplan-Meier plots were compared between different scoring levels by Log-rank method. Age <50, 1p/19q co-deletion, IDH1/2 mutation, negative MGMT and EGFR expression were correlated with longer PFS and OS. Cox regression confirmed age <50 and 1p/19q co-deletion as independent prognostic markers. This scoring scale mainly based on prognostic molecular markers stratified patients into four levels with different prognoses.  Longer PFS and OS were correlated with higher scores (P < 0.05). This scoring scale based on prognostic molecular markers identified four levels with significantly different prognoses, and could be used to predict the prognosis of  patients with primary WHO grade III gliomas.

 

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[66]

TÍTULO / TITLE:  - BMI, apolipoprotein B/apolipoprotein A-I ratio, and insulin resistance in patients with prolactinomas: a pilot study in a Chinese cohort.

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

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0660-z

AUTORES / AUTHORS:  - Jiang XB; He DS; Mao ZG; Fan X; Lei N; Hu B; Song BB; Zhu YH; Wang HJ

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Pituitary Adenoma in Guangdong Province and Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

RESUMEN / SUMMARY:  - Deranged metabolic profiles and insulin resistance (IR) have been documented in patients with prolactinomas. Few data are yet available on the apolipoprotein (apo) B/apoA-I ratio and its relationship with IR in patients with prolactinomas. This study was aimed to evaluate the level of apoB/apoA-I ratio and its association with IR in a Chinese subgroup with prolactinomas. Twenty-three prolactinoma patients and 20 healthy controls were enrolled in this study. The clinical anthropometric parameters and laboratory evaluation were collected. Insulin sensitivity was estimated using homeostatic model assessment [homeostasis model assessment of insulin resistance (HOMA-IR)]. Waist circumference and body weight index (BMI) were significantly higher in patients with prolactinomas than  those in the controls (p < 0.05). Meanwhile, the prevalence of general and abdominal obesity seemed more pronounced in male patients compared to that in healthy subjects (57.14 vs. 0 % and 71.43 vs. 16.7 %, respectively). Furthermore, fasting glucose, insulin, HOMA-IR, triglyceride, and apoB/apoA-I ratio were also  significantly higher in prolactinoma patients, but with lower level of apoA-I (p  < 0.05). Univariate regression analysis revealed that prolactin, waist circumference, BMI, and presence of hypogonadism were significantly associated with IR (p < 0.05). However, only BMI [odds ratio (OR) = 1.937, 95 % confidence interval (CI) 1.112-3.375, p = 0.02] and prolactin (OR = 5.173, 95 % CI 1.073-24.94, p = 0.041) were shown to be independent predictors for the presence  of IR in multivariate logistic analysis. This study confirmed the altered metabolic profile, including body weight gain, IR, disordered lipids, and apolipoproteins in prolactinoma patients. Prolactin and BMI were independently associated with IR. The effect of apoB/apoA-I ratio on IR is warranted to be determined in further studies.

 

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[67]

TÍTULO / TITLE:  - A phase I study of temozolomide and lapatinib combination in patients with recurrent high-grade gliomas.

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

REVISTA / JOURNAL:  - J Neurol. 2013 Jan 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00415-012-6812-z

AUTORES / AUTHORS:  - Karavasilis V; Kotoula V; Pentheroudakis G; Televantou D; Lambaki S; Chrisafi S; Bobos M; Fountzilas G

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, “Papageorgiou” General Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece, karavasv@auth.gr.

RESUMEN / SUMMARY:  - We undertook this phase I study to investigate the feasibility of the combination of temozolomide (TMZ) and lapatinib (LP) and to define the maximum tolerated dose (MTD) of LP in patients with relapsed high-grade gliomas. Eligible patients were  enrolled in this dose escalation study of LP. TMZ was administered at a fixed dose of 200 mg/m(2) d1-d5 every 28 days. Starting dose of LP was set at 1,000 mg  daily continuously, escalated by 250 mg in cohorts of minimum three patients. Translational research investigations were also undertaken in available biopsy material. Between January 2009 and December 2010, 16 patients were entered into the study at three LP levels: 1,000 mg sid (11 patients), 1,250 mg sid (4 patients) and 1,500 mg sid (1 patient). A total of 55 cycles had been delivered.  Fourteen patients had stopped treatment because of disease progression, and two because of toxicity. Three patients received 10, 11 and 17 cycles of treatment. Dose-limiting hematological toxicity was observed in 2 patients at the second LP  dose level of 1,250 mg sid. MTD was defined at LP 1,000 mg sid. Median progression-free survival (PFS) and survival were 2.4 and 5.9 months, respectively. EGFR amplification and EGFRvIII expression were not related to PFS. Combination of TMZ and LP is feasible with manageable toxicity. The activity of this combination in patients with recurrent glioblastoma multiforme is further investigated in a recently initiated phase II trial.

 

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[68]

TÍTULO / TITLE:  - Interstitial flow in a 3D microenvironment increases glioma invasion by a CXCR4-dependent mechanism.

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

REVISTA / JOURNAL:  - Cancer Res. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2838

AUTORES / AUTHORS:  - Munson JM; Bellamkonda RV; Swartz MA

INSTITUCIÓN / INSTITUTION:  - Institute of Bioengineering and Swiss Institute for Experimental Cancer Research, EPFL.

RESUMEN / SUMMARY:  - Brain tumor invasion leads to recurrence and resistance to treatment. Glioma cells invade in distinct patterns possibly determined by microenvironmental cues  including chemokines, structural heterogeneity, and fluid flow. We hypothesized that flow originating from pressure differentials between the brain and tumor is  active in glioma invasion. Using in vitro models, we show that interstitial flow  promotes cell invasion in multiple glioma cell lines. Flow effects were CXCR4-dependent, because they were abrogated by CXCR4 inhibition. Further, CXCR4  was activated in response to flow which could be responsible for enhanced cell motility. Flow was seen to enhance cell polarization in the flow direction, and this flow-induced polarization could be blocked by CXCR4 inhibition or CXCL12 oversaturation in the matrix. Further, using live imaging techniques in a 3D flow chamber, there were more cells migrating and more cells migrating in the direction of flow. This study demonstrates that interstitial flow is an active regulator of glioma invasion. The new mechanisms of glioma invasion that we identify here - namely, interstitial flow-enhanced motility, activation of CXCR4, and CXCL12-driven autologous chemotaxis - are significant in therapy to prevent or treat brain cancer invasion. Current treatment strategies can lead to edema and altered flow in the brain, and one popular experimental treatment in clinical trials, convection enhanced delivery, involves enhancement of flow in and around  the tumor. A better understanding of how interstitial flow at the tumor margin can alter chemokine distributions, cell motility, and directed invasion offers a  better understanding of treatment failure.

 

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[69]

TÍTULO / TITLE:  - The transcription factor Forkhead box P3 (FoxP3) is expressed in glioma cells and associated with increased apoptosis.

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

REVISTA / JOURNAL:  - Exp Cell Res. 2012 Dec 1. pii: S0014-4827(12)00475-2. doi: 10.1016/j.yexcr.2012.11.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexcr.2012.11.018

AUTORES / AUTHORS:  - Held-Feindt J; Hattermann K; Sebens S; Krautwald S; Mehdorn HM; Mentlein R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, 24105 Kiel, Germany.

RESUMEN / SUMMARY:  - The forkhead transcription factor FoxP3 is critically involved in the development and function of regulatory T cells (Tregs) that populate tumors and are considered as powerful parts of their immune evasion. However, also tumor cells are reported to express FoxP3. Since gliomas are particularly immunosuppressive tumors, we investigated the occurrence and possible functions of FoxP3 in these malignant cells. By quantitative RT-PCR, immunohistochemistry and FACS analysis,  we detected FoxP3 in glioma cells in situ and in vitro. After exposure of glioma  cell lines to chemotherapeutics, expression of FoxP3 was significantly enhanced,  and it was dislocated from more nuclear to perinuclear localization. Overexpression of FoxP3 in glioma cell lines considerably favored apoptotic damage of nuclei, DNA fragmentation, increased cleavage of the pro-apoptotic enzyme poly(ADP-ribose) polymerase (PARP) and basal activities of effector caspases-3/7. In FoxP3-transfected cells, apoptotic stimuli like Camptothecin, Temozolomide or tumor necrosis factor-alpha synergistically enhanced caspases-3/7-activities over controls. Taking together, FoxP3 occurs in glioma cells, is induced by chemotherapeutics, and its expression is correlated with increased apoptosis of glioma cells, especially when propagated by apoptotic stimuli. Thus, FoxP3 is a novel pro-apoptotic transcription factor in gliomas that is critically involved in the action of apoptotic agents.

 

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[70]

TÍTULO / TITLE:  - Optimizing Glioblastoma Temozolomide Chemotherapy Employing Lentiviral-based Anti-MGMT shRNA Technology.

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

REVISTA / JOURNAL:  - Mol Ther. 2013 Jan 15. doi: 10.1038/mt.2012.278.

            ●● Enlace al texto completo (gratuito o de pago) 1038/mt.2012.278

AUTORES / AUTHORS:  - Viel T; Monfared P; Schelhaas S; Fricke IB; Kuhlmann MT; Fraefel C; Jacobs AH

INSTITUCIÓN / INSTITUTION:  - European Institute for Molecular Imaging (EIMI), Westfalische Wilhelms-Universitat (WWU) Munster, Muenster, Germany.

RESUMEN / SUMMARY:  - Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor’s overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM.Molecular Therapy (2013); doi:10.1038/mt.2012.278.

 

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[71]

TÍTULO / TITLE:  - Cathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs375

AUTORES / AUTHORS:  - Rao JS; Gopinath S; Malla RR; Alapati K; Gorantla B; Gujrati M; Dinh DH

INSTITUCIÓN / INSTITUTION:  - Departments of 1Cancer Biology & Pharmacology.

RESUMEN / SUMMARY:  - Cancer-initiating cells comprise a heterogeneous population of undifferentiated cells with the capacity for self-renewal and high proliferative potential. We investigated the role of uPAR and cathepsin B in the maintenance of stem cell nature in glioma initiating cells. Simultaneous knockdown of uPAR and cathepsin B significantly reduced the expression of CD133, Nestin, Sox2, and Bmi1 at the protein level and GLI1 and GLI2 at the mRNA level. Also, knockdown of uPAR and cathepsin B resulted in a reduction in the number of glioma-initiating cells as well as sphere size. These changes are mediated by Sox2 and Bmi1, downstream of hedgehog signaling. Addition of Cyclopamine reduced the expression of Sox-2 and Bmi1 along with GLI1 and GLI2 expression, induced differentiation, and reduced subsphere formation of glioma-initiating cells thereby indicating that hedgehog signaling acts upstream of Sox2 and Bmi1. Further confirmation was obtained from  increased luciferase expression under the control of a GLI-bound Sox2 and Bmi1 luciferase promoter. Simultaneous knockdown of uPAR and cathepsin B also reduced  the expression of CD133, Sox2 and Bmi1 in vivo. Thus, our study highlights the importance of uPAR and cathepsin B in the regulation of malignant stem cell self-renewal through hedgehog components, Bmi1 and Sox2.

 

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[72]

TÍTULO / TITLE:  - Bradykinin-Induced Chemotaxis of Human Gliomas Requires the Activation of KCa3.1  and ClC-3.

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

REVISTA / JOURNAL:  - J Neurosci. 2013 Jan 23;33(4):1427-40. doi: 10.1523/JNEUROSCI.3980-12.2013.

            ●● Enlace al texto completo (gratuito o de pago) 1523/JNEUROSCI.3980-12.2013

AUTORES / AUTHORS:  - Cuddapah VA; Turner KL; Seifert S; Sontheimer H

INSTITUCIÓN / INSTITUTION:  - Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294.

RESUMEN / SUMMARY:  - Previous reports demonstrate that cell migration in the nervous system is associated with stereotypic changes in intracellular calcium concentration ([Ca(2+)](i)), yet the target of these changes are essentially unknown. We examined chemotactic migration/invasion of human gliomas to study how [Ca(2+)](i) regulates cellular movement and to identify downstream targets. Gliomas are primary brain cancers that spread exclusively within the brain, frequently migrating along blood vessels to which they are chemotactically attracted by bradykinin. Using simultaneous fura-2 Ca(2+) imaging and amphotericin B perforated patch-clamp electrophysiology, we find that bradykinin raises [Ca(2+)](i) and induces a biphasic voltage response. This voltage response is mediated by the coordinated activation of Ca(2+)-dependent, TRAM-34-sensitive K(Ca)3.1 channels, and Ca(2+)-dependent, 4,4’-diisothiocyanato-stilbene-2,2’-disulfonic acid (DIDS)-sensitive and gluconate-sensitive Cl(-) channels. A significant portion of these Cl(-) currents can be attributed to Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation of ClC-3, a voltage-gated Cl(-) channel/transporter, because pharmacological inhibition of CaMKII or shRNA-mediated knockdown of ClC-3 inhibited Ca(2+)-activated Cl(-) currents. Western blots show that K(Ca)3.1 and ClC-3 are expressed in tissue samples obtained from patients diagnosed with grade IV gliomas. Both K(Ca)3.1 and ClC-3 colocalize to the invading processes of glioma cells. Importantly, inhibition of either channel abrogates bradykinin-induced chemotaxis and reduces tumor expansion in mouse brain slices in situ. These channels should be further explored as future targets for anti-invasive drugs. Furthermore, these data elucidate a novel mechanism placing  cation and anion channels downstream of ligand-mediated [Ca(2+)](i) increases, which likely play similar roles in other migratory cells in the nervous system.

 

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[73]

TÍTULO / TITLE:  - Distance to the neurooncological center: a negative prognostic factor in patients with glioblastoma multiforme. An epidemiological study.

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

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5515-9.

AUTORES / AUTHORS:  - Kerschbaumer J; Freyschlag CF; Bauer R; Obwegeser AA; Schubert GA; Thome C; Seiz M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.

RESUMEN / SUMMARY:  - BACKGROUND: Regardless of current multimodal treatment strategies, the prognosis  of patients harboring glioblastoma multiforme (GBM) is still dismal. The introduction of concomitant radiochemotherapy and adjuvant cyclic temozolomide has significantly improved the overall survival, compared to postoperative radiotherapy-alone. Furthermore this regimen shows a lower toxicity profile compared to previous nitrosourea-based chemotherapy and can easily be applied on  an outpatient basis, thus potentially facilitating chemotherapy in rural and more remote areas. The distance to the oncological center has been shown to be a negative prognostic parameter in other types of cancer. Therefore, we aimed to investigate whether the introduction of temozolomide as the standard regimen in the treatment of GBM has influenced the administration of chemotherapy and the prognosis of patients depending on the distance to our neurooncological center. PATIENTS AND METHODS: A total of 208 patients diagnosed with GBM (M:F=1.4:1), surgically resected between 1990 and 2009, thus covering the pre-temozolomide and the temozolomide-era, were included retrospectively in this analysis. The distance from the patients’ residences to the neurooncological center was determined and statistical analysis was performed to assess its influence on overall survival and administration of adjuvant treatment (radiotherapy-only, nitrosourea-based chemotherapy and adjuvant temozolomide). RESULTS: Overall, 41.3% of the cohort underwent subtotal surgical resection, whereas a gross total  resection was accomplished in 57.2%. The median distance to the neurooncological  center was 75 km (range=1-870 km). Postoperatively, 68 patients (32.7%) received  concomitant and adjuvant radiochemotherapy with temozolomide, 31 (14.9%) were treated with nitrosourea other than the Procarbazin, Lomustin, Vincristin (PCV),  34 (16.3%) with PCV, and 71 patients (34.1%) had radiotherapy-alone. The distance to the neurooncological center had a significant influence on overall survival for the whole cohort (p=0.027) and patients with increasing distances, were significantly less often treated with chemotherapy (p=0.05). With the introduction of temozolomide this relation was lost (overall survival, temozolomide and other agents: p=0.685/p=0.007; administration of adjuvant chemotherapy in the temozolomide-era/whole cohort: p=0.612/p=0.05). CONCLUSION: The distance to the neurooncological center negatively-influenced the prognosis of patients with GBM. Patients were less often treated with adjuvant chemotherapy in the pre-temozolomide era with increasing distance to the neurooncological center. Although the introduction of temozolomide as the standard chemotherapeutic agent in GBM treatment changed this fact, the influence of the distance to the specialized center should be kept in mind as a prognostic factor  for this disease.

 

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[74]

TÍTULO / TITLE:  - Deep venous thrombosis and pulmonary embolisms in adult patients undergoing craniotomy for brain tumors.

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

REVISTA / JOURNAL:  - Neurol Res. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1179/1743132812Y.0000000126

AUTORES / AUTHORS:  - Chaichana KL; Pendleton C; Jackson C; Martinez-Gutierrez JC; Diaz-Stransky A; Aguayo J; Olivi A; Weingart J; Gallia G; Lim M; Brem H; Quinones-Hinojosa A

RESUMEN / SUMMARY:  - OBJECTIVE: The development of venothromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary emboli (PE), is common in brain tumor patients. Their development can be catastrophic. Studies evaluating pre-operative clinical  factors that predispose patients to the development of VTE are few and limited. An understanding may help risk stratify patients and guide subsequent therapy aimed at reducing the risk of DVTs/PEs. METHODS: All adult patients who underwent surgery for an intracranial tumor at an academic tertiary care institution between 1998 and 2008 were retrospectively reviewed. Stepwise multivariate logistical regression analysis was used to identify pre-operative factors associated with the development of peri-operative (within 30 days of surgery) DVTs/PEs among patients who underwent surgery of their intracranial tumor. RESULTS: Of the 4293 patients in this study, 126 (3%) patients developed DVT and/or PE in the peri-operative period. The pre-operative factors independently associated with the development of DVTs/PEs were: poorer Karnofsky performance scale (KPS) [odds ratio (OR), 1.040; 95% confidence interval (CI), 1.026-1.052; P<0.0001], high grade glioma (OR, 1.702; 95% CI, 1.176-2.465; P=0.005), older age (OR, 1.033; 95% CI, 1.020-1.046; P<0.0001), hypertension (OR, 1.785; 95% CI, 1.180-2.699; P=0.006), and motor deficit (OR, 1.854; 95% CI, 1.244-2.763; P=0.002). Eighty-six per cent of the patients with DVTs/PEs were treated with either unfractionated or low molecular weight heparin, and 4% of these patients developed intracranial hemorrhage. DISCUSSION: The present study found that poorer functional status, older age, pre-operative motor deficit, high grade glioma, and hypertension each independently increased the risk of developing peri-operative DVTs/PEs. These findings may provide patients and physicians with  prognostic information that may guide therapies aimed at minimizing the development of peri-operative DVTs/PEs.

 

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[75]

TÍTULO / TITLE:  - alphavbeta 8 Integrin Interacts with RhoGDI1 to Regulate Rac1 and Cdc42 Activation and Drive Glioblastoma Cell Invasion.

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

REVISTA / JOURNAL:  - Mol Biol Cell. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 1091/mbc.E12-07-0521

AUTORES / AUTHORS:  - Reyes SB; Narayanan AS; Lee HS; Tchaicha JH; Aldape KD; Lang FF; Tolias KF; McCarty JH

INSTITUCIÓN / INSTITUTION:  - *Departments of Cancer Biology, University of Texas M.D. Anderson Cancer Center and Departments of Biochemistry ^Pathology, University of Texas M.D. Anderson Cancer Center and Departments of Biochemistry #Neurosurgery, University of Texas  M.D. Anderson Cancer Center and Departments of Biochemistry YMolecular Biology, Baylor College of Medicine +Neuroscience, Baylor College of Medicine.

RESUMEN / SUMMARY:  - The malignant brain cancer glioblastoma multiforme (GBM) displays invasive growth behaviors that are regulated by extracellular matrix (ECM) cues within the neural microenvironment. The cell adhesion and signaling mechanisms that drive GBM invasion remain largely uncharacterized. Here we have utilized human GBM cell lines, primary patient samples, and pre-clinical mouse models to demonstrate that integrin alphavbeta8 is a major driver of GBM cell invasion. beta8 integrin is overexpressed in many human GBM cells, with higher integrin expression correlating with increased invasion and diminished patient survival. Silencing beta8 integrin in human GBM cells leads to impaired tumor cell invasion due to hyperactivation of the Rho GTPases Rac1 and Cdc42. beta8 integrin coimmunoprecipitates with Rho GDP Dissociation Inhibitor 1 (RhoGDI1), an intracellular signaling effector that sequesters Rho GTPases in their inactive GDP-bound states. Silencing RhoGDI1 expression or uncoupling alphavbeta8 integrin-RhoGDI1 protein interactions blocks GBM cell invasion due to Rho GTPase  hyperactivation. These data reveal for the first time that alphavbeta8 integrin,  via interactions with RhoGDI1, regulates activation of Rho proteins to promote GBM cell invasiveness. Hence, targeting the alphavbeta8 integrin-RhoGDI1 signaling axis may be an effective strategy for blocking GBM cell invasion.

 

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[76]

TÍTULO / TITLE:  - Sphenoid wing lymphoplasmacyte-rich meningioma with occasional emperipolesis closely simulating an intracranial Rosai-Dorfman disease: a diagnostic dilemma.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300517

AUTORES / AUTHORS:  - Majumdar K; Saran RK; Chaurasia PK; Tyagi I; Singh D

RESUMEN / SUMMARY:  - In lymphoplasmacyte-rich meningioma (LRM) meningothelial whorls are overshadowed  by exuberant infiltration by lymphocytes, plasma cells and few histiocytes. Hence, lesions with lymphoplasmacytic proliferation form the histological differentials. We describe the, to the best of our knowledge, first case of LRM with occasiona emperipolesis, creating a diagnostic dilemma with Rosai-Dorfman disease (RDD), around the region of sphenoid wing. LRM was favored due to the presence of epithelial membrane antigen (EMA) and vimentin positive meningothelial whorls, forming approximately 10% of the tumor tissue. Documentation of such cases may help to understand the importance of inflammatory cells and meningothelial whorls, as a manifestation of host response at the leptomeninges.

 

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[77]

TÍTULO / TITLE:  - Combination therapy using Notch and Akt inhibitors is effective for suppressing invasion but not proliferation in glioma cells.

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

REVISTA / JOURNAL:  - Neurosci Lett. 2013 Feb 8;534:316-21. doi: 10.1016/j.neulet.2012.12.008. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neulet.2012.12.008

AUTORES / AUTHORS:  - Jin R; Nakada M; Teng L; Furuta T; Sabit H; Hayashi Y; Demuth T; Hirao A; Sato H; Zhao G; Hamada J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Bethune Clinical Hospital of Jilin University, 71 Xinmin Avenue, Changchun 130021, People’s Republic of China; Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.

RESUMEN / SUMMARY:  - Molecular targeted therapy can potentially provide more effective treatment for patients with high-grade gliomas. Notch and Akt are notable target molecules as they play important roles in a variety of cellular processes, such as regeneration, differentiation, proliferation, migration, and invasion. Here, we assessed the therapeutic possibility of inhibiting Notch and Akt in gliomas using the clinically available, selective small molecule inhibitors MRK003 and MK-2206. We evaluated their efficacy individually and as a combination therapy in U251 and U87 glioma cell lines. We confirmed that MK-2206 effectively inhibits Akt phosphorylation in a dose-dependent manner, whereas MRK003 inhibits Notch signaling and Akt phosphorylation. Both MRK003 and MK-2206 significantly inhibited cell growth, migration, and invasion in a dose-dependent manner. Akt dephosphorylation was enhanced by combination therapy with MRK003 and MK-2206. However, the effect of combination treatment did not exceed that of MK-2206 monotherapy in proliferation assay. Inhibition of invasion, further enhanced by combination therapy, correlated with increased Akt inactivation. In summary, combination therapy with MRK003 and MK-2206 may be effective for inhibiting invasion but not proliferation.

 

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[78]

TÍTULO / TITLE:  - Correction: the kynurenine pathway in brain tumor pathogenesis.

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

REVISTA / JOURNAL:  - Cancer Res. 2012 Dec 15;72(24):6524. doi: 10.1158/0008-5472.CAN-12-4230. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4230

 

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[79]

TÍTULO / TITLE:  - Acute and fractionated irradiation differentially modulate glioma stem cell division kinetics.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3429

AUTORES / AUTHORS:  - Gao X; McDonald JT; Hlatky L; Enderling H

INSTITUCIÓN / INSTITUTION:  - Center of Cancer Systems Biology, Tufts University School of Medicine, Steward Research Institute.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is one of the most aggressive human malignancies with a poor patient prognosis. Ionizing radiation (IR) either alone or adjuvant after surgery is part of standard treatment for GBM but remains primarily non-curative. The mechanisms underlying tumor radioresistance are manifold and, in part, accredited to a special subpopulation of tumorigenic cells. The so-called glioma stem cells (GSCs) are bestowed with the exclusive ability to self-renew and repopulate the tumor, and have been reported to be less sensitive  to radiation-induced damage through preferential activation of DNA damage checkpoint responses and increased capacity for DNA damage repair. During each fraction of radiation, non-stem cancer cells (CCs) die and GSCs become enriched and potentially increase in number, which may lead to accelerated repopulation. We propose a cellular Potts model (CPM) that simulates the kinetics of GSCs and CCs in glioblastoma growth and radiation response. We parameterize and validate this model with experimental data of the U87-MG human glioblastoma cell line. Simulations are performed to estimate GSC symmetric and asymmetric division rates and explore potential mechanisms for increased GSC fractions after irradiation. Simulations reveal that, in addition to their higher radioresistance, a shift from asymmetric to symmetric division or a fast cycle of GSCs following fractionated radiation treatment is required to yield results that match experimental observations. We hypothesize a constitutive activation of stem cell  division kinetics signaling pathways during fractionated treatment, which contributes to the frequently observed accelerated repopulation after therapeutic irradiation.

 

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[80]

TÍTULO / TITLE:  - Disruption of Wild-Type IDH1 Suppresses D-2-Hydroxyglutarate Production in IDH1-Mutated Gliomas.

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

REVISTA / JOURNAL:  - Cancer Res. 2013 Jan 15;73(2):496-501. doi: 10.1158/0008-5472.CAN-12-2852. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2852

AUTORES / AUTHORS:  - Jin G; Reitman ZJ; Duncan CG; Spasojevic I; Gooden DM; Rasheed BA; Yang R; Lopez GY; He Y; McLendon RE; Bigner DD; Yan H

INSTITUCIÓN / INSTITUTION:  - Authors’ Affiliations: The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, and The Department of Pathology, The Clinical Pharmacology Laboratory, Duke Cancer Institute and Department of Medicine/Oncology, and The Small Molecule Synthesis Facility, Department of Chemistry, Duke University Medical Center, Durham, North Carolina.

RESUMEN / SUMMARY:  - Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the “oncometabolite” D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually associated with a wild-type IDH1 allele (heterozygous) in cancer. Here, we identify 2 gliomas that underwent loss of the  wild-type IDH1 allele but retained the mutant IDH1 allele following tumor progression from World Health Organization (WHO) grade III anaplastic astrocytomas to WHO grade IV glioblastomas. Intratumoral D-2HG was 14-fold lower  in the glioblastomas lacking wild-type IDH1 than in glioblastomas with heterozygous IDH1 mutations. To characterize the contribution of wild-type IDH1 to cancer cell D-2HG production, we established an IDH1-mutated astrocytoma (IMA) cell line from a WHO grade III anaplastic astrocytoma. Disruption of the wild-type IDH1 allele in IMA cells by gene targeting resulted in an 87-fold decrease in cellular D-2HG levels, showing that both wild-type and mutant IDH1 alleles are required for D-2HG production in glioma cells. Expression of wild-type IDH1 was also critical for mutant IDH1-associated D-2HG production in the colorectal cancer cell line HCT116. These insights may aid in the development of therapeutic strategies to target IDH1-mutated cancers. Cancer Res; 73(2); 496-501. ©2012 AACR.

 

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[81]

TÍTULO / TITLE:  - Disability, body image and sports/physical activity in adult survivors of childhood CNS tumors: population-based outcomes from a cohort study.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1039-5

AUTORES / AUTHORS:  - Boman KK; Hornquist L; De Graaff L; Rickardsson J; Lannering B; Gustafsson G

INSTITUCIÓN / INSTITUTION:  - Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Astrid Lindgren Children’s Hospital, Q6:05, 17176, Stockholm, Sweden, krister.boman@ki.se.

RESUMEN / SUMMARY:  - Childhood CNS tumor survivors risk health and functional impairments that threaten normal psychological development and self-perception. This study investigated the extent to which health and functional ability predict adult survivors’ body image (BI) and self-confidence regarding sports and physical activity. The study cohort covered 708 eligible >/=18 year old CNS tumor survivors, and data from 528 (75 %) were analyzed. Disability was estimated using the Health Utilities Index Mark2/3, a multidimensional self-report instrument. Physical self-confidence in terms of BI and sports/physical activity-related self-confidence (SPAS) were assessed using the BI and the Sports/Athletics modules of a standardized self-report assessment scale. In adjusted regression models, global health and functional status (GHFS) predicted BI (B = 0.94, 95 % CI 0.69-1.19) and SPAS (B = 0.79, 95 % CI 0.55-1.04). Emotion and pain, and to a  lesser degree cognition, speech and vision disability, were associated with poorer BI and SPAS. Gender, sub-diagnosis, and time since diagnosis influenced the relationship between health status and physical self-confidence outcomes. Females had poorer GHFS, BI and SPAS than males. Decreased health and functional  ability following childhood CNS cancer intrudes on physical self-confidence, with females being at heightened risk for both disability and negative self-confidence. Identified disability and gender-related risk calls for a follow-up plan that integrates treatment of psychological sequelae in lifetime monitoring of childhood CNS tumor survivors to restore and protect self-image and self-confidence, essential mental health correlates. An expanded plan should recognize the need for such services, optimizing life-long quality of survival for CNS tumor survivors.

 

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[82]

TÍTULO / TITLE:  - Parental smoking and risk of childhood brain tumours.

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

REVISTA / JOURNAL:  - Int J Cancer. 2012 Dec 22. doi: 10.1002/ijc.28004.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28004

AUTORES / AUTHORS:  - Milne E; R Greenop K; Scott RJ; Ashton LJ; Cohn RJ; de Klerk NH; K Armstrong B

INSTITUCIÓN / INSTITUTION:  - Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia. lizm@ichr.uwa.edu.au.

RESUMEN / SUMMARY:  - Childhood brain tumors (CBT) are the leading cause of cancer death in children, yet their etiology remains largely unknown. Tobacco smoke contains 61 known carcinogens and increases the risk of several adult cancers. This study investigated associations between parental smoking and risk of CBT in a population-based case-control study conducted between 2005 and 2010. Cases were identified through all 10 Australian paediatric oncology centres, controls via nationwide random-digit dialling, frequency matched to cases on age, sex and state of residence. Parental smoking information was obtained for 302 cases and 941 controls through mailed questionnaires that requested average daily cigarette use in each calendar year from age 15 to the child’s birth, linked to residential and occupational histories. Data were analysed using unconditional logistic regression, adjusting for frequency matching variables and potential confounders. Overall, parental smoking before or during pregnancy showed no association with CBT risk. The odds ratios for maternal smoking before and during pregnancy were 0.99 (95% CI: 0.70, 1.40) and 0.89 (95% CI: 0.61, 1.21) respectively, and those for paternal smoking before and during pregnancy were 0.99 (95% CI: 0.71, 1.38) and 1.04 (95% CI: 0.74, 1.46) respectively. In children under 24 months of age, the odds ratios for maternal smoking preconception and during pregnancy were 5.06 (95% CI 1.35-19.00) and 4.61 (95% CI: 1.08, 19.63), although these results were based on modest numbers. Future studies should investigate the associations between maternal smoking and risk of CBT by the child’s age of diagnosis. © 2012 Wiley Periodicals, Inc.

 

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[83]

TÍTULO / TITLE:  - The prognostic implications of Hyam’s subtype for patients with Kadish stage C esthesioneuroblastoma.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Feb;20(2):281-6. doi: 10.1016/j.jocn.2012.05.029. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.05.029

AUTORES / AUTHORS:  - Kaur G; Kane AJ; Sughrue ME; Madden M; Oh MC; Sun MZ; Safaee M; El-Sayed I; Aghi M; McDermott MW; Berger MS; Parsa AT

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of California at San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.

RESUMEN / SUMMARY:  - Esthesioneuroblastoma (EN) is a rare sinonasal tumor with varied aggressiveness and potential for intracranial invasion. EN is staged anatomically with radiographic evaluation using the Kadish staging system (stages A, B, and C) and  histologically by using Hyam’s criteria (grades 1-4). Here we show that despite radiographic evidence of aggressive features, the prognosis of patients with Kadish stage C EN is best predicted by tumor histology using Hyam’s criteria. We  retrospectively analyzed patients with EN with Kadish stage C who were evaluated  and treated at our institution between 1995 and 2009. Clinical information was collected using patient medical records, imaging, and review of pathological specimens. Twenty patients with Kadish stage C EN were identified with mean age of 51years (31-70years) with a median follow-up of 41.4months (1.3-175months). Upon pathological review, 44.4% of patients had low-grade (1/2) and 55.6% had high-grade (3/4) histology. About 37.5% of patients with low-grade EN had undergone gross total resection (GTR) and the remaining 62.5% had GTR and adjuvant radiation, whereas 50% of patients with high-grade ER had undergone GTR, 20% had undergone GTR and adjuvant radiation, and 30% had been treated with a subtotal resection (STR) and adjuvant radiation. The 5-year and 10-year survival  in patients with low-grade EN was 86% in comparison to 56% and 28% with high-grade EN, respectively. In patients with low-grade EN, the 2-year progression free survival (PFS) was 86% and the 5-year PFS was 65% in comparison  to 73% and 49% in patients with high-grade EN, respectively. The patient’s tumor  histology (Hyam’s criteria) appeared to be the best way of predicting the prognosis and for selecting patients for adjuvant radiotherapy.

 

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[84]

TÍTULO / TITLE:  - Central Neurocytoma: Long-term Outcomes of Multimodal Treatments and Management Strategies Based on 30 Years’ Experience in a Single Institute.

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

REVISTA / JOURNAL:  - Neurosurgery. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e3182804662

AUTORES / AUTHORS:  - Kim JW; Kim DG; Kim IK; Kim YH; Choi SH; Han JH; Park CK; Chung HT; Park SH; Paek SH; Jung HW

INSTITUCIÓN / INSTITUTION:  - *Department of Neurosurgery daggerRadiology double daggerPathology, Seoul National University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - BACKGROUND:: A thorough investigation of the long-term outcomes of central neurocytoma (CN) after different treatments is required to establish optimal management strategies. OBJECTIVE:: We retrospectively reviewed the long-term clinical outcomes of patients with CN according to various treatments, and suggest treatment strategies based on 30 years of experience in a single institution. METHODS:: Fifty-eight consecutive patients with CN were treated at our institution between 1982 and 2008. Patient demographics, overall survival, local control rates according to multimodal treatments, and functional outcomes were evaluated. The mean clinical and radiological follow-up periods were 119 months (range, 18-304 months) and 98 months (range, 13-245 months), respectively. RESULTS:: The initial treatment modality was classified into four subgroups: operation only (34 patients), operation followed by radiation therapy (seven patients) or radiosurgery (seven patients), and radiosurgery alone (10 patients). The actuarial overall survival was 91% at 5 years and 88% at 10 years. The actuarial overall survival and local tumor control rate did not differ significantly according to the various treatments and the initial extent of the surgical resection. However, functional outcomes, such as the postoperative seizure outcome at the last follow-up, differed according to the surgical approach. CONCLUSION:: The long-term clinical outcomes of CN after multimodal treatment seem to be excellent. Our study suggests that treatment strategies for  CN should focus on the patient’s quality of life, as well as on tumor control, because of the benign nature of CN.

 

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[85]

TÍTULO / TITLE:  - Intracellular distribution of the DeltaNp73 protein isoform in medulloblastoma cells: a study with newly generated rabbit polyclonal antibodies.

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

REVISTA / JOURNAL:  - Histol Histopathol. 2013 Jan 22.

AUTORES / AUTHORS:  - Veselska R; Neradil J; Nekulova M; Dobrucka L; Vojtesek B; Sterba J; Zitterbart K

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Biology, School of Science, Masaryk University, Brno,  Czech Republic. veselska@sci.muni.cz.

RESUMEN / SUMMARY:  - The p73 protein is a member of the p53 family of transcription factors that has two N-terminal isoforms: the TAp73 isoform is reported to have a tumor suppressor function, whereas the DeltaNp73 isoform likely has oncogenic potential. The expression of these isoforms and the differences in their intracellular distribution have been described in many cancer types; however, little is known about the p73 isoforms in brain tumors. Our study is focused on the intracellular localization of DeltaNp73 in medulloblastoma cell lines. Due to a lack of suitable anti-DeltaNp73 antibodies, we developed two new rabbit polyclonal antibodies, DeltaNp73-26 and DeltaNp73-27, with sufficient specificity, as demonstrated by immunodetection methods using transiently transfected cell lines. Both of these new antibodies were subsequently used for analysis of the DeltaNp73 distribution in medulloblastoma cells using immunofluorescence, immunoblotting and immunogold labeling for transmission electron microscopy. We found a nuclear  localization of the DeltaNp73 isoform in all of the medulloblastoma cell lines included in this study. Furthermore, a non-random accumulation of the DeltaNp73 isoform near the cell nuclei was observable in all of these cell lines. By double-labeling with DeltaNp73 and golgin-97, we showed the co-localization of the DeltaNp73 isoform with the Golgi apparatus. Nevertheless, further detailed analyses of possible interactions of DeltaNp73 with the proteins accumulated in the Golgi apparatus should be performed to explain the dynamics of DeltaNp73 outside the cell nucleus.

 

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[86]

TÍTULO / TITLE:  - Prolonged survival after treatment of diffuse intrinsic pontine glioma with radiation, temozolamide, and bevacizumab: report of 2 cases.

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

REVISTA / JOURNAL:  - J Pediatr Hematol Oncol. 2013 Jan;35(1):e42-6. doi: 10.1097/MPH.0b013e318279aed8.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318279aed8

AUTORES / AUTHORS:  - Aguilera DG; Mazewski C; Hayes L; Jordan C; Esiashivilli N; Janns A; Macdonald TJ

INSTITUCIÓN / INSTITUTION:  - *Aflac Center for Cancer and Blood Disorders Service, Children’s Healthcare of Atlanta, Emory University School of Medicine daggerDepartment of Radiology, Children’s Healthcare of Atlanta double daggerDepartment of Radiation Oncology, Winship Cancer Center Institute of Emory University, Atlanta, GA.

RESUMEN / SUMMARY:  - BACKGROUND: : Diffuse intrinsic pontine gliomas have poor prognosis. OBSERVATION: : We report on 2 patients with diffuse intrinsic pontine glioma treated with radiation, followed by temozolamide 200 mg/m/d for 5 days every 28 days and bevacizumab 10 mg/kg/dose every 14 days. Both patients have ongoing PFS of 37 and 47 months from diagnosis. A decrease in tumor size by >65% was observed in both the patients. Both patients continue treatment. No steroid requirement since 10 weeks after radiation. Quality of life is excellent and the chemotherapy regimen  is well tolerated. CONCLUSIONS: : A clinical trial in an expanded cohort is warranted to determine the toxicity and evaluate response.

 

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[87]

TÍTULO / TITLE:  - SUNCT, SUNA and pituitary tumors: Clinical characteristics and treatment.

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

REVISTA / JOURNAL:  - Cephalalgia. 2013 Feb;33(3):160-70. doi: 10.1177/0333102412468672. Epub 2012 Nov  29.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0333102412468672

AUTORES / AUTHORS:  - Chitsantikul P; Becker WJ

INSTITUCIÓN / INSTITUTION:  - Department of Clinical Neurosciences, University of Calgary and Alberta Health Services, Canada.

RESUMEN / SUMMARY:  - Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are rare types of trigeminal autonomic cephalalgias (TACs). Objective To describe a series of patients with SUNCT and SUNA including relationship to pituitary tumors. Method All patients diagnosed with SUNCT or SUNA in the Calgary Headache Assessment and Management Program were reviewed. Results Six patients (five SUNCTs and one SUNA) were identified. The pain was severe, sharp, showed fixed-laterality, involved mainly the orbito-fronto-temporal region and was associated with autonomic symptoms. Attack duration ranged from 3 to 300 seconds  and frequency was 1-200 paroxysms/day. MRI showed ipsilateral pituitary adenomas  to the pain in five out of five of the SUNCT patients. Patients with adenomas underwent surgery. Pathology included three prolactinomas, and one mixed adenoma  and gangliocytoma. One patient has remained headache free for 4 years after surgery. One was pain free for a year, and then headaches returned with tumor recurrence. Another had major improvement, and two have not improved. Patients were generally refractory to medications. Conclusion All five of our patients with typical SUNCT had pituitary tumors, with headache ipsilateral to the pituitary tumors in all cases. Tumor removal provided major improvement in three  out of five patients. Medical treatment was only partially effective.

 

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[88]

TÍTULO / TITLE:  - The VHL tumor suppressor protein regulates tumorigenicity of U87-derived glioma stem-like cells by inhibiting the JAK/STAT signaling pathway.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):881-6. doi: 10.3892/ijo.2013.1773. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1773

AUTORES / AUTHORS:  - Kanno H; Sato H; Yokoyama TA; Yoshizumi T; Yamada S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan.

RESUMEN / SUMMARY:  - The signal transducer and activator of transcription 3 (STAT3) factor plays an important role in the tumorigenicity of cancer stem cells. The purpose of this study was to investigate the inhibitory mechanism of this pathway acting through  the tumor suppressor von Hippel-Lindau (VHL) protein in glioma cancer stem cells. We isolated floating neurosphereforming CD133+ cells as glioma stem-like cells (GSLCs) by the MACS method. Furthermore, we examined these cells for their growth rate, ability to form colonies and neurospheres in soft agar, capacity for implantation into SCID mice and expression of CD133, STAT3, JAK2, Elongin A, PTEN and VHL. Furthermore, we transferred the VHL gene, an inhibitor of STAT3, into GSLCs using an adenovirus vector and compared these transfectants with control vector-transfected GSLCs. GSLCs proved to be implantable and formed a tumor in the subcutaneous tissue of SCID mice, the histology of which was similar to that  of human glioblastomas. In addition, GSLCs exhibited a high capacity for soft agar colony and neurosphere formation, nearly all of which were CD133 positive. The majority of GSLCs were immunopositive for STAT3, JAK2 and Elongin A, but immunonegative for PTEN and VHL. When the VHL gene was transferred to GSLCs and these cells were transplanted into SCID mice, they did not result in tumor formation. Their capacity for soft agar colony and neurosphere formation was significantly inhibited, although their proliferation was only moderately inhibited. Regarding the expression of various factors, that of CD133 was decreased in the VHL transfectants and those of STAT3, JAK2 and Elongin A were eliminated. However, the expression of PTEN and of VHL was upregulated. These findings suggest that VHL regulated the tumorigenicity and selfrenewal ability of glioma cancer stem cells by inhibiting the JAK/STAT signaling pathway.

 

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[89]

TÍTULO / TITLE:  - Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: preliminary results.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS111893

AUTORES / AUTHORS:  - Salmaggi A; Milanesi I; Silvani A; Gaviani P; Marchetti M; Fariselli L; Solero CL; Maccagnano C; Casali C; Guzzetti S; Pollo B; Ciusani E; Dimeco F

INSTITUCIÓN / INSTITUTION:  - Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.

RESUMEN / SUMMARY:  - Object Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. Methods In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with  glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. Results After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had  to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4(+) lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Conclusions Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with  the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.

 

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[90]

TÍTULO / TITLE:  - The histone deacetylase inhibitor valproic acid enhances equine herpesvirus type  1 (EHV-1)-mediated oncolysis of human glioma cells.

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

REVISTA / JOURNAL:  - Cancer Gene Ther. 2013 Jan 11. doi: 10.1038/cgt.2012.89.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2012.89

AUTORES / AUTHORS:  - White MC; Frampton AR Jr

INSTITUCIÓN / INSTITUTION:  - Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC, USA.

RESUMEN / SUMMARY:  - Histone deacetylase (HDAC) inhibitors represent a promising new therapy against malignant glioma. When used in conjunction with oncolytic viral vectors, these compounds have been shown to augment virotherapy. In the current study, we examined the antitumor effect of combining the lytic animal virus equine herpesvirus type 1 (EHV-1) with the HDAC inhibitor valproic acid (VPA). Pretreatment of two human glioblastoma cell lines (U251 and SNB19) with VPA resulted in a significant increase in virus entry, replication, cell to cell spread and cell lysis. Overall, these data indicate that VPA significantly improves EHV-1-mediated oncolysis of human glioma cells that are only moderately  killed by EHV-1 alone.Cancer Gene Therapy advance online publication, 11 January  2013; doi:10.1038/cgt.2012.89.

 

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[91]

TÍTULO / TITLE:  - Effect of cabergoline on insulin sensitivity, inflammation, and carotid intima media thickness in patients with prolactinoma.

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

REVISTA / JOURNAL:  - Endocrine. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-012-9857-y

AUTORES / AUTHORS:  - Inancli SS; Usluogullari A; Ustu Y; Caner S; Tam AA; Ersoy R; Cakir B

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Metabolism, School of Medicine, Near East University, Nicosia, Cyprus, inanclis@yahoo.com.

RESUMEN / SUMMARY:  - The aim of this study was to evaluate the effect of Cabergoline on insulin sensitivity, inflammatory markers, and carotid intima media thickness in prolactinoma patients. Twenty-one female, newly diagnosed patients with prolactinoma were included in the study. None of the patients were treated previously. Cabergoline was given as treatment, starting with 0.5 mg/day and tapered necessarily. Blood samples were taken for prolactin, highly sensitive C-reactive protein, homocysteine, total cholesterol, low density lipoprotein (LDL) cholesterol, fasting glucose, insulin, and HOMA (homeostasis model assessment of insulin resistance) score was calculated, prior to and 6 months after starting treatment. The body mass index (BMI) was measured and carotid intima media thickness (CIMT) was evaluated for each patient prior to and 6 months after the treatment. The prolactin levels and LDL decreased significantly  after cabergoline treatment. Insulin sensitivity improved independently from the  decrease in prolactin levels and BMI. The significant decrease in homocysteine and hs-CRP was not related with the decrease in prolactin levels. The significant decrease in CIMT was independent from the decrease in prolactin levels, HOMA score, and BMI. Our data suggest that cabergoline treatment causes an improvement in insulin sensitivity and inflammatory markers and causes a decrease in CIMT independent from the decrease in prolactin, LDL cholesterol, and BMI. We conclude that short term cabergoline treatment can improve endothelial function independently from the changes in metabolic disturbances and inflammatory markers.

 

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[92]

TÍTULO / TITLE:  - Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

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

REVISTA / JOURNAL:  - J Med Ethics. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1136/medethics-2012-100996

AUTORES / AUTHORS:  - Patel UJ

RESUMEN / SUMMARY:  - A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that  appears under-referred and/or unaccepted is patients with primary brain tumours.  In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from  donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families  with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed  in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours.

 

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[93]

TÍTULO / TITLE:  - Phase II study of CNS-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas.

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

REVISTA / JOURNAL:  - Haematologica. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3324/haematol.2012.077917

AUTORES / AUTHORS:  - Korfel A; Elter T; Thiel E; Hanel M; Mohle R; Schroers R; Reiser M; Dreyling M; Eucker J; Scholz CW; Metzner B; Roth A; Birkmann J; Schlegel U; Martus P; Illerhaus G; Fischer L

INSTITUCIÓN / INSTITUTION:  - Berlin, Germany;

RESUMEN / SUMMARY:  - Background. The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established thus far. In a prospective multicenter phase II study we evaluated a potentially curative chemotherapy-only regimen in these patients. Design and Methods. Adult immunocompetent patients </=65 years received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 i.v. day1, ifosfamide 2 g/m2 i.v. day3-5 and liposomal cytarabine 50mg intrathecally day6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. day1-2, thiotepa 40 mg/m2 i.v. day2 and i.th. liposomal cytarabine 50mg intrathecally day3) followed by high-dose chemotherapy with carmustine 400 mg/m2  i.v. day -5, thiotepa 2x5mg/kg i.v. day -4 to -3 and etoposide 150 mg/m2 i.v. day -5 to -3 and autologous stem cell transplantation day0 (HD-ASCT). Results. Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24) there was a complete remission in 15 (63%), partial remission in two (8%) and progressive disease in seven (29%) patients. Myelotoxicity was the most adverse event with CTC grade ¾ infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%+/-19 for all patients and 58%+/-22 for patients completing HD-ASCT. Conclusions. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).

 

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[94]

TÍTULO / TITLE:  - 5’benzylglycinyl-amiloride kills proliferating and non-proliferating malignant glioma cells through caspase-independent necroptosis mediated by apoptosis-inducing factor.

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

REVISTA / JOURNAL:  - J Pharmacol Exp Ther. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1124/jpet.112.200519

AUTORES / AUTHORS:  - Pasupuleti N; Leon L; Carraway KL; Gorin FA

INSTITUCIÓN / INSTITUTION:  - University of California, Davis.

RESUMEN / SUMMARY:  - 5’benzylglycinyl-amiloride (UCD38B) and glycinyl-amiloride (UCD74A) are cell permeant and cell impermeant derivatives of Amiloride, respectively, and used here to identify the cellular mechanisms of action underlying their anti-glioma effects. UCD38B comparably kills proliferating and non-proliferating gliomas cells when cell cycle progression is arrested either by cyclin D1 siRNA or by acidosis. Cell impermeant UCD74A inhibits plasmalemal urokinase plasminogen activator (uPA) and the type 1 sodium-proton exchanger (NHE1) with potencies analogous to UCD38B, but is cytostatic. In contrast, UCD38B targets intracellular uPA causing mis-trafficking of uPA into perinuclear mitochondria, reducing the mitochondrial membrane potential (MMP), and followed by the release of apoptotic  inducible factor (AIF). AIF nuclear translocation is followed by a caspase-independent necroptotic cell death. Reduction in AIF expression by siRNA  reduces the anti-glioma cytotoxic effects of UCD38B, while not activating the caspase pathway. Ultrastructural changes shortly following treatment with UCD38B  demonstrate dilation of endoplasmic reticulum (ER), mitochondrial swelling followed by nuclear condensation within hours consistent with a necroptotic cell  death differing from apoptosis and from autophagy. These drug mechanism of action studies demonstrated that UCD38B induces a cell cycle independent, caspase-independent necroptotic glioma cell death that is mediated by AIF and independent of PARP and H2AX activation.

 

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[95]

TÍTULO / TITLE:  - Photodynamic Therapy in Combination with Talaporfin Sodium Induces Mitochondrial  Apoptotic Cell Death Accompanied with Necrosis in Glioma Cells.

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

REVISTA / JOURNAL:  - Biol Pharm Bull. 2012 Nov 29.

AUTORES / AUTHORS:  - Miki Y; Akimoto J; Yokoyama S; Homma T; Tsutsumi M; Haraoka J; Hirano K; Beppu M

INSTITUCIÓN / INSTITUTION:  - School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.

RESUMEN / SUMMARY:  - Photodynamic therapy (PDT) induces selective cell death of neoplastic tissue and  connecting vasculature by combining photosensitizers with light. Here we clarified the types of cell death induced by PDT in combination with the photosensitizer talaporfin sodium (mono-L-aspartyl chlorine e6, NPe6) in order to evaluate the potential of this therapy as a treatment for glioma. PDT with NPe6 (NPe6-PDT) induces dose-dependent cell death in human glioblastoma T98G cells. Specifically, cell death modalities were observed in NPe6-PDT treated T98G cells, including signs of apoptosis (activation of caspase-3, expression of phosphatidylserine, and DNA fragmentation) and necrosis (stainability of propidium iodide). In addition, high doses of NPe6-PDT decreased the proportion of apoptotic cell death, while increasing necrosis. Closer examination of apoptotic characteristics revealed release of cytochrome-c from mitochondria as well as activation of both caspse-9 and caspase-3 in cells treated with low doses of NPe6-PDT. Z-LEHD-fmk, a caspase-9 specific inhibitor, and Z-DQMD-fmk, a caspase-3 specific inhibitor, showed dose-dependent prevention of cell death in NPe6-PDT treated cells, indicating that mitochondrial apoptotic pathway was a factor in the observed cell death. Further, the cell morphology was observed after PDT. Time- and NPe6-dose dependent necrotic features were increased in NPe6-PDT treated cells. These results suggest that NPe6-PDT could be an effective treatment for glioma if used in mild doses to avoid the increased necrosis that may induce undesirable obstacles.

 

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[96]

TÍTULO / TITLE:  - Treatment of glioblastoma multiforme using a combination of small interfering RNA targeting epidermal growth factor receptor and beta-catenin.

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

REVISTA / JOURNAL:  - J Gene Med. 2013 Jan;15(1):42-50. doi: 10.1002/jgm.2693.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jgm.2693

AUTORES / AUTHORS:  - Wang K; Park JO; Zhang M

INSTITUCIÓN / INSTITUTION:  - Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Epidermal growth factor receptor (EGFR) and beta-catenin are two key  mediators of cell signal transduction implicated in the pathogenesis of a variety of tumors. There is emerging evidence indicating that they are overexpressed in glioblastoma multiforme (GBM) and both play significant roles in GBM carcinogenesis. Moreover, down-regulating EGFR individually only provides limited therapeutic efficacy. Therefore, we aimed to determine the feasibility and efficacy of gene therapy of GBM using combinatorial inhibition of EGFR and beta-catenin in view of the cross-talk between these two signaling pathways. METHODS: The down-regulatory effect of small interfering RNA (siRNA) targeting EGFR and beta-catenin alone or in combination in human GBM cells U-87 MG was evaluated by Quantitative RT-PCR. Cell proliferation in the short- and long-term  was investigated by alamar blue and clonogenic assays, respectively. An annexin-V assay was performed to detect apoptosis caused by siRNA treatment. The effect of  downregulating EGFR and beta-catenin on cell cycle progression, cell migration and invasive potential were also examined. RESULTS: The siRNA treatment potently  reduced gene expression of EGFR and beta-catenin at the mRNA level. Simultaneous  inhibition of EGFR and beta-catenin greatly decreased GBM cell proliferation. Although no significant increase in apoptosis was demonstrated, combinatorial siRNA treatment delayed the progression of cell cycle with an increased proportion of cells arrested in the G0/1 phase. Furthermore, EGFR and beta-catenin siRNA in combination significantly inhibited the migratory and invasive ability of GBM cells. CONCLUSIONS: Simultaneous inhibition of EGFR and beta-catenin expression could represent an effective therapy for human GBM, and warrants further study in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

 

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[97]

TÍTULO / TITLE:  - Proteasome inhibitor MG132 induces NAG-1/GDF15 expression through the p38 MAPK pathway in glioblastoma cells.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2013 Jan 25;430(4):1277-82. doi: 10.1016/j.bbrc.2012.11.137. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.11.137

AUTORES / AUTHORS:  - Shimizu S; Kadowaki M; Yoshioka H; Kambe A; Watanabe T; Kinyamu HK; Eling TE

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States; Division of Neurosurgery, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Tottori 683-8503, Japan.

RESUMEN / SUMMARY:  - The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is regulated by the p53 and Egr-1 tumor suppressor pathways. Many anti-cancer drugs  and chemicals induce NAG-1 expression, but the mechanisms are not fully understood. Transgenic mice expressing human NAG-1 are resistant to intestinal and prostate cancer, suggesting that NAG-1 is a tumor suppressor. Proteasome inhibitors exhibit anti-glioblastoma activities in preclinical studies. Here, we  show that the proteasome inhibitors MG132 and bortezomib induced NAG-1 expression and secretion in glioblastoma cells. MG132 increased NAG-1 expression through transcriptional and post-transcriptional mechanisms. At the transcriptional level, the induction of NAG-1 required the -133 to +41bp region of the promoter.  At post-transcriptional levels, MG132 stabilized NAG-1 mRNA by increasing the half-life from 1.5h to >8h. Because of the dramatic increase in mRNA stability, this is likely the major contributor to MG132-mediated NAG-1 induction. Further probing into the mechanism revealed that MG132 increased phosphorylation of the p38 MAPK pathway. Consequently, inhibiting p38 phosphorylation blocked activation of the NAG-1 promoter and decreased mRNA stability, indicating that p38 MAPK activation mediates both MG132-dependent promoter activation and mRNA stabilization of NAG-1. We propose that the induction of NAG-1 by p38 MAPK is a potential contributor to the anti-glioblastoma activity of proteasome inhibitors.

 

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[98]

TÍTULO / TITLE:  - Fractionated stereotactic radiotherapy using Novalis for confined intra-orbital optic nerve glioma in pediatric patient.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2031-x

AUTORES / AUTHORS:  - Han SR; Kim KN; Yee GT; Choi CY; Lee DJ; Sohn MJ; Lee CH

INSTITUCIÓN / INSTITUTION:  - The Graduate School, College of Medicine, Yonsei University, Seoul, South Korea,  hsrkmj@paik.ac.kr.

RESUMEN / SUMMARY:  - INTRODUCTION: Optic gliomas are the most common tumors in the optic pathways during childhood. Among them, about 10 % are located within intra-orbital cavity. However, the optimal management for intra-orbital optic nerve gliomas remains controversial. An 11-year-old male complained about progressive decline of vision in his right eye. Brain MRI revealed a fusiform enlargement of right optic nerve  within intra-orbital cavity. MATERIALS AND METHODS: A presumptive diagnosis of optic nerve glioma was made. Therefore, we performed fractionated stereotactic radiotherapy (FSRT) using Novalis. DISCUSSION: Five years after FSRT treatment, follow-up MRI revealed size reduction of tumor and visual acuity improvement without radiation-related complications.

 

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[99]

TÍTULO / TITLE:  - Genomic Mapping and Survival Prediction in Glioblastoma: Molecular Subclassification Strengthened by Hemodynamic Imaging Biomarkers.

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

REVISTA / JOURNAL:  - Radiology. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12120846

AUTORES / AUTHORS:  - Jain R; Poisson L; Narang J; Gutman D; Scarpace L; Hwang SN; Holder C; Wintermark M; Colen RR; Kirby J; Freymann J; Brat DJ; Jaffe C; Mikkelsen T

INSTITUCIÓN / INSTITUTION:  - Division of Neuroradiology, Department of Radiology, Department of Neurosurgery,  and Department of Public Health Sciences, Henry Ford Health System, 2799 W Grand  Blvd, Detroit, MI 48202; Departments of Pathology and Laboratory Medicine and Department of Radiology, Emory University School of Medicine, Atlanta, Ga Department of Radiology, University of Virginia, Charlottesville, Va; Department  of Radiology, Brigham and Women’s Hospital, Boston, Mass; Clinical Research Directorate, CMRP, SAIC-Frederick, Inc, NCI-Frederick, Frederick, Md.

RESUMEN / SUMMARY:  - Purpose:To correlate tumor blood volume, measured by using dynamic susceptibility contrast material-enhanced T2*-weighted magnetic resonance (MR) perfusion studies, with patient survival and determine its association with molecular subclasses of glioblastoma (GBM).Materials and Methods:This HIPAA-compliant retrospective study was approved by institutional review board. Fifty patients underwent dynamic susceptibility contrast-enhanced T2*-weighted MR perfusion studies and had gene expression data available from the Cancer Genome Atlas. Relative cerebral blood volume (rCBV) (maximum rCBV [rCBV(max)] and mean rCBV [rCBV(mean)]) of the contrast-enhanced lesion as well as rCBV of the nonenhanced  lesion (rCBV(NEL)) were measured. Patients were subclassified according to the Verhaak and Phillips classification schemas, which are based on similarity to defined genomic expression signature. We correlated rCBV measures with the molecular subclasses as well as with patient overall survival by using Cox regression analysis.Results:No statistically significant differences were noted for rCBV(max), rCBV(mean) of contrast-enhanced lesion or rCBV(NEL) between the four Verhaak classes or the three Phillips classes. However, increased rCBV measures are associated with poor overall survival in GBM. The rCBV(max) (P = .0131) is the strongest predictor of overall survival regardless of potential confounders or molecular classification. Interestingly, including the Verhaak molecular GBM classification in the survival model clarifies the association of rCBV(mean) with patient overall survival (hazard ratio: 1.46, P = .0212) compared with rCBV(mean) alone (hazard ratio: 1.25, P = .1918). Phillips subclasses are not predictive of overall survival nor do they affect the predictive ability of rCBV measures on overall survival.Conclusion:The rCBV(max) measurements could be  used to predict patient overall survival independent of the molecular subclasses  of GBM; however, Verhaak classifiers provided additional information, suggesting  that molecular markers could be used in combination with hemodynamic imaging biomarkers in the future.© RSNA, 2012.

 

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[100]

TÍTULO / TITLE:  - Inhibition of T-type calcium channels disrupts Akt signaling and promotes apoptosis in glioblastoma cells.

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

REVISTA / JOURNAL:  - Biochem Pharmacol. 2013 Jan 1. pii: S0006-2952(12)00825-8. doi: 10.1016/j.bcp.2012.12.017.

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

AUTORES / AUTHORS:  - Valerie NC; Dziegielewska B; Hosing AS; Augustin E; Gray LS; Brautigan DL; Larner JM; Dziegielewski J

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University of Virginia, Charlottesville, VA, United States.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) are brain tumors that are exceptionally resistant to both radio- and chemotherapy regimens and novel approaches to treatment are needed. T-type calcium channels are one type of low voltage-gated channel (LVCC)  involved in embryonic cell proliferation and differentiation; however they are often over-expressed in tumors, including GBM. In this study, we found that inhibition of T-type Ca(2+) channels in GBM cells significantly reduced their survival and resistance to therapy. Moreover, either T-type selective antagonists, such as mibefradil, or siRNA-mediated knockdown of the T-type channel alpha subunits not only reduced cell viability and clonogenic potential,  but also induced apoptosis. In response to channel blockade or ablation, we observed reduced phosphorylation of Akt and Rictor, suggesting inhibition of the  mTORC2/Akt pathway. This was followed by reduction in phosphorylation of anti-apoptotic Bad and caspases activation. The apoptotic response was specific for T-type Ca(2+) channels, as inhibition of L-type Ca(2+) channels did not induce similar effects. Our results implicate T-type Ca(2+) channels as distinct  entities for survival signaling in GBM cells and suggest that they are a novel molecular target for tumor therapy.

 

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[101]

TÍTULO / TITLE:  - Mortality is higher in patients with leptomeningeal metastasis in spinal cord tumors.

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

REVISTA / JOURNAL:  - Arq Neuropsiquiatr. 2013 Jan;71(1):40-5. Epub 2013 Jan 8.

AUTORES / AUTHORS:  - Gepp Rde A; Couto JM; Silva MD; Quiroga MR

INSTITUCIÓN / INSTITUTION:  - SARAH Network of Rehabilitation Hospitals, Brasilia, DF, Brazil.

RESUMEN / SUMMARY:  - Spinal cord tumors are a rare neoplasm of the central nervous system (CNS). The occurrence of metastases is related to poor prognosis. The authors analyzed one series of metastasis cases and their associated mortality. METHODS: Clinical characteristics were studied in six patients with intramedullary tumors with metastases in a series of 71 surgical cases. RESULTS: Five patients had ependymomas of which two were WHO grade III. The patient with astrocytoma had a grade II histopathological classification. Two patients required shunts for hydrocephalus. The survival curve showed a higher mortality than the general group of patients with no metastases in the CNS (p<0.0001). CONCLUSION: Mortality is elevated in patients with metastasis and greater than in patients with only primary lesions. The ependymomas, regardless of their degree of anaplasia, are more likely to cause metastasis than spinal cord astrocytomas.

 

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[102]

TÍTULO / TITLE:  - Inhibition of formyl peptide receptor in high-grade astrocytoma by CHemotaxis Inhibitory Protein of S. aureus.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15. doi: 10.1038/bjc.2012.603.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.603

AUTORES / AUTHORS:  - Boer JC; Domanska UM; Timmer-Bosscha H; Boer IG; de Haas CJ; Joseph JV; Kruyt FA; de Vries EG; den Dunnen WF; van Strijp JA; Walenkamp AM

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.

RESUMEN / SUMMARY:  - Background:High-grade astrocytomas are malignant brain tumours that infiltrate the surrounding brain tissue and have a poor prognosis. Activation of formyl peptide receptor (FPR1) on the human astrocytoma cell line U87 promotes cell motility, growth and angiogenesis. We therefore investigated the FPR1 inhibitor,  Chemotaxis Inhibitory Protein of S. aureus (CHIPS), as a potential anti-astrocytoma drug.Methods and results:FPR1 expression was studied immunohistochemically in astrocytomas WHO grades I-IV. With intracellular calcium mobilisation and migration assays, human ligands were tested for their ability to activate FPR1 on U87 cells and on a cell line derived from primary astrocytoma grade IV patient material. Thereafter, we selectively inhibited these ligand-induced responses of FPR1 with an anti-inflammatory compound called Chemotaxis Inhibitory Protein of S. aureus (CHIPS). U87 xenografts in NOD-SCID mice served to investigate the effects of CHIPS in vivo. FPR1 was expressed in 29 out of 32 (90%) of all grades of astrocytomas. Two human mitochondrial-derived formylated peptides, formyl-methionil-leucine-lysine-isoleucine-valine (fMLKLIV)  and formyl-methionil-methionil-tyrosine-alanine-leucine-phenylalanine (fMMYALF),  were potent activators of FPR1 on tumour cells. Ligand-induced responses of FPR1-expressing tumour cells could be inhibited with FPR1 inhibitor CHIPS. Treatment of tumour-bearing mice with CHIPS slightly reduced tumour growth and improved survival as compared to non-treated animals (P=0.0019).Conclusion:Targeting FPR1 with CHIPS reduces cell motility and tumour  cell activation, and prolongs the survival of tumour-bearing mice. This strategy  could be explored in future research to improve treatment results for astrocytoma patients.British Journal of Cancer advance online publication, 15 January 2013; doi:10.1038/bjc.2012.603 www.bjcancer.com.

 

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[103]

TÍTULO / TITLE:  - The ultrastructural difference between CD133-positive U251 glioma stem cells and  normal U251 glioma cells.

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

REVISTA / JOURNAL:  - Ultrastruct Pathol. 2012 Dec;36(6):404-8. doi: 10.3109/01913123.2012.708011.

            ●● Enlace al texto completo (gratuito o de pago) 3109/01913123.2012.708011

AUTORES / AUTHORS:  - Yang B; Wang Y; Yang C; Ouyang W; Zhou F; Zhou Y; Xie C

INSTITUCIÓN / INSTITUTION:  - Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuchang District, Wuhan, China.

RESUMEN / SUMMARY:  - Glioma stem cells (GSC) have higher tumorigenic potential and stronger chemoresistance and radioresistance than normal glioma cells. The mechanisms behind these phenomena have remained elusive. The authors have isolated CD133-positive U251 GSCs from U251 glioma cells and detected the expression of stem cell markers (CD133 and nestin) of U251 GSCs by immunofluorescence staining. Then the ultrastructures of U251 GSCs and normal U251 glioma cells were observed  by transmission electron microscopy and the ultrastructural differences between them were compared. Increased cell nucleus atypia, rougher endoplasmic reticulum, and more microvilli were observed in CD133-positive U251 GSCs than in normal U251 glioma cells. In summary, these ultrastructural differences support the hypothesis that GSCs have stronger tumorigenic ability and resistance to chemotherapy and radiotherapy.

 

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[104]

TÍTULO / TITLE:  - Pediatric diffuse intrinsic pontine glioma patients from a single center.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-1986-3

AUTORES / AUTHORS:  - Kebudi R; Cakir FB; Agaoglu FY; Gorgun O; Ayan I; Darendeliler E

INSTITUCIÓN / INSTITUTION:  - Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty and Oncology Institute, Istanbul University, Istanbul, Turkey, rejinkebudi@yahoo.com.

RESUMEN / SUMMARY:  - BACKGROUND: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG) is dismal. This study aims to evaluate the characteristics and treatment outcome of children with DIPG in a single center. METHODS: We reviewed the outcome of children with DIPG treated at the Oncology Institute of Istanbul University from February 1999 to May 2012. RESULTS: Fifty children (26 female, 24 male) with the median age of 7 years were analyzed. The median duration of symptoms was 30 days. All patients received radiotherapy (RT). Before the year 2000, 12 patients received only RT. Thirty-eight had concomitant and/or adjuvant  chemotherapy with RT. Between 2000 and 2004, 17 patients received cis-platinum or vincristine as sensitizers during RT and CCNU + vincristine combination after RT. Since 2004, 21 patients received temozolomide (TMZ) concomitantly during RT and as adjuvant chemotherapy after RT. The median survival time of all patients was 13 months (1-160 months). Patients receiving RT + TMZ had a significantly higher  overall survival than patients with only RT (p = 0.018). Patients receiving RT +  chemotherapy other than TMZ also had a significantly higher overall survival than patients receiving only RT (p = 0.013). Patients receiving RT + TMZ + and chemotherapy other than TMZ had a significantly higher survival than patients receiving only RT (p = 0.005). CONCLUSION: In our series, patients receiving RT + TMZ and also patients receiving RT + chemotherapy other than TMZ had a significantly higher overall survival than patients treated with only RT. Hence,  administering chemotherapy during and after RT seems to prolong survival in some  DIPG patients.

 

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[105]

TÍTULO / TITLE:  - Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 10. pii: S0967-5868(12)00451-1. doi: 10.1016/j.jocn.2012.03.044.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.03.044

AUTORES / AUTHORS:  - Lee JH; Jung TY; Jung S; Kim IY; Jang WY; Moon KS; Jeong EH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, 160 Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeollanam-do 519-809, South Korea.

RESUMEN / SUMMARY:  - For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70years or older with a newly diagnosed GBM were treated with radiotherapy (60Gy in 16 patients and 40Gy  in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8months (95% confidence interval [CI], 8.7-14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0months (95% CI, 2.4-3.5), and the time to ECOG  performance status grade 3 was 5.8months (95% CI, 1.6-9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%),  leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p=0.003) and a longer time with good performance status for gross total removal  (GTR) (p=0.003). An initial good performance status was related to a good performance status during and after treatment (p=0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR]=0.236; 95% CI, 0.060-0.922, p=0.038) and a good performance status (HR=0.124; 95% CI, 0.022-0.693, p=0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.

 

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[106]

TÍTULO / TITLE:  - TNF receptor-associated factor 6 regulates proliferation, apoptosis, and invasion of glioma cells.

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

REVISTA / JOURNAL:  - Mol Cell Biochem. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1573-2

AUTORES / AUTHORS:  - Peng Z; Shuangzhu Y; Yongjie J; Xinjun Z; Ying L

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, NO.88, Jian-kang Road, Xinxiang, 453100, Henan, China, zhangpeng_hn@163.com.

RESUMEN / SUMMARY:  - Tumor necrosis factor receptor-associated factor 6 (TRAF6), which plays an important role in inflammation and immune response, is an essential adaptor protein for the NF-kappaB (nuclear factor kappaB) signaling pathway. Recent studies have shown that TRAF6 played an important role in tumorigenesis and invasion by suppressing NF-kappaB activation. However, up to now, the biologic role of TRAF6 in glioma has still remained unknown. To address the expression of  TRAF6 in glioma cells, four glioma cell lines (U251, U-87MG, LN-18, and U373) and a non-cancerous human glial cell line SVG p12 were used to explore the protein expression of TRAF6 by Western blot. Our results indicated that TRAF6 expression  was upregulated in human glioma cell lines, especially in metastatic cell lines.  To investigate the role of TRAF6 in cell proliferation, apoptosis, invasion, and  migration of glioma, we generated human glioma U-87MG cell lines in which TRAF6 was either overexpressed or depleted. Subsequently, the effects of TRAF6 on cell  viability, cell cycle distribution, apoptosis, invasion, and migration in U-87MG  cells were determined with 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium  bromide (MTT) assay, flow cytometry analysis, transwell invasion assay, and wound-healing assay. The results showed that knockdown of TRAF6 could decrease cell viability, suppress cell proliferation, invasion and migration, and promote  cell apoptosis, whereas overexpression of TRAF6 displayed the opposite effects. In addition, the effects of TRAF6 on the expression of phosphor-NF-kappaB (p-p65), cyclin D1, caspase 3, and MMP-9 were also probed. Knockdown of TRAF6 could lower the expression of p-p65, cyclin D1, and MMP-9, and raise the expression of caspase 3. All these results suggested that TRAF6 might be involved in the potentiation of growth, proliferation, invasion, and migration of U-87MG cell, as well as inhibition of apoptosis of U-87MG cell by abrogating activation  of NF-kappaB.

 

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[107]

TÍTULO / TITLE:  - Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated  pilocytic astrocytoma.

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

REVISTA / JOURNAL:  - Genome Res. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1101/gr.142604.112

AUTORES / AUTHORS:  - Gutmann DH; McLellan MD; Hussain I; Wallis JW; Fulton LL; Fulton RS; Magrini V; Demeter R; Wylie T; Kandoth C; Leonard JR; Guha A; Miller CA; Ding L; Mardis ER

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;

RESUMEN / SUMMARY:  - Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis  type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result  from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes  may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion  of stromal cells, such that only 50%-60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment.

 

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[108]

TÍTULO / TITLE:  - Visual Field Improvement After Pituitary Tumor Surgery in Patients With McCune-Albright Syndrome.

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

REVISTA / JOURNAL:  - J Neuroophthalmol. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WNO.0b013e3182726b69

AUTORES / AUTHORS:  - Ma J; Zhao C; Wang R; Feng F; Wang E; You H; Jiang Y; Zhang M; Zhong Y

INSTITUCIÓN / INSTITUTION:  - Departments of Ophthalmology (JM, CZ, EW, MZ, YZ), Neurosurgery (RW), Radiology (FF, HY), and Pathology (YJ), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

RESUMEN / SUMMARY:  - BACKGROUND:: McCune-Albright syndrome (MAS) is a rare, sporadic congenital disorder, in which optic neuropathy may cause devastating visual consequences. Pituitary adenoma with overproduction of growth hormone (GH) is present in approximately two-thirds of MAS patients, and its role in the pathogenesis of MAS-associated optic neuropathy has not been studied. METHODS:: Three MAS patients with GH-secreting pituitary adenoma and optic chiasm compression diagnosed between January 2008 and November 2010 were included in this case series. Transsphenoidal pituitary resection was performed in all 3 patients. Neuro-ophthalmologic evaluation was performed at presentation and every 6 months  during follow-up. RESULTS:: Of the 3 patients, 2 were female and 1 was male; their ages ranged from 17 to 27 years. Visual acuity ranged from 20/20 to 20/200  before surgery and all had visual field loss. The patients were followed up for 6-18 months with substantial improvement in their visual fields. CONCLUSIONS:: GH-secreting pituitary adenoma may contribute to optic nerve damage, at least partially, in MAS patients. Pituitary surgery may be important for visual recovery in some MAS patients in whom there is compression of the optic chiasm.

 

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[109]

TÍTULO / TITLE:  - Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells.

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

REVISTA / JOURNAL:  - Invest New Drugs. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10637-012-9917-4

AUTORES / AUTHORS:  - Castro-Gamero AM; Borges KS; Moreno DA; Suazo VK; Fujinami MM; de Paula Gomes Queiroz R; de Oliveira HF; Carlotti CG Jr; Scrideli CA; Tone LG

INSTITUCIÓN / INSTITUTION:  - Department of Genetics, Faculty of Medicine of Ribeirao Preto, University of Sao  Paulo (USP), Ribeirao Preto, Brazil, amcgen@gmail.com.

RESUMEN / SUMMARY:  - Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcription factor, such as Survivin and Cdk1. In the present study we evaluated the gene expression of Survivin, its spliced variants and Cdk1 in GBM samples and cell lines. Moreover, we investigated the effects of M4N combined or not with TMZ and/or radiation on GBM primary cultures and cell lines. qRT-PCR assays were performed to determine the Survivin-spliced variants and Cdk1 gene mRNA expression in GBM tumor samples and cell lines. Cell proliferation was measured by XTT assay and cell cycle and apoptosis were determined by flow cytometry. Drug combination analyses using different schedules of administration (simultaneous and sequential) were performed on GBM cell lines and primary cultures based on the Chou-Talalay method. For clonogenic survival, doses of 2, 4, and 6 Gy of gamma radiation. were used. All Survivin-spliced variants and the Cdk1 gene were  expressed in GBM samples (n = 16) and cell lines (n = 6), except the Survivin-2B  variant that was only expressed in GBM cell lines. M4N treatment down regulated the expression of Cdk1, Survivin and the Survivin-DeltaEx3 variant, while the Survivin-2B variant was up-regulated. M4N decreased the cell proliferation separately and synergistically with TMZ, and enhanced the effects of radiation, mainly when associated with TMZ. M4N also induced apoptotic cell death, decreased the mitotic index and arrested the cell cycle mainly in the G2/M phase. Our results suggest a potential clinical application of M4N in combination with TMZ and radiation for GB treatment.

 

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[110]

TÍTULO / TITLE:  - Prognostic Significance of Ror2 and Wnt5a Expression in Medulloblastoma.

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

REVISTA / JOURNAL:  - Brain Pathol. 2012 Dec 20. doi: 10.1111/bpa.12017.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12017

AUTORES / AUTHORS:  - Lee SE; Lim SD; Kang SY; Suh SB; Suh YL

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Medulloblastoma (MB) is a clinically and biologically heterogeneous group of tumors, and currently classified into four molecular subgroups (Wnt, Shh, Group 3 and Group 4). Intracellular signaling of the Wnt pathway has been divided into two classes: the “canonical” and the “non-canonical” signaling pathway. The canonical signaling pathway is a well-established, beta-catenin-dependent signaling pathway in MB. In contrast, very little research about the non-canonical WNT signaling pathway in MB exists. In order to identify the roles  of Wnt-5a and Ror2, two non-canonical WNT pathway-related genes, we studied 76 cases of MB with immunohistochemistry and quantitative real-time PCR and correlated the results with clinicopathological and other molecular parameters and prognosis. Wnt5a and Ror2 were immunopositive in 20 (29.4%) and 35 (51.5%) of 68 cases, respectively. There were positive associations among protein expressions of Wnt5a, Ror2 and beta-catenin. Ror2 mRNA levels were well correlated with immunoexpression. Ror2 mRNA expression was significantly associated with CTNNB1 mutation. High Ror2 mRNA expression was an independent favorable prognostic factor. In conclusion, our study demonstrates the first attempt to identify Wnt5a and Ror2 as additional mechanisms contributing to dysregulation of the non-canonical WNT signaling pathway in MB. Ror2 may play a role as an oncosuppressor in MB.

 

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[111]

TÍTULO / TITLE:  - Comparative functional properties of two structurally similar selective nonpeptide drug-like ligands for the angiotensin II type-2 (AT(2)) receptor. Effects on neurite outgrowth in NG108-15 cells.

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

REVISTA / JOURNAL:  - Eur J Pharmacol. 2012 Dec 2;699(1-3):160-171. doi: 10.1016/j.ejphar.2012.11.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2012.11.032

AUTORES / AUTHORS:  - Guimond MO; Wallinder C; Alterman M; Hallberg A; Gallo-Payet N

INSTITUCIÓN / INSTITUTION:  - Service of Endocrinology and Department of Physiology and Biophysics, Faculty of  Medicine, Universite de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.

RESUMEN / SUMMARY:  - There is increasing evidence that angiotensin II (Ang II), through binding to the type 2 (AT(2)) receptor may have beneficial effects in various physiological and  pathological situations. However, specific action presumably mediated by the angiotensin AT(2) receptor has been hampered by the absence of appropriate selective ligands. The aim of this study was to compare the biological properties of two related and selective drug-like nonpeptide AT(2) ligands, namely an agonist called M024 (also known as Compound 21) and a new ligand, presumably an antagonist, C38/M132, (originally called C38). Properties of the compounds were investigated in NG108-15 cells expressing angiotensin AT(2) receptor and known to develop neurite outgrowth upon Ang II stimulation. NG108-15 cells stimulated for  three days with C21/M024 (0.1 or 100nM) exhibited the same neurite outgrowth as cells stimulated with Ang II (100nM) while co-incubation of Ang II or C21/M024 with C38/M132 (10 or 100nM) inhibited their effects, similarly to the angiotensin AT(2) receptor antagonist, PD123319 (10muM). As Ang II, C21/M024 induced a Rap1-dependent activation of p42/p44(mapk) whereas preincubation of cells with C38/M132 inhibited p42/p44(mapk) and Rap1 activation induced by Ang II. Three-day treatment with C21/M024 or Ang II decreased cell number in culture, an effect that was rescued by preincubation with C38/M132. Taken together, these results indicate that the nonpeptide ligand C21/M024 is a potent angiotensin AT(2) receptor agonist while C38/M132 acts as an antagonist. These selective nonpeptide angiotensin AT(2) ligands may represent unique and long-awaited tools for the pursuit of in vivo studies.

 

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[112]

TÍTULO / TITLE:  - The Combination of 13N-Ammonia and 18F-FDG in Predicting Primary Central Nervous  System Lymphomas in Immunocompetent Patients.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb;38(2):98-102. doi: 10.1097/RLU.0b013e318279b6cc.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279b6cc

AUTORES / AUTHORS:  - Shi X; Zhang X; Yi C; Wang X; Chen Z; Zhang B

INSTITUCIÓN / INSTITUTION:  - From the Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

RESUMEN / SUMMARY:  - OBJECTIVE: Accurate identification of primary central nervous system lymphoma (PCNSL) and its differentiation from other brain tumors remain difficult but are  essential for treatment. In this study, we investigated whether N-ammonia combined with F-FDG could distinguish PCNSL from solid gliomas effectively. METHODS: Ten consecutive patients with final diagnosis of PCNSL (5 female and 5 male patients; mean [SD] age, 59.10 [12.47] years; range, 43-74 years) and another fifteen consecutive patients with solid glioma lesions (5 female and 10 male patients; mean [SD] age, 46.73 [19.61] years; range, 14-72 years) were included in this study. PET/CT imaging was performed for all of them with both F-FDG and N-ammonia as tracers. Tumor-to-gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. Both Student t test and discriminant analysis were recruited to assess the differential efficacy of these 2 tracers. RESULTS: The T/G ratios of F-FDG in PCNSL lesions were higher than in solid gliomas (3.26  [1.18] vs 1.56 [0.41], P < 0.001), whereas the T/G ratios of N-ammonia in PCNSL lesions were lower than in solid gliomas significantly (1.38 [0.20] vs 2.11 [0.69], P < 0.001). All the lesions of PCNSL displayed higher T/G ratios of F-FDG than N-ammonia, whereas 14 (77.8%) of 18 glioma lesions showed contrary results.  Tumor classification by means of canonical discriminant analysis yielded an overall accuracy of 96.9%, and only one glioma lesion was misclassified into the  PCNSL group. CONCLUSIONS: PCNSLs and solid gliomas have different metabolic profiles on N-ammonia and F-FDG imaging. The combination of these 2 tracers can distinguish these 2 clinical entities effectively and make an accurate prediction of PCNSL.

 

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[113]

TÍTULO / TITLE:  - Use of statins and risk of glioma: a nationwide case-control study in Denmark.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15. doi: 10.1038/bjc.2012.536.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.536

AUTORES / AUTHORS:  - Gaist D; Andersen L; Hallas J; Toft Sorensen H; Schroder HD; 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, 5000 Odense C, Denmark.

RESUMEN / SUMMARY:  - Background:Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the  influence of statin use on the risk of glioma in a population-based setting.Methods:We conducted a nationwide case-control study in Denmark based on  population-based medical registries. We identified all patients aged 20 to 85 years with a first diagnosis of histologically verified glioma during 2000-2009.  These cases were matched on birth year and sex with population controls. Prior use of statins since 1995 was classified into short-term use (<5 years) and long-term use (5+ years). We used conditional logistic regression to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with statin use, adjusted for potential confounders.Results:A total of 2656 cases and  18 480 controls were included in the study. The risk of glioma was reduced among  long-term statin users (OR=0.76; 95% CI: 0.59-0.98) compared with never users of  statins, and was inversely related to the intensity of statin treatment among users (OR=0.71; 95% CI: 0.44-1.15 for highest intensity). The inverse association between long-term statin treatment and glioma risk was more pronounced among men  aged </=60 years (OR=0.40; 95% CI: 0.17-0.91) compared with men aged 60+ years (OR=0.71; 95% CI: 0.49-1.03). An inverse association was also observed among women aged </=60 years (OR=0.28; 95% CI: 0.06-1.25), but not among women over age 60 years (OR=1.23; 95% CI: 0.82-1.85).Conclusion:Long-term statin use may reduce  the risk of glioma.British Journal of Cancer advance online publication, 15 January 2013; doi:10.1038/bjc.2012.536 www.bjcancer.com.

 

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[114]

TÍTULO / TITLE:  - Harmol induces autophagy and subsequent apoptosis in U251MG human glioma cells through the downregulation of survivin.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Jan 18. doi: 10.3892/or.2013.2242.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2242

AUTORES / AUTHORS:  - Abe A; Kokuba H

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.

RESUMEN / SUMMARY:  - The beta-carboline alkaloids are plant substances that exhibit a wide spectrum of neuropharmacological, psychopharma-cological and antitumor effects. In the present study, we found that harmol, a beta-carboline alkaloid, induced autophagy and suppression of survivin expression, and subsequently induced apoptotic cell death in U251MG human glioma cells. Autophagy was induced within 12 h by treatment with harmol. When treated for over 36 h, however, apoptotic cell death  was induced. Harmol treatment also reduced survivin protein expression. Small interfering RNA (siRNA)-mediated knockdown of survivin enhanced the harmol-induced apoptosis. Knockdown of survivin by siRNA also induced autophagy.  Therefore, harmol-induced apoptosis is a result of the reduction in survivin protein expression. Treatment with 3-methyladenine (3-MA) in the presence of harmol did not affect the expression of survivin and diminished harmol-induced cell death. Treatment with chloroquine in the presence of harmol did not suppress the reduction of survivin expression and increased harmol-induced cell death. From these results, harmol-induced reduction of survivin expression was closely related to autophagy. It is assumed that when isolation membrane formation is inhibited by treatment with 3-MA, reduction of survivin protein expression and apoptotic cell death were not induced. However, when isolation membrane formation is started and an autophagosome is formed, survivin expression is suppressed and  apoptosis is executed. Harmol treatment reduced phosphorylation of Akt, mammalian target of rapamycin (mTOR) and its downstream targets p70-ribosomal protein S6 kinase and 4E-binding protein 1, resulting in induction of autophagy. Conversely, activation of the Akt/mTOR pathway inhibited harmol-induced autophagy and cell death. These findings indicate that harmol-induced autophagy involves the Akt/mTOR pathway. Taken together, autophagy induced by harmol represented a pro-apoptotic mechanism, and harmol suppressed the expression of survivin and subsequently induced apoptosis.

 

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[115]

TÍTULO / TITLE:  - Combination therapy of cilengitide with belotecan against experimental glioblastoma.

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

REVISTA / JOURNAL:  - Int J Cancer. 2013 Jan 25. doi: 10.1002/ijc.28058.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28058

AUTORES / AUTHORS:  - Kim YH; Lee JK; Kim B; Dewitt JP; Lee JE; Han JH; Kim SK; Oh CW; Kim CY

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si 463-707, Korea; Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.

RESUMEN / SUMMARY:  - The prognosis of patients diagnosed with glioblastoma remains dismal in spite of  the current concomitant chemoradiotherapy with temozolomide. In particular, the resistance to temozolomide appears to be the greatest obstacle to the treatment of glioblastoma. In the present study, we evaluated in vitro and in vivo the anti-tumor effects of combination therapy of cilengitide with belotecan, a camptothecin derivate, to treat experimental glioblastoma. The therapeutic effects of the drugs on the U87MG and U251MG human glioblastoma cell lines were assessed using in vitro cell viability and apoptosis assays. The combination treatment group with cilengitide and belotecan enhanced the cytotoxic effects to  the glioblastoma cell lines and increased the apoptosis of the tumor cells compared with monotherapy with either drug alone in vitro. Nude mice with established U87MG glioblastoma were assigned to the following 4 groups: control,  cilengitide, belotecan, and combination treatment. The volume of tumors and length of survival were also measured. Animals in the combination therapy group demonstrated a significant reduction of tumor volume and an increase in survival  (p < 0.05). Immunohistochemistry revealed a decrease in angiogenesis by cilengitide and an increase in apoptosis by cilengitide and belotecan in vivo. The combination therapy of cilengitide with belotecan presented more cytotoxic effects compared to the monotherapy of either drug in vitro and in vivo. This combination protocol may serve as an alternative treatment option for glioblastoma.

 

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[116]

TÍTULO / TITLE:  - P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2.

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

REVISTA / JOURNAL:  - Neurosci Lett. 2013 Feb 8;534:327-32. doi: 10.1016/j.neulet.2012.11.047. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neulet.2012.11.047

AUTORES / AUTHORS:  - Chen L; Zhang R; Li P; Liu Y; Qin K; Fa ZQ; Liu YJ; Ke YQ; Jiang XD

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; The National Key Clinic Specialty; The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou 510282,  China.

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs) are small noncoding RNAs that function as tumor suppressors or oncogenes. MicroRNA-107 (miR-107), a transcriptional target of p53, is deregulated in many cancer cell lines. Here, we showed that miR-107 is down-regulated in glioma tissues and cell lines, in particular, p53-mutated U251  and A172. Transfection of wild-type p53 into these cells stimulated miR-107 expression. To investigate the role of miR-107 in tumorigenesis, we constructed a lentiviral vector overexpressing miR-107. Notably, miR-107 inhibited proliferation and arrested the cell cycle at the G0-G1 phase in glioma cells. Transduction of Lenti-GFP-miR-107 into glioma cells inhibited CDK6 and Notch-2 protein expression. Our findings collectively demonstrate that p53-induced miR-107 suppresses brain tumor cell growth and down-regulates CDK6 and Notch-2 expression, supporting its tumor suppressor role and utility as a target for glioma therapy.

 

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[117]

TÍTULO / TITLE:  - Bortezomib Downregulates MGMT Expression in T98G Glioblastoma Cells.

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

REVISTA / JOURNAL:  - Cell Mol Neurobiol. 2013 Jan 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10571-013-9910-2

AUTORES / AUTHORS:  - Vlachostergios PJ; Hatzidaki E; Stathakis NE; Koukoulis GK; Papandreou CN

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece, pvlacho@med.uth.gr.

RESUMEN / SUMMARY:  - The efficacy of treatment for glioblastoma multiforme is currently limited by the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) in  a significant proportion of astrocytic tumors. MGMT is post-translationally regulated by the 26S proteasome, a multi-subunit organelle responsible for degradation of misfolded cellular proteins. The boronic acid dipeptide bortezomib is the first and only proteasome inhibitor in clinical use so far, and has been reported as a strategy to restrict growth and promote apoptosis of glioblastoma cells. In this study we investigated the effect of bortezomib on MGMT expression  in T98G cells, looking for an effect on the nuclear factor kappa B (NFkappaB) pathway, which is a major player in MGMT regulation and is also under tight control by the ubiquitin-proteasome system. Administration of bortezomib led to a significant reduction of T98G cell viability and induction of DNA fragmentation.  These effects coincided with reduced expression of MGMT transcript levels, and a  decrease in cellular amount and IkappaBalpha-mediated, proteasomal activity-dependent nuclear translocation of NFkappaB. In addition, bortezomib-induced phosphorylation of the translation initiation factor 2alpha (eIF2alpha) was in parallel with translational repression of MGMT. Taken together, these results suggest a novel role for bortezomib as a potent MGMT inhibitor and support its ongoing testing as a chemosensitizer in glioblastoma.

 

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[118]

TÍTULO / TITLE:  - Clinical neuropathology practice guide 1-2013: Molecular subtyping of glioblastoma: ready for clinical use?

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2013 Jan-Feb;32(1):5-8.

AUTORES / AUTHORS:  - Woehrer A; Marosi C; Widhalm G; Oberndorfer S; Pichler J; Hainfellner JA

INSTITUCIÓN / INSTITUTION:  - Institute of Neurology, Department of Medicine I, Department of Neurosurgery, Medical University of Vienna, Vienna, Department of Neurology, State Hospital St. Polten, St. Polten, and Internal Medicine and Neurooncology, Landesnervenklinik Wagner-Jauregg, Linz, Austria.

RESUMEN / SUMMARY:  - Recently, integrated genomewide analyses have revealed several glioblastoma (GB)  subtypes, which differ in terms of key pathogenetic pathways and point to different cells of origin. Even though the proneural and mesenchymal GB signatures evolved as most robust, there is no consensus on the exact number of subtypes and defining criteria. Moreover, important issues concerning within-tumor heterogeneity and class-switching upon recurrence remain to be addressed. Early evidence indicates an association of different GB subtypes with  patient outcome and response to therapy, which argues for the implementation of molecular GB subtyping, and consideration of GB subtypes in subsequent patient management. As genome-wide analyses are not routinely available to the majority of neuropathology laboratories, first attempts to implement immunohistochemical testing of surrogate markers are underway. However, so far, confirmatory studies  are lacking and there is no consensus on which markers to use. Further, the rationale for testing is compromised from a clinical point of view by a lack of effective therapies for individual GB subtypes. Thus, incorporation of genomic research findings as a basis for GB patient management and clinical decision making currently remains a perspective for the future.

 

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[119]

TÍTULO / TITLE:  - Reply: Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells.

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 22. doi: 10.1038/bjc.2013.19.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.19

AUTORES / AUTHORS:  - Liu P; Brown S; Channathodiyil P; Kannappan V; Armesilla AL; Darling JL; Wang W

INSTITUCIÓN / INSTITUTION:  - Research Institute in Healthcare Science, School of Applied Sciences, University  of Wolverhampton, Wolverhampton WV1 1LY, UK.

 

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[120]

TÍTULO / TITLE:  - Comment on ‘Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells’

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

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 22. doi: 10.1038/bjc.2013.18.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.18

AUTORES / AUTHORS:  - Cvek B

INSTITUCIÓN / INSTITUTION:  - Department of Cell Biology & Genetics, Palacky University, Olomouc, Czech Republic.

 

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[121]

TÍTULO / TITLE:  - Resistance to two heterologous neurotropic oncolytic viruses, semliki forest virus and vaccinia virus, in experimental glioma.

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

REVISTA / JOURNAL:  - J Virol. 2013 Feb;87(4):2363-6. doi: 10.1128/JVI.01609-12. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1128/JVI.01609-12

AUTORES / AUTHORS:  - Vaha-Koskela MJ; Le Boeuf F; Lemay C; De Silva N; Diallo JS; Cox J; Becker M; Choi Y; Ananth A; Sellers C; Breton S; Roy D; Falls T; Brun J; Hemminki A; Hinkkanen A; Bell JC

INSTITUCIÓN / INSTITUTION:  - Centre for Innovative Cancer Therapeutics, Ottawa Health Research Institute, Ottawa, Canada.

RESUMEN / SUMMARY:  - Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells  may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference.

 

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[122]

TÍTULO / TITLE:  - HDAC inhibitor DWP0016 activates p53 transcription and acetylation to inhibit cell growth in U251 glioblastoma cells.

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

REVISTA / JOURNAL:  - J Cell Biochem. 2013 Jan 7. doi: 10.1002/jcb.24491.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24491

AUTORES / AUTHORS:  - Jin H; Liang L; Liu LF; Deng WP; Liu JW

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China.

RESUMEN / SUMMARY:  - Here we report a hydroacid named DWP0016, which exhibited HDAC inhibition and induced p53 acetylation in U251 glioblastoma cells. DWP0016 effectively inhibited the cell growth of U251 cells and other 4 carcinoma cell lines but did not affect the normal cells. Cell cycle distribution analysis showed DWP0016 arrested at G(1) phase cell cycle dose-dependently in U251 cells. DWP0016 induced caspase-dependent and independent apoptosis in U251 cells, which was identified by flow cytometry analysis, caspases activity analysis, western blotting assay and caspases inhibition. Mechanisms research suggested that DWP0016 activated transcription and acetylation of tumor suppressor p53. DWP0016 regulated p300, CBP and PCAF to facilitate p53 acetylation at lys382 in U251 cells. In addition,  activation of p53 by DWP0016 promoted PUMA to catalyze mitochondrial pathway. Besides, siRNA assay indicated p53 was the key gene to induce growth inhibition,  cell cycle arrest and apoptosis in DWP0016 treated U251 cells. Conclusively, our  results show DWP0016 is a potent HDAC inhibitor and the anti-tumor activity is consistent with its intended p53 activation mechanisms. These findings indicate the promising antitumor potential of DWP0016 for further glioblastoma treatment applications. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

 

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[123]

TÍTULO / TITLE:  - IGF1 Receptor Signaling Regulates Adaptive Radioprotection in Glioma Stem Cells.

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

REVISTA / JOURNAL:  - Stem Cells. 2013 Jan 17. doi: 10.1002/stem.1328.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1328

AUTORES / AUTHORS:  - Osuka S; Sampetrean O; Shimizu T; Saga I; Onishi N; Sugihara E; Okubo J; Fujita S; Takano S; Matsumura A; Saya H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan; Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.

RESUMEN / SUMMARY:  - Cancer stem cells play an important role in disease recurrence after radiation treatment as a result of intrinsic properties such as high DNA repair capability  and antioxidative capacity. It is unclear, however, how cancer stem cells further adapt to escape the toxicity of the repeated irradiation regimens used in clinical practice. Here, we have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation in order to investigate the associated adaptive  changes, with the ultimate goal of identifying a targetable factor that regulates acquired radioresistance. We have shown that fractionated radiation induces an increase in IGF1 secretion and a gradual up-regulation of the IGF type 1 receptor (IGF1R) in GSCs. Interestingly, IGF1R up-regulation exerts a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induces down-regulation of Akt/ERK and FoxO3a activation, which results in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the  abundance of IGF1R and increased secretion of IGF1 promote a rapid shift from a latent state towards activation of Akt survival signaling, protecting GSCs from radiation toxicity. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity, suggesting that blockade of IGF1R signaling is an effective strategy to reverse radioresistance. Together, our results show that GSCs evade the damage of repeated radiation not only through innate properties, but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by  IGF1R signaling as a novel mechanism of adaptive radioprotection.

 

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[124]

TÍTULO / TITLE:  - Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma.

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

REVISTA / JOURNAL:  - Neurology. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1212/WNL.0b013e3182815428

AUTORES / AUTHORS:  - Krueger DA; Care MM; Agricola K; Tudor C; Mays M; Franz DN

INSTITUCIÓN / INSTITUTION:  - From the Departments of Pediatrics and Neurology (D.A.K., K.A., C.T., M.M., D.N.F.) and the Departments of Pediatrics and Radiology (M.M.C.), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

RESUMEN / SUMMARY:  - OBJECTIVE: To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC). METHODS: This was an open-label extension phase of a prospective, phase 1-2 trial (NCT00411619) in patients >/=3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m(2) per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5-15 ng/mL. Change in SEGA volume, seizures, and safety  assessments were the main outcome measures. RESULTS: Of 28 patients enrolled, 25  were still under treatment at the time of analysis. Median dose was 5.3 mg/m(2)/day and median treatment duration was 34.2 months (range 4.7-47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by >/=30% from baseline (treatment response) in 65%-79% of patients. All patients reported >/=1 adverse event (AE), mostly grade ½ in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related  grade 4 or 5 events occurred. CONCLUSION: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.

 

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[125]

TÍTULO / TITLE:  - Multinodular and Vacuolating Neuronal Tumors of the Cerebrum: Ten cases of a distinctive seizure-associated lesion.

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

REVISTA / JOURNAL:  - Brain Pathol. 2013 Jan 17. doi: 10.1111/bpa.12035.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12035

AUTORES / AUTHORS:  - Huse JT; Edgar M; Halliday J; Mikolaenko I; Lavi E; Rosenblum MK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.

RESUMEN / SUMMARY:  - We report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On MRI, the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament, and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or  CD34, though CD34-labeling ramified neural elements were present in the adjoining cortex of 7 cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, WHO grade I fashion and is amenable to surgical control.

 

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[126]

TÍTULO / TITLE:  - Assessment of Autoantibodies to Meningioma in a Population-based Study.

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

REVISTA / JOURNAL:  - Am J Epidemiol. 2013 Jan 1;177(1):75-83. doi: 10.1093/aje/kws221. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1093/aje/kws221

AUTORES / AUTHORS:  - Wiemels JL; Bracci PM; Wrensch M; Schildkraut J; Bondy M; Pfefferle J; Zhou M; Sison J; Calvocoressi L; Claus EB

RESUMEN / SUMMARY:  - Meningioma is an intracranial tumor with few confirmed risk factors. Recent research points to an impact on meningioma risk from factors related to immune function and development, such as allergy, immunoglobulin E, and Varicella infection status. To further explore an association with immune function, the authors assessed individual seroreactivity to meningioma tumor-associated antigens among participants enrolled in a multicenter, population-based US case-control study of meningioma (2006-2009). Serum samples from cases (n = 349)  and controls (n = 348) were screened for autoantibody reactivity to 3 proteins identified in previous studies: enolase 1 (ENO1), NK-tumor recognition protein (NKTR), and nuclear mitotic apparatus protein 1 (NUMA1). Case-control differences were not strong overall (adjusted odds ratio (OR)(ENO1 (continuous)) = 1.1, 95% confidence interval (CI): 0.6, 1.9 (P(trend) = 0.3); adjusted OR(NKTR (continuous)) = 1.3, 95% CI: 0.7, 2.4 (P(trend) = 0.02); and adjusted OR(NUMA1 (continuous)) = 1.1, 95% CI: 0.7, 1.8 (P(trend) = 0.06)); however, antibodies to  NKTR and NUMA1 were detected at higher levels in cases than in controls, particularly among men (for men, adjusted OR(ENO1 (continuous)) = 1.6, 95% CI: 0.5, 4.7 (P(trend) = 0.24); adjusted OR(NKTR (continuous)) = 4.3, 95% CI: 1.2, 15 (P(trend) = 0.009); and adjusted OR(NUMA1 (continuous)) = 3.6, 95% CI: 1.1, 11 (P(trend) = 0.006)). These results indicate that men with meningioma commonly react with a serologic antimeningioma response; if supported by further research, this finding suggests a distinctive etiology for meningioma in men.

 

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[127]

TÍTULO / TITLE:  - Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca(2+) ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: Relevant similarities to and important differences from celecoxib.

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

REVISTA / JOURNAL:  - J Neurosci Res. 2013 Mar;91(3):393-406. doi: 10.1002/jnr.23169. Epub 2012 Dec 30.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jnr.23169

AUTORES / AUTHORS:  - White MC; Johnson GG; Zhang W; Hobrath JV; Piazza GA; Grimaldi M

INSTITUCIÓN / INSTITUTION:  - Laboratory of Neuropharmacology, Medicinal Chemistry Department, Drug Discovery Division, Southern Research Institute, Birmingham, Alabama.

RESUMEN / SUMMARY:  - Malignant gliomas have low survival expectations regardless of current treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent cell transformation and slow cancer cell growth by mechanisms independent of cyclooxygenase (COX) inhibition. Certain NSAIDs trigger the endoplasmic reticulum stress response (ERSR), as revealed by upregulation of molecular chaperones such  as GRP78 and C/EBP homologous protein (CHOP). Although celecoxib (CELE) inhibits  the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), an effect known to induce ERSR, sulindac sulfide (SS) has not been reported to affect SERCA. Here, we investigated these two drugs for their effects on Ca(2+) homeostasis, ERSR, and glioma cell survival. Our findings indicate that SS is a reversible inhibitor of  SERCA and that both SS and CELE bind SERCA at its cyclopiazonic acid binding site. Furthermore, CELE releases additional Ca(2+) from the mitochondria. In glioma cells, both NSAIDS upregulate GRP78 and activate ER-associated caspase-4 and caspase-3. Although only CELE upregulates the expression of CHOP, it appears  that CHOP induction could be associated with mitochondrial poisoning. In addition, CHOP induction appears to be uncorrelated with the gliotoxicity of these NSAIDS in our experiments. Our data suggest that activation of ERSR is primarily responsible for the gliotoxic effect of these NSAIDS. Because SS has good brain bioavailability, has lower COX-2 inhibition, and has no mitochondrial  effects, it represents a more appealing molecular candidate than CELE to achieve  gliotoxicity via activation of ERSR. © 2012 Wiley Periodicals, Inc.

 

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[128]

TÍTULO / TITLE:  - Risk Factors for Pediatric Arachnoid Cyst Rupture/Hemorrhage: A Case-Control Study.

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

REVISTA / JOURNAL:  - Neurosurgery. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e318285b3a4

AUTORES / AUTHORS:  - Cress M; Kestle JR; Holubkov R; Riva-Cambrin J

INSTITUCIÓN / INSTITUTION:  - 1Department of Neurosurgery, University of Missouri, Columbia, Missouri 2Division of Pediatric Neurosurgery, Department of Neurosurgery, Primary Children’s Medical Center, University of Utah, Salt Lake City, Utah 3Division of Critical Care Medicine, Department of Pediatrics, University of Utah, Salt Lake City, Utah.

RESUMEN / SUMMARY:  - BACKGROUND:: As the availability of imaging modalities has increased, the finding of arachnoid cysts has become common. Accurate patient counseling regarding physical activity or risk factors for cyst rupture or hemorrhage has been hampered by the lack of definitive association studies. OBJECTIVE:: This case-control study evaluated factors that are associated with arachnoid cyst rupture (intracystic hemorrhage, adjacent subdural hematoma, or adjacent subdural hygroma) in pediatric patients with previously asymptomatic arachnoid cysts. METHODS:: Patients with arachnoid cysts and intra-cystic hemorrhage, adjacent subdural hygroma, or adjacent subdural hematoma treated at a single institution from 2005 to 2010 were retrospectively identified. Two unruptured/non-hemorrhagic controls were matched to each case based on patient age, sex, anatomical cyst location, and side. Risk factors evaluated included arachnoid cyst size, recent history of head trauma, and altitude at residence. RESULTS:: The proportion of imaged arachnoid cysts that presented either originally or subsequently with a rupture or hemorrhage was 6.0%. Larger cyst size, as defined by maximal cyst diameter, was significantly associated with cyst rupture/hemorrhage (p < .001). When dichotomized with a 5-cm cut-off, 9/13 larger cysts ruptured and/or hemorrhaged, whereas only 5/29 smaller cysts ruptured/hemorrhaged (odds ratio=16.5 (CI [2.5, infinity]). A recent history of head trauma was also significantly associated with the outcome (p < .001; odds ratio=25.1 (CI [4.0, infinity]). Altitude was not associated with arachnoid cyst rupture or hemorrhage. CONCLUSION:: This case-control study suggests that larger arachnoid cyst size and recent head trauma are risk factors for symptomatic arachnoid cyst  rupture/hemorrhage.

 

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[129]

TÍTULO / TITLE:  - Feasibility and Comparison of Visual Acuity Testing Methods in Children with Neurofibromatosis Type 1 and or Optic Pathway Gliomas.

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

REVISTA / JOURNAL:  - Invest Ophthalmol Vis Sci. 2013 Jan 17. pii: iovs.12-11385v1. doi: 10.1167/iovs.12-11385.

            ●● Enlace al texto completo (gratuito o de pago) 1167/iovs.12-11385

AUTORES / AUTHORS:  - Avery RA; Bouffet E; Packer RJ; Reginald A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Children’s National Medical Center, 111 Michigan Ave, NW, Washington, DC, 20010, United States.

RESUMEN / SUMMARY:  - PURPOSE: Longitudinal ophthalmologic clinical trials in young children require multiple visual acuity (VA) testing methods-especially when the subjects have cognitive and developmental delay. This study evaluated the success rate and comparability of two different VA testing methods in children with Neurofibromatosis type 1 (NF1) and or optic pathway gliomas (OPGs). Methods: Two  institutions prospectively enrolled children </= 10 years with NF1 and or an OPG. Both Teller grating acuity (TAC) and recognition acuity using the computerized version of the Amblyopia Treatment Study VA testing protocol that limits responses to four letters (H,O,T, or V) was attempted in all subjects. The association of age and diagnosis of NF1 on success rate was analyzed. Differences in grating and recognition acuity were compared. Results: One-hundred twenty-seven children met inclusion criteria (median age = 5.58 years). Eleven of 127 (8.7%) subjects could not complete monocular TAC testing in either eye. Thirty-nine of 127 subjects (30.7%) could not complete HOTV testing and were younger than those able to complete HOTV testing (mean = 2.9 versus 7.0 years, respectively; Z = -8.3, P < 0.01). Older age was associated with successful HOTV  testing and remained significant in all regression analyses (P < 0.01). The within subject logMAR values for TAC and HOTV testing results were significantly  correlated (r = 0.69, P < 0.01). CONCLUSION: Young children with NF1 and or OPGs  were frequently unable to complete recognition acuity testing. These factors are  important to consider when designing a clinical trial for children with NF1 and or OPGs.

 

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[130]

TÍTULO / TITLE:  - Histologically Proven, Low-grade Brainstem Gliomas in Children: 30-Year Experience With Long-term Follow-up at Mayo Clinic.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31826b9903

AUTORES / AUTHORS:  - Ahmed KA; Laack NN; Eckel LJ; Orme NM; Wetjen NM

INSTITUCIÓN / INSTITUTION:  - *Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL Departments of daggerRadiation Oncology double daggerRadiology section signInternal Medicine  parallelNeurologic Surgery, Mayo Clinic, Rochester, MN.

RESUMEN / SUMMARY:  - INTRODUCTION:: To evaluate long-term overall survival (OS), progression-free survival (PFS), and outcomes in pathologically proven brainstem low-grade gliomas (BS-LGG) in children. METHODS:: The Mayo Clinic tumor registry identified 48 consecutive children (</=20 y, 52% female) with biopsy-proven BS-LGG treated at Mayo Clinic between January 1971 and December 2004. Medical records were retrospectively reviewed. For analysis, patients were censored at the time of recurrence, death, or last follow-up. RESULTS:: The median age at diagnosis was 12 years with a median follow-up of 6.0 years. The majority of tumors were grade  I (69%) and pathology was consistent with an astrocytoma in the majority of patients (98%). Gross total resection was obtained in 4, subtotal in 17, and 27 patients were biopsied only. Postoperative radiotherapy (RT) was used in 29 patients. Median OS for the entire group was 14.8 years with a 1-, 5-, and 10-year OS of 85%, 67% and 59%, respectively. Median PFS for the entire group was 7.3 years. Improved survival was associated with undergoing resection versus biopsy-only with 5-year OS rates of 85% and 50% (P=0.002), respectively. A high proportion of patients (42%) had diffuse tumors and 13 patients (27%) had diffuse pontine gliomas (DPGs). DPGs had an OS of 1.8 years with a worse median PFS than  non-DPGs (1.8 vs. 11.1 y; P=0.009). RT was used preferentially in patients with poor prognosis such as those who had a biopsy-only procedure (19/27) and DPGs (9/13). CONCLUSIONS:: OS in this single institution retrospective study in pathologically proven BS-LGG with extensive follow-up displayed favorable long-term outcomes. Improved outcomes were associated with nondiffuse classification.

 

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[131]

TÍTULO / TITLE:  - ZFX regulates glioma cell proliferation and survival in vitro and in vivo.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1032-z

AUTORES / AUTHORS:  - Zhu Z; Li K; Xu D; Liu Y; Tang H; Xie Q; Xie L; Liu J; Wang H; Gong Y; Hu Z; Zheng J

INSTITUCIÓN / INSTITUTION:  - School of Pharmacy, East China University of Science and Technology, 130 Meilong  Road, Shanghai, 200237, People’s Republic of China.

RESUMEN / SUMMARY:  - The zinc finger transcription factor ZFX functions as an important regulator of self-renewal in multiple stem cell types, as well as a sex determinant of mammals. Moreover, ZFX expression is abnormally elevated in several cancers, and  correlates with malignancy grade. To investigate its role in the pathogenesis of  gliomas, we used lentivirus-mediated RNA interference (RNAi) to knockdown ZFX expression in human glioma cell lines. Our results demonstrate that ZFX plays a crucial role in glioma proliferation and survival, confirming recent reports. We  also show for the first time that ZFX knockdown decreases the in vivo growth potential of U87 glioma xenografts in both subcutaneous and intracranial models in nude mice. We conclude that lentivirus-mediated RNAi targeting of ZFX may serve as a promising strategy for glioma therapy.

 

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[132]

TÍTULO / TITLE:  - Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.

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

REVISTA / JOURNAL:  - Phys Med Biol. 2012 Dec 21;57(24):8377-91. doi: 10.1088/0031-9155/57/24/8377. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1088/0031-9155/57/24/8377

AUTORES / AUTHORS:  - Ceberg C; Jonsson BA; Prezado Y; Pommer T; Nittby H; Englund E; Grafstrom G; Edvardsson A; Stenvall A; Stromblad S; Wingardh K; Persson B; Elleaume H; Baldetorp B; Salford LG; Strand SE

INSTITUCIÓN / INSTITUTION:  - Medical Radiation Physics, Department of Clinical Sciences Lund, Lund University, 22100 Lund, Sweden. crister.ceberg@med.lu.se

RESUMEN / SUMMARY:  - 75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups  were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the  median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups.  The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.

 

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[133]

TÍTULO / TITLE:  - Miniaturized hand-held confocal microscopy identifies focal brain invasion in a mouse model of aggressive meningioma.

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

REVISTA / JOURNAL:  - Brain Pathol. 2013 Jan 29. doi: 10.1111/bpa.12039.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12039

AUTORES / AUTHORS:  - Peyre M; Clermont-Taranchon E; Stemmer-Rachamimov A; Kalamarides M

INSTITUCIÓN / INSTITUTION:  - AP-HP, Hopital Beaujon, Service de Neurochirurgie, F-92110, Clichy, France; Universite Sorbonne Paris Cite, Paris, France; Inserm Unit U674, F-75010, Paris,  France.

RESUMEN / SUMMARY:  - Invasion of the brain parenchyma by a meningioma classified by histological criteria as World Health Organization (WHO) Grade I meningioma, implies that the  tumor has greater likelihood of recurrence and a biological behavior similar to the more aggressive WHO Grade II meningiomas. It is therefore important to detect microscopic foci of brain invasion during surgery in order to maximize the resection and/or adapt imaging follow-up. In this study we tested the sensitivity of two handheld confocal imaging devices to detect foci of brain invasion in two  types of meningioma mouse models: in a genetically engineered mouse model and in  a syngenic xenograft model. Confocal imaging offered precise images of meningothelial and fibroblastic mouse meningiomas as well as malignant meningiomas, which corresponded exactly to the pathological findings. Imaging showed a sharp definition of the brain-tumor interface and enabled identification of embedded nerves and vessels. Importantly, in both mouse models used in this study, extension of tumor along Virchow-Robin spaces into adjacent brain was detected by imaging. In conclusion, this novel technique, following validation in clinical trials, may open new possibilities for use in operating rooms to influence both decision making during the surgery and planning for additional treatments.

 

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[134]

TÍTULO / TITLE:  - Early treatment response of a rare papillary tumor of the pineal region after primary proton-beam therapy using the raster-scanning technique at HIT.

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

REVISTA / JOURNAL:  - Tumori. 2012 Sep-Oct;98(5):122e-125e. doi: 10.1700/1190.13212.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1190.13212

AUTORES / AUTHORS:  - Habermehl D; Blachutzik F; Ecker S; Dittmar JO; Rieken S; Debus J; Welzel T; Combs SE

INSTITUCIÓN / INSTITUTION:  - Department of Radiooncology, University Hospital of Heidelberg, Heidelberg, Germany. daniel.habermehl@med.uni-heidelberg.de

RESUMEN / SUMMARY:  - Pineocytomas are rare intracranial tumors occurring in the pineal gland region. The curative therapy of choice is gross total resection, which cannot be performed in all patients because of the frequent eloquent location of these tumors. Percutaneous fractionated radiotherapy is an alternative treatment approach that may result in high local control rates. Nevertheless, our knowledge of this tumor entity is limited and based on retrospective case series only. We present a patient with a papillary tumor of the pineal region who was treated with highly conformal proton-beam therapy at the Heidelberg Ion Therapy Center (HIT) using the raster-scanning technique.

 

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[135]

TÍTULO / TITLE:  - Tandem high-dose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age.

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

REVISTA / JOURNAL:  - Bone Marrow Transplant. 2013 Jan 14. doi: 10.1038/bmt.2012.263.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bmt.2012.263

AUTORES / AUTHORS:  - Sung KW; Lim DH; Lee SH; Yoo KH; Koo HH; Kim JH; Suh YL; Joung YS; Shin HJ

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School  of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - In an effort to improve survival and reduce late adverse effects of radiation therapy (RT), 25 children <3 years of age with malignant brain tumors received tandem high-dose chemotherapy (HDCT) and auto-SCT following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age  if the patient was in CR after tandem HDCT/auto-SCT. Tumors relapsed or progressed in nine patients (five during induction treatment), and two of these patients survived after receiving salvage treatment, including RT. Two patients died due to toxicities during tandem HDCT/auto-SCT. A total of 16 patients survived to a median follow-up period of 52 months (range 18-96) from the time of diagnosis. Four of these patients did not receive RT, two received local RT (L-RT), three received craniospinal RT (CSRT), and seven received both L-RT and CSRT. The 5-year OS and EFS rates were 67.8+/-9.4% and 55.5+/-10.0%, respectively. Neuroendocrine and neurocognitive functions evaluated 3 years after tandem HDCT/auto-SCT were acceptable. Our results indicate that tandem HDCT/auto-SCT may improve survival in young children with malignant brain tumors  with an acceptable level of risk of long-term toxicity.Bone Marrow Transplantation advance online publication, 14 January 2013; doi:10.1038/bmt.2012.263.

 

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[136]

TÍTULO / TITLE:  - Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan;111(2):177-85. doi: 10.1007/s11060-012-0997-y. Epub 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-0997-y

AUTORES / AUTHORS:  - Farace P; Amelio D; Ricciardi GK; Zoccatelli G; Magon S; Pizzini F; Alessandrini F; Sbarbati A; Amichetti M; Beltramello A

INSTITUCIÓN / INSTITUTION:  - Anatomy and Histology Section, Department of Morphological and Biomedical Sciences, University of Verona, Via Le Grazie 8, 37134, Verona, VR, Italy, paolofarace@gmail.com.

RESUMEN / SUMMARY:  - To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were  analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before  adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR  diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria.

 

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[137]

TÍTULO / TITLE:  - Visual Loss without Headache in Children with Pseudotumor Cerebri and Growth Hormone Treatment.

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

REVISTA / JOURNAL:  - Neuropediatrics. 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330855

AUTORES / AUTHORS:  - Besch D; Makowski C; Steinborn MM; Bonfig W; Sadowski B

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Centre for Ophthalmology, University Eye Hospital, Tuebingen, Germany.

RESUMEN / SUMMARY:  - We report on two prepubescent girls with visual loss due to idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, both treated with recombinant human growth hormone for growth failure. The interval from starting hormone therapy to diagnosis of IIH was 3 and 18 months, respectively. Both girls did not complain of headache and nausea. They were neither obese nor did they suffer from renal insufficiency. In both patients, we observed bilateral optic disc edema with visual loss and elevated cerebrospinal fluid (CSF) pressures. Other causes of IIH were excluded with neuroimaging and CSF examination. Cessation of drug administration is often sufficient for symptom resolution in cases of hormone therapy-associated IIH. However, visual field defects in one girl remained unchanged during follow-up of 8 months. In children with IIH, the spectrum of neurologic and visual manifestations might be variable and unspecific. Diagnosis and management of IIH can be difficult in the absence of headache. Blurred or double vision due to cranial nerve palsy might be the only symptom rather than complaints about reduced visual acuity. Therefore, regular clinical monitoring of visual function and fundus appearance is essential for early diagnosis, efficient management, and improvement of visual outcome in children receiving recombinant human growth hormone.

 

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[138]

TÍTULO / TITLE:  - Shared associations of nonatherosclerotic, large-vessel, cerebrovascular arteriopathies: considering intracranial aneurysms, cervical artery dissection, moyamoya disease and fibromuscular dysplasia.

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

REVISTA / JOURNAL:  - Curr Opin Neurol. 2013 Feb;26(1):13-28. doi: 10.1097/WCO.0b013e32835c607f.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WCO.0b013e32835c607f

AUTORES / AUTHORS:  - Southerland AM; Meschia JF; Worrall BB

INSTITUCIÓN / INSTITUTION:  - aDepartment of Neurology bDepartment of Public Health Sciences, University of Virginia, Charlottesville, Virginia cDepartment of Neurology, Mayo Clinic, Jacksonville, Florida dCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.

RESUMEN / SUMMARY:  - PURPOSE OF REVIEW: With ongoing advancements in noninvasive vascular imaging and  high-throughput genomics, we have the opportunity to reclassify the cerebrocervical disorders by these shared associations, rather than their downstream events, and to better understand etiology, mechanism and preventive treatments going forward. RECENT FINDINGS: The common nonatherosclerotic, large-vessel arteriopathies affecting the cerebrovasculature include intracranial aneurysms, cervical artery dissection, fibromuscular dysplasia and moyamoya disease. Together, these entities contribute to a high incidence of devastating cerebrovascular outcomes, including ischemic stroke and subarachnoid hemorrhage,  leading to long-term physical and cognitive disability frequently in young otherwise healthy adults. In addition to well reported clinical overlap, these polygenic phenotypes share epidemiological characteristics, environmental risk and a common pathological weakening of the arterial wall. SUMMARY: We reviewed both past and present studies relating these shared associations, including reported candidate gene analyses and genome-wide association data. We also catalogue recent descriptions of novel arteriopathic syndromes that add to the growing list of monogenic connective tissue disease affecting the arterial wall,  and further inform our understanding of more common polygenic phenotypes. We also place these cerebrocervical arteriopathies in the context of other systemic nonatherosclerotic, large-vessel vascular disease (e.g. aortic aneurysm and dissection).

 

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[139]

TÍTULO / TITLE:  - Relapsing, remitting hypercortisolism in Cushing’s disease due to intratumoral hemorrhages in pituitary microadenoma.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 24. pii: S0967-5868(12)00491-2. doi: 10.1016/j.jocn.2012.05.039.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.05.039

AUTORES / AUTHORS:  - Marko NF; Hamrahian AH; Hatipoglu B; Weil RJ

INSTITUCIÓN / INSTITUTION:  - The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Neurosurgery, Neurological Institute, The Cleveland Clinic, Cleveland, OH, USA; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom. Electronic address: Nicholas.Marko@cancer.org.uk.

RESUMEN / SUMMARY:  - We report two patients with Cushing’s disease (CD) from adrenocorticotropic hormone-secreting microadenomas in whom intralesional hemorrhage caused an episodic, remitting and relapsing pattern of hypercortisolism. To our knowledge this is the first report of patients in whom hemorrhage within a microadenoma caused cyclic CD. Both patients were treated successfully with transsphenoidal surgery.

 

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[140]

TÍTULO / TITLE:  - Protein kinase Cgamma antibodies and paraneoplastic cerebellar degeneration.

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

REVISTA / JOURNAL:  - J Neuroimmunol. 2012 Dec 25. pii: S0165-5728(12)00335-9. doi: 10.1016/j.jneuroim.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jneuroim.2012.12.002

AUTORES / AUTHORS:  - Hoftberger R; Kovacs GG; Sabater L; Nagy P; Racz G; Miquel R; Dalmau J; Graus F

INSTITUCIÓN / INSTITUTION:  - Service of Neurology, Hospital Clinic, Universitat de Barcelona, Barcelona, España; Institut d Investigacio Biomedica August Pi i Suyer (IDIBAPS), Barcelona,  España.

RESUMEN / SUMMARY:  - Onconeural antibodies are diagnostic markers for paraneoplastic neurological syndromes and indicate the underlying tumor type. Recently, a new antibody against protein-kinase Cgamma (PKCgamma) was detected in a patient with paraneoplastic cerebellar degeneration (PCD). We report here a second patient. A  70-year-old woman presented with cerebellar ataxia, dysdiadochokinesia, and dysarthria. Her serum showed immunoreactivity against the cytoplasm, dendrites and axons of Purkinje cells in tissue-based screening, later confirmed by immunoblot and phage plaques as anti-PKCgamma. Tumor search revealed an adenocarcinoma of hepatobiliary origin. Detection of PKCgamma antibodies should be considered in PCD and adenocarcinoma without typical onconeural antibodies.

 

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[141]

TÍTULO / TITLE:  - Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal  region: a multicenter study.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1050-5

AUTORES / AUTHORS:  - Fauchon F; Hasselblatt M; Jouvet A; Champier J; Popovic M; Kirollos R; Santarius T; Amemiya S; Kumabe T; Frappaz D; Lonjon M; Fevre Montange M; Vasiljevic A

INSTITUCIÓN / INSTITUTION:  - Centre de Haute Energie, Centre de Radiotherapie Prive and ADeRTU, Nice, France.

RESUMEN / SUMMARY:  - Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal  therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median  follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.

 

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[142]

TÍTULO / TITLE:  - H3.3 G34R mutations in pediatric primitive neuroectodermal tumors of central nervous system (CNS-PNET) and pediatric glioblastomas: possible diagnostic and therapeutic implications?

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1040-z

AUTORES / AUTHORS:  - Gessi M; Gielen GH; Hammes J; Dorner E; Muhlen AZ; Waha A; Pietsch T

INSTITUCIÓN / INSTITUTION:  - Institute of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany, mgessimd@yahoo.com.

RESUMEN / SUMMARY:  - Pediatric glioblastomas recently have been exon sequenced with evidence that approximately 30 % of cases harbour mutations of the histone H3.3 gene. Although  studies to determinate their role in risk stratification are on-going, it remains to be determined whether H3.3 mutations could be found in other tumors such as pediatric primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) and whether the presence of H3.3 mutations in glioblastomas could be  used as diagnostic tool in their differential diagnosis with CNS-PNETs. We performed a large mutational pyrosequencing-based screening on 123 pediatric glioblastomas and 33 CNS-PNET. The analysis revealed that 39/123 (31.7 %) glioblastomas carry H3.3 mutations. The K27M (AAG --> ATG, lysine --> methionine) mutation was found in 33 glioblastomas (26 %); the G34R (GGG --> AGG, glycine --> arginine) was observed in 6 glioblastomas (5.5 %). However, we also identified 4  of 33 cases (11 %) of CNS-PNETs harbouring a H3.3 G34R mutation. Multiplex ligation-dependent probe amplification analysis revealed PDGFR-alpha amplification and EGFR gain in two cases and N-Myc amplification in one case of H3.3 G34R mutated CNS-PNET. None of H3.3 mutated tumors presented a CDKN2A loss.  In conclusion, because pediatric patients with glioblastoma and CNS-PNET are treated according to different therapeutic protocols, these findings may raise further concerns about the reliability of the histological diagnosis in the case  of an undifferentiated brain tumor harbouring G34R H3.3 mutation. In this view, additional studies are needed to determine whether H3.3 G34 mutated CNS-PNET/glioblastomas may represent a defined tumor subtype.

 

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[143]

TÍTULO / TITLE:  - Knockdown of RLIP76 expression by RNA interference inhibits invasion, induces cell cycle arrest, and increases chemosensitivity to the anticancer drug temozolomide in glioma cells.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1045-2

AUTORES / AUTHORS:  - Wang Q; Qian J; Wang J; Luo C; Chen J; Hu G; Lu Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China.

RESUMEN / SUMMARY:  - RLIP76, a GTPase-activating protein, is a central regulator in multiple pathways  that respond to redox states and control cell growth, motility, division, and apoptosis in many malignant cancer cells. In this study, human glioblastoma cell  lines U87 and U251 were stably transfected with a lentivirus vector expressing a  short hairpin RNA (shRNA) targeting RLIP76. shRNA knockdown of RLIP76 induced cell cycle arrest in U87 and U251 cells and inhibited their invasiveness. Quantitative Western blot analysis revealed that cells stably underexpressing RLIP76 showed lower expression of cyclin D1 and decreased expression and activity of matrix metalloproteinase 2 compared to cells stably transfected with a control vector. Furthermore, RLIP76 expression levels were correlated with IC(50) values  for the antitumor drug temozolomide (TMZ). Compared with TMZ alone (17.19 +/- 1.78 and 22.18 +/- 1.99 mug/mL in U87 and U251 cells, respectively) or combined shGFP and TMZ (18.04 +/- 1.07 and 23.040 +/- 1.77 mug/mL in U87 and U251 cells, respectively), combined shRNA and TMZ therapy resulted in a significant decrease  in IC(50) value (7.61 +/- 2.99 and 6.91 +/- 2.59 mug/mL in U87 and U251 cells, respectively). Combined RLIP76 knockdown and TMZ treatment inhibited cell proliferation in vitro more effectively than either treatment alone. Furthermore, RLIP76 downregulation enhanced chemosensitivity to TMZ without affecting protein  expression of MDR1 and MRP1. The results indicate that inhibition of RLIP76 expression may be an effective means for overcoming RLIP76-associated chemoresistance in human malignant glioma cells and may represent a potential gene-targeting approach for glioma treatment.

 

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[144]

TÍTULO / TITLE:  - Does hypopituitarism recover when macroprolactinomas are treated with cabergoline?

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

REVISTA / JOURNAL:  - Clin Endocrinol (Oxf). 2012 Dec 8. doi: 10.1111/cen.12124.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cen.12124

AUTORES / AUTHORS:  - Karavitaki N; Dobrescu R; Byrne JV; Grossman AB; Wass JA

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.

RESUMEN / SUMMARY:  - OBJECTIVE: The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits. SUBJECTS AND METHODS: The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a two-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for 3 consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis. RESULTS: Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within one year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal  in 25% of deficient patients). CONCLUSIONS: In our study in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects  following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought. © 2012 Blackwell Publishing Ltd.

 

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[145]

TÍTULO / TITLE:  - National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden.

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

REVISTA / JOURNAL:  - J Clin Endocrinol Metab. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3362

AUTORES / AUTHORS:  - Onnestam L; Berinder K; Burman P; Dahlqvist P; Engstrom BE; Wahlberg J; Nystrom HF

INSTITUCIÓN / INSTITUTION:  - Sahlgrenska Academy (L.O., H.F.N.), University of Gothenburg, SE-405 30 Goteborg, Sweden; Department of Endocrinology (K.B.), Karolinska University Hospital Solna, SE-171 64 Stockholm, Sweden; Department of Endocrinology (P.B.), Skane University Hospital, SE-214 28 Malmo-Lund, Sweden; Department of Public Health and Clinical  Medicine (P.D.), Umea University, SE-901 87 Umea, Sweden; Department of Endocrinology (B.E.E.), Uppsala University Hospital, SE-751 85 Uppsala, Sweden; Department of Endocrinology (J.W.), University Hospital, SE-581 85 Linkoping, Sweden; and Department of Endocrinology, Sahlgrenska University Hospital (H.F.N.), SE-413 45 Goteborg, Sweden.

RESUMEN / SUMMARY:  - Context:TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence.Objective:The objective  of the study was to estimate the national Swedish incidence and prevalence of TSHomas.Design:This was an observational study.Setting:The study was conducted at tertiary referral centers.Patients:The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify  patients diagnosed with TSHomas 1990-2010. The identified patients’ medical records were studied until the latest follow-up [median 5.0 years (range < 1-20 years)].Main Outcome Measurements:Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured.Results:The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in  2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis  (P = .013). The median time to diagnosis was longer for women than men (4 vs < 1  year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022).Conclusion:This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.

 

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[146]

TÍTULO / TITLE:  - Immunohistochemical study of MRP5 expression in meningiomas.

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

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2057-x

AUTORES / AUTHORS:  - Alexiou GA; Goussia A; Ntoulia A; Zagorianakou P; Malamou-Mitsi V; Voulgaris S; Kyritsis AP

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital of Ioannina, Neohoropoulo, PO Box 103, 45500, Ioannina, Greece, alexiougrg@yahoo.gr.

RESUMEN / SUMMARY:  - PURPOSE: Meningiomas are the most common benign intracranial tumor, accounting for 30 % of all primary intracranial tumors. Although benign meningiomas rarely recur after a complete resection, anaplastic tumors are associated with high recurrence rate and unfavorable outcome. In the current study, we investigated the expression of the multidrug resistance protein 5 (MRP5) in patients with meningiomas. METHODS: We retrospectively studied twenty patients with meningiomas that were treated surgically in our institute over a 3-year period. MRP5 protein  expression was determined immunohistochemically. RESULTS: The immunohistochemical expression of MRP5 was observed only in anaplastic meningiomas. No MRP5 expression was detected in benign or atypical meningiomas. No significant correlation was found between MRP5 expression and Ki-67 index. After a mean follow-up period of 23 months, there were 4 cases of tumor recurrence. No correlation was found between extent of resection and tumor recurrence. CONCLUSION: Immunohistochemical MRP5 protein expression was observed only in anaplastic meningiomas. Further research is needed to clarify whether MRP5 is indicative of malignant pathological features in meningiomas and whether possible therapeutic implications exist.

 

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[147]

TÍTULO / TITLE:  - Prevention of postoperative cerebrospinal fluid leaks with multilayered reconstruction using titanium mesh-hydroxyapatite cement cranioplasty after translabyrinthine resection of acoustic neuroma.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121365

AUTORES / AUTHORS:  - Manjila S; Weidenbecher M; Semaan MT; Megerian CA; Bambakidis NC

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Object Several prophylactic surgical methods have been tried to prevent CSF leakage after translabyrinthine resection of acoustic neuroma (TLAN). The authors report an improvised technique for multilayer watertight closure using titanium mesh-hydroxyapatite cement (HAC) cranioplasty in addition to dural substitute and abdominal fat graft after TLAN. Methods The study was limited to 42 patients who  underwent TLAN at University Hospitals Case Medical Center using this new technique from 2006 to 2012. Systematic closure of the surgical wound in layers using temporalis fascia, dural substitute, dural sealant, adipose graft, titanium mesh, and then HAC was performed in each case. Temporalis muscle and eustachian tube obliteration were not used. The main variables studied were patient age, tumor size, tumor location, cosmetic outcome, length of hospitalization, and the  incidence of CSF leak, pseudomeningocele, and infection. Results Excellent cosmetic outcome was achieved in all patients. There were no cases of postoperative CSF rhinorrhea, incisional CSF leak, or meningitis. Cosmetic results were comparable to those achieved using HAC alone. This cost-effective technique used only a third of the HAC required for traditional closure in which  the entire mastoid defect is filled with cement, predisposing to infection. Postoperative CT and MRI showed excellent bony contouring and dural reconstitution, respectively. Conclusions The authors report on successful use of titanium mesh-HAC cranioplasty in preventing postoperative CSF leak after TLAN in all cases in their series. The titanium mesh provides a well-defined anatomical dissection plane that would make reoperation easier than working through scarred  soft tissue. The mesh bolsters the fat graft and keeps HAC out of direct contact  with mastoid air cells, thereby reducing the risk of infection. The cement cranioplasty does not preclude subsequent implantation of a bone-anchored hearing aid.

 

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[148]

TÍTULO / TITLE:  - Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the  cochlear spiral ganglion via neural cell adhesion molecule (NCAM).

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

REVISTA / JOURNAL:  - Mol Cell Neurosci. 2012 Dec 20. pii: S1044-7431(12)00214-X. doi: 10.1016/j.mcn.2012.12.004.

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

AUTORES / AUTHORS:  - Euteneuer S; Yang KH; Chavez E; Leichtle A; Loers G; Olshansky A; Pak K; Schachner M; Ryan AF

INSTITUCIÓN / INSTITUTION:  - Department of Surgery/Otolaryngology, Veteran’s Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Department of Otorhinolaryngology - Head and Neck Surgery, University of Lubeck, Ratzeburger Allee 160, Haus 28, 23538 Lubeck, Germany; Zentrum fuer Molekulare Neurobiologie Hamburg, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany. Electronic address: sara.euteneuer@med.uni-heidelberg.de.

RESUMEN / SUMMARY:  - Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory  system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor alpha1 (GFRalpha1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and  mice. Addition of GFRalpha1-Fc increases this effect. GDNF/GFRalpha1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished  GDNF/GFRalpha1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRalpha1-Fc, we  conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion.

 

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[149]

TÍTULO / TITLE:  - Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS12362

AUTORES / AUTHORS:  - Watanabe T; Ohtani T; Aihara M; Ishiuchi S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Faculty of Clinical Medicine, University of the Ryukyus, Okinawa;

RESUMEN / SUMMARY:  - Object Blockade of Ca(++)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) inhibits the proliferation of human glioblastoma by inhibiting Akt phosphorylation, which  is independent of the phosphatidylinositol 3-kinase pathway. Inhibiting platelet-derived growth factor receptor (PDGFR)-mediated phosphorylation causes growth inhibition in glioblastoma cells. The authors of this study investigated the effects of YM872 and AG1296, singly and in combination and targeting different pathways upstream of Akt, on Akt-mediated tumor growth in glioblastoma  cells in vivo and in vitro. Methods The expression of AMPAR, PDGFR, and c-kit in  glioblastoma cells was analyzed via immunofluorescence. Glioblastoma cells, both  in culture and in xenografts grown in mice, were treated with YM872 and AG1296, singly or in combination. Inhibition of tumor growth was observed after treatment in the xenograft model. Cell proliferation assays were performed using anti-Ki 67 antibody in vivo and in vitro. The CD34-positive tumor vessel counts within the vascular hot spots of tumor specimens were evaluated. Phosphorylation of Akt was  studied using Western blot analysis. Results Combined administration of YM872 and AG1296 had a significant enhanced effect on the inhibition of cell proliferation  and reduction of tumor vascularity in the xenograft model. These agents singly and in combination demonstrated a significant reduction of Akt phosphorylation at Ser473 and inhibition of tumor proliferation in vitro, although combined administration had no enhanced antitumor effects. Conclusions The strongly enhanced antitumor effect of this combination therapy in vivo rather than in vitro may be attributable to disruption of the aberrant vascular niche. This combination therapy might provide substantial benefits to patients with glioblastoma.

 

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[150]

TÍTULO / TITLE:  - The expression of moesin in astrocytoma: correlation with pathologic grade and poor clinical outcome.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):372. doi: 10.1007/s12032-012-0372-z. Epub 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0372-z

AUTORES / AUTHORS:  - Wu M; Liu DY; Yuan XR; Liu Q; Jiang XJ; Yuan D; Huang J; Li XJ; Yang ZQ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xiangya Hospital, Central South University; The Institute of Skull Base Surgery and Neurooncology at Hunan, 87 Xiangya Road, Changsha, 410008, Hunan, China.

RESUMEN / SUMMARY:  - Moesin, a member of the ERM family, acts as a linker between the actin cytoskeleton and the plasma membrane and plays a key role in the control of cell  morphology, motility, adhesion and other processes of tumourigenesis. The expression pattern and clinical significance of moesin in astrocytoma remain unknown. In this study, we used RT-PCR to systematically investigate the expression of moesin in 49 astrocytomas of different pathological grade and 6 normal brain tissues. We found that the mRNA expression levels of moesin in astrocytomas were significantly higher in comparison with normal brain tissues. Furthermore, moesin up-regulation was correlated with pathological grade of astrocytomas. Subsequently, we tested 112 astrocytomas and 14 normal brain tissues by immunohistochemistry. Similar results were also confirmed. Univariate  and multivariate survival analysis were used to determine the correlations of moesin expression with overall survival and progression-free survival. Our results showed the expression of moesin was strongly negatively correlated with the patient progression-free survival and overall survival. These results suggest moesin protein involved in the genesis and progression of astrocytomas and might  be regarded as an independent predictor of poor prognosis.

 

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[151]

TÍTULO / TITLE:  - The Utility of Parent Report in the Assessment of Working Memory among Childhood  Brain Tumor Survivors.

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

REVISTA / JOURNAL:  - J Int Neuropsychol Soc. 2013 Jan 28:1-10.

            ●● Enlace al texto completo (gratuito o de pago) 1017/S1355617712001567

AUTORES / AUTHORS:  - Howarth RA; Ashford JM; Merchant TE; Ogg RJ; Santana V; Wu S; Xiong X; Conklin HM

INSTITUCIÓN / INSTITUTION:  - 1 Department of Neuropsychology, Children’s Healthcare of Atlanta, Atlanta, Georgia.

RESUMEN / SUMMARY:  - Childhood brain tumor survivors are at increased risk for neurocognitive impairments, including working memory (WM) problems. WM is typically assessed using performance measures. Little is known about the value of parent ratings for identifying WM difficulties, the relationship between rater and performance measures, or predictors of parent-reported WM problems in this population. Accordingly, the current study examined the utility of parent report in detecting WM difficulties among childhood brain tumor survivors treated with conformal radiation therapy (n = 50) relative to siblings (n = 40) and solid tumor survivors not receiving central nervous system-directed therapy (n = 40). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants were administered WM measures (digit span, self-ordered search tasks). Findings revealed parents rated brain tumor survivors as having significantly more WM problems (p < .01) compared to controls. However, the BRIEF-WM scale demonstrated poor sensitivity and specificity for detecting performance-based problems. Significant, albeit modest, correlations were found between the BRIEF-WM scale and performance measures (r = -.24-.22; p < .05) for the combined group. Age at testing, socioeconomic status, and IQ were significant predictors of parent reported WM problems. Rater and performance measures offer complimentary yet different information in assessing WM, which reiterates the importance of using both within the context of clinical assessment. (JINS, 2013,  19, 1-10).

 

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[152]

TÍTULO / TITLE:  - Stereotactic Radiosurgical Salvage Treatment for Locally Recurrent Esthesioneuroblastoma.

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

REVISTA / JOURNAL:  - Neurosurgery. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e31827fcdc2

AUTORES / AUTHORS:  - Van Gompel JJ; Carlson ML; Pollock BE; Moore EJ; Foote RL; Link MJ

INSTITUCIÓN / INSTITUTION:  - 1Departments of Neurosurgery 2Otorhinolaryngology Radiation Oncology3, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA.

RESUMEN / SUMMARY:  - BACKGROUND:: Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor considered to be radiation-sensitive. Local recurrence may be treated in a variety of ways, including stereotactic radiosurgery (SRS); however, there is little available information about its effectiveness. OBJECTIVE:: We hypothesize  SRS is effective in providing local control for recurrent ENB. METHODS:: This was a retrospective single institutional experience, including 109 patients with ENB  treated at our institution (1962-2009). Sixty-three patients presented with Kadish stage C disease, and 21 patients developed local recurrence. Of these 21,  7 underwent SRS at our institution and an additional patient underwent SRS after  transnasal biopsy. Therefore, a total of 8 patients are reported. RESULTS:: The median age at time of local recurrence was 50 years. All patients had Kadish C disease at initial diagnosis. Six of 8 patients were found to have Hyams’ grade 3 disease; the remaining 2 had grade 2. The median treatment volume was 8.4 cm (mean: 18.9 cm, range 1.4 - 76.3 cm), and the median dose to the tumor margin was 15 Gy (mean 14.4 +/- 2.2 Gy, range: 10- 18 Gy). Of the 16 treatments, 13 had adequate follow-up to assess treatment response, with 92% achieving local control over a median follow-up of 42 months from the time of SRS. Five lesions decreased in size, 7 stabilized, and only 1 had in-field progression. There were no documented complications secondary to SRS. CONCLUSION:: SRS appears to be a reasonable and safe option for treatment of intracranial recurrence of ENB.

 

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[153]

TÍTULO / TITLE:  - Calcium entry via TRPC1 channels activates chloride currents in human glioma cells.

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

REVISTA / JOURNAL:  - Cell Calcium. 2012 Dec 19. pii: S0143-4160(12)00201-1. doi: 10.1016/j.ceca.2012.11.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ceca.2012.11.013

AUTORES / AUTHORS:  - Cuddapah VA; Turner KL; Sontheimer H

INSTITUCIÓN / INSTITUTION:  - Department of Neurobiology and Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.

RESUMEN / SUMMARY:  - Malignant gliomas are highly invasive brain cancers that carry a dismal prognosis. Recent studies indicate that Cl(-) channels facilitate glioma cell invasion by promoting hydrodynamic cell shape and volume changes. Here we asked how Cl(-) channels are regulated in the context of migration. Using patch-clamp recordings we show Cl(-) currents are activated by physiological increases of [Ca(2+)](i) to 65 and 180nM. Cl(-) currents appear to be mediated by ClC-3, a voltage-gated, CaMKII-regulated Cl(-) channel highly expressed by glioma cells. ClC-3 channels colocalized with TRPC1 on caveolar lipid rafts on glioma cell processes. Using perforated-patch electrophysiological recordings, we demonstrate that inducible knockdown of TRPC1 expression with shRNA significantly inhibited glioma Cl(-) currents in a Ca(2+)-dependent fashion, placing Cl(-) channels under the regulation of Ca(2+) entry via TRPC1. In chemotaxis assays epidermal growth factor (EGF)-induced invasion was inhibition by TRPC1 knockdown to the same extent as pharmacological block of Cl(-) channels. Thus endogenous glioma Cl(-) channels are regulated by TRPC1. Cl(-) channels could be an important downstream  target of TRPC1 in many other cells types, coupling elevations in [Ca(2+)](i) to  the shape and volume changes associated with migrating cells.

 

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[154]

TÍTULO / TITLE:  - Expression and clinical significance of microRNA-326 in human glioma miR-326 expression in glioma.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):373. doi: 10.1007/s12032-012-0373-y. Epub 2013 Jan 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0373-y

AUTORES / AUTHORS:  - Wang S; Lu S; Geng S; Ma S; Liang Z; Jiao B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Shijiazhuang City, 050000, Hebei Province, China.

RESUMEN / SUMMARY:  - As a suppressor of Hedgehog signaling pathway, microRNA-326 (miR-326) has been demonstrated to control the development of cerebellar neuronal progenitor and tumor cells. More recently, it has been reported that miR-326 was down-regulated  in glioblastoma tissues and might regulate the metabolic activity of glioma and glioma stem cells, suggesting the involvement of miR-326 in tumorigenesis and progression of gliomas. However, the role of miR-326 in human glioma has not been clearly understood. Therefore, the aim of this study was to investigate the clinical significance of miR-326 expression in human glioma. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-326 in 108 glioma and 20 normal brain tissues. The associations of miR-326 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. The expression levels of miR-326 in glioma tissues were significantly lower than those in normal brain tissues (P < 0.001). Additionally, the decreased miR-326 expression in glioma was significantly associated with advanced pathological grade (P = 0.01) and low Karnofsky performance score (KPS, P = 0.03). Moreover, Kaplan-Meier survival and  Cox regression analyses showed that low expression of miR-326 (P = 0.01) and advanced pathological grade (P = 0.02) were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-326 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III-IV: P < 0.001). Down-regulation of miR-326 may have potential value for predicting clinical outcomes in glioma patients with high pathological grades, suggesting that miR-326 is an important candidate tumor suppressor, and its down-regulated expression may contribute to glioma progression.

 

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[155]

TÍTULO / TITLE:  - Galpha(h)/transglutaminase-2 activity is required for maximal activation of adenylylcyclase 8 in human and rat glioma cells.

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

REVISTA / JOURNAL:  - Cell Signal. 2013 Mar;25(3):589-97. doi: 10.1016/j.cellsig.2012.11.021. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cellsig.2012.11.021

AUTORES / AUTHORS:  - Obara Y; Yanagihata Y; Abe T; Dafik L; Ishii K; Nakahata N

INSTITUCIÓN / INSTITUTION:  - Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan; Department of  Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata  990-9585, Japan. Electronic address: obaray@med.id.yamagata-u.ac.jp.

RESUMEN / SUMMARY:  - Galpha(h) (or transglutaminase-2 (TG2)) is an atypical guanine nucleotide binding-protein that associates with G protein-coupled receptors. TG2 also exerts transglutaminase activity that catalyzes posttranslational protein cross-linking  with the formation of epsilon-(gamma-glutamyl) lysine or (gamma-glutamyl) polyamine bonds. Here, the role of Galpha(h)/TG2 in signal transduction in glial  cells was examined in detail. In 1321N1 human astrocytoma cells that lack Galpha(h)/TG2, overexpression of Galpha(h)/TG2 caused an enhancement of cAMP accumulation stimulated with the beta-adrenergic receptor agonist, isoproterenol, or the adenylylcyclase activator, forskolin. This cAMP-enhancement was reversed by the TG2 inhibitor, ERW1069. In rat C6 glioma cells that express endogenous Galpha(h)/TG2, cAMP accumulation induced by isoproterenol or forskolin was significantly inhibited by overexpression of Galpha(h)/TG2-C277V, a dominant-negative mutant that lacks transglutaminase activity, but was not inhibited by the Galpha(h)/TG2-S171E mutant that cannot bind GTP/GDP. These results suggest Galpha(h)/TG2 potentiates adenylylcyclase activity by its transglutaminase activity and not by its G-protein activity. Galpha(h)/TG2 also increased the activities of the cAMP response element and interleukin-6 promoter, accompanied by an of cAMP in both glioma cells. Since adenylylcyclase 8 plays a major role in cAMP production, we focused on post-translational modification of adenylylcyclase 8 by Galpha(h)/TG2. Adenylylcyclase 8 is expressed in both 1321N1 and C6 cells; however, Galpha(h)/TG2 affected neither adenylylcyclase 8 expression levels, glycosylation, nor dimerization status. In contrast, pentylamine, a substrate of Galpha(h)/TG2, was incorporated into adenylylcyclase  8 in a transglutaminase activity-dependent manner. Taking these results together, Galpha(h)/TG2 promotes cAMP production accompanied by a modification of adenylylcyclase 8 in glioma cells.

 

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[156]

TÍTULO / TITLE:  - Outcome analysis of childhood pilocytic astrocytomas: a retrospective study of 148 cases at a single institution.

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

REVISTA / JOURNAL:  - Neuropathol Appl Neurobiol. 2012 Dec 26. doi: 10.1111/nan.12013.

            ●● Enlace al texto completo (gratuito o de pago) 1111/nan.12013

AUTORES / AUTHORS:  - Colin C; Padovani L; Chappe C; Mercurio S; Scavarda D; Loundou A; Frassineti F; Andre N; Bouvier C; Korshunov A; Lena G; Figarella-Branger D

INSTITUCIÓN / INSTITUTION:  - INSERM, UMR 911, Marseille, F-13000; Aix-Marseille University, Medecine School, Marseille, F-13000.

RESUMEN / SUMMARY:  - Pilocytic astrocytomas (PAs) are characterized by an excellent prognosis although several factors of adverse outcome have been reported. The mitogen-activated protein kinase pathway plays a major role in their tumorigenesis. AIM: To report  a series of 148 PAs in children to define clinico-pathological and biological prognostic factors. METHODS: Clinical data were collected from patient files and  mail inquiry. Pathological specimens were centrally reviewed. The three major KIAA1549:BRAF fusion subtypes were analysed by Reverse Transcription - Polymerase Chain Reaction (RT-PCR) in a subset of 47 frozen cases and by Fluorescence In Situ Hybridization on formalin fixed paraffin embedded tissue in 23 cases. Tumour location, age at surgery, extent of surgical removal, histological subtype and KIAA1549:BRAF fusion by RT-PCR were searched for prognostic significance. RESULTS: Pilomyxoid astrocytoma (PMA) and the hypothalamo-chiasmatic (H/C) location were associated with a worse prognosis (P<0.001 for OS and P=0.001 for PFS). Patients who underwent complete surgical excision had a better OS (P=0.004) and a longer PFS (P<0.001) than the others. Age was also a strong prognostic factor for OS but not for PFS. Infants (<1 year) and young children (<3 years) had a much worse outcome than the others (P<0.001 and P=0.004 respectively). KIAA1549:BRAF fusion status was not predictive of outcome. CONCLUSION: This study highlights the good prognostic factors of PAs but H/C PA remains a subgroup with  dismal prognosis associated with young age, PMA variant and incomplete surgery. Search for KIAA1549:BRAF fusion in tumours with PA pattern is recommended even though the prognostic impact is still unclear.

 

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[157]

TÍTULO / TITLE:  - Differentiation of Primary Central Nervous System Lymphomas and Glioblastomas: Comparisons of Diagnostic Performance of Dynamic Susceptibility Contrast-Enhanced Perfusion MR Imaging without and with Contrast-Leakage Correction.

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

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3383

AUTORES / AUTHORS:  - Toh CH; Wei KC; Chang CN; Ng SH; Wong HF

INSTITUCIÓN / INSTITUTION:  - Departments of Medical Imaging and Intervention and Neurosurgery, Chang Gung Memorial Hospital, Linkou and Chang Gung University College of Medicine, Tao-Yuan, Taiwan.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Contrast leakage results in underestimation of the CBV of  brain tumors. Our aim was to compare the diagnostic performance of DSC perfusion  MR imaging without and with mathematic contrast-leakage correction in differentiating PCNSLs and glioblastomas.MATERIALS AND METHODS:Perfusion parameters-CBV, corrected CBV, and leakage coefficient-were measured in enhancing tumor portions and contralateral NAWM of 15 PCNSLs and 20 glioblastomas, respectively. The ratios of CBV and corrected CBV were calculated by dividing the tumor values by those obtained from contralateral NAWM. A paired t test was used  to compare tumor K(2) and NAWM K(2), as well as tumor CBV ratios without and with leakage correction. Comparisons of CBV, corrected CBV, and K(2) between PCNSLs and glioblastomas were done by using a 2-sample t test. The diagnostic performance of DSC perfusion MR imaging without and with contrast-leakage correction was assessed with receiver operating characteristic curve analysis.RESULTS:PCNSLs and glioblastomas demonstrated higher K(2) than those in  their contralateral NAWM. Corrected CBV ratios were significantly higher than the uncorrected ones for both tumors. PCNSLs had lower CBV ratios (P < .001), lower corrected CBV ratios (P < .001), and higher K(2) (P = .001) compared with glioblastomas. In differentiating between PCNSLs and glioblastomas, the area under the curve of the CBV ratio, corrected CBV ratio, and K(2) were 0.984, 0.940, and 0.788, respectively.CONCLUSIONS:PCNSL can be differentiated from glioblastoma with CBV ratios, corrected CBV ratios, and K(2). CBV without contrast-leakage correction seems to have the best diagnostic performance in differentiating the 2 tumors.

 

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[158]

TÍTULO / TITLE:  - ADAM17 regulates self-renewal and differentiation of U87 glioblastoma stem cells.

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

REVISTA / JOURNAL:  - Neurosci Lett. 2013 Jan 25. pii: S0304-3940(13)00053-0. doi: 10.1016/j.neulet.2013.01.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neulet.2013.01.021

AUTORES / AUTHORS:  - Chen X; Chen L; Zhang R; Yi Y; Ma Y; Yan K; Jiang X; 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) play an important role in the progression and recurrence of malignant glioblastoma because of their potential for self-renewal, multilineage differentiation and tumor initiation. A disintegrin and metalloproteinase 17 (ADAM17)is responsible for the proteolytic cleavage of Notch within its extracellular domain leading to the activation of Notch signaling, which is involved in the formation and maintenance of GSCs. Here, we show that glioma cells expressing the stem cell marker CD133 coexpress higher levels of ADAM17 than matched CD133- glioma cells. Knockdown of the ADAM17 gene in U87 GSCs down-regulated the expression of CD133, inhibited secondary neurosphere formation and induced multi-lineage differentiation. Furthermore, knockdown of ADAM17 inhibited Hes1 and Hes5 and activated Notch1 expression, which may explain the ADAM17 shRNA-induced suppression of self-renewal and differentiation of U87 GSCs. Our results suggest that ADAM17 may maintain the stemness of GSCs by promoting their self-renewal and inhibiting their differentiation via Notch signaling.

 

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[159]

TÍTULO / TITLE:  - Plausible role of naringenin against cerebrally implanted C6 glioma cells in rats.

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

REVISTA / JOURNAL:  - Mol Cell Biochem. 2013 Mar;375(1-2):171-8. doi: 10.1007/s11010-012-1539-9. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11010-012-1539-9

AUTORES / AUTHORS:  - Sabarinathan D; Vanisree AJ

INSTITUCIÓN / INSTITUTION:  - Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, Tamilnadu, India, sabkilbio@gmail.com.

RESUMEN / SUMMARY:  - Gliomas encompass a significant percentage of intrinsic neoplasms of the central  nervous system in both adults and children. The constitutive activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B is the hallmark of glioma. The up-regulated protein kinase B could influence the expression of cyclooxygenase-2, an indicator of aggressive glioma. The present study was embarked to demonstrate the effect of naringenin (50 mg/kg bw for 30 days administrated orally) on PI3K, protein kinase B, and cyclooxygenase-2 in cerebrally implanted rat C6 glioma model. After the experimental period of 30 days, the animals were sacrificed and excised brain tissues were subjected to study the expressions of PI3K, protein kinase B, and cyclooxygenase-2 by reverse  transcriptase polymerase chain reaction followed Western blot analysis. The activity of COX-2 (production of prostaglandin-E(2)) was also determined by high  pressure liquid chromatography. The results showed that the naringenin could down-regulate the expressions of PI3K and protein kinase B along with activity and expression of cyclooxygenase-2 in C6 glioma cells implanted rat brain. In conclusion, it can be argued that the reduced expressions of phosphatidylinositol 3-kinase and protein kinase B in naringenin-treated glioma-induced rat brain might be involved in the down-regulation of cyclooxygenase-2 expression and activity. Thus, fine-tuned investigation of which will be helpful for targeted drug discovery against glioma.

 

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[160]

TÍTULO / TITLE:  - Promoter methylation of WNT inhibitory factor-1 and expression pattern of WNT/beta-catenin pathway in human astrocytoma: pathologic and prognostic correlations.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Jan 18. doi: 10.1038/modpathol.2012.215.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.215

AUTORES / AUTHORS:  - Kim SA; Kwak J; Nam HY; Chun SM; Lee BW; Lee HJ; Khang SK; Kim SW

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - WNT inhibitory factor-1 (WIF1) is an antagonist of the WNT signaling pathway. We  investigated the relationship between WIF1 promoter methylation and regulation of the WNT/beta-catenin signaling pathway, tumor grade, and survival in patients with astrocytoma. This study included 86 cases of astrocytoma, comprising 20 diffuse astrocytomas and 66 glioblastomas. In addition, 17 temporal lobectomy specimens from patients with epilepsy were included as controls. The ratio of methylated DNA to total methylated and unmethylated DNA (% methylation) was measured by methylation- and unmethylation-specific PCR. Representative tumor tissue was immunostained for WIF1, beta-catenin, cyclin D1, c-myc, and isocitrate dehydrogenase 1. Levels of WIF1 promoter methylation, mRNA expression, and protein expression in a glioblastoma cell line were compared before and after demethylation treatment. The mean percent methylation of the WIF1 promoter in astrocytomas was higher than that in control brain tissue. WIF1 protein expression was lower in the tumor group with >5% methylation than in the group with <5% methylation. Cytoplasmic beta-catenin staining was more frequently observed in tumors with a low WIF1 protein expression level. Demethylation treatment of a glioblastoma cell line increased WIF1 mRNA and protein expression. Increased WIF1 promoter methylation and decreased WIF1 protein expression were not related to patient survival. In conclusion, WIF1 expression is downregulated  by promoter methylation and is an important mechanism of aberrant WNT/beta-catenin pathway activation in astrocytoma pathogenesis.Modern Pathology  advance online publication, 18 January 2013; doi:10.1038/modpathol.2012.215.

 

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[161]

TÍTULO / TITLE:  - BAG-1 expression in human meningioma and correlation with clinical characteristics.

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

REVISTA / JOURNAL:  - Med Oncol. 2013 Mar;30(1):458. doi: 10.1007/s12032-013-0458-2. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0458-2

AUTORES / AUTHORS:  - Zhou K; Jin H; Zhou T; Luo Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Taizhou Municipal Hospital, Taizhou Medical College,  Taizhou, 318000, China, kerry2000year@163.com.

RESUMEN / SUMMARY:  - The aim of this study is to investigate BAG-1 expression in human meningiomas and to assess its association with pathological and clinical characteristics. BAG-1 expression was analyzed in 158 specimens of meningiomas using immunohistochemical staining, and the results were graded according to the positivity ratio and the staining intensity. We examined the correlations between BAG-1 expression and the 2007 WHO pathological classification, peritumoral edema and postoperative recurrence. There were no significant differences in BAG-1 expression among meningioma subtypes within the same histopathologic grade, as well as between grades II and III. BAG-1 expression in grade I was much higher than in grade II (P < 0.05) or III (P < 0.01). BAG-1 expression was gradually decreased with increasing WHO pathologic classification (chi (2) = 141.49, P < 0.01), as well as with the increase in peritumoral edema (chi (2) = 43.93, P < 0.01) and postoperative recurrence (chi (2) = 55.13, P < 0.01). BAG-1 expression in meningioma depends upon WHO pathologic classification and is decreased in higher  tumor classification. It is associated with heavier peritumoral edema and more postoperative recurrences.

 

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[162]

TÍTULO / TITLE:  - miR-24-3p and miR-27a-3p promote cell proliferation in glioma cells via cooperative regulation of MXI1.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Feb;42(2):757-66. doi: 10.3892/ijo.2012.1742. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2012.1742

AUTORES / AUTHORS:  - Xu W; Liu M; Peng X; Zhou P; Zhou J; Xu K; Xu H; Jiang S

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P.R. China.

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs) are small, noncoding RNAs which regulate gene expression at the post-transcriptional level. Abnormal expression of miRNAs occurs frequently in tumors. Although the two miRNAs miR243p and miR27a3p come from two duplicated  gene clusters of miR23a~27a~242 and miR23b~27b~241 which are found to be deregulated in a variety of cancers, the role of cooperation of the two clusters  and the function of the two miRNAs in tumors have not been completely characterized. Here, we show that overexpression of miR243p and miR27a3p could promote cell proliferation using the MTT assay. By integrated bioinformatic analysis and experimental confirmation, we identified MXI1, which has been found  to act as a tumor suppressor gene by affecting cMyc, as a direct target of miR243p and miR27a3p. While targeting the MXI1 3’ untranslated region by miR243p  or miR27a3p, luciferase activity was attenuated. The two miRNAs promote glioma cell proliferation via targeting MXI1 and the experiment was confirmed by the rescue experiments. Furthermore, our results show that two clusters of miR-23a~27a~24-2 and miR23b~27b~241 regulate MXI1 synergistically. These findings reveal, for the first time, the novel functions of cooperation of miR243p and miR27a3p from two clusters in promoting cell proliferation through MXI1. Additionally, we observed that miR27a3p is upregulated in glioma tissues.

 

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[163]

TÍTULO / TITLE:  - Phase I study of GRN1005 in recurrent malignant glioma.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2481

AUTORES / AUTHORS:  - Drappatz J; Brenner A; Wong ET; Eichler A; Schiff D; Groves MD; Mikkelsen T; Rosenfeld S; Sarantopoulos J; Meyers CA; Fielding RM; Elian K; Wang X; Lawrence B; Shing M; Kelsey S; Castaigne JP; Wen PY

INSTITUCIÓN / INSTITUTION:  - Neuro-Oncology, Hillman Cancer Center.

RESUMEN / SUMMARY:  - PURPOSE: GRN1005 is a peptide-drug conjugate with the ability to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein-1 (LRP-1). We conducted a first-in-human phase I trial of GRN1005 in patients with recurrent glioma. Methods: Patients received GRN1005 by intravenous infusion every three weeks. Doses were escalated  using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine if therapeutic concentrations of GRN1005 were achieved. RESULTS: 63 patients received GRN1005 at doses of 30-700 mg/m2 every 3 weeks. Therapy was well-tolerated with neutropenia, leucopenia and fatigue as the most frequent drug-associated grade ¾ or higher toxicities. The MTD was 650 mg/m2 every 3 weeks. Dose-limiting toxicities (DLTs) were grade 3 mucositis and grade 4 neutropenia. There was no evidence of CNS toxicity or antibody production. Pharmacokinetic analysis showed exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. 8/27 patients dosed >/= 420 mg/m2 had stable disease which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were demonstrated in tumor tissue of surgical patients dosed with >/= 200 mg/m2. CONCLUSION: GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m2 every 3 weeks.

 

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[164]

TÍTULO / TITLE:  - NG2-cells are not the cell of origin for murine neurofibromatosis-1 (Nf1) optic glioma.

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

REVISTA / JOURNAL:  - Oncogene. 2013 Jan 14. doi: 10.1038/onc.2012.580.

            ●● Enlace al texto completo (gratuito o de pago) 1038/onc.2012.580

AUTORES / AUTHORS:  - Solga AC; Gianino SM; Gutmann DH

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

RESUMEN / SUMMARY:  - Low-grade glial neoplasms (astrocytomas) represent one of the most common brain tumors in the pediatric population. These tumors frequently form in the optic pathway (optic pathway gliomas, OPGs), especially in children with the neurofibromatosis type 1 (NF1)-inherited tumor predisposition syndrome. To model  these tumors in mice, we have previously developed several Nf1 genetically-engineered mouse strains that form optic gliomas. However, there are  three distinct macroglial cell populations in the optic nerve (astrocytes, NG2+ (nerve/glial antigen 2) cells and oligodendrocytes). The presence of NG2+ cells in the optic nerve raises the intriguing possibility that these cells could be the tumor-initiating cells, as has been suggested for adult glioma. In this report, we used a combination of complementary in vitro and novel genetically-engineered mouse strains in vivo to determine whether NG2+ cells could give rise to Nf1 optic glioma. First, we show that Nf1 inactivation results in a cell-autonomous increase in glial fibrillary acidic protein+ (GFAP+), but not in NG2+, cell proliferation in vitro. Second, similar to the GFAP-Cre transgenic strain that drives Nf1 optic gliomagenesis, NG2-expressing cells also  give rise to all three macroglial lineages in vivo. Third, in contrast to the GFAP-Cre strain, Nf1 gene inactivation in NG2+ cells is not sufficient for optic  gliomagenesis in vivo. Collectively, these data demonstrate that NG2+ cells are not the cell of origin for mouse optic glioma, and support a model in which gliomagenesis requires Nf1 loss in specific neuroglial progenitors during embryogenesis.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.580.

 

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[165]

TÍTULO / TITLE:  - Wnt3a mediated activation of Wnt/beta-catenin signalling promotes tumor progression in glioblastoma.

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

REVISTA / JOURNAL:  - Mol Cell Neurosci. 2013 Jan 18. pii: S1044-7431(13)00002-X. doi: 10.1016/j.mcn.2013.01.001.

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

AUTORES / AUTHORS:  - Kaur N; Chettiar S; Rathod S; Rath P; Mujumdar D; Shaikh M; Shiras A

INSTITUCIÓN / INSTITUTION:  - National Centre for Cell Science (NCCS), NCCS Complex, University of Pune Campus, Ganeshkhind, Pune 411007, Maharashtra, India. Electronic address: navjot@nccs.res.in.

RESUMEN / SUMMARY:  - Presence of a distinct population of cells that drives tumor progression supports the hierarchical model of tumor development in Glioblastoma (GBM) and substantiates the cancer stem cell hypothesis. Amongst the various developmental  signalling pathways that are aberrantly activated, we here show that activated Wnt /beta-catenin signalling pathway plays a critical role in malignant transformation and tumor progression in gliomas. We demonstrate that Wnt ligands  - Wnt1 and Wnt3a are expressed in a graded manner in these tumors as well as over-expressed in glioma stem cell-lines. A selective inhibition of Wnt signalling pathway by selective knock-down of its ligands Wnt1 and Wnt3a in glioma-derived stem-like cells led to decreased cell proliferation, cell migration and chemo-resistance. Furthermore, Wnt silencing in glioma cells reduced the capacity to form intra-cranial tumors in vivo. Taken together, our study indicates Wnt /beta-catenin signalling pathway as an essential driver of glioma tumorigenesis, recognizing role of Wnt3a as an oncogene and thereby offering novel therapeutic strategies for management of these tumors.

 

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[166]

TÍTULO / TITLE:  - Clinical outcomes of tuberculum sellae meningiomas focusing on reversibility of postoperative visual function.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan;155(1):25-31. doi: 10.1007/s00701-012-1551-6. Epub 2012 Nov 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1551-6

AUTORES / AUTHORS:  - Seol HJ; Park HY; Nam DH; Kong DS; Lee JI; Kim JH; Park K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul, 135-710, South Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Tuberculum sellae meningiomas present a special challenge because of  their proximity to major arteries, visual pathways, and the hypothalamus. The aim of this study was to determine the prognostic determinants of clinical and visual outcomes of these tumors, focusing on the functional reversibility of an unserviceable eye after surgery. METHODS: We retrospectively reviewed 86 patients on the basis of clinical and radiological factors that appeared to affect outcome. The visual acuity and visual fields were analyzed according to the visual impairment score (VIS). Unserviceable visual acuity included no perception of light (NPL), hand movement (HM), and counting fingers (CF). Ophthalmological functioning was tested in the preoperative period, the postoperative short-term period (</=2 weeks after surgery), and the postoperative long-term period (>6 months after surgery). Our own clinical outcome criteria including tumor control, visual improvement, and complications were used for evaluation. RESULTS: Seventy-four of 86 patients (86 %) underwent total removal of the tumor. In three of these cases (3.4 %), recurrence developed. Thirty patients were classified into the “Excellent” group, 21 into the “Good” group, 20 into the “Fair” group, and 15 into the “Poor” group. In multivariate analysis, adhesion to optic nerve was an independent and significant predictor of clinical outcome. Favorable visual outcomes in both short- and long-term postoperative periods were achieved  in 80.8 % of cases. Preoperative and short-term visual outcomes were closely related to long-term visual outcome. Six of eight patients with preoperative CF status showed reversibility to a serviceable status after surgery. However, there was no conversion to serviceable status from NPL or HM. CONCLUSIONS: For patients with unilateral unserviceable visual function, maintenance of serviceable visual  function on the opposite side might be more important. Of the patients with unserviceable visual function, careful surgery might be able to improve the visual function in CF eyes.

 

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[167]

TÍTULO / TITLE:  - Lipoxygenase inhibitor MK886 potentiates TRAIL-induced apoptosis through CHOP- and p38 MAPK-mediated up-regulation of death receptor 5 in malignant glioma.

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

REVISTA / JOURNAL:  - Biochem Biophys Res Commun. 2012 Dec 19. pii: S0006-291X(12)02395-9. doi: 10.1016/j.bbrc.2012.11.134.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2012.11.134

AUTORES / AUTHORS:  - Woo JS; Kim SM; Jeong CH; Ryu CH; Jeun SS

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Science, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Republic of Korea.

RESUMEN / SUMMARY:  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers specific apoptosis in tumor cells and is one of the most promising candidates for cancer gene therapy. However, resistance to TRAIL is one of the main impediments to use  of TRAIL in cancer treatment. We showed previously that the lipoxygenase inhibitor MK886 in combination with TRAIL exhibits enhanced antitumor activities  compared with each agent alone in human glioma cells. In this study, we elucidated the molecular mechanisms responsible for MK886-mediated sensitization  to TRAIL-induced apoptosis. We found that MK886 sensitized glioma cells to TRAIL-induced apoptosis by upregulating the death receptor 5 (DR5) and that specific knockdown of DR5 attenuated cell death. The mechanisms underlying this sensitization involved activation of the MK886-induced p38 mitogen-activated protein kinase (MAPK) pathway and subsequent DR5 overexpression. However, treatment with a specific inhibitor or gene silencing of p38 MAPK abolished both  the DR5 induction and the increase in apoptosis caused by TRAIL. Taken together,  our findings indicate that the increased expression of DR5 in a p38 MAPK-dependent manner plays an important role in the sensitization of MK886 to TRAIL-induced apoptosis.

 

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[168]

TÍTULO / TITLE:  - Multimodal MR Imaging (Diffusion, Perfusion, and Spectroscopy): Is It Possible To Distinguish Oligodendroglial Tumor Grade and 1p/19q Codeletion in the Pretherapeutic Diagnosis?

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

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3352

AUTORES / AUTHORS:  - Fellah S; Caudal D; De Paula AM; Dory-Lautrec P; Figarella-Branger D; Chinot O; Metellus P; Cozzone PJ; Confort-Gouny S; Ghattas B; Callot V; Girard N

INSTITUCIÓN / INSTITUTION:  - Centre de Resonance Magnetique Biologique et Medicale, Center for Research in Oncobiology and Oncopharmacology (CRO2), and Mathematics Department, Aix-Marseille University, Marseille, France; and Departments of Neuroradiology, Pathology and Neuropathology, Neurooncology, and Neurosurgery, APHM, Hopital de la Timone, Marseille, France.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE:Pretherapeutic determination of tumor grade and genotype in grade II and III oligodendroglial tumors is clinically important but is still  challenging. Tumor grade and 1p/19q status are currently the 2 most important factors in therapeutic decision making for patients with these tumors. Histopathology and cMRI studies are still limited in some cases. In the present study, we were interested in determining whether the combination of PWI, DWI, and MR spectroscopy could help distinguish oligodendroglial tumors according to their histopathologic grade and genotype.MATERIALS AND METHODS:We retrospectively reviewed 50 adult patients with grade II and III oligodendrogliomas and oligoastrocytomas who had DWI, PWI, and MR spectroscopy at short and long TE data and known 1p/19q status. Univariate analyses and multivariate random forest models were performed to determine which criteria could differentiate between grades and genotypes.RESULTS:ADC, rCBV, rCBF, and rK2 were significantly different between grade II and III oligodendroglial tumors. DWI, PWI, and MR spectroscopy showed no significant difference between tumors with and without 1p/19q loss. Separation between tumor grades and genotypes with cMRI alone showed 31% and 48% misclassification rates, respectively. Multimodal MR imaging helps to determine tumor grade and 1p/19q genotype more accurately (misclassification rates of 17% and 40%, respectively).CONCLUSIONS:Although multimodal investigation of oligodendroglial tumors has a lower contribution to 1p/19q genotyping compared with cMRI alone, it greatly improves the accuracy of grading of these neoplasms.  Use of multimodal MR imaging could thus provide valuable information that may assist clinicians in patient preoperative management and treatment decision making.

 

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[169]

TÍTULO / TITLE:  - A contemporary review of molecular candidates for the development and treatment of childhood medulloblastoma.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-2014-3

AUTORES / AUTHORS:  - Sumer-Turanligil NC; Cetin EO; Uyanikgil Y

INSTITUCIÓN / INSTITUTION:  - Department of Biophysics, School of Medicine, Ege University, Izmir, Turkey.

RESUMEN / SUMMARY:  - INTRODUCTION: Medulloblastoma is the most common pediatric central nervous system tumor; however, the causes are not well established. There has been some emphasis on mutations in developmental pathways and their impact on tumor pathology in hereditary diseases, but, in order to better understand the nature of diseases like medulloblastoma, other mechanisms also require attention. PURPOSE: The purpose of this review is to provide an overview of the main genes involved in neurodevelopment, their downstream targets, and modulatory links by growth factors. Occurrence of pediatric brain tumors including medulloblastoma are mostly sporadic, but some hereditary diseases like Li-Fraumeni syndrome, Gorlin’s syndrome, Turcot’s syndrome, and Rubenstein-Tarbi syndrome are known to contribute their development as consequences of germline mutations at specific points: DNA-repairing gene Tp53 for Li-Fraumeni syndrome or Patch for Gorlin’s, and apoptosis-related gene product adenomatous polyposis coli for Turcot’s disease. CONCLUSION: Intracellular relations at molecular level and future therapeutics that specifically target the corresponding pathways should be well understood in order to prevent and cure childhood medulloblastoma.

 

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[170]

TÍTULO / TITLE:  - Malignant pheochromocytoma and paraganglioma: A population level analysis of long-term survival over two decades.

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

REVISTA / JOURNAL:  - J Surg Oncol. 2012 Dec 11. doi: 10.1002/jso.23297.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jso.23297

AUTORES / AUTHORS:  - Goffredo P; Sosa JA; Roman SA

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Milano-Bicocca University, Monza, Italy.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVES: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare tumors. Aims of this study were to describe and to compare demographic, clinical, pathologic, and survival characteristics of malignant PHEO and PGL. METHODS: Patients were identified in SEER, 1988-2009. Analyses included chi-square, ANOVA, Kaplan-Meier, and Cox proportional hazard regression. RESULTS: Gender distribution and mean age were similar for PHEO and PGL. Surgery was performed in 74.3% of PHEO and 78.9% of PGL; external beam radiation was administered in 8.0% of PHEO and 28.1% of PGL (P < 0.001). Compared to PGL, PHEO  were larger (mean size 7.7 vs. 4.5 cm PGL, P = 0.001) and more were SEER-staged as localized (17.3% vs. 49.6%, respectively, P < 0.001). PGLs were more often located in the trunk than in the head/neck (53.8% vs. 38.0%, P < 0.001). PHEO had lower overall and disease-specific survival than PGL (54.0% and 73.5% vs. 73.3% and 80.5% for PGL, respectively, P < 0.001 and P = 0.118). Independent factors associated with mortality for PHEO included not undergoing surgery and metastases at diagnosis; for PGL, these were age 61-75 years, size >/=5 cm, and presenting with metastases. CONCLUSIONS: Malignant PHEO has a more aggressive course than malignant PGL; long-term survival has not improved over the last two decades. Multi-institutional efforts should be pursued to seek novel treatments. J. Surg.  Oncol © 2012 Wiley Periodicals, Inc.

 

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[171]

TÍTULO / TITLE:  - Diagnostic Performance of 18F-FET PET in Newly Diagnosed Cerebral Lesions Suggestive of Glioma.

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

REVISTA / JOURNAL:  - J Nucl Med. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.109603

AUTORES / AUTHORS:  - Rapp M; Heinzel A; Galldiks N; Stoffels G; Felsberg J; Ewelt C; Sabel M; Steiger HJ; Reifenberger G; Beez T; Coenen HH; Floeth FW; Langen KJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Heinrich-Heine University, Dusseldorf, Germany.

RESUMEN / SUMMARY:  - The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET in the initial diagnosis of cerebral lesions suggestive of glioma. METHODS: In a retrospective study, we analyzed the clinical, radiologic, and neuropathologic data of 174 patients (77 women and 97 men; mean age, 45 +/- 15 y) who had been referred for neurosurgical  assessment of unclear brain lesions and had undergone (18)F-FET PET. Initial histology (n = 168, confirmed after surgery or biopsy) and the clinical course and follow-up MR imaging in 2 patients revealed 66 high-grade gliomas (HGG), 77 low-grade gliomas (LGG), 2 lymphomas, and 25 nonneoplastic lesions (NNL). In a further 4 patients, initial histology was unspecific, but during the course of the disease all patients developed an HGG. The diagnostic value of maximum and mean tumor-to-brain ratios (TBR(max/)TBR(mean)) of (18)F-FET uptake was assessed  using receiver-operating-characteristic (ROC) curve analyses to differentiate between neoplastic lesions and NNL, between HGG and LGG, and between high-grade tumor (HGG or lymphoma) and LGG or NNL. RESULTS: Neoplastic lesions showed significantly higher (18)F-FET uptake than NNL (TBR(max), 3.0 +/- 1.3 vs. 1.8 +/- 0.5; P < 0.001). ROC analysis yielded an optimal cutoff of 2.5 for TBR(max) to differentiate between neoplastic lesions and NNLs (sensitivity, 57%; specificity, 92%; accuracy, 62%; area under the curve [AUC], 0.76; 95% confidence interval [CI], 0.68-0.84). The positive predictive value (PPV) was 98%, and the negative predictive value (NPV) was 27%. ROC analysis for differentiation between HGG and  LGG (TBR(max), 3.6 +/- 1.4 vs. 2.4 +/- 1.0; P < 0.001) yielded an optimal cutoff  of 2.5 for TBR(max) (sensitivity, 80%; specificity, 65%; accuracy, 72%; AUC, 0.77; PPV, 66%; NPV, 79%; 95% CI, 0.68-0.84). Best differentiation between high-grade tumors (HGG or lymphoma) and both NNL and LGG was achieved with a TBR(max) cutoff of 2.5 (sensitivity, 79%; specificity, 72%; accuracy, 75%; AUC, 0.79; PPV, 65%; NPV, 84%; 95% CI, 0.71-0.86). The results for TBR(mean) were similar with a cutoff of 1.9. CONCLUSION: (18)F-FET uptake ratios provide valuable additional information for the differentiation of cerebral lesions and the grading of gliomas. TBR(max) of (18)F-FET uptake beyond the threshold of 2.5  has a high PPV for detection of a neoplastic lesion and supports the necessity of an invasive procedure, for example, biopsy or surgical resection. Low (18)F-FET uptake (TBR(max) < 2.5) excludes a high-grade tumor with high probability.

 

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[172]

TÍTULO / TITLE:  - Pediatric microcystic meningioma: a clinical, histological, and radiographic case-based review.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-1991-6

AUTORES / AUTHORS:  - Manwaring J; Ahmadian A; Stapleton S; Gonzalez-Gomez I; Rodriguez L; Carey C; Tuite GF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and Brain Repair, Morsani School of Medicine, University of South Florida, Tampa, FL, USA.

RESUMEN / SUMMARY:  - BACKGROUND: Microcystic meningioma (MM) is a World Health Organization grade I tumor that is rare in the pediatric population. Meningiomas account for approximately 2-4 % of all childhood central nervous system (CNS) tumors compared to approximately 20 % of all adult CNS tumors. The authors present one of the few confirmed cases of microcystic meningioma in a child and discuss the characteristic radiographic appearance and histological findings. HISTORY: We report the case of an 11-year-old boy who presented with first-time seizure and imaging consistent with brain tumor. There was significant vasogenic edema within the entire right hemisphere, disproportionate to the size of the falcine-based tumor. Histopathological analysis revealed the microcystic subtype of meningioma. DISCUSSION: We review the radiographic characteristics, histopathological findings, and reported pediatric cases of MM in conjunction with our case. CONCLUSION: MM has distinct radiographic characteristics (variable enhancement, lack of a dural tail, and disproportionate vasogenic edema) that can be misinterpreted in the pediatric population, suggesting a more aggressive tumor.

 

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[173]

TÍTULO / TITLE:  - Malignant potential of skull base versus non-skull base meningiomas: clinical series of 1,663 cases.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1611-y

AUTORES / AUTHORS:  - Cornelius JF; Slotty PJ; Steiger HJ; Hanggi D; Polivka M; George B

INSTITUCIÓN / INSTITUTION:  - Neurochirurgische Klinik, Universitatsklinikum Dusseldorf, Heinrich-Heine-Universitat, Moorenstrasse 5, 40229, Dusseldorf, Germany.

RESUMEN / SUMMARY:  - BACKGROUND: About 90 % of meningiomas are benign (WHO grade I), atypical and anaplastic variants exist (WHO grade II/III, 10 %). Tumour grade has important implications for management. Non-invasive diagnosis of tumour grade is still not  feasible. The purpose of this survey was to analyse epidemiological risk factors  such as sex, age and location for a higher grade (WHO grade II/III) meningioma in a large surgical series. METHODS: A retrospective study comprising 1,663 patients operated on for an intracranial meningioma in a single tertiary-care centre. The  population was analysed for correlations including WHO grade, histological subtype, tumour localisation, patient age and gender. Additionally correlations between Ki67 index/WHO grade and localisation were analysed. RESULTS: A binary logistic regression analysis revealed non-skull base localisation (OR 1.779 [CI 1.069-2.960, p = 0.0027]) and age >/=65 years (OR 1.549 [CI 1.214-2.624, p = 0.012]) as significant risk factors for a higher WHO grade. Male gender showed a  trend for a higher risk in chi(2) analysis. An analysis of the Ki67 index revealed an increased index for non-skull base localisation compared with skull base (p < 0.001). Correlation analysis of Ki67 distribution in WHO grade I meningiomas revealed higher Ki67 indices for non skull base localisation (p = 0.0024). CONCLUSIONS: Non-skull base localisation and age >/=65 years are independent risk factors for higher grade meningiomas. In other terms, the malignant potential of skull base meningiomas is low. This information is important when advising a patient about individual treatment options (observation, surgery or radio-surgery) and prognosis.

 

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[174]

TÍTULO / TITLE:  - CD133 glycosylation is enhanced by hypoxia in cultured glioma stem cells.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):1011-7. doi: 10.3892/ijo.2013.1787. Epub 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1787

AUTORES / AUTHORS:  - Lehnus KS; Donovan LK; Huang X; Zhao N; Warr TJ; Pilkington GJ; An Q

INSTITUCIÓN / INSTITUTION:  - Cellular and Molecular Neuro-Oncology Research Group, Institute of Biomedical and Biomolecular Science, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.

RESUMEN / SUMMARY:  - The cancer stem cell (CSC) marker CD133 is widely expressed in gliomas and employed mostly by use of the CD133/1 antibody which binds the extracellular glycosylated AC133 epitope. CD133 recognition may, however, be affected by its glycosylation pattern and oxygen tension. The present study investigates the effect of oxygen deprivation on CD133 expression and glycosylation status employing a high AC133-expressing glioblastoma multiforme (GBM) cell line, IN699. IN699 cells were cultured under normoxic (21% O2) and hypoxic (3% O2) conditions. CD133 expression was analysed by western blotting (WB), qRT-PCR, immunocytochemistry (ICC) and flow cytometry using the glycosylation-specific antibody CD133/1 and ab19898 which binds the unglycosylated intra-cellular residues of CD133. By flow cytometry, ab19898 detected 94.1% and 96.2% CD133+ cells under normoxia and hypoxia, respectively. Hypoxia significantly increased the percentage of CD133+ cells from 69% to 92% using CD133/1 (p<0.005). Moreover, a significantly higher geomean fluorescence intensity (GMI) was demonstrated by ab19898 (p<0.005) in CD133+ cells. WB and qRT-PCR results were consistent with flow cytometry data. Furthermore, over a period of 72-h incubation under normoxic and hypoxic conditions after autoMACS sorting, an average of 31.8% and 42.2%, respectively, of CD133-negative IN699 cells became positive using CD133/1. Our data show that a) previously reported CD133- cells may have been misidentified using the glycosylation-specific CD133/1 as constitutive expression of CD133 was  detected by the intracellular antibody ab19898; b) hypoxia promotes glycosylation status of CD133, indicating possible involvement of glycosylated CD133 in the process of anti-hypoxia-mediated apoptosis.

 

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[175]

TÍTULO / TITLE:  - B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine  glioma.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1021-2

AUTORES / AUTHORS:  - Zhou Z; Luther N; Ibrahim GM; Hawkins C; Vibhakar R; Handler MH; Souweidane MM

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Weill Medical College of Cornell University,  1300 York Ave, Box 99, New York, NY, 10065, USA, zhz2004@med.cornell.edu.

RESUMEN / SUMMARY:  - Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival  of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.

 

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[176]

TÍTULO / TITLE:  - PIVL, a new serine protease inhibitor from Macrovipera lebetina transmediterranea venom, impairs motility of human glioblastoma cells.

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

REVISTA / JOURNAL:  - Matrix Biol. 2012 Dec 20. pii: S0945-053X(12)00152-7. doi: 10.1016/j.matbio.2012.11.015.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.matbio.2012.11.015

AUTORES / AUTHORS:  - Morjen M; Kallech-Ziri O; Bazaa A; Othman H; Mabrouk K; Zouari-Kessentini R; Sanz L; Calvete JJ; Srairi-Abid N; El Ayeb M; Luis J; Marrakchi N

INSTITUCIÓN / INSTITUTION:  - Laboratoire des Venins et Biomolecules Therapeutiques, Institut Pasteur de Tunis, Tunisia. Electronic address: maram.morjen@yahoo.fr.

RESUMEN / SUMMARY:  - A novel Kunitz-type serine proteinase inhibitor, termed PIVL, was purified to homogeneity from the venom of the Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric polypeptide chain cross-linked by three disulfide linkages with an isotope-averaged molecular mass of 7691.7Da. The 67-residue full-length PIVL sequence was deduced from a venom gland cDNA clone. Structurally, PIVL is built by a single Kunitz/BPTI-like domain. Functionally, it is able to specifically inhibit trypsin activity. Interestingly, PIVL exhibits an anti-tumor effect and displays integrin inhibitory activity without being cytotoxic. Here we show that PIVL is able to dose-dependently inhibit the adhesion, migration and invasion of human glioblastoma U87 cells. Our results also show that PIVL impairs the function of alphavbeta3 and to a lesser extent, the activity of alphavbeta6, alphavbeta5, alpha1beta1 and alpha5beta1 integrins.  Interestingly, we demonstrate that the (41)RGN(43) motif of PIVL is likely responsible for its anti-cancer effect. By using time lapse videomicroscopy, we found that PIVL significantly reduced U87 cells motility and affected cell directionality persistence by 68%. These findings reveal novel pharmacological effects for a Kunitz-type serine proteinase inhibitor.

 

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[177]

TÍTULO / TITLE:  - AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

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

REVISTA / JOURNAL:  - Eur J Histochem. 2012 Oct 11;56(4):e44. doi: 10.4081/ejh.2012.e44.

AUTORES / AUTHORS:  - Fassina L; Magenes G; Inzaghi A; Palumbo S; Allavena G; Miracco C; Pirtoli L; Biggiogera M; Comincini S

INSTITUCIÓN / INSTITUTION:  - Dipartimento di Biologia e Biotecnologie, University of Pavia, Pavia, Italy. sergio.comincini@unipv.it.

RESUMEN / SUMMARY:  - An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as  a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore  represent a suitable algorithmic tool for in vitro autophagy modulation studies.

 

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[178]

TÍTULO / TITLE:  - Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 20. pii: S0304-3835(13)00026-8. doi: 10.1016/j.canlet.2012.12.024.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.12.024

AUTORES / AUTHORS:  - Wang Y; Jiang T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.

RESUMEN / SUMMARY:  - High-grade gliomas (HGGs) account for the vast majority of all gliomas, including glioblastoma (World Health Organization (WHO) grade IV) and anaplasticgliomas (WHO grade III). Despite tremendous efforts in developing multimodal treatments,  the overall prognosis remains poor; however, survival time varies considerably between patients. The nature of diffuse permeation into surrounding brain parenchyma poses dilemma for neurosurgeons between extensive surgical resection to eliminate as much as tumor cells as possible and adverse effects associated with brain function. Heterogeneity in both cytology and gene expression makes it  difficult to coordinate an effective therapy which works for every patient. This  article reviews recent advancements in the molecular mechanism, multimodal treatment and clinical management, and the updated view on the biomarkers in patients with HGG, both in primary and recurrent setting, with an emphasis on targeted therapies tailored to the patient.

 

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[179]

TÍTULO / TITLE:  - Reactive Retinal Astrocytic Tumors (So-called Vasoproliferative Tumors): Histopathologic, Immunohistochemical, and Genetic Studies of Four Cases.

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

REVISTA / JOURNAL:  - Am J Ophthalmol. 2012 Dec 6. pii: S0002-9394(12)00616-2. doi: 10.1016/j.ajo.2012.09.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ajo.2012.09.002

AUTORES / AUTHORS:  - Poole Perry LJ; Jakobiec FA; Zakka FR; Reichel E; Herwig MC; Perry A; Brat DJ; Grossniklaus HE

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; Cogan Eye Pathology Laboratory, Massachusetts Eye  and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal “vasoproliferative tumors.” DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records and microscopic  slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed. RESULTS: Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid-Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1R132H mutation typically associated with low-grade astrocytic neoplasms were absent. CONCLUSIONS: Retinal “vasoproliferative” tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term “reactive retinal astrocytic tumor” is proposed as more  appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous  metaplasia ensues.

 

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[180]

TÍTULO / TITLE:  - Impact of Genetic Targets on Primary Brain Tumor Therapy: What’s Ready for Prime  Time?

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

REVISTA / JOURNAL:  - Adv Exp Med Biol. 2013;779:267-89. doi: 10.1007/978-1-4614-6176-0_12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6176-0_12

AUTORES / AUTHORS:  - Zalatimo O; Zoccoli CM; Patel A; Weston CL; Glantz M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Penn State College of Medicine, Hershey Medical Center, EC 1001, 30 Hope Drive, Hershey, PA, 17033, USA, ozz101@gmail.com.

RESUMEN / SUMMARY:  - Primary brain tumors constitute a substantial public health problem with 66,290 cases diagnosed in the US in 2012, and 13,700 deaths recorded. With discovery of  genetic factors associated with specific brain tumor subtypes, the goal of therapy is changing from treating a class of tumors to developing individualized  therapies catering to the molecular composition of the actual tumor. For oligodendrogliomas, the loss of 1p/19q due to an unbalanced translocation improves both survival and the response to therapy, and is thus both a prognostic and a predictive marker. Several additional genetic alterations such as EGFR amplification, MGMT methylation, PDGFR activation, and 9p and 10q loss, have improved our understanding of the characteristics of these tumors and may help guide therapy in the future. For astrocytic tumors, MGMT is associated with a better prognosis and an improved response to temozolomide, and for all glial tumors, mutations in the IDH1 gene are possibly the most potent of good prognostic markers. Three of these markers - 1p/19q deletions, MGMT methylation status, and mutations in the IDH1 gene - are so potent that a new brain tumor subtype, the “triple negative” glioma (1p/19q intact, MGMT unmethylated, IDH1 non-mutated) has entered common parlance. Newer markers, such as CD 133, require  additional investigation to determine their prognostic and predictive utility. In medulloblastomas, markers of WNT activation, MYCC/MCYN amplification, and TrkC expression levels are reliable prognostic indicators, but do not yet drive specific treatment selection. Many other proposed markers, such as 17q gain, TP53 mutations, and hMOF protein expression show promise, but are not yet ready for prime time. In this chapter, we focus on the markers that have shown convincing prognostic, predictive, and diagnostic value, and discuss potential markers that  are being currently being intensively investigated. We also discuss serum profiling of tumors in an effort to discover additional potential markers.

 

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[181]

TÍTULO / TITLE:  - 18F-FDG PET Is an Independent Outcome Predictor in Primary Central Nervous System Lymphoma.

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

REVISTA / JOURNAL:  - J Nucl Med. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.108654

AUTORES / AUTHORS:  - Kasenda B; Haug V; Schorb E; Fritsch K; Finke J; Mix M; Hader C; Weber WA; Illerhaus G; Meyer PT

INSTITUCIÓN / INSTITUTION:  - Department of Hematology/Oncology, Freiburg University Medical Center, Freiburg,  Germany.

RESUMEN / SUMMARY:  - Primary central nervous system (CNS) lymphoma is an aggressive non-Hodgkin lymphoma with poor prognosis. We evaluated pretreatment (18)F-FDG PET as a prognostic marker in primary CNS lymphoma. METHODS: Forty-two immunocompetent patients with newly diagnosed primary CNS lymphoma who underwent pretreatment (18)F-FDG PET were retrospectively analyzed. Baseline status and response to treatment were evaluated by MR imaging. Tumor maximum standardized uptake values  were assessed by volume-of-interest analyses using an automatic isocontour definition. A 10-step semiquantitative visual rating system (metabolic imaging lymphoma aggressiveness scale, or MILAS) was used to assess primary CNS lymphoma  metabolism as a marker of clinical aggressiveness. Logistic regression, log-rank  testing, and multivariable Cox regression were used to investigate the association between (18)F-FDG uptake and tumor response and survival. RESULTS: Mean maximum standardized uptake value correlated linearly with MILAS. The distribution of patients according to MILAS (0-9) was 0%, 28.6%, 23.8%, 21.4%, 11.9%, 4.8%, 7.1%, 0%, 0%, and 2.4%. There was no correlation between MILAS and response to treatment. Respective 2- and 5-y survival rates were 52% and 32% for  progression-free survival (PFS) and 64% and 50% for overall survival (OS). A cutoff at MILAS 3 was a good separator for PFS (median: 54.7 mo [</=3], 3.8 mo [>3], P = 0.0272) and OS (median: not reached [</=3], 13.8 mo [>3], P = 0.131). In multivariable analyses, increasing MILAS was significantly associated with shorter PFS (hazard ratio, 1.49, P = 0.006) and OS (hazard ratio, 1.43, P = 0.018). CONCLUSION: Increased pretreatment (18)F-FDG uptake may offer new opportunities for baseline risk evaluation in untreated primary CNS lymphoma.

 

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[182]

TÍTULO / TITLE:  - Optic Nerve Meningeal Hemangiopericytoma: A Clinicopathological Case Report.

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

REVISTA / JOURNAL:  - Surv Ophthalmol. 2013 Jan 4. pii: S0039-6257(12)00248-2. doi: 10.1016/j.survophthal.2012.10.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.survophthal.2012.10.001

AUTORES / AUTHORS:  - Manjandavida FP; Honavar SG; Gowrishankar S; Mulay K; Reddy VA; Vemuganti GK

INSTITUCIÓN / INSTITUTION:  - Ocular Oncology Services and the Ophthalmic Pathology Service, LV Prasad Eye Institute, Hyderabad, India.

RESUMEN / SUMMARY:  - A 36-year-old woman presented with progressive loss of vision in the left eye for 3 years, and rapid progression and painful protrusion of the eye for one month. Clinical evaluation revealed no light perception, severe proptosis and hypoglobus, optic atrophy, and optociliary shunt vessels. Orbital imaging showed  a well-defined heterogeneous intraconal mass partially encasing the optic nerve.  A clinical diagnosis of optic nerve sheath meningioma was made, and the tumor was completely excised along with enucleation, followed by postoperative adjuvant external beam radiotherapy. There was no local recurrence at 15 month follow-up.  Histopathologically, the tumor was found to be arising from the optic nerve meninges with classical “stag-horn” pattern and abundant cellularity. Immunohistochemistry supported the histopathological diagnosis of hemangiopericytoma. Optic nerve meningeal hemangiopericytoma is extremely rare-only two such cases have been reported in the literature.

 

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[183]

TÍTULO / TITLE:  - Primary Diffuse Leptomeningeal Gliomatosis in Children: A Clinical Pathologic Correlation.

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

REVISTA / JOURNAL:  - Ophthal Plast Reconstr Surg. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1097/IOP.0b013e318279fe23

AUTORES / AUTHORS:  - Bernardini FP; Croxatto JO; Nozza P; Rossi A; Capris P

INSTITUCIÓN / INSTITUTION:  - *Department of Ophthalmology, Ospedale Gaslini, Genova, Italy; daggerDepartment of Ocular Pathology, Fundacion Oftalmologica Argentina Jorge Malbran, Buenos Aires, Argentina; double daggerDepartment of Neuroradiology, Ospedale Gaslini, Genova, Italy; and section signDepartment of Pathology, Ospedale Gaslini, Genova, Italy.

RESUMEN / SUMMARY:  - PURPOSE:: To describe a rare case of primary diffuse leptomeningeal gliomatosis (PDLG) presenting with progressive proptosis and direct involvement of the optic  nerve sheath in a child and review of the relevant literature. METHODS:: Retrospective review of a single case and systematic literature review of 26 biopsy-proven cases reported in the MEDLINE-indexed English literature. A 10-year-old girl developed proptosis and progressive visual loss associated with  thickening of the optic nerve sheaths and dilation of the subarachnoid spaces with multilobulated appearance of the brain meninges and thickened peripheral nerve root sheaths. Biopsy of the optic nerve sheath was diagnostic. The patient  underwent chemotherapy combined with oral temozolomide and conformational radiotherapy to the brain and spine. She died 3 years after the onset of the disease. An extensive review of the published literature using the key words “primary diffuse leptomeningeal gliomatosis” and “optic nerve” confirmed the case herein reported to be the first case of primary diffuse leptomeningeal gliomatosis in which direct optic nerve infiltration was demonstrated during the  course of the disease. RESULTS:: Immunohistochemistry demonstrated expression of  CD56 and glial fibrillary acidic protein, and an elevated level of Ki-67; all the other markers were negative. CONCLUSIONS:: According to a comprehensive literature review, we report the first case of PDLG that presented with bilateral proptosis and direct involvement of the optic nerve during the course of the disease. These new findings may explain an alternative mechanism of visual loss and proptosis in PDLG. We emphasize the importance of close collaboration between neurologists and ophthalmologists in all cases of visual symptoms associated with a neurologic condition. In case of optic nerve involvement, ophthalmologists could provide an easier route to achieve tissue specimen early in the course of this rare and fatal disease.

 

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[184]

TÍTULO / TITLE:  - PDGFRA Gain in Low-Grade Diffuse Gliomas.

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

REVISTA / JOURNAL:  - J Neuropathol Exp Neurol. 2013 Jan;72(1):61-66.

            ●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e31827c4b5b

AUTORES / AUTHORS:  - Motomura K; Mittelbronn M; Paulus W; Brokinkel B; Keyvani K; Sure U; Wrede K; Nakazato Y; Tanaka Y; Nonoguchi N; Pierscianek D; Kim YH; Mariani L; Vital A; Perry A; Ohgaki H

INSTITUCIÓN / INSTITUTION:  - From the International Agency for Research on Cancer, Lyon, France (KM, NN, DP, Y-HK, HO); Edinger Institute (Neurological Institute), Goethe University Hospital, Frankfurt am Main, Germany (MM); Institute of Neuropathology (WP) and Department of Neurosurgery (BB), University Hospital Munster, Munster, Germany; Institute of Pathology and Neuropathology (KK) and Department of Neurosurgery, University Hospital Essen, Essen, Germany (US, KW, DP); Department of Pathology,  Gunma University, Gunma, Japan (YN, YT); University Hospital, Basel, Switzerland  (LM); University Hospital, Bern, Switzerland (LM); The Bordeaux Institute of Neuroscience, CNRS, Bordeaux, France (AV); and Department of Pathology, Division  of Neuropathology, University of California-San Francisco, San Francisco, California (AP).

RESUMEN / SUMMARY:  - ABSTRACT: Glioblastomas with a proneural expression signature are characterized by frequent IDH1 mutations (i.e. genetic hallmarks of secondary glioblastomas) and PDGFRA (platelet-derived growth factor receptor-alpha) amplification. Mutations in IDH1/2 are frequent and early genetic events in diffuse astrocytomas (World Health Organization grade II), precursor to secondary glioblastomas, but little is known about the role and timing of PDGFRA amplification in these tumors. We assessed PDGFRA gain in 342 low-grade diffuse gliomas by quantitative  polymerase chain reaction. Gain in PDGFRA was detected in 27 (16.3%) of 166 diffuse astrocytomas, significantly more frequent than in oligodendrogliomas (3 [2.6%] of 115, p < 0.0001). Analyses using previously published data from our laboratory showed an inverse correlation between PDGFRA gain and IDH1/2 mutations (p = 0.018) or 1p/19q loss (p < 0.0001). The vast majority of diffuse astrocytomas showed IDH1/2 mutations and/or PDGFRA gain (154 [93%] of 166). Mean  survival of diffuse astrocytoma patients with PDGFRA gain was 8.8 +/- 1.6 years,  similar to that with IDH1/2 mutations (7.8 +/- 0.5 years) or TP53 mutations (7.6  +/- 0.6 years) but significantly longer than those with MET gain (4.4 +/- 0.7 years). Dual-color fluorescence in situ hybridization in 6 diffuse astrocytomas with PDGFRA/MET co-gain identified by quantitative polymerase chain reaction revealed that PDGFRA and MET were typically amplified in different tumor cell populations. Tumor cells with coamplification were also focally observed, suggesting intratumoral heterogeneity, even in diffuse astrocytomas.

 

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[185]

TÍTULO / TITLE:  - Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):348-54. doi: 10.1016/j.ijrobp.2012.11.031.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.031

AUTORES / AUTHORS:  - Gondi V; Hermann BP; Mehta MP; Tome WA

INSTITUCIÓN / INSTITUTION:  - Department of Human Oncology, University of Wisconsin, Madison, WI.

RESUMEN / SUMMARY:  - PURPOSE: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult  brain tumors treated with fractionated stereotactic radiotherapy (FSRT). METHODS  AND MATERIALS: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a  prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score </=-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD(2)) assuming an alpha/beta ratio of 2 Gy were computed. Fisher’s exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. RESULTS: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD(2) to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD(2) to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). CONCLUSION: EQD(2) to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with  long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy  techniques can reduce the dose to the bilateral hippocampi below this dosimetric  threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

 

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[186]

TÍTULO / TITLE:  - Granulomatous angiitis of the CNS revealing a Hodgkin lymphoma.

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

REVISTA / JOURNAL:  - Neurology. 2013 Jan 15;80(3):323-4. doi: 10.1212/WNL.0b013e31827deb26. Epub 2012  Dec 26.

            ●● Enlace al texto completo (gratuito o de pago) 1212/WNL.0b013e31827deb26

AUTORES / AUTHORS:  - Le Guennec L; Roos-Weil D; Mokhtari K; Chauvet D; Psimaras D; Reiner P; Demeret S; Bolgert F; Choquet S; Weiss N

INSTITUCIÓN / INSTITUTION:  - From the Neurological Intensive Care Unit (L.L.C., S.D., F.B., N.W.), Neurology Department (D.P.); Hematology Department (D.R.-W., S.C.); Neuropathology Department (K.M.); and Neurosurgery Department (D.C.), La Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris and Pierre and Marie Curie University Paris 6, Paris; and Neurology Department (P.R.), Lariboisiere Hospital, Assistance Publique-Hopitaux de Paris and Universite Paris 7, Denis Diderot, Paris, France.

RESUMEN / SUMMARY:  - Apart from the iatrogenic effects of treatment, neurologic complications of Hodgkin lymphoma (HL) can be divided into direct (meningeal or intracranial/spinal localization) and indirect (paraneoplastic/immune complications).(1) Here, we present a patient with granulomatous angiitis of the  CNS (GANS) associated with HL that dramatically improved after the treatment of the angiitis by cyclophosphamide, methylprednisolone, and specific chemotherapy.

 

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[187]

TÍTULO / TITLE:  - MiR-383 is Downregulated in Medulloblastoma and Targets Peroxiredoxin 3 (PRDX3).

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

REVISTA / JOURNAL:  - Brain Pathol. 2012 Dec 11. doi: 10.1111/bpa.12014.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12014

AUTORES / AUTHORS:  - Li KK; Pang JC; Lau KM; Zhou L; Mao Y; Wang Y; Poon WS; Ng HK

INSTITUCIÓN / INSTITUTION:  - Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.

RESUMEN / SUMMARY:  - Accumulating evidence suggests that microRNAs (miRNAs) are over- or under-expressed in tumors, and abnormalities in miRNA expression may contribute to carcinogenesis. MiR-383 was previously identified as one of the under-expresssed miRNAs in medulloblastoma (MB) by miRNA expression profiling. Quantitative reverse transcription polymerase chain reaction (RT-PCR)-based miRNA assays showed an enrichment of miR-383 in normal brain. Based on these data, we speculated that miR-383 is important in MB pathogenesis. In this study, we demonstrated significant downregulation of miR-383 in 23/29 (79%) MB samples and  7/7 (100%) MB cells lines. Ectopic expression of miR-383 in MB cells led to suppression of cell growth, cell accumulation at sub-G1 phase and alteration of apoptosis-related proteins. By transcriptomic analysis and computational algorithms, we identified peroxiredoxin 3 (PRDX3) as a target gene of miR-383. Luciferase reporter assay confirmed that miR-383 negatively regulated PRDX3 by interaction between miR-383 and complementary sequences in the 3’ UTR of PRDX3. MiR-383 repressed PRDX3 at transcriptional and translational levels as revealed by quantitative RT-PCR and Western blot analysis. Furthermore, depletion of PRDX3 by siRNAs resulted in similar effects as observed in miR-383-transfected cells. In conclusion, miR-383 acts as a regulator controlling cell growth of MB, at least in part, through targeting PRDX3.

 

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[188]

TÍTULO / TITLE:  - Arginine Vasopressin Immunoreactivity is Decreased in the Hypothalamic Suprachiasmatic Nucleus of Subjects with Suprasellar Tumors.

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

REVISTA / JOURNAL:  - Brain Pathol. 2012 Dec 20. doi: 10.1111/bpa.12016.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12016

AUTORES / AUTHORS:  - Borgers AJ; Fliers E; Siljee JE; Swaab DF; Van Someren EJ; Bisschop PH; Alkemade A

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

RESUMEN / SUMMARY:  - Suprasellar tumors with compression of the optic chiasm are associated with an impaired sleep-wake rhythm. We hypothesized that this reflects a disorder of the  biological clock of the human brain, the suprachiasmatic nucleus (SCN), which is  located just above the optic chiasm. In order to test this hypothesis, we investigated the expression of two key neuropeptides of the SCN, that is, arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), as assessed by quantitative immunocytochemistry in post-mortem hypothalamic tissue of patients with a suprasellar tumor inducing permanent visual field defects. Post-mortem hypothalamic tissue of 5 patients with a suprasellar tumor inducing permanent visual field defects (acromegaly n = 2, nonfunctioning macro-adenoma n  = 1, macroprolactinoma n = 1, infundibular metastasis of a colorectal adenocarcinoma n = 1) and 15 age- and gender-matched controls was obtained from the Netherlands Brain Bank. Total AVP immunoreactivity in the SCN was lower in patients with a suprasellar tumor than in controls (P = 0.03). By contrast, total VIP immunoreactivity was not different between patients and controls (P = 0.44).  Suprasellar tumors leading to permanent visual field defects are associated with  reduced AVP, but not VIP immunoreactivity, in the SCN. These findings raise the possibility that selective impairment of the SCN contributes to sleep-wake disturbances in these patients.

 

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[189]

TÍTULO / TITLE:  - MIR-137 Suppresses Growth and Invasion, is Downregulated in Oligodendroglial Tumors and Targets CSE1L.

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

REVISTA / JOURNAL:  - Brain Pathol. 2012 Dec 17. doi: 10.1111/bpa.12015.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bpa.12015

AUTORES / AUTHORS:  - Li KK; Yang L; Pang JC; Chan AK; Zhou L; Mao Y; Wang Y; Lau KM; Poon WS; Shi Z; Ng HK

INSTITUCIÓN / INSTITUTION:  - Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.

RESUMEN / SUMMARY:  - MicroRNA-137 (miR-137) expression has been reported to be decreased in astrocytic tumors in two expression profiling studies but its role in the pathogenesis of oligodendroglial tumors is still limited. In this study, we demonstrate that miR-137 expression is significantly downregulated in a cohort of 35 oligodendroglial tumors and nine glioma cell lines compared with normal brains. Lower miR-137 expression is associated with shorter progressive-free survival and overall survival. Restoration of miR-137 expression in an oligodendroglial cells  TC620, and also glioblastoma cells of U87 and U373 significantly suppressed cell  growth, anchorage-independent growth, as well as invasion. Demethylation and deacetylation treatments resulted in upregulation of miR-137 expression in TC620  cells. In silico analysis showed that CSE1 chromosome segregation 1-like (yeast)  (CSE1L) is a potential target gene of miR-137. Luciferase reporter assay demonstrated that miR-137 negatively regulates CSE1L by interaction between miR-137 and complementary sequences in the 3’ UTR of CSE1L. Immunohistochemistry  revealed that CSE1L is upregulated in oligodendroglial tumors. Knockdown of CSE1L resulted in similar outcomes as overexpressing miR-137 in oligodendroglioma cells and glioblastoma cells. Overall, our data suggest that miR-137 regulates growth of glioma cells and targets CSE1L, providing further understanding in the tumorigenesis of gliomas.

 

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[190]

TÍTULO / TITLE:  - Molecular alterations in meningiomas: association with clinical data.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300527

AUTORES / AUTHORS:  - Jaskolski DJ; Gresner SM; Zakrzewska M; Zawlik I; Piaskowski S; Sikorska B; Szybka M; Papierz W; Rieske P; Liberski PP

RESUMEN / SUMMARY:  - The aim of our study was to evaluate the frequency of deletions on chromosomes 1, 9, 10, 14, 18 and 22 in 75 benign and 15 atypical meningiomas and correlate them  with clinical findings. Paired normal and tumor DNA samples were analyzed for loss of heterozygosity (LOH), using 24 microsatellite markers and PCR techniques. Statistical analysis showed that deletions on chromosomes 14 and 18 were significantly associated with tumor grade of meningiomas (p = 0.048 and p = 0.03, respectively). In addition, we found a marginally increased frequency of LOH on chromosome 9 in atypical meningiomas (p = 0.06). Interestingly, LOH on chromosome 14 was significantly associated with tumor size (p = 0.049), as the risk of developing a tumor of more than 4 cm in diameter was 6-times the risk of developing tumor with diameter below 4 cm. The most frequent genetic abnormality  in meningiomas is 22 LOH, which seems to be confirmed by the present study in which high frequency of such abnormality was observed (67%). We found associations between chromosome 22 status and histological subtype. LOH on chromosome 22 was more frequent in fibrous meningiomas than in the meningothelial variant (p = 0.001). Besides that, we found a relationship between 22 LOH status  and tumor localization: the frequency of LOH in skull base-localized tumors was significantly lower compared to parasagittal meningiomas (p = 0.0004). Our results indicated that allelic loss on chromosomes 9, 10, 14, 18 and 22 may be associated with meningioma pathogenesis and progression.

 

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[191]

TÍTULO / TITLE:  - Successful Treatment of a Recurrent Choroid Plexus Carcinoma with Surgery Followed by High-Dose Chemotherapy and Stem Cell Rescue.

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

REVISTA / JOURNAL:  - Pediatr Hematol Oncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 3109/08880018.2012.756089

AUTORES / AUTHORS:  - Mosleh O; Tabori U; Bartels U; Huang A; Schechter-Finkelstein T; Bouffet E

INSTITUCIÓN / INSTITUTION:  - Neuro-oncology Program, The Hospital for Sick Children, University of Toronto , Toronto , Canada.

RESUMEN / SUMMARY:  - Choroid plexus carcinoma (CPC) is a rare central nervous system malignant tumor with a dismal prognosis, especially in the case of incomplete resection or recurrence. The authors report long-term survival of a 1-year-old patient with recurrent CPC and Li-Fraumeni syndrome with surgical resection and high-dose chemotherapy (HDC) consisting of single cycle of Busulfan and Thiotepa followed by autologous stem cell rescue without the use of radiation therapy. Remarkably the patient remains without evidence of recurrence 5 years after completion of therapy. Additional studies are necessary to determine the role of HDC and stem cell rescue in patients with recurrent CPC.

 

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[192]

TÍTULO / TITLE:  - A Comparative Study of Stereotactic Radiosurgery, Hypofractionated, and Fractionated Stereotactic Radiotherapy in the Treatment of Skull Base Meningioma.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318271b36a

AUTORES / AUTHORS:  - Han J; Girvigian MR; Chen JC; Miller MJ; Lodin K; Rahimian J; Arellano A; Cahan BL; Kaptein JS

INSTITUCIÓN / INSTITUTION:  - *Department of Radiation Oncology, Kaiser Permanente Los Angeles Medical Center daggerSouthern California Permanente Medical Group double daggerUCLA David Geffen School of Medicine, Los Angeles, CA.

RESUMEN / SUMMARY:  - OBJECTIVES:: To compare the outcomes of skull base meningiomas treated with stereotactic radiosurgery (SRS), hypofractionated stereotactic radiotherapy (hFSRT), and fractionated stereotactic radiotherapy (FSRT). METHODS:: A total of  220 basal meningiomas in 213 patients were treated using SRS (N=55), hFSRT (N=22), and FSRT (N=143). The median age was 59 years (28 to 84 y). Prior surgery was performed in 74 cases; 39 patients received adjuvant radiotherapy after incomplete resection and 35 patients received salvage radiotherapy after tumor progression. In 146 cases, radiation was the primary therapy. Ten patients had World Health Organization II or III meningiomas. RESULTS:: The median follow-up was 32 months (7 to 97 mo). Median tumor volume was 2.8 cm (0.10 to 16.94 cm), 4.8 cm (0.88 to 20.38 cm), and 11.1 cm (0.43 to 214.00 cm) and the median dose was 1250 cGy in 1 fraction to the 80% isodose line (IDL), 2500 cGy in 5 fractions to the 90% IDL, and 5040 cGy in 28 fractions to the 90% IDL for the SRS, hFSRT, and FSRT groups, respectively. Radiographic control was achieved in 91%, 94%, and 95% (P=0.25), whereas clinical response was seen in 89%, 100%, and 91% (P=0.16) in the SRS, hFSRT, and FSRT groups, respectively. CONCLUSIONS:: There is no significant difference in the radiographic and clinical response in patients with skull base meningioma treated with SRS, hFSRT, or FSRT and thus gives the clinician the impetus to tailor treatment techniques to the location and size of  the tumor at presentation.

 

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[193]

TÍTULO / TITLE:  - Observations on the viability of C6-glioma cells after sonoporation with low-intensity ultrasound and microbubbles.

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

REVISTA / JOURNAL:  - IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Jan;60(1):34-45. doi: 10.1109/TUFFC.2013.2535.

            ●● Enlace al texto completo (gratuito o de pago) 1109/TUFFC.2013.2535

AUTORES / AUTHORS:  - Ruijssevelt L; Smirnov P; Yudina A; Bouchaud V; Voisin P; Moonen C

RESUMEN / SUMMARY:  - Ultrasound (US) and microbubbles can be used to facilitate cellular uptake of drugs through a cavitationinduced enhancement of cell membrane permeability. The  mechanism is, however, still incompletely understood. A direct contact between microbubbles and cell membrane is thought to be essential to create membrane perturbations lasting from seconds to minutes after US exposure of the cells. A recent study showed that the effect may even last up to 8 h after cavitation (with residual permeability up to 24 h after cavitation). In view of possible membrane damage, the purpose of this study was to further investigate the evolution of cell viability in the range of the 24-h temporal window. Furthermore, a description of the functional changes in tumor cells after US exposure was initiated to obtain a better understanding of the mechanism of membrane perturbation after sonication with microbubbles. Our results suggest that US does not reduce cell viability up to 24 h post-exposure. However, a perturbation of the entire cell population exposed to US was observed in terms of enzymatic activity and characteristics of the mitochondrial membrane. Furthermore, we demonstrated that US cavitation induces a transient loss of cell  membrane asymmetry, resulting in phosphatidylserine exposure in the outer leaflet of the cell membrane.

 

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[194]

TÍTULO / TITLE:  - Gliomatosis cerebri: clinical characteristics, management, and outcomes.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1058-x

AUTORES / AUTHORS:  - Chen S; Tanaka S; Giannini C; Morris J; Yan ES; Buckner J; Lachance DH; Parney IF

INSTITUCIÓN / INSTITUTION:  - Department of Neurologic Surgery, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA, chen.selby@mayo.edu.

RESUMEN / SUMMARY:  - Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single  discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery’s role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although  selection bias could be present in this retrospective study. Chemotherapy’s value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.

 

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[195]

TÍTULO / TITLE:  - Primary gliomatosis cerebri involving gray matter in pediatrics: a distinct entity? A multicenter study of 14 cases.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-2016-1

AUTORES / AUTHORS:  - Chappe C; Riffaud L; Treguier C; Carsin-Nicol B; Veillard D; Chiforeanu DC; Grill J; Frappaz D; Andre N; Millot F; Vinchon M; Sirvent N; Edan C

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Oncology, Pontchaillou University Hospital, Rennes, France.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: Gliomatosis cerebri (GC) is a rare neoplasm including a variety of tumors, with extremely variable evolution and heterogeneity of prognosis. It may appear either de novo or after a focal glioma, involve predominantly the white or the gray matter, and concern either pediatric or adult patients. We focused on primary GC involving exclusively gray matter in a pediatric population in order better to define the presentation and outcome of this disease. PATIENTS AND METHODS: We reviewed the databases of seven Departments of Pediatric Oncology to identify pediatric cases of GC between 1990  and 2007. Patients were included if they demonstrated a diffuse infiltrative process involving gray matter in magnetic resonance imaging (MRI) and histological tissue analyses, confirming a proliferative glial disorder. RESULTS: Fourteen patients with a median age of 8 years were identified. Epilepsy was the  main presenting symptom. Brain MRI showed a lesion of the temporal and insular cerebral cortex associated with tumoral infiltration of the thalami and the basal ganglia. Histological examination confirmed the diagnosis of high-grade glioma. Prognosis was always very gloomy in the short term, with a median survival of less than a year. CONCLUSION: This rare entity, whose prognosis is appalling whatever the treatment proposed, should be clearly identified within the heterogeneous group of GC in the same way as diffuse intrinsic pontine gliomas have been identified among brain stem tumors. Systematic biopsies appear essential to permit the molecular studies which will assist in guiding the choice of future targeted treatments.

 

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[196]

TÍTULO / TITLE:  - Aldehyde dehydrogenase and HSP90 co-localize in human glioblastoma biopsy cells.

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

REVISTA / JOURNAL:  - Biochimie. 2012 Nov 29. pii: S0300-9084(12)00452-X. doi: 10.1016/j.biochi.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biochi.2012.11.007

AUTORES / AUTHORS:  - Rappa F; Cappello F; Halatsch ME; Scheuerle A; Kast RE

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Biomedicine and Clinical Neurosciences, University of  Palermo, Palermo, Italy.

RESUMEN / SUMMARY:  - The concept of a stem cell subpopulation as understood from normal epithelial tissue or bone marrow function has been extended to our understanding of cancer tissue and is now the target of treatment efforts specifically directed to this subpopulation. In glioblastoma, as well as in other cancers, increased expression of aldehyde dehydrogenase (ALDH) has been found localized within a minority sub-population of tumor cells which demonstrate stem cell properties. A separate  body of research associated increased expression of heat-shock protein-90 (HSP90) with stem cell attributes. We present here results from our initial immunohistochemistry study of human glioblastoma biopsy tissue where both ALDH and HSP90 tended to be co-expressed in high amounts in the same minority of cells. Since 12% of all cells in the six biopsies studied were ALDH positive and  17% were HSP90 positive, by chance alone 2% would have been expected to be positive for both. In fact 7% of all cells simultaneously expressed both markers-a significant difference (p = 0.037). That two previously identified proteins associated with stem cell attributes tend to be co-expressed in the same individual glioblastoma cells might have clinical utility. Disulfiram, used to treat alcoholism for half-a century now, is a potent ALDH inhibitor and the old anti-viral drug ritonavir inhibits HSP90. These should be explored for the potential to retard aspects of glioblastoma stem cells’ function subserved by ALDH and HSP90.

 

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[197]

TÍTULO / TITLE:  - RLIP76 is overexpressed in human glioblastomas and is required for proliferation, tumorigenesis and suppression of apoptosis.

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

REVISTA / JOURNAL:  - Carcinogenesis. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgs401

AUTORES / AUTHORS:  - Wang Q; Wang JY; Zhang XP; Lv ZW; Fu D; Lu YC; Hu GH; Luo C; Chen JX

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.

RESUMEN / SUMMARY:  - The guanosine triphosphatase-activating protein RLIP76 is overexpressed in many malignant tumor cells, but it is unclear if RLIP76 overexpression contributes to  the high proliferative potential of glioma cells. We demonstrate that RLIP76 messenger RNA and protein expression are positively correlated with glioma grade  and that higher RLIP76 expression correlates with shorter patient survival. Immunohistochemical staining revealed that RLIP76 expression was positively correlated with the expression of Ki-67, a biomarker for cell proliferation. Inhibition of RLIP76 expression in U87 and U251 glioma cell lines by stable transfection of a targeted siRNA suppressed anchorage-independent growth and enhanced apoptosis in vitro. Conversely, overexpression of RLIP76 in SW1088 and U251 cell lines enhanced proliferation and reduced apoptosis. Inhibition of RLIP76 in U251 cells also significantly suppressed tumorigenicity and induced apoptosis in an endotopic xenograft mouse model. Moreover, we demonstrate that knockdown of RLIP76 increases apoptosis in different human gliomas independently  of p53 status. In addition, a constitutively active Rac1 reversed both the suppression of proliferation and the promotion of apoptosis induced by the RLIP76-targeted siRNA, indicating that RLIP76 is an upstream activator of Rac1. Rac1-mediated suppression of apoptosis and promotion of proliferation were dependent on intact c-jun N-terminal kinase (JNK) signaling. Furthermore, we demonstrate that RLIP76 promotes proliferation and suppresses glioma cell apoptosis through a mechanism independent of Rho-selective GTPase-activating protein. Instead, we found that the adenosine triphosphatase function of Rlip76 modulates Rac1 activity by regulating Rac1 protein ubiquitylation and degradation. These data demonstrate that RLIP76 may suppress apoptosis and promote the proliferation of glioma cells by direct adenosine triphosphate-dependent xenobiotic transport and by activating the Rac1-JNK signaling pathway. Inhibition of RLIP76 signaling is a potential treatment for malignant glioma.

 

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[198]

TÍTULO / TITLE:  - Novel Polyomavirus associated with Brain Tumors in Free-Ranging Raccoons, Western United States.

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

REVISTA / JOURNAL:  - Emerg Infect Dis. 2013 Jan;19(1):77-84. doi: 10.3201/eid1901.121078.

            ●● Enlace al texto completo (gratuito o de pago) 3201/eid1901.121078

AUTORES / AUTHORS:  - Dela Cruz FN Jr; Giannitti F; Li L; Woods LW; Del Valle L; Delwart E; Pesavento PA

RESUMEN / SUMMARY:  - Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in  10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.

 

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[199]

TÍTULO / TITLE:  - Antiangiogenic-targeting drug-loaded microbubbles combined with focused ultrasound for glioma treatment.

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

REVISTA / JOURNAL:  - Biomaterials. 2013 Mar;34(8):2142-55. doi: 10.1016/j.biomaterials.2012.11.048. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2012.11.048

AUTORES / AUTHORS:  - Fan CH; Ting CY; Liu HL; Huang CY; Hsieh HY; Yen TC; Wei KC; 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:  - Current chemotherapeutic agents do not only kill tumor cells but also induce systemic toxicity that significantly limits their dosage. Focused ultrasound (FUS) in the presence of microbubbles (MBs) is capable of transient and local opening of the blood-brain barrier (BBB) that enhances chemotherapeutic drug delivery into the brain parenchyma for glioma treatment. Our previous results demonstrated the success of combining the use of drug (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-loaded MBs with FUS-induced BBB opening to improve local drug delivery and reduce systemic toxicity. Here we introduce novel VEGF-targeting, drug-loaded MBs that significantly further enhance targeted drug release and reduce tumor progression in a rat model, using  the FUS-BBB opening strategy. This study suggests a promising direction for future MB design aimed at targeted brain tumor therapy, and the possible future extension of MB application towards theragnostic use.

 

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[200]

TÍTULO / TITLE:  - The transmembrane chemokines CXCL16 and CX3CL1 and their receptors are expressed  in human meningiomas.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb;29(2):563-70. doi: 10.3892/or.2012.2164. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2164

AUTORES / AUTHORS:  - Li G; Hattermann K; Mentlein R; Mehdorn HM; Held-Feindt J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Arnold-Heller-Str. 3, 24105 Kiel, Germany.

RESUMEN / SUMMARY:  - Meningiomas are common slowly growing benign tumors, however, anaplastic meningiomas have an aggressive biological and clinical behavior associated with high rates of recurrence and unfavorable prognosis. Since the molecular mechanisms involved in progression of meningiomas are not yet fully understood and recent investigations have suggested a possible role of chemokines in tumor biology, the aim of the study was to investigate the expression of CX3CL1/CX3CR1  and CXCL16/CXCR6 on mRNA and protein level in human meningiomas. Quantitative reverse-transcription polymerase chain reaction, immunohistochemistry and double  immuno-staining techniques were used for the investigations. We showed that mRNA  and protein expression of the chemokine/receptor pairs CX3CL1/CX3CR1 and CXCL16/CXCR6 were detectable in human meningioma samples. Double immunostaining revealed that the chemokines/receptors were predominantly expressed in the tumor  cells themselves, in infiltrating microglia cells/macrophages and endothelial cells of blood vessels. Nevertheless, not all cells of different kinds were positive for different chemokine/receptors. Of note, in comparison to more benign meningioma samples, CX3CR1 and CXCL16 were found to be expressed at lower levels  in anaplastic variants. Moreover, a positive correlation between expression levels of ligands and corresponding receptors could be observed for some malignancy grades. Taken together, these results showed that chemokines and their receptors are involved in the pathogenesis of human meningiomas. Our results provide an interesting basis for further investigations that should be performed  to characterize the functional roles of chemokines and their receptors in human meningiomas, and also enhance future therapeutic design.

 

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[201]

TÍTULO / TITLE:  - Correlation between Rho-kinase pathway gene expressions and development and progression of glioblastoma multiforme.

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

REVISTA / JOURNAL:  - Tumour Biol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0655-9

AUTORES / AUTHORS:  - Erkutlu I; Cigiloglu A; Kalender ME; Alptekin M; Demiryurek AT; Suner A; Ozkaya E; Ulasli M; Camci C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, School of Medicine, Gaziantep University, 27310, Gaziantep, Turkey.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common and the most aggressive primary  malignant tumor of the brain. Prognostic factors in GBM can be sorted as age, tumor localization, tumor diameter, symptom period and type, the extent of surgery, postoperative tumor volume, and adjuvant radiotherapy and/or chemotherapy status. Besides the interactions between actin microfilaments, microtubules, and intermediate filaments, environmental factors and intracellular signals which regulate them affect the cell invasion. Rho proteins and therefore  Rho-kinase activation play important role at these changes. The aim of this study is to evaluate the relationship between the Rho-kinase pathway gene expressions and prognosis in GBM. Ninety-eight patients diagnosed as GBM between 2001 and 2010 were enrolled into the study. RNA was obtained from the paraffinized tumor tissue of the patients with formalin-fixed, paraffin-embedded RNA isolation kit and the mRNA expressions of 26 genes were investigated. There was a statistically significant negative correlation between the ages at the diagnosis and survival.  There was a significant relationship between the overexpression of Rho-kinase pathway-related genes LIMK1, CFL1, CFL2, and BCL2 and low expression of MAPK1 gene and the survival of the patients. These results demonstrate for the first time that there is a marked contribution of Rho-kinase pathway-related genes to the progression and survival of the GBM. The expression of these genes may be related to response of multimodal therapy or these parameters could be used to determine possible unresponsive patients before treatment.

 

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[202]

TÍTULO / TITLE:  - Na-K-2Cl cotransporter and aquaporin 1 in arachnoid granulations, meningiomas, and meningiomas invading dura.

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

REVISTA / JOURNAL:  - Hum Pathol. 2013 Jan 11. pii: S0046-8177(12)00364-4. doi: 10.1016/j.humpath.2012.09.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.09.020

AUTORES / AUTHORS:  - Johnson MD; O’Connell M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Division of Neuropathology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Electronic address: mahlon_johnson@urmc.rochester.edu.

RESUMEN / SUMMARY:  - Meningioma invasion of the dura may contribute to the high rate of recurrence. Recently, ion channels that affect cell shape and movement have been implicated in cancer invasion. Combined Na-K-2Cl cotransporter (NKCC1) and aquaporin 1 (AQP1) expression in arachnoid granulations and meningiomas with and without dural invasion has not been characterized. Arachnoid granulations associated with dura were collected from 10 adult formalin-fixed dura/leptomeninges. Thirty-four  frozen meningiomas were evaluated by Western blot. An additional 58 formalin-fixed, paraffin-embedded meningiomas including 36 World Health Organization grade I, 15 grade II, and 7 grade III meningiomas were evaluated by  immunohistochemistry. By Western blot, NKCC1 was found in 17 (100%) of 17 World Health Organization grade I, 13 (87%) of 15 grade II, and both grade III meningiomas. Distinct AQP1 was not detected in the meningioma lysates tested. By  immunohistochemistry, extensive NKCC1 but no AQP1 immunoreactivity was detected in the arachnoid granulation cells. Extensive NKCC1 was detected in meningioma cells in 56 and in capillaries in 43 by immunohistochemistry. In those tumors with dural or bone/soft tissue invasion, NKCC1 immunoreactivity was seen in invading cells in all cases and in their capillaries in the majority. AQP1 was detected in meningioma cells in 29 and in capillaries in all. AQP1 was also detected in cells and capillaries invading the dura or bone in 10 and 18 of 18, respectively. This was extensive in all subtypes of meningiomas studied. These findings suggest that NKCC1 and AQP1 participate in meningioma biology and invasion. NKCC1 might be targeted by FDA-approved NKCC1 inhibitors.

 

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[203]

TÍTULO / TITLE:  - GABAB receptor antibodies in paraneoplastic cerebellar ataxia.

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

REVISTA / JOURNAL:  - J Neuroimmunol. 2013 Jan 14. pii: S0165-5728(12)00339-6. doi: 10.1016/j.jneuroim.2012.12.006.

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

AUTORES / AUTHORS:  - Jarius S; Steinmeyer F; Knobel A; Streitberger K; Hotter B; Horn S; Heuer H; Schreiber SJ; Wilhelm T; Trefzer U; Wildemann B; Ruprecht K

INSTITUCIÓN / INSTITUTION:  - Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany.

RESUMEN / SUMMARY:  - Autoantibodies to the gamma-aminobutyric acid-B (GABAB) receptor were recently described in patients with limbic encephalitis presenting with early or prominent seizures. We report on a 64-year-old man with malignant melanoma who during adjuvant therapy with interferon (IFN)-alpha developed cerebellar ataxia. Indirect immunofluorescence on brain tissue sections revealed high-titer (1:20,000) IgG1 serum autoantibodies to the cerebellar molecular and granular layer, which were confirmed to be directed against GABAB receptor in a cell-based assay. This case highlights cerebellar ataxia in the absence of seizures as a clinical manifestation of GABAB receptor autoimmunity and extends the spectrum of tumors underlying this condition to malignant melanoma. IFN-alpha therapy may have contributed to the development of autoimmunity in this patient.

 

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[204]

TÍTULO / TITLE:  - The Definition of Primary and Secondary Glioblastoma.

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

REVISTA / JOURNAL:  - Clin Cancer Res. 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3002

AUTORES / AUTHORS:  - Ohgaki H; Kleihues P

INSTITUCIÓN / INSTITUTION:  - Pathology Group, IARC/WHO.

RESUMEN / SUMMARY:  - Glioblastoma is the most frequent and malignant brain tumor. The vast majority of glioblastomas (approximately 90%) develop rapidly de novo in elderly patients, without clinical or histological evidence of a less malignant precursor lesion (primary glioblastomas). Secondary glioblastomas progress from low-grade diffuse  astrocytoma or anaplastic astrocytoma. They manifest in younger patients, have a  lesser degree of necrosis, are preferentially located in the frontal lobe and carry a significantly better prognosis. Histologically, primary and secondary glioblastomas are largely indistinguishable, but they differ in their genetic and epigenetic profiles. Decisive genetic signpost of secondary glioblastoma are IDH1 mutations, that are absent in primary glioblastomas and which are associated with a hypermethylation phenotype. IDH1 mutations are the earliest detectable genetic  alteration in precursor low-grade diffuse astrocytomas and in oligodendrogliomas, indicating that these tumors are derived from neural precursor cells that differ  from those of primary glioblastomas. In this review, we summarize epidemiological, clinical, histopathological, genetic, and expression features of primary and secondary glioblastomas, and the biological consequences of IDH1 mutations. We conclude that this genetic alteration is a definitive diagnostic molecular marker of secondary glioblastomas and more reliable and objective than  clinical criteria. Despite a similar histological appearance, primary and secondary glioblastomas are distinct tumor entities that originate from different precursor cells and may require different therapeutic approaches.

 

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[205]

TÍTULO / TITLE:  - Inhibition of glioblastoma and enhancement of survival via the use of mibefradil  in conjunction with radiosurgery.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121087

AUTORES / AUTHORS:  - Sheehan JP; Xu Z; Popp B; Kowalski L; Schlesinger D

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Object The survival of patients with high-grade gliomas remains unfavorable. Mibefradil, a T-type calcium channel inhibitor capable of synchronizing dividing  cells at the G1 phase, has demonstrated potential benefit in conjunction with chemotherapeutic agents for gliomas in in vitro studies. In vivo study of mibefradil and radiosurgery is lacking. The authors used an intracranial C6 glioma model in rats to study tumor response to mibefradil and radiosurgery. Methods Two weeks after implantation of C6 cells into the animals, each rat underwent MRI every 2 weeks thereafter for 8 weeks. After tumor was confirmed on  MRI, the rats were randomly assigned to one of the experimental groups. Tumor volumes were measured on MR images. Experimental Group 1 received 30 mg/kg of mibefradil intraperitoneally 3 times a day for 1 week starting on postoperative day (POD) 15; Group 2 received 8 Gy of cranial radiation via radiosurgery delivered on POD 15; Group 3 underwent radiosurgery on POD 15, followed by 1 week of mibefradil; and Group 4 received mibefradil on POD 15 for 1 week, followed by  radiosurgery sometime from POD 15 to POD 22. Twenty-seven glioma-bearing rats were analyzed. Survival was compared between groups using Kaplan-Meier methodology. Results Median survival in Groups 1, 2, 3, and 4 was 35, 31, 43, and 52 days, respectively (p = 0.036, log-rank test). Two animals in Group 4 survived to POD 60, which is twice the expected survival of untreated animals in this model. Analysis of variance and a post hoc test indicated no tumor volume differences on PODs 15 and 29. However, significant volume differences were found on POD 43; mean tumor volumes for Groups 1, 2, 3, and 4 were 250, 266, 167, and 34 mm(3), respectively (p = 0.046, ANOVA). A Cox proportional hazards regression  test showed survival was associated with tumor volume on POD 29 (p = 0.001) rather than on POD 15 (p = 0.162). In vitro assays demonstrated an appreciable and dose-dependent increase in apoptosis between 2- and 7-muM concentrations of mibefradil. Conclusions Mibefradil response is schedule dependent and enhances survival and reduces glioblastoma when combined with ionizing radiation.

 

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[206]

TÍTULO / TITLE:  - Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1018-x

AUTORES / AUTHORS:  - Liu J; Guo S; Li Q; Yang L; Xia Z; Zhang L; Huang Z; Zhang N

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The 1st Affiliated Hospital of Sun Yat-sen University, No 58, Zhongshan 2 Road, Guangzhou, Guangdong Province, 510080, People’s Republic of China.

RESUMEN / SUMMARY:  - Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme branching from glycolysis in the three-step serine biosynthetic pathway. Recent evidence has shown that PHGDH is amplified in human breast cancer and melanoma and plays a key role in cancer metabolism. However, PHGDH expression in glioma and a potential non-metabolic role in tumorigenesis have not been reported. We analyzed PHGDH levels in specimens from glioma patients and found that PHGDH, although negative  in normal brain tissues, was highly expressed in astrocytic tumors and increasingly expressed in more aggressive cancer types. Inhibition of PHGDH expression in glioma cells downregulated the expression of VEGF, MMP-2, CHK2 and  cyclin D1 and reduced glioma cell proliferation, invasion and tumorigenicity in vitro and in vivo. Interestingly, we found that the oncogenic transcription factor FOXM1 was also downregulated in PHDGH-silenced glioma cells. Using LC/LC MS analysis, we identified PHGDH as a novel binding partner of FOXM1. PHGDH interacted with and stabilized FOXM1 at the protein level, promoting the proliferation, invasion and tumorigenicity of glioma cells. Our data identified PHGDH as a potential prognostic marker of glial brain tumors and identified a non-metabolic role for PHGDH in glioma tumorigenesis, providing a novel angle of  targeting the PHGDH-FOXM1 axis in future brain tumor therapy.

 

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[207]

TÍTULO / TITLE:  - Adult Low-Grade Gliomas: Surgery vs Biopsy?

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

REVISTA / JOURNAL:  - Neurosurgery. 2013 Feb;72(2):N19. doi: 10.1227/01.neu.0000426216.20454.22.

            ●● Enlace al texto completo (gratuito o de pago) 1227/01.neu.0000426216.20454.22

AUTORES / AUTHORS:  - Horowitz PM; Chi J

 

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[208]

TÍTULO / TITLE:  - Diffusion-Weighted MR Imaging and MGMT Methylation Status in Glioblastoma: A Reappraisal of the Role of Preoperative Quantitative ADC Measurements.

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

REVISTA / JOURNAL:  - AJNR Am J Neuroradiol. 2013 Jan;34(1):E10-1. doi: 10.3174/ajnr.A3467. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 3174/ajnr.A3467

AUTORES / AUTHORS:  - Gupta A; Prager A; Young RJ; Shi W; Omuro AM; Graber JJ

INSTITUCIÓN / INSTITUTION:  - Department of RadiologyWeill Cornell Medical College/New-York Presbyterian HospitalNew York, New York.

 

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[209]

TÍTULO / TITLE:  - A new approach to screening cancer stem cells from the U251 human glioma cell line based on cell growth state.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):1013-8. doi: 10.3892/or.2012.2206. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2206

AUTORES / AUTHORS:  - Cao X; Gu Y; Jiang L; Wang Y; Liu F; Xu Y; Deng J; Nan Y; Zhang L; Ye J; Li Q

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, P.R. China.

RESUMEN / SUMMARY:  - Cancer stem cells (CSCs) play important roles in the biological behaviour of malignant tumours. To study their properties, they must be carefully identified and purified. Cancer cells can acquire three different morphological types during single cell cloning. A small subpopulation of clones acquires a regular and compact shape, and these clones are enriched for CSCs; however, the majority of clones have an irregular morphology with loose intercellular junctions, with fewer characteristics of CSCs. At present, the main method to isolate CSCs is to  collect the regular clones in low-density culture conditions; therefore, an insufficient amount of CSCs is obtained for clonal expansion. To obtain a more sufficient amount of CSCs, the clones with an irregular and loose morphology were examined in our study. We found a small subpopulation of U251 glioma cells that arrested in the suspended state and that subsequently migrated to form new clones. The suspended cells were isolated from the irregular and loose clones. Clonogenic assays were performed in which 43.70% of the suspended cells and 32.91% of the adherent cells formed new clones. To determine the biological differences between the suspended and adherent cells, carboxyfluorescein succinimidyl ester (CFSE) labelling, MTT assays, and cell cycle assays were performed. The results demonstrated that the suspended cells had the characteristics of CSCs, including higher proliferation rates, as well as self-maintenance and self-renewal capabilities, and they stained positively for markers of brain CSCs and had multilineage potential. Thus, we established a new  and efficient approach for screening CSCs from the U251 human glioma cell line based on the cell growth state.

 

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[210]

TÍTULO / TITLE:  - Multiple cerebral infarcts and intravascular central nervous system lymphoma: A rare but potentially treatable association.

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

REVISTA / JOURNAL:  - J Neurol Sci. 2013 Feb 15;325(1-2):183-5. doi: 10.1016/j.jns.2012.10.012. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jns.2012.10.012

AUTORES / AUTHORS:  - Cruto C; Taipa R; Monteiro C; Moreira I; Melo-Pires M; Correia M

INSTITUCIÓN / INSTITUTION:  - Neurology Department, Hospital de Santo Antonio, Centro Hospitalar do Porto, Porto, Portugal; Neurology Department, Hospital Pero da Covilha, Centro Hospitalar Cova da Beira, Covilha, Portugal. Electronic address: Caticruto@gmail.com.

RESUMEN / SUMMARY:  - Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoproliferative disorder characterized by massive intravascular growth of lymphoma cells with a predilection for the central nervous system (CNS). Diagnosis is generally delayed by variable clinical presentation and nonspecific laboratory findings. Brain biopsy is the gold standard diagnostic test. Prognosis is poor with a high mortality rate. We report a case of “in vivo” diagnosis of IVLBCL presenting with rapidly progressive encephalopathy secondary to multiple cerebral infarcts. This  case highlights IVLBCL as a possible cause of unexplained multifocal and recurrent strokes. Earlier diagnosis and consequent earlier treatment may be associated with better prognosis.

 

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[211]

TÍTULO / TITLE:  - An analysis of intracranial epidermoid tumors with malignant transformation: treatment and outcomes.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2012 Dec 5. pii: S0303-8467(12)00560-4. doi: 10.1016/j.clineuro.2012.10.026.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.10.026

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

INSTITUCIÓN / INSTITUTION:  - UCLA Department of Neurological Surgery, University of California Los Angeles, 695 Charles E. Young Drive South, UCLA Gonda 3357, Los Angeles, CA 90095-1761, United States.

RESUMEN / SUMMARY:  - OBJECTIVE: While typically benign, epidermoid tumors upon rare occasion can undergo malignant transformation, which carries a poor prognosis. Here, we reviewed treatment strategies and analyzed outcomes for every case of malignant epidermoid tumor reported since its original description in 1912. METHODS: A comprehensive literature review identified all reported cases of malignant transformation of intracranial epidermoid tumor. Treatments were categorized as follows: palliative management, stereotactic radiosurgery (SRS), chemotherapy, and surgery plus multiple (2+) adjuvant therapies. Survival data of these groups  were compared to treatment outcomes for patients receiving only surgical resection, as reported in our previous study. RESULTS: We identified 58 cases of  intracranial epidermoid tumor with malignant degeneration. Average survival regardless of therapy was 11.8 months. Mean survival outcomes for groups treated  with palliative management, chemotherapy, SRS, and multiple postoperative adjuvant therapies were 5.3 months, 25.7 months, 29.2 months, and 36.3 months, respectively. Outcomes for the groups including SRS, chemotherapy, and multiple post-operative adjuvant therapies were statistically significant compared to surgical resection alone. CONCLUSION: While there remains a lack of consensus regarding the best approach to the management of patients with malignant epidermoid tumors, our systematic analysis characterizes and confirms the added benefit of SRS, chemotherapy, and multimodal adjuvant therapies.

 

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[212]

TÍTULO / TITLE:  - Oncogenic effects of miR-10b in glioblastoma stem cells.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1047-0

AUTORES / AUTHORS:  - Guessous F; Alvarado-Velez M; Marcinkiewicz L; Zhang Y; Kim J; Heister S; Kefas B; Godlewski J; Schiff D; Purow B; Abounader R

INSTITUCIÓN / INSTITUTION:  - Departments of Microbiology, Immunology and Cancer Biology, University of Virginia, PO Box 800168, Charlottesville, VA, 22908, USA.

RESUMEN / SUMMARY:  - MicroRNAs and cancer stem cells have emerged as critical players in glioblastoma, one of the deadliest human cancers. In this study, we investigated the expression and function of microRNA-10b in glioblastoma cells and stem cells. An analysis of The Cancer Genome Atlas data revealed a correlation between high miR-10b levels and poor prognosis in glioblastoma patients. We measured the levels of miR-10b and found that it is upregulated in human glioblastoma tissues, glioblastoma cell and stem cell lines as compared to normal human tissues or astrocytes. Inhibition of miR-10b with a specific antagomir inhibited the proliferation of glioblastoma  established and stem cell lines. Inhibition of miR-10b strongly reduced cell invasion and migration in glioblastoma cell and stem cell lines while overexpression of miR-10b induced cell migration and invasion. We also investigated several predicted targets of miR-10b but could not verify any of them experimentally. Additionally, miR-10b inhibition significantly decreased the in vivo growth of stem cell-derived orthotopic GBM xenografts. Altogether, our findings confirm the oncogenic effects of miR-10b in GBM cells and show for the first time a role of this microRNA in GBM stem cells. Targeting miR-10b might therefore inhibit glioblastoma stem cells, which are thought to be at the origin  of glioblastoma and to contribute its recurrence and resistance to therapy.

 

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[213]

TÍTULO / TITLE:  - Human chorionic gonadotropin beta induces cell motility via ERK1/2 and MMP-2 activation in human glioblastoma U87MG cells.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1017-y

AUTORES / AUTHORS:  - Li Z; Du L; Li C; Wu W

INSTITUCIÓN / INSTITUTION:  - Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capital Medical University, Beijing, 100069, China.

RESUMEN / SUMMARY:  - Human chorionic gonadotropin beta (hCGbeta) promotes tumorigenesis in a variety of tumors including glioblastoma, breast and prostate cancer cells, etc. However, the involved mechanisms remain elusive. Distinct from the other tumors, glioblastoma is a highly invasive brain tumor; invasion causes high recurrence and mortality. Characterization of hCGbeta signaling is to determine therapeutic  targets to inhibit invasion and lower recurrence. Through both a stable cell line over-expressing hCGbeta and hCGbeta standards, we tested hCGbeta signaling, migration and invasion in human glioblastoma U87MG cells. ELISA showed that hCGbeta secreted into culture medium at an amount of 237.8 +/- 7.8 ng/10(7) cells in hCGbeta transfected stable cells after the cells were grown for 24 h. Through  Western blot and Gelatin zymography, we found that hCGbeta standards phosphorylated ERK1/2 and upregulated MMP-2 expression in dose- and time-dependent manners. Meanwhile, overexpressed hCGbeta phosphorylated ERK1/2, and upregulated MMP-2 expression and activity, whereas ERK1/2 blocker PD98059 (25 muM) significantly decreased both ERK1/2 and MMP-2 expression and activity. In addition, in the same conditions as the signaling test, hCGbeta promoted cell migration and invasion, whereas the PD98059 diminished these effects. These findings demonstrated that hCGbeta phosphorylated ERK1/2 upregulating MMP-2 expression and activity leading to cell migration and invasion, suggesting that hCGbeta, ERK1/2 and MMP-2 are the potential targets to inhibit glioblastoma invasion.

 

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[214]

TÍTULO / TITLE:  - MicroRNA-183 upregulates HIF-1alpha by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1027-9

AUTORES / AUTHORS:  - Tanaka H; Sasayama T; Tanaka K; Nakamizo S; Nishihara M; Mizukawa K; Kohta M; Koyama J; Miyake S; Taniguchi M; Hosoda K; 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:  - MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and contribute to cell proliferation, differentiation and metabolism. Our previous study revealed the extensive modulation of a set of miRs in malignant glioma. In  that study, miR microarray analysis demonstrated the upregulation of microRNA-183 (miR-183) in glioblastomas. Therefore, we examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3’-untranslated region (3’UTR). In present study, we used real-time PCR analysis to demonstrate that miR-183 is upregulated in the majority of high-grade gliomas and glioma cell lines compared with peripheral, non-tumorous brain tissue. The mRNA and protein expression levels of IDH2 are downregulated via the  overexpression of miR-183 mimic RNA in glioma cells. Additionally, IDH2 mRNA expression is upregulated in glioma cells expressing anti-miR-183. We verified that miR-183 directly affects IDH2 mRNA levels in glioma cells using luciferase assays. In malignant glioma specimens, the expression levels of IDH2 were lower in tumors than in the peripheral, non-tumorous brain tissues. HIF-1alpha levels were upregulated in glioma cells following transfection with miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor and glucose transporter  1, which are downstream molecules of HIF-1alpha, were upregulated in cells transfected with miR-183 mimic RNA. These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1alpha expression by targeting IDH2 and may play a role in glioma biology.

 

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[215]

TÍTULO / TITLE:  - Meningioma with intense I(123) FP-CIT uptake.

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

REVISTA / JOURNAL:  - Mov Disord. 2012 Dec;27(14):1744-5. doi: 10.1002/mds.25277.

            ●● Enlace al texto completo (gratuito o de pago) 1002/mds.25277

AUTORES / AUTHORS:  - Cilia R; Allegra R; Pezzoli G

INSTITUCIÓN / INSTITUTION:  - Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. roberto.cilia@gmail.com, roberto.cilia@icp.mi.it.

 

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[216]

TÍTULO / TITLE:  - Anticancer Activity of beta-Elemene and its Synthetic Analogs in Human Malignant  Brain Tumor Cells.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):65-76.

AUTORES / AUTHORS:  - Li QQ; Lee RX; Liang H; Zhong Y

INSTITUCIÓN / INSTITUTION:  - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A. E-mail: liquenti@mail.nih.gov and Dr. Yuhua Zhong, Beihai Institute of Endocrine and Metabolic Diseases, Guangxi 536000, P.R.C. zhongyh111@163.com.

RESUMEN / SUMMARY:  - Malignant brain tumors are aggressive in both children and adults. Despite recent improvements in diagnostic techniques, therapeutic approaches remain disappointing and unsuccessful. There is an urgent need for promising anticancer  agents to improve overall survival of patients with brain cancer. beta-Elemene has been shown to have antiproliferative effects on many types of carcinomas. In  this study, we compared the cytotoxic efficacy of beta-elemene and its synthetic  analogs in the brain tumor cell lines A172, CCF-STTG1, and U-87MG. beta-Elemene exhibited cytotoxicity towards the tumor lines, effectively suppressing tumor cell survival. The inhibitory effect of beta-elemene was mediated by the induction of apoptosis, as demonstrated by three assays. The annexin V assay showed that beta-elemene increased the percentage of early- and late-apoptotic cells. Apoptotic nuclei were detected in cancer cells in situ by the terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end labeling (TUNEL) staining, and the number of TUNEL-positive cells was significantly increased at 24-72 h following drug treatment of the cell lines. Cell death enzyme-linked immunosorbent assay (ELISA) gave similar results. Furthermore, beta-elemene increased caspase-3/7/10 activity, up-regulated protein expression of BAX, and down-regulated the one of BCL-2, BCL-XL, and of X-linked inhibitor of apoptosis (XIAP) in the cells, suggesting that apoptotic signaling pathways are involved in the responses triggered by beta-elemene. Compared with beta-elemene,  only three of the 10 synthetic beta-elemene analogs studied here, exerted comparable cytotoxic efficacy towards the three brain tumor lines: the analogs Lr-1 and Lr-2 had the same antitumor efficacy, while Lr-3 was less potent than beta-elemene. Thus, some synthetic analogs of beta-elemene may inhibit brain cancer cell growth and proliferation, and the synthetic analogs Lr-1 and Lr-2 may have great potential as alternatives to beta-elemene for anticancer therapy. Overall, this study provides, to our knowledge, the first evidence showing that synthetic analogs of beta-elemene hold promise for patients with brain tumors.

 

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[217]

TÍTULO / TITLE:  - Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological  efficacy of curcumin in glioma treatment.

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

REVISTA / JOURNAL:  - Eur J Pharm Biopharm. 2012 Nov 28. pii: S0939-6411(12)00345-1. doi: 10.1016/j.ejpb.2012.10.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejpb.2012.10.019

AUTORES / AUTHORS:  - Zanotto-Filho A; Coradini K; Braganhol E; Schroder R; de Oliveira CM; Simoes-Pires A; Battastini AM; Pohlmann AR; Guterres SS; Forcelini CM; Beck RC; Moreira JC

INSTITUCIÓN / INSTITUTION:  - Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.

RESUMEN / SUMMARY:  - In this study, we developed curcumin-loaded lipid-core nanocapsules (C-LNCs) in an attempt to improve the antiglioma activity of this polyphenol. C-LNC showed nanotechnological properties such as nanometric mean size (196nm), 100% encapsulation efficiency, polydispersity index below 0.1, and negative zeta potential. The in vitro release assays demonstrated a controlled release of curcumin from lipid-core nanocapsules. In C6 and U251MG gliomas, C-LNC promoted a biphasic delivery of curcumin: the first peak occurred early in the treatment (1-3h), whereas the onset of the second phase occurred after 48h. In C6 cells, the cytotoxicity of C-LNC was comparable to non-encapsulated curcumin only after  96h, whereas C-LNCs were more cytotoxic than non-encapsulated curcumin after 24h  of incubation in U251MG. Induction of G2/M arrest and autophagy were observed in  C-LNC as well as in free-curcumin treatments. In rats bearing C6 gliomas, C-LNC (1.5mg/kg/day, i.p.) decreased the tumor size and malignance and prolonged animal survival when compared to same dose of non-encapsulated drug. In addition, serum  markers of tissue toxicity and histological parameters were not altered. Considered overall, the data suggest that the nanoencapsulation of curcumin in LNC is an important strategy to improve its pharmacological efficacy in the treatment of gliomas.

 

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[218]

TÍTULO / TITLE:  - Venous preservation-guided resection: a changing paradigm in parasagittal meningioma surgery.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS112011

AUTORES / AUTHORS:  - Tomasello F; Conti A; Cardali S; Angileri FF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Messina, Italy.

RESUMEN / SUMMARY:  - Object Surgical treatment of parasagittal meningiomas is challenging. Preserving  the venous outflow is the key point, but this may preclude radical resection. Different surgical strategies have been proposed. To contribute to the debate on  the optimal strategy for treating these tumors, a single-institutional, single-surgeon series of patients with parasagittal meningiomas was analyzed and  the available literature reviewed. Methods Clinical charts of patients with parasagittal meningioma, managed at the University of Messina between 1988 and 2008, were retrospectively reviewed. A microsurgical resection, the goal of which was to preserve the venous outflow, was performed. Only if the superior sagittal  sinus (SSS) was angiographically occluded, but if alternative venous outflow was  clearly recognized, was the tumor resected, together with the sinus without further flow restoration. A MEDLINE review of the literature published between 1955 and 2011 was performed. Results Long-term follow-up (mean 80 months) data obtained in 67 patients with meningiomas involving the SSS were analyzed. The recurrence rate was 10.4%; the morbidity and mortality rates were 10.4% and 4.5%, respectively. The authors identified in the literature 19 relevant studies on this issue, and based on their review of the literature, there is no evidence that aggressive management offers an advantage in terms of recurrence rate. Conclusions Analysis of the data obtained in the 67 patients confirmed good outcome and long-term tumor control following a surgical strategy aimed to preserve venous outflow. These findings and the results of the authors’ analysis  of the literature emphasize that the goal of radical tumor resection should be balanced by an awareness of the increased surgical risk attendant on aggressive management of the SSS and bridging veins.

 

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[219]

TÍTULO / TITLE:  - Paediatric spinal glioblastoma: case report and review of therapeutic strategies.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2023-x

AUTORES / AUTHORS:  - O’Halloran PJ; Farrell M; Caird J; Capra M; O’Brien D

INSTITUCIÓN / INSTITUTION:  - National Neurosurgical Centre, Beaumont Hospital, Dublin 9, Ireland, phiohalloran@rcsi.ie.

RESUMEN / SUMMARY:  - INTRODUCTION: Although uncommon, there is significant morbidity and mortality associated with paediatric spinal glioblastoma. The paucity of cases makes treatment options difficult. The current recommended standard of care is biopsy followed by adjuvant chemo-radiotherapy, with emerging data supporting the role of safe gross total resection. OBJECTIVE: The purpose of this paper is to provide a single-institution case study and to discuss current and future therapeutic treatment strategies. CASE PRESENTATION: A 14-year-old boy presented with a 2-year history of intermittent back pain with recent progressively worsening motor and sensory deficits of the right side. Pre-operative MRI revealed an enhancing intra-medullary tumour extending from C2 to C7. During the operative case, no tumour-cord margin could be identified, and the patient underwent a subtotal excision. Histopathology confirmed glioblastoma. In the subsequent weeks, the patient’s clinical condition deteriorated. Adjuvant therapy was declined by the family, and the patient died 9 weeks after initial presentation.  CONCLUSION: Despite major advances in surgical techniques, peri-operative neuro-imaging as well as chemo-radiotherapy, the prognosis of a paediatric intra-medullary high-grade spinal tumour remains poor. Detailed analysis of our understanding of tumour dynamics in this patient group is important in establishing future therapeutic strategies.

 

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[220]

TÍTULO / TITLE:  - Diffusion-tensor imaging derived metrics of the corpus callosum in children with  neurofibromatosis type I.

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

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Jan;200(1):44-9. doi: 10.2214/AJR.12.9590.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.9590

AUTORES / AUTHORS:  - Filippi CG; Watts R; Duy LA; Cauley KA

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, University of Vermont College of Medicine-Fletcher Allen Health Care, Burlington, VT.

RESUMEN / SUMMARY:  - OBJECTIVE: MR morphometric studies have suggested that structural brain abnormalities including corpus callosum enlargement may, in part, explain cognitive deficits in children with neurofibromatosis type 1 (NF-1). Diffusion tensor imaging (DTI) metrics of the corpus callosum in adults with NF-1 have recently been reported, but such studies in children with NF-1 are needed. The purpose of this study was to quantify the DTI metrics at 3 T of different regions of the corpus callosum in children with NF-1. SUBJECTS AND METHODS: DTI metrics from seven consecutively identified patients with NF-1 (6 boys and 1 girl; age range, 3-17 years; average age, 7.0 years) were compared with 11 age- and sex-matched control subjects (10 boys and one girl; age range, 3-17 years; average age, 7.1 years) at 3 T. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated in different sections of the  corpus callosum as well as whole-brain mean diffusivity. RESULTS: Comparing children with NF-1 to control subjects, there were statistically significant decreases in fractional anisotropy in the genu, anterior body, and isthmus of the corpus callosum and significant increases in radial diffusivity in the genu and anterior body. Whole-brain mean diffusivity histograms revealed significant increases in whole-brain mean diffusivity in children with NF-1. CONCLUSION: Children with NF-1 have abnormal DTI metrics, particularly in the genu, and elevated whole-brain mean diffusivity. NF-1-related microstructural abnormalities of the corpus callosum are detectable in childhood and likely persist through myelination maturation.

 

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[221]

TÍTULO / TITLE:  - Peritumoral edema following Gamma Knife radiosurgery as the primary treatment for intraventricular meningiomas.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 10. pii: S0967-5868(12)00445-6. doi: 10.1016/j.jocn.2012.03.041.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.03.041

AUTORES / AUTHORS:  - Nundkumar N; Guthikonda M; Mittal S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI 48201, USA.

RESUMEN / SUMMARY:  - Intraventricular meningiomas represent a small proportion of intracranial meningiomas. Stereotactic radiosurgery (SRS) as a primary treatment for intraventricular meningiomas has been reported only recently. We present two patients with trigonal meningiomas who developed peritumoral edema 5months and 12months following SRS. The patients’ inability to wean off corticosteroids and progressive worsening of neurologic symptoms required eventual microsurgical resection of the intraventricular tumors. Follow-up MRI at 3 and 4 years after surgery demonstrated no evidence of tumor recurrence. Reports of patients with ventricular meningiomas treated primarily with Gamma Knife radiosurgery are sparse. To our knowledge, this is the first report of the development of extensive peritumoral edema following SRS for intraventricular meningioma. Larger case series with longer follow-up are required to define the incidence and timing of edema formation surrounding intraventricular meningiomas following treatment with radiosurgery.

 

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[222]

TÍTULO / TITLE:  - Expression of beta-catenin and E- and N-cadherin in human brainstem gliomas and clinicopathological correlations.

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

REVISTA / JOURNAL:  - Int J Neurosci. 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 3109/00207454.2012.758123

AUTORES / AUTHORS:  - Wu W; Tian Y; Wan H; Ma J; Song Y; Wang Y; Zhang L

INSTITUCIÓN / INSTITUTION:  - 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital, Medical University , Beijing 100050 , China.

RESUMEN / SUMMARY:  - Abstract Brainstem gliomas are usually associated with serious dysfunction and poor prognosis especially for diffuse intrinsic brainstem gliomas, however the reasons are still unclear. Some clinical studies have suggested that the invasive ability may be different among brainstem gliomas, and the dysfunction of beta-catenin and E- and N-cadherin appears to be connected with tumor invasion and progression. In this study, the expression of beta-catenin and E- and N-cadherin was detected in 40 brainstem glioma samples using immunochemistry and  was further analyzed in 18 samples using reverse transcription-polymerase chain reaction. The clinicopathological characteristics were also analyzed. The results show that there was no obvious staining for E-cadherin, but weak expression at the mRNA level could be seen in a few samples. The protein and mRNA expression levels of beta-catenin and N-cadherin were significantly associated with the pathological grades of brainstem gliomas. No significant differences in the expression levels of beta-catenin and N-cadherin were observed for age, sex, location, or diffuse growing pattern. The overall survival of patients with low beta-catenin expression was longer than that with high beta-catenin expression, and there was a trend toward increased expression of N-cadherin with shorter survival, however both of them had no statistical differences. These results demonstrate that expression of beta-catenin and N-cadherin is associated with the malignant progression of brainstem gliomas but not correlated with the diffuse and invasive growing pattern. beta-catenin and N-cadherin are potential therapeutic targets and prognostic markers for brainstem glioma, which need to be validated in a larger patient cohort.

 

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[223]

TÍTULO / TITLE:  - Identification of venous sinus, tumor location, and pial supply during meningioma surgery by transdural indocyanine green videography.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121113

AUTORES / AUTHORS:  - Ueba T; Okawa M; Abe H; Nonaka M; Iwaasa M; Higashi T; Inoue T; Takano K

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Object Indocyanine green (ICG) videography is commonly used in the neurosurgical  field for minimally invasive neurosurgery. The aim of this study was to evaluate  a new intraoperative imaging modality by performing transdural ICG videography during surgery for meningiomas. Methods Between March 2011 and April 2012, 10 patients with meningiomas received intravenous injection of 12.5 mg ICG just prior to dural opening. The cases comprised 8 convexity meningiomas and 2 foramen magnum meningiomas. Efficacy of the transdural ICG videography was assessed in terms of the tumor volume, the circulation time from the first appearance of the  vessel to the appearance of the venous sinus, the tendency to bleed, and the discrimination of the venous sinus. Results The mean tumor volume was 71.6 +/- 87.9 ml (the mean is expressed +/- SD throughout). The cortical arteries, veins,  and the venous sinus were identified by the ICG videography transdurally. The projection of the meningiomas was identified by a shadow (which the authors call  the eclipse sign). Total eclipse signs were obtained in 8 cases and partial eclipse signs were obtained in 2 cases; tumor volume in the latter was more than  200 ml. In 5 of 10 cases the adjacent venous sinuses were exposed and were successfully visualized by ICG videography in 5.92 +/- 1.05 seconds from the first appearance of the vessel. In 5 of 10 cases the total and the partial eclipse signs were diminished in 3.46 +/- 1.31 seconds. The diminishment of the total and the partial eclipse sign was earlier than the visualization of the venous sinus (p = 0.011, t-test), revealing bleeding from the tumor that was observed until coagulation of the feeding arteries from the intracranial arteries. Conclusions Prior to opening of the dura mater, transdural ICG videography was used successfully to visualize the dural attachment of meningiomas and the venous sinus, resulting in safe and appropriate dural opening. The diminishment of the total and partial eclipse signs may represent significant feeding from the intracranial arteries and a tendency to bleed during resection.

 

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[224]

TÍTULO / TITLE:  - A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c.

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

REVISTA / JOURNAL:  - Curr Med Chem. 2013 Jan 4.

AUTORES / AUTHORS:  - Chen CH; Xiao WW; Jiang XB; Wang JW; Mao ZG; Lei N; Fan X; Song BB; Liao CX; Wang HJ; She ZG; Zhu YH

INSTITUCIÓN / INSTITUTION:  - Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, China. zhuyongh@mail.sysu.edu.cn.

RESUMEN / SUMMARY:  - Objective: We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims  of this study were to observe the effectiveness of SZ-685C on pituitary adenoma cells and determine the underlying mechanisms of action. Methods: A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ-685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V-FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ-685C. The effect of SZ-685C on prolactin expression was also evaluated using RT-PCR and immunoblotting. Quantitative RT-PCR was used to detect the expression of miR-200c in SZ-685C-stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR-200c mimic to identify  the mechanism underling the anti-tumor effect of SZ-685C. Results: SZ-685C inhibited MMQ cell growth in a dose-dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ-685C in MMQ cells and RPCs were 13.2 +/- 1.3 muM and 49.1 +/- 11.5 muM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ-685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR-200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR-200c was observed in SZ-685C-treated MMQ cells. Furthermore, the overexpression of miR-200c weakened the effect of SZ-685C-induced apoptosis of MMQ cells. Conclusions: Our results suggest that SZ-685C induces MMQ cell apoptosis in a miR-200c-dependent manner. Therefore, SZ-685C might be a useful alternative treatment for pituitary adenoma.

 

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[225]

TÍTULO / TITLE:  - Current and Future Therapeutic Approaches for Metastatic Pheochromocytoma and Paraganglioma: Focus on SDHB Tumors.

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

REVISTA / JOURNAL:  - Horm Metab Res. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1331211

AUTORES / AUTHORS:  - Matro J; Giubellino A; Pacak K

INSTITUCIÓN / INSTITUTION:  - Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National  Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

RESUMEN / SUMMARY:  - As a result of intense genetic studies of families with specific mutations, the road to better therapeutic intervention for pheochromocytoma (PHEOs) and parangangliomas (PGLs) has more recently become populated with several promising  molecular targets. Consequently a change in paradigm from a previous view on nonspecific therapy has shifted towards more selective molecular targeted therapies. In particular, malignant PHEOs/PGLs, more specifically the tumors that result from mutations in succinate dehydrogenase subunit B (SDHB), are a clear concern, and novel therapies should be developed to address this problem. Here we summarize current and future therapeutic approaches.

 

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[226]

TÍTULO / TITLE:  - Innervated ectopic salivary gland associated with Rathke’s cleft cyst clinically  mimicking pituitary adenoma.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300560

AUTORES / AUTHORS:  - Stefanits H; Matula C; Frischer JM; Furtner J; Hainfellner JA; Woehrer A

RESUMEN / SUMMARY:  - Herein, we report an exceptional case of a young female patient with progressive  enlargement of a sellar mass, clinically suggestive of pituitary adenoma. Histopathology, however, demonstrated Rathke’s cleft cyst associated with salivary gland remnants. In contrast to the majority of prior reports, the ectopic salivary glands were found in close proximity to the anterior pituitary lobe and showed active production of mucous secret, which caused progressive growth and symptoms in this patient. We further demonstrate nerve fibers surrounding the ectopic salivary glands, thereby suggesting parasympathetic innervation as a plausible mechanism triggering seromucous secretion. Neurosurgeons and neuropathologists need to be aware of this rare clinical condition expanding the spectrum of differential diagnoses of sellar masses.

 

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[227]

TÍTULO / TITLE:  - Association study on MTHFR polymorphisms and meningioma in northern China.

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

REVISTA / JOURNAL:  - Gene. 2012 Dec 28. pii: S0378-1119(12)01528-4. doi: 10.1016/j.gene.2012.12.019.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2012.12.019

AUTORES / AUTHORS:  - Li R; Wang R; Li Y; Li X; Feng Y; Li Y; Jiang C

INSTITUCIÓN / INSTITUTION:  - The Third Ward of Neurosurgery, the Second Affiliated Hospital of Harbin Medical  University, Harbin 150086, China. Electronic address: ruiyanli@yeah.net.

RESUMEN / SUMMARY:  - BACKGROUND: Meningioma is the second most common primary tumor of the central nervous system, and multiple genetic and environmental factors contribute to its  etiology. Methylene tetrahydrofolate reductase (MTHFR) is a pivotal enzyme in folate metabolism. We conducted a case-control study to investigate the association of the MTHFR gene and meningioma in a Han population in northern China. METHODS: We genotyped two SNPs (C677T and A1298C) using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). In this study 317 meningioma patients were compared to 320 normal controls. Data were analyzed by SPSS 13.0 and HaploView software. RESULTS: We found a significant difference in the frequency distribution of 677CC and 677TT between cases and control groups; another SNP exhibited no differences in any genotype between the two cohorts. CONCLUSION: The results revealed that variations of the MTHFR gene were associated with meningioma; this finding indicates that the MTHFR gene potentially plays an important role in the pathogenesis of meningioma in the Northern Chinese Han population.

 

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[228]

TÍTULO / TITLE:  - Metabolic Mapping of Gliomas Using Hybrid MR-PET Imaging: Feasibility of the Method and Spatial Distribution of Metabolic Changes.

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

REVISTA / JOURNAL:  - Invest Radiol. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e31827188d6

AUTORES / AUTHORS:  - Bisdas S; Ritz R; Bender B; Braun C; Pfannenberg C; Reimold M; Naegele T; Ernemann U

INSTITUCIÓN / INSTITUTION:  - From the Departments of *Neuroradiology, daggerNeurosurgery, double daggerRadiology, section signNeurology, and parallelNuclear Medicine, Eberhard Karls University, Tubingen, Germany.

RESUMEN / SUMMARY:  - BACKGROUND AND PURPOSE: The most powerful adjunct to histopathology for the grading of gliomas seems to be the metabolic imaging using positron emission tomography and magnetic resonance spectroscopy (MRS). The purposes of this study  were to examine the feasibility of simultaneous acquisition of both techniques for purposes of tumor grading in a newly launched hybrid magnetic resonance positron emission tomography (MR-PET) and to examine the spatial distributions of metabolic changes in gliomas. MATERIALS AND METHODS: Twenty-eight consecutive patients with gliomas underwent simultaneous methionine (Met) MR-PET imaging for  detection of the most malignant tumor part before surgical sampling. After coregistration and fusion of MR-PET and MRS data, tumor to normal brain (T/N) Met uptake ratios and the corresponding metabolites peaks (choline [Cho], creatine [Cr], and N-acetylaspartate [NAA]) in MRS were recorded. The patients were divided into 4 types on the basis of the relation between the Met uptake area and the increased metabolite ratios: type I, the increased Met uptake area had at least 50% overlap or was completely within the area of increased Cho/NAA ratio; type II, the increased Met uptake site had less than 50% overlap of increased Cho/NAA ratio site; type III, the increased Met uptake region had no spatial relationship with the “hot” lesions in the MRS maps; and type IV, there was no pathologically increased Met uptake. The surgical sampling was performed in the tumor part with the highest Met uptake and, in the absence of increased Met accumulation, in the site with the highest Cho/NAA ratio. All surgical samples were referred to the neuropathology division for histological grading. RESULTS: A total of 16 low-grade gliomas (World Health Organization grade II) and 12 high-grade gliomas (World Health Organization grade III) were included. Three lesions (10%) of type I were identified. Four lesions (14%) were classified as type II and 6 lesions (21%) were classified as type 3, where the increased Met uptake region had no spatial relationship with the hot lesions in the MRS maps. In 15 of the 28 patients (54%), there was no increased Met accumulation (type 4 lesions). Maps of Cho/NAA and Cr/NAA showed a close spatial relationship in most  of the patients. Median T/N Met uptake ratio in the pooled surgically sampled tumor sites was 1.6 (range, 1-3), and median Cho/NAA and Cho/Cr ratios were 2.1 (range, 0.9-5.8) and 1.5 (range, 0.5-8.3), respectively. Spearman rank correlations of the metabolic markers in the low-grade gliomas showed significant correlations between Met uptake and Cr/NAA ratio (rho = 0.59; P= 0.015) as well as between Cho/NAA and Cr/NAA ratios (rho = 0.79; P = 0.0002). The normalized tumor creatine was significantly higher in anaplastic tumors compared with the low-grade gliomas (P = 0.001). A tendency for a significant positive correlation  was found between normalized tumor creatine and Met uptake in the anaplastic tumors. CONCLUSIONS: Metabolic mapping before histological sampling is feasible using simultaneous MR-PET imaging. High T/N Met uptake ratio reflecting high expression of amino-acid membrane transporters, which is indicative of proliferating tumor cell populations, does not always spatially correlate with neuronal cell loss and cell membrane proliferation (Cho/NAA) seen in MRS. Increased Cr/NAA is associated with increased methionine uptake in low-grade gliomas, whereas normalized creatine in tumor tends to correlate with methionine  accumulation, which indicates a possible coupling of these metabolic indices in anaplastic tumors. Thus, spatial distribution differences in gliomas should be taken into account when planning surgical sampling.

 

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[229]

TÍTULO / TITLE:  - A Pineal Region Germ Cell Tumor with Rapid Enlargement After a Long-term Follow-up.

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

REVISTA / JOURNAL:  - Neurosurgery. 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e318284708a

AUTORES / AUTHORS:  - Jinguji S; Fukuda M; Nagasaki K; Fujii Y

INSTITUCIÓN / INSTITUTION:  - 1Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan 2Division of Pediatrics, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.

RESUMEN / SUMMARY:  - BACKGROUND AND IMPORTANCE:: The natural history of pineal region germ cell tumors (GCTs) is not well known. We report a rare case of a pineal region GCT showing rapid enlargement within 2 months, after 7 years with no growth. CLINICAL PRESENTATION:: A boy presented with gonadotropin-independent precocious puberty at 6 years and 10 months of age. Although a slight elevation of beta-human chorionic gonadotropinbeta-HCG) suggested that a small pineal cystic lesion observed on magnetic resonance imaging might be an HCG-producing tumor, it was not clear whether the mass was truly a GCT. Accordingly, we followed the pineal lesion and serum pituitary-gonadotropin levels for approximately 7 years. After this period without essential tumor growth, the pineal tumor suddenly showed rapid enlargement, which prompted treatment. A histopathological investigation revealed a mixed GCT with a germinoma and an immature teratoma. Serum pituitary-gonadotropin levels at 5 years after the first examination had increased to normal pubertal ranges. Although the pituitary-gonadotropin levels had remained low during the period with no tumor growth, the gonadotropin levels  were elevated and had continued to increase at least 2 years before the rapid enlargement of the tumor. CONCLUSION:: These phenomena suggest that levels of neuroendocrinological parameters, such as pituitary-gonadotropin, at puberty might affect the enlargement of pineal region GCTs, which might account for the natural history of GCTs, i.e., their frequent detection at puberty.

 

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[230]

TÍTULO / TITLE:  - Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1044-3

AUTORES / AUTHORS:  - Hundsberger T; Brugge D; Putora PM; Weder P; Weber J; Plasswilm L

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Cantonal Hospital St. Gallen, Rorschacherstr. 95, 9007,  St. Gallen, Switzerland, thomas.hundsberger@kssg.ch.

RESUMEN / SUMMARY:  - The optimal treatment for recurrent high-grade gliomas is unknown and a standard  of care does not exist. Re-irradiation with concomitant bevacizumab represents an option. Retrospectively, we analyzed a cohort of heavily pretreated patients (n = 14) with relapsing HGGs who underwent re-irradiation with conventional 3D-conformal or intensified modulated radiotherapy (IMRT). Ten of them received re-irradiation in combination with bevacizumab. The study population consisted of eight GBMs and six anaplastic gliomas. All patients had previously undergone irradiation for first-line therapy, including seven patients with radiochemotherapy with temozolomide. Patients without contraindications started with two infusions of bevacizumab (10 mg/kg of body weight every other week) prior to re-irradiation and continued through re-irradiation until progression. The median patient age was 45 years with a median Karnofsky performance scale of  70. The median dose of re-irradiation was 41.6 Gy [39-55 Gy]. The median physical cumulative radiation dose was 101.6 Gy [65-110.4 Gy]. The median PFS from re-irradiation was 5.1 months [1.6-17.4] based on clinical and RANO criteria. Median OS from re-irradiation was 9.0 months [6.4-17.8]. We detected radionecrosis due to advanced imaging in one patient. Other toxicities were expected and attributable well known side effects of bevacizumab. This retrospective study provides additional feasibility and safety data of conventional 3D-conformal re-irradiation and IMRT in combination with bevacizumab in relapsing high-grade gliomas.

 

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[231]

TÍTULO / TITLE:  - Mutant TP53 enhances the resistance of glioblastoma cells to temozolomide by up-regulating O(6)-methylguanine DNA-methyltransferase.

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

REVISTA / JOURNAL:  - Neurol Sci. 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10072-012-1257-9

AUTORES / AUTHORS:  - Wang X; Chen JX; Liu YH; You C; Mao Q

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guo Xuexiang, Chengdu, 610041, Sichuan, China.

RESUMEN / SUMMARY:  - The “gain of function” of mutant TP53 is an important determinant in human tumor  development and progression. This study aimed to investigate the possible mechanism of mutant TP53 inducing temozolomide resistance in glioblastoma cells.  Three established human glioma cell lines, T98G, U87, and U138, were chemoresistant cells. The mRNA of cells was sequenced to confirm the status of TP53. Synthetic small interfering RNA (siRNA) was used to knock down TP53 in cells. TP53 mRNA was detected “silenced” by reverse transcriptase-polymerase chain reaction (RT-PCR) in five consecutive days. Viable cell survival was measured when these cells were exposed to temozolomide or semustine in step-up concentrations. The expression of O(6)-methylguanine DNA-methyltransferase (MGMT) at mRNA level was also determined. T98G, U87, and U138 cells were resistant to temozolomide. T98G and U138 cells expressed mutant-type TP53 with positive MGMT,  while U87 cell expressed wild-type TP53 with negative MGMT. TP53-siRNA knocked down TP53 effectively (P = 0.021) in five consecutive days. Knockdown of mutant TP53 in T98G and U138 cells led to a fivefold increase in chemosensitivity to temozolomide, but not semustine. Knockdown of wild TP53 in U87 cell did not affect the chemoresistance. In addition, mutant TP53 knockdown induced a dramatic decrease of MGMT expression (P = 0.0000034). TP53 mutation decreases the chemosensitivity of malignant gliomas to temozolomide. This “gain of function” in drug resistance may be obtained by increasing MGMT expression.

 

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[232]

TÍTULO / TITLE:  - Ten years of experience with microsurgical treatment of large and giant petroclival meningiomas.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Feb;20(2):238-43. doi: 10.1016/j.jocn.2012.02.025. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.02.025

AUTORES / AUTHORS:  - Fang T; Zhu H; Yan R; Yang J; Xing J; Li Y

INSTITUCIÓN / INSTITUTION:  - Department of Functional Neurosurgery, Xuanwu Hospital, Capital University of Medical Sciences, 45 Changchun Street, Haidian District, Beijing 100053, China. Electronic address: victorft369@yahoo.com.

RESUMEN / SUMMARY:  - During a 10-year period, 41 patients underwent surgery for resection of large or  giant petroclival meningiomas. Gross total resection (GTR) was accomplished in 25 patients (61.0%), subtotal resection (STR) in 15 patients (36.6%), and partial resection in one patient (2.4%). Postoperative complications were observed in 27  patients (65.9%). Postoperative radiosurgery was administered in six patients who had residual tumors. Survival and postoperative quality of life are the goals of  successful surgery on large or giant petroclival meningiomas, and the strategic surgical approach is based on the tumor location, the direction of growth, the invasion of adjacent structures, patient age and neurosurgeon expertise. Selectively pursuing STR with radiotherapy rather than GTR is a reasonable strategy.

 

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[233]

TÍTULO / TITLE:  - Laparoscopic vertical sleeve gastrectomy for the treatment of pseudotumor cerebri.

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

REVISTA / JOURNAL:  - Am Surg. 2013 Feb;79(2):61-2.

AUTORES / AUTHORS:  - Um S; Koleilat A; Dutson E; Mehran A

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, University of California-Los Angeles, Los Angeles, California, USA.

 

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[234]

TÍTULO / TITLE:  - Fractionated stereotactic radiotherapy for acoustic neuromas: A prospective monocenter study of about 158 cases.

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

REVISTA / JOURNAL:  - Radiother Oncol. 2012 Dec 4. pii: S0167-8140(12)00463-X. doi: 10.1016/j.radonc.2012.10.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2012.10.013

AUTORES / AUTHORS:  - Litre F; Rousseaux P; Jovenin N; Bazin A; Peruzzi P; Wdowczyk D; Colin P

INSTITUCIÓN / INSTITUTION:  - Hopital Maison Blanche, Reims Cedex, France. Electronic address: flitre@chu-reims.fr.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate long-term outcomes and efficacy of fractionated stereotactic radiotherapy in the treatment of acoustic neuromas. MATERIAL AND METHODS: Between January 1996 and December 2009, 158 acoustic neuromas were treated by FSR in 155  patients. They received a dose of 50.4Gy, with a safety margin of 1-2mm with a median tumor volume at 2.45mL (range: 0.17-12.5mL) and a median follow-up duration at 60months (range: 24-192). RESULTS: FSR was well tolerated in all patients with mild sequelae consisting in radiation-induced trigeminal nerve impairments (3.2%), Grade 2 facial neuropathies (2.5%), new or aggravated tinnitus (2.1%) and VP shunting (2.5%). The treatment failed in four patients (2.5%) who had subsequent surgery respectively at 20, 38, 45 and 84months post-FSR. The local tumor control rates were respectively 99.3%, 97.5% and 95.2%  at 3, 5 and >7-year of follow-up. For initial Gardner-Robertson Grade 1 and 2 ANs, the preservation of useful hearing was possible in 54% of the cases; only Grade 1 ANs had stabilized during the course of the follow-up with 71% >7years. However, hearing preservation was not correlated to the initial Koos Stage and to the radiation dose delivered to the cochlea. Tinnitus (70%), vertigo (59%), imbalance (46%) and ear mastoid pain (43%) had greatly improved post-FRS in most  patients. Tumor control, hearing preservation and FRS toxicity were quite similar in patients with NF2, cystic acoustic neuroma, prior surgical resection and Koos  Stage 4 AN. No secondary tumors were observed. CONCLUSION: FSR is a safe and effective therapeutic for acoustic neuromas and could be an alternative to microsurgery. Compared to radiosurgery, there are no contraindications for fractioned doses of stereotactic radiotherapy especially for Stage-4 tumors and patients at high risk of hearing loss.

 

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[235]

TÍTULO / TITLE:  - Body Mass Index Predicts Risk for Complications from Transtemporal Cerebellopontine Angle Surgery.

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

REVISTA / JOURNAL:  - Otolaryngol Head Neck Surg. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1177/0194599812471518

AUTORES / AUTHORS:  - Mantravadi AV; Leonetti JP; Burgette R; Pontikis G; Marzo SJ; Anderson D

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Loyola University of Chicago  Stritch School of Medicine, Maywood, Illinois, USA.

RESUMEN / SUMMARY:  - ObjectivesTo determine the relationship between body mass index (BMI) and risk for specific complications from transtemporal cerebellopontine angle (CPA) surgery for nonmalignant disease.Study DesignCase series with chart review.SettingTertiary-care academic hospital.Subjects and MethodsRetrospective review of 134 consecutive patients undergoing transtemporal cerebellopontine angle surgery for nonmalignant disease from 2009 to 2011. Data were collected regarding demographics, body mass index, intraoperative details, hospital stay, and complications including cerebrospinal fluid leak, wound complications, and brachial plexopathy.ResultsOne hundred thirty-four patients were analyzed with a  mean preoperative body mass index of 28.58. Statistical analysis demonstrated a significant difference in body mass index between patients with a postoperative cerebrospinal fluid leak and those without (P = .04), as well as a similar significant difference between those experiencing postoperative brachial plexopathy and those with no such complication (P = .03). Logistical regression analysis confirmed that body mass index is significant in predicting both postoperative cerebrospinal fluid leak (P = .004; odds ratio, 1.10) and brachial  plexopathy (P = .04; odds ratio, 1.07). Elevated body mass index was not significant in predicting wound complications or increased hospital stay beyond postoperative day 3.ConclusionRisk of cerebrospinal fluid leak and brachial plexopathy is increased in patients with elevated body mass index undergoing surgery of the cerebellopontine angle. Consideration should be given to preoperative optimization via dietary and lifestyle modifications as well as intraoperative somatosensory evoked potential monitoring of the brachial plexus to decrease these risks.

 

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[236]

TÍTULO / TITLE:  - Analysis of 60 Reported Glioma Risk SNPs Replicates Published GWAS Findings but Fails to Replicate Associations From Published Candidate-Gene Studies.

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

REVISTA / JOURNAL:  - Genet Epidemiol. 2013 Feb;37(2):222-8. doi: 10.1002/gepi.21707. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 1002/gepi.21707

AUTORES / AUTHORS:  - Walsh KM; Anderson E; Hansen HM; Decker PA; Kosel ML; Kollmeyer T; Rice T; Zheng S; Xiao Y; Chang JS; McCoy LS; Bracci PM; Wiemels JL; Pico AR; Smirnov I; Lachance DH; Sicotte H; Eckel-Passow JE; Wiencke JK; Jenkins RB; Wrensch MR

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of California, San Francisco, San  Francisco, California; Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.

RESUMEN / SUMMARY:  - Genomewide association studies (GWAS) and candidate-gene studies have implicated  single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated.  We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P < 0.05), with all associations in the same direction as in previous reports. Several SNP associations showed considerable differences across histologic subtype. All eight successfully replicated associations were first identified by GWAS, although none of the putative risk SNPs from candidate-gene studies was associated in the full case-control sample (all P values > 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes.

 

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[237]

TÍTULO / TITLE:  - Reduction in the recurrence of meningiomas by combining somatostatin receptor scintigraphy of 99mTc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held gamma-probe during surgery.

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

REVISTA / JOURNAL:  - Nucl Med Commun. 2013 Mar;34(3):249-53. doi: 10.1097/MNM.0b013e32835bdfc9.

            ●● Enlace al texto completo (gratuito o de pago) 1097/MNM.0b013e32835bdfc9

AUTORES / AUTHORS:  - Wang S; Yang W; Deng J; Zhang J; Ma F; Wang J

INSTITUCIÓN / INSTITUTION:  - Departments of aNuclear Medicine bNeurosurgery cPathology, Xijing Hospital, Fourth Military Medical University, Xi’an, China.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this study was to determine whether recurrence of meningiomas could be reduced by combining somatostatin receptor scintigraphy (SRS) of Tc-HYNIC-octreotide SPECT/CT and radio guidance with a hand-held gamma-probe during surgery. MATERIALS AND METHODS: Thirty patients with meningiomas diagnosed by MRI and considered as the study group were treated with Tc-HYNIC-octreotide SPECT/CT preoperatively and pathologically examined postoperatively. Another 60 patients considered as the control group underwent only an MRI preoperatively and a pathological examination postoperatively. For the patients in the study group,  meningiomas were removed by a hand-held gamma-probe 4-12 h after SRS; these patients were followed up by MRI examination each year for 5 years to monitor the recurrence rate of the meningiomas. For the control group, routine operations without radio guidance were performed and followed up with MRI examination simultaneously. RESULTS: All patients in the study group, comprising 20 with grade I and 10 with grade II meningiomas, showed high Tc-HYNIC-octreotide accumulation with a sensitivity of 100% for SRS; four patients (13.3%) relapsed after a 5-year follow-up, including one (5%) patient with a grade I and three (30%) patients with a grade II meningioma. However, among the 60 control patients, 30 were of grade I and 30 were of grade II; 18 patients (30%) experienced recurrence, including five (16.7%) grade I patients and 13 (43.3%) grade II patients. There were significant differences in recurrence between the study group and the control group when considering all the patients and those in  grade I and grade II (all P values were below 0.001). CONCLUSION: Tc-HYNIC-octreotide SPECT/CT SRS is a sensitive technique for detecting meningiomas, and radio guidance using a hand-held gamma-probe with Tc-HYNIC-octreotide during surgery can significantly reduce the recurrence of meningiomas.

 

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[238]

TÍTULO / TITLE:  - Microsurgical Resection of Large Medial Sphenoid Wing Meningiomas: Technique.

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

REVISTA / JOURNAL:  - Neurosurgery. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e318288a21f

AUTORES / AUTHORS:  - Rey-Dios R; Cohen-Gadol AA

INSTITUCIÓN / INSTITUTION:  - 1Goodman Campbell Brain and Spine, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 2Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS.

RESUMEN / SUMMARY:  - ABSTRACT: Resection of medial sphenoid wing meningiomas poses surgical challenges due to close contact with important cerebrovascular structures. The standard treatment for large tumors is microsurgical resection. Complete removal includes  maximal resection of the dura and any involved bone, but this approach is not always feasible when the tumor encases the arteries or cranial nerves. In these cases, there is evidence that a more conservative resection followed by radiation treatment can reduce operative morbidity with acceptable tumor control rates.In this 3-D video, the authors demonstrate their preferred technical nuances to resect a large middle to medial sphenoid wing meningioma. The patient is a 41-year-old man with a large left sphenoid wing meningioma found during routine imaging after a minor head trauma. MRI evaluation revealed minimal edema associated with this tumor. The resection was performed via a standard pterional  craniotomy and drilling of the sphenoid wing. Important steps in resection of this tumor include: 1) tumor devascularization extradurally and then intradurally, 2) tumor debulking, 3) microdissection of middle cerebral artery branches and corresponding perforators from tumor capsule, 4) identification of optic nerve and internal carotid artery at the skull base, and 5) tumor capsule dissection to expose the distal internal carotid artery and proximal middle cerebral artery. In this case, the tumor adhered to but did not encase the arterial trunks/perforators or the cranial nerves. Complete resection was achieved and most of the dura at the base of implantation was resected or heavily cauterized. The patient remained neurologically intact after surgery.

 

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[239]

TÍTULO / TITLE:  - Discovering gene-environment interactions in Glioblastoma through a comprehensive data integration bioinformatics method.

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

REVISTA / JOURNAL:  - Neurotoxicology. 2012 Dec 20. pii: S0161-813X(12)00264-1. doi: 10.1016/j.neuro.2012.11.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neuro.2012.11.001

AUTORES / AUTHORS:  - Kunkle B; Yoo C; Roy D

INSTITUCIÓN / INSTITUTION:  - Department of Environmental and Occupational Health, Florida International University, Miami, FL 33199, United States.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common and aggressive type of human brain tumor. Although considerable efforts to delineate the underlying pathophysiological pathways have been made during the last decades, only very limited progress on treatment have been achieved because molecular pathways that  drive the aggressive nature of GBM are largely unknown. Recent studies have emphasized the importance of environmental factors and the role of gene-environment interactions (GEI) in the development of GBM. Factors such as small sample sizes and study costs have limited the conduct of GEI studies in brain tumors however. Additionally, advances in high-throughput microarrays have  produced a wealth of information concerning molecular biology of glioma. In particular, microarrays have been used to obtain genetic and epigenetic changes between normal non-tumor tissue and glioma tissue. Due to the relative rarity of  gliomas, microarray data for these tumors is often the product of small studies,  and thus pooling this data becomes desirable. To address the challenge of small sample sizes and GEI study difficulties, we introduce a comprehensive bioinformatics method using genetic variations (copy number variations and small-scale variations) and environmental data integration that links with Glioblastoma (GEG) to identify: (1) genes that interact with chemicals and have genetic variants linked to the development of GBM, (2) important pathways that may be influenced by environmental exposures (or endogenous chemicals), and (3) genes with variants in GBM that have been understudied in relation to GBM development. The first step in our GEG method identified genes responsive to environmental exposures using the Environmental Genome Project, Comparative Toxicology, and Seattle SNPs databases. These environmentally responsive genes were then compared to a curated list of genes containing copy number variation and/or mutations in GBM. This comparison produced a list of genes responsive to the environment and important to GBM that was then further analyzed using gene networking tools such as RSpider, Cytoscape, and DAVID. Using this GEG bioinformatics method we were able to identify 173 genes with the potential to be involved in GEI that may be important to the development of GBM. Sixty five of these environmentally responsive genes have not been reported as important to GBM development, despite several of them having substantial potential for response to chemicals and subsequent disease related actions. The main biological functions of these 173 genes include signaling by Nerve Growth Factor, DNA Repair, Integrin Cell Surface Interactions, Biological Oxidations, Apoptosis, Synaptic Transmission, Cell Cycle Checkpoints, and Arachidonic Acid Metabolism. Importantly, some of these functions have been implicated in the development of several cancers, including glioma. In summary, our GEG bioinformatics approach revealed potential gene-environment interactions, and generated new data for hypothesis generation, in GBM.

 

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[240]

TÍTULO / TITLE:  - Expanding the spectrum of IDH1 mutations in gliomas.

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

REVISTA / JOURNAL:  - Mod Pathol. 2013 Jan 11. doi: 10.1038/modpathol.2012.210.

            ●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2012.210

AUTORES / AUTHORS:  - Gupta R; Flanagan S; Li CC; Lee M; Shivalingham B; Maleki S; Wheeler HR; Buckland ME

INSTITUCIÓN / INSTITUTION:  - 1] Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia [2] Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

RESUMEN / SUMMARY:  - Mutations in isocitrate dehydrogenase -1 or -2 (IDH1 or IDH2) are found in the majority of WHO grade II and III diffuse gliomas and secondary glioblastomas. IDH mutation screening is rapidly becoming part of the routine pathological work up of human brain tumors, providing both diagnostic and prognostic information. Here, we characterize four rare and novel IDH1 mutations identified in surgical human glioma samples: two instances of an IDH1 p.R132S mutation caused by a previously undescribed dinucleotide deletion/insertion mutation, a novel homozygous somatic IDH1 p.R132L mutation, and an IDH1 p.R100Q mutation. Characterization of novel and rare IDH mutations may provide additional insight into the mechanisms of mutant IDH in neoplasia. Furthermore, given the clinical import of IDH status, these results highlight the need for comprehensive mutation screening, beyond the targeted identification of common pathogenic variants.Modern Pathology advance online publication, 11 January 2013; doi:10.1038/modpathol.2012.210.

 

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[241]

TÍTULO / TITLE:  - Intracellular NAD(H) levels control motility and invasion of glioma cells.

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

REVISTA / JOURNAL:  - Cell Mol Life Sci. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00018-012-1249-1

AUTORES / AUTHORS:  - van Horssen R; Willemse M; Haeger A; Attanasio F; Guneri T; Schwab A; Stock CM; Buccione R; Fransen JA; Wieringa B

INSTITUCIÓN / INSTITUTION:  - Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences (NCMLS),  Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, r.vanhorssen@ncmls.ru.nl.

RESUMEN / SUMMARY:  - Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD(+) and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD(+)-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we  show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD(+) or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate  dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of  [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an  important metabolic component of cancer cell motility. Nutrient or drug-mediated  modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors.

 

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[242]

TÍTULO / TITLE:  - Survival of children with malignant brain tumors receiving valproate: a retrospective study.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Feb;29(2):195-7. doi: 10.1007/s00381-012-1997-0. Epub 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-1997-0

AUTORES / AUTHORS:  - Felix FH; de Araujo OL; da Trindade KM; Trompieri NM; Fontenele JB

INSTITUCIÓN / INSTITUTION:  - Pediatric Hemato-oncology Service, Hospital Infantil Albert Sabin, R Alberto Montezuma, 350, Vila Uniao, 60410-770, Fortaleza, Ceara, Brazil, heldercfelix@gmail.com.

RESUMEN / SUMMARY:  - PURPOSE: The treatment of pediatric patients with malignant brain tumors has evolved considerably in the past decades. However, results are still unsatisfactory for some patients. Valproate has been shown to positively affect the survival of adult glioblastoma patients. We have been giving prophylactic antiepileptic drugs to newly diagnosed children with brain tumors. Since then, we noted a trend towards a better survival from our patients. In order to study this, we performed a retrospective evaluation in our institution. METHODS: Standard survival analysis was used, calculating survival until death by all causes or censoring. Comparisons were made by Cox’s proportional hazards model regression. RESULTS: Between 2000 and 2010, 94 patients were treated (12 with high-grade gliomas, 56 medulloblastomas, and 26 ependymomas); median and mean ages were 7.7 and 7.8 years. Median follow-up was 60 months (35 for treated and 109 for untreated patients). Of these, 47 received valproate 10-15 mg/kg/day every 8-12 h and 47 did not. Patients who received valproate had a median survival of 34 months, whereas the other group had a median survival of 24 months (hazard ratios = 0.99, 0.57-1.75, p = 0.99). CONCLUSIONS: These results do not prove that valproate prophylactic treatment in pediatric patients with malignant  brain tumors had an influence on their survival. However, our cohort showed an effect of higher size than the recent European Organization for Research and Treatment of Cancer trial analysis, even though not significant. Clinical trials  with valproate in pediatric malignant brain tumors should be carefully planned, in order to detect a possible effect of this drug in survival.

 

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[243]

TÍTULO / TITLE:  - Familial isolated pituitary adenomas: An emerging clinical entity.

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

REVISTA / JOURNAL:  - J Endocrinol Invest. 2012 Dec;35(11):1003-14.

AUTORES / AUTHORS:  - Martucci F; Trivellin G; Korbonits M

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Barts and the London School of Medicine, Queen Mary  University of London, Charterhouse Square, London, UK, EC1M 6BQ.

RESUMEN / SUMMARY:  - Familial pituitary tumors are increasingly recognized. While some of these cases  are related to wellknown syndromic conditions such as multiple endocrine neoplasia type 1 (MEN1) or Carney complex, others belong to the familial isolated pituitary adenoma (FIPA) patient group. The discovery of heterozygous, loss-of-function germline mutations in the gene encoding the aryl hydrocarbon receptor interacting protein (AIP) in 2006 has subsequently enabled the identification of a mutation in this gene in 20% of FIPA families and 20% of childhood-onset simplex soma- totroph adenomas. The exact mechanism by which the  lack of AIP leads to pituitary adenomas is not clear. AIP mutations cause a low penetrance autosomal dominant disease with often a distinct phenotype characterized by young-onset, aggressive, large GH, mixed GH and PRL or PRL-secreting adenomas. This review aims to summarize currently available clinical data on AIP mutation-positive and negative FIPA patients.

 

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[244]

TÍTULO / TITLE:  - Expression of mRNAs of urocortin and corticotropin-releasing factor receptors in  malignant glioma cell lines.

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

REVISTA / JOURNAL:  - Anticancer Res. 2012 Dec;32(12):5299-307.

AUTORES / AUTHORS:  - Kamada M; Ikeda K; Fujioka K; Akiyama N; Akiyoshi K; Inoue Y; Hanada S; Yamamoto K; Tojo K; Manome Y

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Cell Biology, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, Japan 105-8461.

RESUMEN / SUMMARY:  - BACKGROUND: Urocortin and corticotropin-releasing factors (CRFs) and their receptors are expressed in many organs, including the central nervous system. In  this study, the expression of mRNAs of urocortin 1, 2, 3, and CRF and CRF receptors 1 and 2 in malignant glioma, was examined. MATERIALS AND METHODS: The RNAs of human and rat glioma cell lines were isolated. Transcripts in these cells were analyzed using cDNA. In addition, the effects of proliferative and cytotoxic stimulation by serum supplementation, ionizing radiation, and the antineoplastic  agent temozolomide were investigated. RESULTS: Human and rat cells transcribed urocortin. CRF receptors were detected in human glioma cells. When human KNS42 cells were exposed to stimulation, transcription was altered according to the specific condition. CONCLUSION: Expression of mRNAs of urocortin and CRF receptors was confirmed in human glioma cell lines. Although the quantities of transcripts varied with the proliferative and cytotoxic stimulation, the overall  transcription pattern was not influenced by these stimuli.

 

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[245]

TÍTULO / TITLE:  - Targeting Role of Glioma Stem Cells for Gliobastoma Multiforme.

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

REVISTA / JOURNAL:  - Curr Med Chem. 2013 Jan 7.

AUTORES / AUTHORS:  - Zhang X; Zhang W; Mao XG; Zhen HN; Cao WD; Hu SJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University,  Shaanxi Province, 710032, Xi’an, West Changle Road, No.127, People’s Republic of  China. xzhang@fmmu.edu.cn.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) represents the most common and lethal malignant primary brain tumor. Despite vigorous basic and clinical studies over the past decades, the prognosis of patients with GBM has remained dismal. The fundamental  problem with these malignancies is due to tumor cells’ highly infiltrative nature, precluding a complete surgical resection, and a productive or acquired resistance to cytotoxic therapy. Recent studies demonstrated that GBMs exhibited  remarkable cellular heterogeneity and hierarchy containing self-renewing glioma stem cells (GSCs). The malignant growth of GBM can be propagated and sustained by GSCs that are endowed with highly efficient clonogenic and tumor initiation capacities. GSCs can be identified with technique support and are responsible for the invasive potential and recurrence of GBMs. They share core signaling pathways with normal neural stem cells, but also display critical distinctions that provide important clues for useful therapeutic targets. Therefore, targeting GSCs becomes priorities for the development of novel therapeutic paradigms. Herein, we reviewed the existed and promising targeting therapies for GSCs which could effectively inhibit the tumor invasion, proliferation and recurrence of GBMs. Key features of GSCs, such as invasive growth pattern, angiogenic potential, resistance to traditional therapy and differentiation, were important therapeutic targets. More promising strategies should target GSCs themselves by taking advantages of high-throughput technologies and dissecting the intrinsic molecular nature of GSCs. Novel chemical medicines targeting these GSCs may represent one of the most important directions. Hopefully, this could shed a light on the road  we are going to.

 

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[246]

TÍTULO / TITLE:  - Oncology scan-high-grade gliomas.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):283-5. doi: 10.1016/j.ijrobp.2012.11.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.017

AUTORES / AUTHORS:  - Shih HA

 

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[247]

TÍTULO / TITLE:  - PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):921-8. doi: 10.3892/ijo.2013.1765. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1765

AUTORES / AUTHORS:  - Moon SH; Kim DK; Cha Y; Jeon I; Song J; Park KS

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Science, College of Life Science, CHA University, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - Malignant gliomas are the most common primary brain tumor in adults. A number of  genes have been implicated in glioblastoma including mutation and deletion of PTEN. PTEN is a regulator of PI3K-mediated Akt signaling pathways and has been recognized as a therapeutic target in glioblastoma. To achieve potent therapeutic inhibition of the PI3K-Akt pathway in glioblastoma, it is essential to understand the interplay between the regulators of its activation. Here, ectopic expression  of PTEN in the U-87MG human glioblastoma-astrocytoma cell line is shown to result in the depletion of glioblastoma stem cells (GSCs) and to cause growth retardation and senescence. These effects are likely to be associated with PTEN-mediated cooperative perturbation of Akt and Stat3 signals. Using an in vivo rat model of glioblastoma, we showed that PTEN-overexpressing U-87MG cells failed to induce tumor formation, while untreated U-87MG cells did so. Furthermore, cells expressing the phosphorylated form of Stat3 were completely absent from the brain of rats implanted with PTEN-overexpressing U-87MG cells. Based on these results, PTEN appears to function as a crucial inhibitor of GSCs and as an inducer of senescence, suggesting that functional enhancement of the PTEN pathway will be useful to provide a therapeutic strategy for targeting glioblastoma.

 

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[248]

TÍTULO / TITLE:  - Proteins involved in regulating bone invasion in skull base meningiomas.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1577-9

AUTORES / AUTHORS:  - Salehi F; Jalali S; Alkins R; Lee JI; Lwu S; Burrell K; Gentili F; Croul S; Zadeh G

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 4W-439, Toronto, ON, M5T 2S8, Canada, fsalehi@uwo.ca.

RESUMEN / SUMMARY:  - BACKGROUND: Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins  implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion. METHODS: Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations.  RESULTS: MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas. CONCLUSIONS: We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

 

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[249]

TÍTULO / TITLE:  - Untethering of herniated left optic nerve after dopamine agonist treatment for giant prolactinoma.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1613-9

AUTORES / AUTHORS:  - Gkekas N; Primikiris P; Georgakoulias N

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Athens General Hospital G. Gennimatas, Mesogeion 154, Athens, Greece, P.C. 11526, nikolaosgkekasdr@yahoo.gr.

 

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[250]

TÍTULO / TITLE:  - Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2012 Dec 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-1988-1

AUTORES / AUTHORS:  - Kim YG; Jeon S; Sin GY; Shim JK; Kim BK; Shin HJ; Lee JH; Huh YM; Lee SJ; Kim EH; Park EK; Kim SH; Chang JH; Kim DS; Kim SH; Hong YK; Kang SG; Lang FF

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - PURPOSE: It was presented that mesenchymal stem cells (MSCs) can be isolated from western glioma specimens. However, whether MSCs exist in glioma specimens of different ethnicities is unknown. To verify the existence of MSCs in an independent cohort, we undertook studies to isolate MSCs from a group of Korean patients. We hypothesized that cells resembling MSCs that were deemed mesenchymal stemlike cells (MSLCs) exist in an independent cohort of Korean gliomas. METHODS: We cultured fresh glioma specimens using the protocols used for culturing MSCs. The cultured cells were analyzed with fluorescence-activated cell sorting (FACS)  for surface markers associated with MSCs. Cultured cells were exposed to mesenchymal differentiation conditions. To presume possible locations of MSLCs in the glioma, sections of glioma were analyzed by immunofluorescent labeling for CD105, CD31, and NG2. RESULTS: From nine of 31 glioma specimens, we isolated cells resembling MSCs, which were deemed Korean glioma stroma MSLCs (KGS-MSLCs).  KGS-MSLCs were spindle shaped and adherent to plastic. KGS-MSLCs had similar surface markers to MSCs (CD105(+), CD90(+), CD73(+), and CD45(-)). KGS-MSLCs were capable of mesenchymal differentiation and might be located around endothelial cells, pericytes, and in a disorganized perivascular area inside glioma stroma. CONCLUSIONS: We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume  that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.

 

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[251]

TÍTULO / TITLE:  - Antitumor efficacy on glioma models of PHA-848125, a multikinase inhibitor able to cross the blood brain barrier.

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

REVISTA / JOURNAL:  - Br J Pharmacol. 2013 Jan 24. doi: 10.1111/bph.12112.

            ●● Enlace al texto completo (gratuito o de pago) 1111/bph.12112

AUTORES / AUTHORS:  - Albanese C; Alzani R; Amboldi N; Degrassi A; Festuccia C; Fiorentini F; Gravina GL; Mercurio C; Pastori W; Brasca MG; Pesenti E; Galvani A; Ciomei M

INSTITUCIÓN / INSTITUTION:  - BU Oncology, Nerviano Medical Sciences, Nerviano, Milano, Italy.

RESUMEN / SUMMARY:  - BACKGROUND & PURPOSE: Malignant gliomas, the most common primary brain tumors, are highly invasive and neurologically destructive neoplasms with a very bad prognosis due to the difficulty to remove completely the mass by surgery and the  limited activity of current therapeutic agents. PHA-848125 is a multikinase inhibitor with broad antitumor activity in preclinical studies and good tolerability in Phase 1 studies, that could affect two main pathways involved in  glioma pathogenesis, the G1-S phase progression control pathway through the inhibition of CDKs and the signaling pathways mediated by tyrosine kinase growth  factor receptors, such as tropomyosin receptors. For this reason we tested PHA-848125 in glioma models. EXPERIMENTAL APPROACH: PHA-848125 was tested on a panel of glioma cell lines in vitro to evaluate inhibition of proliferation and mechanism of action. In vivo efficacy was evaluated on two glioma models both as  single agent and in combination with standard therapy. KEY RESULTS: When tested on a subset of representative glioma cell lines, PHA-848125 blocked cell proliferation, DNA synthesis and inhibited both cell cycle and signal transduction markers. Relevantly, PHA-848125 was also able to induce cell death through authophagy in all cell lines. Good antitumor efficacy was observed by oral route in different glioma models both with subcutaneous and intracranial implantation. Indeed, we demonstrate that the drug is able to cross the blood brain barrier. Moreover, the combination of PHA-848125 with temozolomide resulted in a synergistic effect and a clear therapeutic gain was also observed with a triple treatment adding PHA-848125 to radiotherapy and temozolomide. CONCLUSIONS  & IMPLICATIONS: All the preclinical data obtained so far suggest that PHA-848125  may become a useful agent in chemotherapy regimens for glioma patients and support its evaluation in phase 2 trials for this indication.

 

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[252]

TÍTULO / TITLE:  - Molecular recognition force spectroscopy study of the dynamic interaction between aptamer GBI-10 and extracellular matrix protein tenascin-C on human glioblastoma  cell.

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

REVISTA / JOURNAL:  - J Mol Recognit. 2013 Jan;26(1):46-50. doi: 10.1002/jmr.2242.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jmr.2242

AUTORES / AUTHORS:  - Li Y; Qiao H; Yan W; Zhang J; Xing C; Wang H; Zhang B; Tang J

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; Graduate University of Chinese Academy of Sciences, Beijing, 100049, China.

RESUMEN / SUMMARY:  - Molecular recognition force spectroscopy (MR-FS) was applied to investigate the dynamic interaction between aptamer GBI-10 and tenascin-C (TN-C) on human glioblastoma cell surface at single-molecule level. The unbinding force between aptamer GBI-10 and TN-C was 39 pN at the loading rate of 0.3 nN sec(-1) . A series of kinetic parameters concerning interaction process such as the unbinding force f(u) , the association rate constant k(on) , dissociation rate constant at  zero force k(off) , and dissociation constant K(D) for aptamer GBI-10/TN-C complexes were acquired. In addition, the interaction of aptamer GBI-10 with TN-C depended on the presence of Mg(2+) . This work demonstrates that MR-FS can be used as an attractive tool for exploring the interaction forces and dynamic process of aptamer and ligand at the single-molecule level. As a future perspective, MR-FS may be used as a potential diagnostic and therapeutic tool by  combining with other techniques. Copyright © 2012 John Wiley & Sons, Ltd.

 

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[253]

TÍTULO / TITLE:  - Staged surgery for sylvian fissure meningiomas without dural attachment: Report of two cases.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 2. pii: S0303-8467(12)00620-8. doi: 10.1016/j.clineuro.2012.12.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.010

AUTORES / AUTHORS:  - Aras Y; Akcakaya MO; Aydoseli A; Izgi N

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.

 

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[254]

TÍTULO / TITLE:  - Clinical, histological and imaging aspects of pleomorphic xanthoastrocytomas: the key is in the name.

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

REVISTA / JOURNAL:  - Arq Neuropsiquiatr. 2013 Jan;71(1):3-4.

AUTORES / AUTHORS:  - Lucato LT

INSTITUCIÓN / INSTITUTION:  - Instituto de Radiologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo.

 

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[255]

TÍTULO / TITLE:  - L1CAM stimulates glioma cell motility and proliferation through the fibroblast growth factor receptor.

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

REVISTA / JOURNAL:  - Clin Exp Metastasis. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10585-012-9555-4

AUTORES / AUTHORS:  - Mohanan V; Temburni MK; Kappes JC; Galileo DS

INSTITUCIÓN / INSTITUTION:  - Department of Biological Sciences, University of Delaware, Newark, DE, 19716.

RESUMEN / SUMMARY:  - The L1CAM cell adhesion/recognition molecule (L1, CD171) and fibroblast growth factor receptor (FGFR) both are expressed by human high-grade glioma cells, but their potential actions in controlling cell behavior have not been linked. L1 actions in cancer cells have been attributed mainly to integrin receptors, and we demonstrated previously that L1-stimulated glioma cell migration correlates with  integrin expression, increased focal adhesion kinase activation and focal complex turnover. Our analyses of datasets revealed FGFR is overexpressed in glioma regardless of grade, while ADAM10 metalloprotease expression increases with glioma grade. Here, we used dominant-negative and short hairpin RNA approaches to inhibit the activation of FGFR1 and expression of L1, respectively. An L1 peptide that inhibits L1-FGFR interaction and PD173074, a chemical inhibitor of FGFR1 activity, also were used to elucidate the involvement of L1-FGFR interactions on  glioma cell behavior. Time-lapse cell motility studies and flow cytometry cell cycle analyses showed that L1 operates to increase glioma cell motility and proliferation through FGFR activation. Shutdown of both L1 expression and FGFR activity in glioma cells resulted in a complete termination of cell migration in  vitro. These studies show for the first time that soluble L1 ectodomain (L1LE) acts on glioma cells through FGFRs, and that FGFRs are used by glioma cells for increasing motility as well as proliferation in response to activation by L1LE ligand. Thus, effective treatment of high-grade glioma may require simultaneous targeting of L1, FGFRs, and integrin receptors, which would reduce glioma cell motility as well as proliferation.

 

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[256]

TÍTULO / TITLE:  - Longitudinal Investigation of Adaptive Functioning Following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma.

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

REVISTA / JOURNAL:  - Int J Radiat Oncol Biol Phys. 2012 Dec 11. pii: S0360-3016(12)03730-3. doi: 10.1016/j.ijrobp.2012.10.031.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.031

AUTORES / AUTHORS:  - Netson KL; Conklin HM; Wu S; Xiong X; Merchant TE

INSTITUCIÓN / INSTITUTION:  - Department of Psychiatry and Behavioral Sciences, Kansas University School of Medicine-Wichita, Kansas.

RESUMEN / SUMMARY:  - PURPOSE: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was  investigated. METHODS AND MATERIALS: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were  conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the  follow-up period. RESULTS: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with  LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. CONCLUSIONS: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional  abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

 

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[257]

TÍTULO / TITLE:  - Central nervous system infiltration of a multiple cytokine-producing double-hit B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma with CC chemokine receptor 7 expression.

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

REVISTA / JOURNAL:  - Acta Oncol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.742961

AUTORES / AUTHORS:  - Nakayama S; Yokote T; Iwaki K; Hiraoka N; Hirata Y; Akioka T; Miyoshi T; Takayama A; Nishiwaki U; Masuda Y; Tsuji M; Hanafusa T

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine (I), Osaka Medical College , Takatsuki City, Osaka , Japan.

 

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[258]

TÍTULO / TITLE:  - Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO Grade II gliomas.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121100

AUTORES / AUTHORS:  - Goze C; Mansour L; Rigau V; Duffau H

INSTITUCIÓN / INSTITUTION:  - Hormone and Cell Biology Laboratory, Hopital Arnaud de Villeneuve, Montpellier University Medical Center;

RESUMEN / SUMMARY:  - Object The molecular profile of diffuse WHO Grade II gliomas involving the insular lobe, with a possible impact on outcome, is controversial. The authors undertook this study to investigate a possible difference of molecular patterns between purely insular Grade II gliomas and paralimbic Grade II gliomas that involve both the insular lobe and the frontal and/or temporal structures. Methods From a consecutive series of 47 patients who underwent resection of a Grade II glioma invading the insula, 2 subgroups were identified. The first subgroup included 11 patients with a purely insular tumor. The second subgroup included 36 patients with a paralimbic Grade II glioma also involving the frontal and/or temporal lobe. The authors searched systematically for TP53 mutations, 1p19q codeletion, and IDH1/IDH2 mutations. Results There was no significant difference  between the 2 subgroups with respect to 1p19q codeletion or TP53 mutations rates. Conversely, IDH1/IDH2 mutations were found in all 11 (100%) of the insular Grade  II gliomas but only 20 (55%) of 36 paralimbic Grade II gliomas (p = 0.008). Ten (28%) of the 36 patients in the paralimbic tumor group experienced a malignant transformation, and 6 of them died; whereas neither transformation nor death occurred in the insular tumor group (trend toward significance, p = 0.088). Conclusions These findings demonstrate for the first time distinct IDH1/IDH2 and  consequently distinct “triplenegative” patterns in purely insular versus paralimbic Grade II gliomas. Such findings could explain discrepancies reported in the literature, because insular and paralimbic gliomas have not been separated in previous reports. These results may enable physicians to refine the management of Grade II gliomas involving the insula according to the presence or lack of invasion of the frontal and/or temporal areas.

 

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[259]

TÍTULO / TITLE:  - A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia.

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

REVISTA / JOURNAL:  - Am J Med Genet A. 2013 Jan;161(1):203-7. doi: 10.1002/ajmg.a.35686. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ajmg.a.35686

AUTORES / AUTHORS:  - Kimura-Ohba S; Kagitani-Shimono K; Hashimoto N; Nabatame S; Okinaga T; Murakami A; Miyake N; Matsumoto N; Osaka H; Hojo K; Tomita R; Taniike M; Ozono K

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan. skimura@ped.med.osaka-u.ac.jp.

RESUMEN / SUMMARY:  - We reported on a male patient with rare leukoencephalopathy and skeletal abnormalities. The condition was first noticed as a developmental delay, nystagmus and ataxia at 1 year of age. At 4 years of age, he was diagnosed as hypomyelination with skeletal abnormalities from clinical features, brain magnetic resonance imaging (MRI) and skeletal X-rays. His brain MRI revealed diffuse hypomyelination. These findings suggested the classical type of Pelizaeus-Merzbacher disease (PMD) caused by proteolipid protein (PLP)-1 gene or  Pelizaeus-Merzbacher-like disease (PMLD). However, we found neither mutation nor  duplication of PLP-1. The patient had severe growth retardation and general skeletal dysplasia compatible with spondylo-epi-metaphyseal dysplasia; however the mutation of discoidin domain receptor (DDR) 2 gene was absent. The co-morbidity of hypomyelination with skeletal abnormalities is rare. We performed array CGH and no causal copy number variation was recognized. Alternatively, this condition may have been caused by a mutation of the gene encoding a molecule that functions in both cerebral myelination and skeletal development. © 2012 Wiley Periodicals, Inc.

 

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[260]

TÍTULO / TITLE:  - Cancer stem cells, cornerstone of radioresistance and perspectives for radiosensitization: glioblastoma as an example.

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

REVISTA / JOURNAL:  - Bull Cancer. 2012 Dec 1;99(12):1153-1160.

            ●● Enlace al texto completo (gratuito o de pago) 1684/bdc.2012.1666

AUTORES / AUTHORS:  - Chargari C; Moncharmont C; Levy A; Guy JB; Bertrand G; Guilbert M; Rousseau C; Vedrine L; Alphonse G; Toillon RA; Rodriguez-Lafrasse C; Deutsch E; Magne N

INSTITUCIÓN / INSTITUTION:  - Hopital d’instruction des armees du Val-de-Grace, service d’oncologie-radiotherapie, 74, boulevard de Port-Royal, 75230 Paris cedex, France, Institut Gustave-Roussy, Inserm 1030, departement de radiotherapie moleculaire, 39, rue Camille-Desmoulins, 94805 Villejuif cedex, France.

RESUMEN / SUMMARY:  - Cancer stem cells are a subject of increasing interest in oncology. In particular, several data suggest that cancer stem cells are involved in the mechanisms of tumor radioresistance, and may explain the therapeutic failures after radiotherapy. Because of its poor prognosis and high recurrence rate after  irradiation, glioblastoma model is often studied in the search for new radiosensitizers. There are several preclinical data suggesting that cancer stem  cells could be a potential therapeutic target for improving the biological effectiveness of radiation therapy. Through the example of glioblastoma, we review the main signaling pathways involved in the mechanisms of radiation resistance of cancer stem cells and for which pharmacological targeting could potentially enhance tumor radiosensitivity.

 

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[261]

TÍTULO / TITLE:  - Evaluation of helical tomotherapy in the treatment of high-grade gliomas near critical structures.

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

REVISTA / JOURNAL:  - Tumori. 2012 Sep-Oct;98(5):636-42. doi: 10.1700/1190.13206.

            ●● Enlace al texto completo (gratuito o de pago) 1700/1190.13206

AUTORES / AUTHORS:  - Donato V; Caruso C; Bressi C; Pressello MC; Salvati M; Delitala A; Delfini R

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, S Camillo-Forlanini Hospital, Rome, Italy. vdonato@scamilloforlanini.rm.it

RESUMEN / SUMMARY:  - BACKGROUND: Our purpose was to investigate the role of helical tomotherapy using  a simultaneous integrated boost technique for the treatment of high-grade gliomas near intracranial critical structures. METHODS AND MATERIALS: Of 27 patients treated with helical tomotherapy, 11 were eligible. Only patients whose tumors were within 0.5 cm of the optic chiasm, the optic nerve or the brainstem were included. The therapeutic approach was a simultaneous integrated boost, prescribing 66 and 60 Gy to the PTV1 and PTV2, respectively, in 30 fractions. All patients received concomitant temozolomide at a dose of 75 mg/m2 daily during radiation therapy. RESULTS: Of the 11 patients considered, 3 patients (27%) died  after 4 months from the completion of the combined treatment. Three patients (27%) presented local progression, and the median time to disease progression was 6 months (range, 1-12). Five patients (45%), at the time of this evaluation, did  not have signs or symptoms of recurrence or progression of the disease. Acute toxicity, evaluated during radiochemotherapy, was minimal, with all patients experiencing RTOG grade 0 and grade 1 toxicity. CONCLUSIONS: . Helical tomotherapy proved to be an effective and safe treatment modality, with an improvement of accuracy in delivery of high-dose radiotherapy despite the presence of nearby critical structures.

 

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[262]

TÍTULO / TITLE:  - Quantification of microvascular cerebral blood flux and late-stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI.

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

REVISTA / JOURNAL:  - NMR Biomed. 2013 Jan 21. doi: 10.1002/nbm.2915.

            ●● Enlace al texto completo (gratuito o de pago) 1002/nbm.2915

AUTORES / AUTHORS:  - Reynaud O; Geffroy F; Ciobanu L

INSTITUCIÓN / INSTITUTION:  - CEA, DSV, I2BM, NeuroSpin, LRMN, Gif sur Yvette, France.

RESUMEN / SUMMARY:  - Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma  cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size < 3 mm) when compared with healthy tissue. At a late developmental stage (tumor size > 3 mm), we observed a significant decrease in the cerebral blood flux inside the gliosarcoma (-33%, p < 0.01) and compartmentalization of the tumor (p < 0.05). FENSI flux maps delineated a low-flux tumor core (58 +/- 17 muL/min/cm(2) ) and higher vascularized regions around the tumor periphery (85 +/- 21 muL/min/cm(2) ). Histology was performed on 11 animals to finely probe the intratumor heterogeneity and microvessel density, and the results were compared with the information derived from FENSI flux maps. The hyper- and hypoperfused tumor regions revealed with FENSI at the late tumor developmental stage correlated well with the ratios of high and low blood vessel density (R(2) = 0.41) and fractional vascular surface (R(2) = 0.67) observed with fluorescence microscopy [cluster of differentiation 31 (CD31) staining]. Copyright © 2013 John Wiley & Sons, Ltd.

 

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[263]

TÍTULO / TITLE:  - Extracting MRS discriminant functional features of brain tumors.

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

REVISTA / JOURNAL:  - NMR Biomed. 2012 Dec 12. doi: 10.1002/nbm.2895.

            ●● Enlace al texto completo (gratuito o de pago) 1002/nbm.2895

AUTORES / AUTHORS:  - Fuster-Garcia E; Tortajada S; Vicente J; Robles M; Garcia-Gomez JM

INSTITUCIÓN / INSTITUTION:  - Biomedical Informatics Group (IBIME-ITACA), Universitat Politecnica de Valencia,  Valencia, España. elfusgar@upv.es.

RESUMEN / SUMMARY:  - The current challenge in automatic brain tumor classification based on MRS is the improvement of the robustness of the classification models that explicitly account for the probable breach of the independent and identically distributed conditions in the MRS data points. To contribute to this purpose, a new algorithm for the extraction of discriminant MRS features of brain tumors based on a functional approach is presented. Functional data analysis based on region segmentation (RSFDA) is based on the functional data analysis formalism using nonuniformly distributed B splines according to spectral regions that are highly  correlated. An exhaustive characterization of the method is presented in this work using controlled and real scenarios. The performance of RSFDA was compared with other widely used feature extraction methods. In all simulated conditions, RSFDA was proven to be stable with respect to the number of variables selected and with respect to the classification performance against noise and baseline artifacts. Furthermore, with real multicenter datasets classification, RSFDA and  peak integration (PI) obtained better performance than the other feature extraction methods used for comparison. Other advantages of the method proposed are its usefulness in selecting the optimal number of features for classification and its simplified functional representation of the spectra, which contributes to highlight the discriminative regions of the MR spectrum for each classification task. Copyright © 2012 John Wiley & Sons, Ltd.

 

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[264]

TÍTULO / TITLE:  - Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS121190

AUTORES / AUTHORS:  - Koutourousiou M; Gardner PA; Fernandez-Miranda JC; Paluzzi A; Wang EW; Snyderman CH

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Object Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique. Methods The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome. Results Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size,  and intraventricular or posterior fossa extension did not influence the surgical  outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1-114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up. Conclusions Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

 

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[265]

TÍTULO / TITLE:  - Inhibition of xenograft human glioma tumor growth by lentivirus-mediated gene transfer of alphastatin.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Mar;29(3):1101-7. doi: 10.3892/or.2012.2187. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2187

AUTORES / AUTHORS:  - Che H; Song J; Guo S; Wang W; Gao G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Second Affiliated Hospital, the Fourth Military Medical University, Xi’an 710038, P.R. China.

RESUMEN / SUMMARY:  - Angiogenesis is crucial for the development and metastasis of human brain glioma. Based on our previous successful construction of a lentivirus-mediated alphastatin (an endogenous angiogenesis inhibitor) gene transfer system and our findings that alphastatin exhibited potent inhibitory effects on the migration and differentiation of human umbilical vein endothelial cell lines (HUVECs) induced by vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro, here, we investigated the effect of using lentiviral vectors to overexpress alphastatin in human glioma cells to show whether sustained long-term expression of alphastatin diminishes tumor growth in a xenograft glioma model. We found that the transduced glioma cells sustainedly secreted alphastatin, which did not affect the proliferative ability of the glioma cells. Furthermore, tumor xenografts treated with the recombinant lentivirus were significantly smaller compared to the control xenografts and vascularity within the treated tumors was evidently decreased. Our data suggest that stable expression of alphastatin inhibits human glioma growth by inhibiting  angiogenesis, with a probable mechanism of suppressing the turnover of VE-cadherin membrane molecules.

 

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[266]

TÍTULO / TITLE:  - Value of endoscopy for maximizing tumor removal in endonasal transsphenoidal pituitary adenoma surgery.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.JNS112020

AUTORES / AUTHORS:  - McLaughlin N; Eisenberg AA; Cohan P; Chaloner CB; Kelly DF

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Center & Pituitary Disorders Program, John Wayne Cancer Institute at  Saint John’s Health Center, Santa Monica; and.

RESUMEN / SUMMARY:  - Object Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding  and removing residual adenoma after initial microscopic removal. Methods Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted  intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study. Results Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140)  of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor  removal in 54% (36/67) of the adenomas measuring >/= 2 cm in diameter and in 19%  (14/73) of the adenomas smaller than 2 cm in diameter (p < 0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of  endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of  endocrine-active adenomas had early remission. Conclusions After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.

 

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[267]

TÍTULO / TITLE:  - Gamma Knife surgery for hemifacial spasm related to cerebellopontine angle tumors.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:170-4. doi: 10.3171/2012.7.GKS12999.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.7.GKS12999

AUTORES / AUTHORS:  - Chang CS; Chuang CC; Wu MF; Liu WS; Tu HT; Huang CF

INSTITUCIÓN / INSTITUTION:  - School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

RESUMEN / SUMMARY:  - OBJECT: Most cases of tumor-related hemifacial spasm (HFS) are treated by open surgery. The authors report the effects of Gamma Knife surgery (GKS) on benign tumor-related HFS at a mean follow-up time of 84 months. METHODS: Between 2000 and 2011, 6 patients (5 women and 1 man) harboring single tumors of the cerebellopontine angle (4 meningiomas and 2 vestibular schwannomas [VSs]) and experiencing HFS underwent GKS as a primary treatment. The mean age of the patients at the time of radiosurgery was 52.7 years (range 45-60 years). The patients’ tumors lay within the radiosurgical target area. In the 4 cases of meningioma, the mean radiosurgical treatment volume was 5.3 cm(3) (range 1.2-9.6  cm(3)), and the mean radiosurgical tumor margin dose was 14.1 Gy (range 12-18 Gy); in the 2 cases of VS, the treatment volume was 2.5 cm(3) in 1 patient and 11.2 cm(3) in the other, and the margin doses were 11.5 and 12 Gy, respectively.  The mean duration of HFS symptoms was 15.5 months (range 3-36 months). RESULTS: The mean follow-up period was 84 months (range 40-110 months). Overall, 4 (66%) of the 6 patients experienced complete relief from HFS without medication after GKS and 1 patient obtained a good outcome. The mean time for improvement to be realized was 12.6 months (range 3-24 months). Only 1 patient failed to experience relief from HFS, and coincidentally, the tumor did not shrink in that case. In all 6 patients (100%), tumor growth was controlled at a mean follow-up of 56 months after GKS: in 5 patients the tumor had decreased in size and in the other  patient the tumor size remained unchanged. No new neurological deficit was noted  after GKS, and 1 patient with facial numbness reported improvement after tumor shrinkage. CONCLUSIONS: Gamma Knife surgery appears to be effective in treating benign tumor-related HFS and in controlling tumor growth. A reduction in tumor volume is related to spasm improvement. Although a time latency for spasm relief  is associated with GKS, minimal side effects are expected.

 

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[268]

TÍTULO / TITLE:  - Gamma Knife surgery for central neurocytomas.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:96-101. doi: 10.3171/2012.6.GKS12214.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.6.GKS12214

AUTORES / AUTHORS:  - Karlsson B; Guo WY; Kejia T; Dinesh N; Pan DH; Jokura H; Kawagishi J; van Eck AT; Horstmann GA; Yeo TT; Yamamoto M

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, National University Hospital, Singapore. nykuttram@yahoo.se

RESUMEN / SUMMARY:  - OBJECT: The optimal management of central neurocytoma (CN) remnants and recurrences is still not clear. To date no large series of patients treated with  Gamma Knife surgery (GKS) for CNs has been published. For that reason the authors decided to combine data from 5 different centers so that they could analyze the largest population of patients treated with GKS for CN currently available. METHODS: Data obtained in 42 patients who were treated for CN with GKS before July 1, 2010, were retrospectively collected and analyzed. The median prescribed  dose was 13 Gy (range 11-25 Gy). The follow-up time in these patients ranged from 0.5 to 14.7 years (mean 6.1 years, median 4.9 years). Eleven patients were followed up for 5-10 years and 9 patients for more than 10 years. All patients were alive and well at the closing of the study except 1 patient, who died of injuries sustained in a traffic accident. RESULTS: Two cases of local tumor progression and 2 cases of distant tumor recurrence occurred among the patient population, yielding 5- and 10-year tumor control rates of 91% and 81%, respectively. No permanent complications occurred. The findings were in line with results reported in earlier publications. Despite the high tumor control rate, enlargement of part of or the whole ventricular system was seen in 45% of patients. CONCLUSIONS: The high tumor control rate and the low complication rate  following GKS indicate that GKS is the preferred treatment for CN tumor remnants  or recurrences following microsurgery. However, data from longer follow-up times  in more patients are needed before this conclusion can be validated. The patients need to be closely monitored and potential hydrocephalus managed despite tumor control.

 

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[269]

TÍTULO / TITLE:  - Low-dose Gamma Knife surgery for nonfunctioning pituitary adenomas.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:84-8. doi: 10.3171/2012.6.GKS12986.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.6.GKS12986

AUTORES / AUTHORS:  - El-Shehaby AM; Reda WA; Tawadros SR; Abdel Karim KM

INSTITUCIÓN / INSTITUTION:  - Gamma Knife Center Cairo, Nasser Institute, Shobra, Egypt.

RESUMEN / SUMMARY:  - OBJECT: The primary concern when performing Gamma Knife surgery for pituitary adenoma is preservation of vision and pituitary function while achieving tumor growth control. Higher prescribed radiation doses are typically correlated with higher incidences of postradiosurgical hormone deficiencies. The goal of the present study was to retrospectively analyze the feasibility of using a lower prescribed radiation dose in the treatment of nonfunctioning pituitary adenomas and the effect of this dose on vision, pituitary function, and tumor growth control. METHODS: The study was conducted in 38 patients with nonfunctioning pituitary adenomas, who were treated between January 2002 and July 2008. Twenty-one patients were available for follow-up (13 men and 8 women). The mean follow-up period was 44 months (range 24-90 months). Nineteen patients had previously undergone surgery. Pituitary dysfunction developed after surgery in 3  patients. One patient had an abnormal pituitary hormone profile before radiosurgery due to an attack of pituitary apoplexy. Visual field defects were present in 12 patients. The prescribed radiation dose was 12 Gy in all patients.  The tumor volume ranged from 0.5 to 11.8 cm(3) (mean 4.8 cm(3)). The maximum dose to the visual pathway was kept below 10 Gy. The mean maximum dose delivered to the visual pathway was 7.9 Gy. RESULTS: The patients were followed up for a period of 24 to 90 months (mean 44 months). The size of the tumor decreased in 11 patients (52%) and remained stable in 9 patients (43%). In 1 patient there was tumor growth outside the previous radiation field (on the contralateral side). Among the 12 patients with visual field defects, 9 (75%) experienced an improvement and the remaining patients’ vision remained stable. In only 4 patients was the visual improvement associated with tumor shrinkage. The hormone  profile remained normal in all patients except for the 4 patients who had pituitary dysfunction before radiosurgery. CONCLUSIONS: The 12-Gy prescribed dose used in this study seems to be sufficient for producing tumor control while sparing the patient from radiation-induced pituitary dysfunction. In addition, visual improvement was reported in a number of cases. A larger series and longer  follow-up are required to confirm these results.

 

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[270]

TÍTULO / TITLE:  - Same-day stereotactic aspiration and Gamma Knife surgery for cystic intracranial  tumors.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:45-8. doi: 10.3171/2012.7.GKS121019.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.7.GKS121019

AUTORES / AUTHORS:  - Liu X; Yu Q; Zhang Z; Zhang Y; Li Y; Liu D; Jia Q; Zheng L; Xu D

INSTITUCIÓN / INSTITUTION:  - Gamma Knife Center, Department of Neurosurgery, Second Hospital of Tianjin Medical University, Tianjin, China.

RESUMEN / SUMMARY:  - OBJECT: The goal of this study was to evaluate the efficacy and safety of same-day stereotactic aspiration and Gamma knife surgery (GKS) for cystic intracranial tumors. METHODS: Between 1996 and 2007, 77 patients harboring cystic intracranial tumors underwent a same-day procedure of MRI-guided cyst aspiration  followed by GKS. The diagnoses were metastatic tumor in 43 patients, glial tumor  in 12 patients, vestibular schwannoma in 10 patients, craniopharyngioma in 9 patients, and hemangioblastoma in 3 patients. RESULTS: An improvement in symptoms was achieved in 68 patients (88.3%) immediately after cyst aspiration. The mean tumor volume in this group of patients was 25.1 cm(3) before aspiration and 11.1  cm(3) afterward. Hemorrhage during the course of aspiration was encountered in 1  patient. Transient nausea after cyst aspiration developed in 3 patients. There was no treatment-related hematoma, seizure, neurological deficit, or infection. The median follow-up period was 16 months (range 6-108 months). Tumor control was achieved in 50 (80.6%) of 62 patients who participated in follow-up for at least  6 months. CONCLUSIONS: The same-day stereotactic aspiration and GKS procedure was safe in patients with cystic brain tumors. Prompt symptom relief was obtained after cyst aspiration. The decrease in tumor volume following aspiration made GKS more effective because a higher prescription dose could be administered with a lower possibility of radiation-induced side effects.

 

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[271]

TÍTULO / TITLE:  - Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec;117 Suppl:17-22. doi: 10.3171/2012.7.GKS121001.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.7.GKS121001

AUTORES / AUTHORS:  - Higuchi F; Kawamoto S; Abe Y; Kim P; Ueki K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Dokkyo Medical University, Mibu, Tochigi, Japan.

RESUMEN / SUMMARY:  - OBJECT: Gamma Knife surgery (GKS) has gained increasing relevance in the treatment of metastatic brain tumors, but many metastatic tumors contain a large  cystic component and often exceed the size limit for GKS. For such lesions, the authors adopted a procedure in which stereotactic aspiration is first performed and followed immediately by GKS on the same day. In this paper, the authors describe this 1-day combined procedure and evaluate its efficacy. METHODS: Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration  of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were  examined. RESULTS: Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11  months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement. CONCLUSIONS: The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases.

 

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[272]

TÍTULO / TITLE:  - Combination of paclitaxel thermal gel depot with temozolomide and radiotherapy significantly prolongs survival in an experimental rodent glioma model.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1014-1

AUTORES / AUTHORS:  - Vellimana AK; Recinos VR; Hwang L; Fowers KD; Li KW; Zhang Y; Okonma S; Eberhart CG; Brem H; Tyler BM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Johns Hopkins University School of Medicine, 1550 Orleans Street CRB2 2M41, Baltimore, MD, 21231, USA.

RESUMEN / SUMMARY:  - OncoGel incorporates paclitaxel, a mitotic inhibitor, into ReGel, a thermosensitive gel depot system to provide local delivery, enhance efficacy and  limit systemic toxicity. In previous studies the alkylating agent temozolomide (TMZ) incorporated into a polymer, pCPP:SA, also for local delivery, and OncoGel  were individually shown to increase efficacy in a rat glioma model. We investigated the effects of OncoGel with oral TMZ or locally delivered TMZ polymer, with and without radiotherapy (XRT) in rats with intracranial gliosarcoma. Eighty-nine animals were intracranially implanted with a 9L gliosarcoma tumor and divided into 12 groups that received various combinations of 4 treatment options; OncoGel 6.3 mg/ml (Day 0), 20 Gy XRT (Day 5), 50 % TMZ-pCPP:SA (Day 5), or oral TMZ (50 mg/kg, qd, Days 5-9). Animals were followed  for survival for 120 days. Median survival for untreated controls, XRT alone or oral TMZ alone was 15, 19 and 28 days, respectively. OncoGel 6.3 or TMZ polymer alone extended median survival to 33 and 35 days, respectively (p = 0.0005; p < 0.0001, vs. untreated controls) with 50 % living greater than 120 days (LTS) in both groups. Oral TMZ/XRT extended median survival to 36 days (p = 0.0002), with  no LTS. The group that received OncoGel and Oral TMZ did not reach median survival with 57 % LTS (p = 0.0002). All other combination groups [OncoGel/XRT],  [TMZ polymer/XRT], [OncoGel/TMZ polymer], [OncoGel/TMZ polymer/XRT], and [OncoGel/oral TMZ/XRT] yielded greater than 50 % LTS (p < 0.0001 for each combination as compared to controls), therefore median survival was not reached.  OncoGel/TMZ polymer and OncoGel/oral TMZ/XRT had 100 % LTS (p < 0.0001 and p = 0.0001 vs. oral TMZ/XRT, respectively). These results indicate that OncoGel given locally with oral or locally delivered TMZ and/or XRT significantly increased the number of LTS and improved median survival compared to oral TMZ and XRT given alone or in combination in a rodent intracranial gliosarcoma model.

 

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[273]

TÍTULO / TITLE:  - Preoperative histological grading of meningiomas using apparent diffusion coefficient at 3T MRI.

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

REVISTA / JOURNAL:  - Eur J Radiol. 2013 Jan 9. pii: S0720-048X(12)00582-7. doi: 10.1016/j.ejrad.2012.11.037.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.11.037

AUTORES / AUTHORS:  - Watanabe Y; Yamasaki F; Kajiwara Y; Takayasu T; Nosaka R; Akiyama Y; Sugiyama K; Kurisu K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: yowatanabe@hiroshima-u.ac.jp.

RESUMEN / SUMMARY:  - PURPOSE: We assessed whether a high b-value DWI at b=4000s/mm(2) would discriminate the histopathological differentiation of the tumor grade of meningiomas, and also focused on the relationship between radiologic features and the tumor grade. MATERIALS AND METHODS: We acquired DWI at 3T with b=1000 and b=4000s/mm(2) in 77 patients (42, 31 and 4 patients were WHO grades I (G1), II (G2), and III (G3), respectively). The apparent diffusion coefficient (ADC) was measured by placing multiple regions of interest (ROIs) on ADC maps. The ADC values of each tumor were determined preoperatively from several ROIs, and expressed as the minimum (ADC(MIN)), mean (ADC(MEAN)), and maximum absolute values (ADC(MAX)). We evaluated the relationship between ADCs and histological findings, and assessed the radiologic features such as tumor location, tumor size, presence/absence of peritumoral edema, shape of the tumor, presence/absence of bone destruction or hyperplasia, status of contrast enhancement, presence/absence of calcification and cyst. RESULTS: ADCs of the meningiomas were inversely correlated with the histological grade of meningiomas. According to results of the discriminant analysis, the apparent log likelihood value was greatest for ADC(MIN) at b=4000. Furthermore, only the ADC(MIN) value at b=4000 was significantly correlated with the histological grade of meningiomas when we performed a multiple logistic regression analysis to identify the significant independent factors such as shape of tumor, presence/absence of bone destruction, status of contrast enhancement, presence/absence of cyst and ADC(MIN) at b=4000.  CONCLUSION: A meningioma with a low ADC(MIN) at a high b-value might imply a high-grade meningioma.

 

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[274]

TÍTULO / TITLE:  - The role of drebrin in glioma migration and invasion.

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

REVISTA / JOURNAL:  - Exp Cell Res. 2012 Nov 29. pii: S0014-4827(12)00454-5. doi: 10.1016/j.yexcr.2012.11.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.yexcr.2012.11.008

AUTORES / AUTHORS:  - Terakawa Y; Agnihotri S; Golbourn B; Nadi M; Sabha N; Smith CA; Croul SE; Rutka JT

INSTITUCIÓN / INSTITUTION:  - The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neurosurgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma. Recently, evidence is mounting to suggest that actin cytoskeleton dynamics are critical components of the cell invasion process. Drebrin is an actin-binding protein involved in the regulation of actin filament  organization, and plays a significant role in cell motility; however, the role of drebrin in glioma cell invasiveness has not yet been fully elucidated. Therefore, this study was aimed to clarify the role of drebrin in glioma cell morphology and cell motility. Here we show that drebrin is expressed in glioma cell lines and in operative specimens of GBM. We demonstrate that stable overexpression of drebrin  in U87 cells leads to alterations in cell morphology, and induces increased invasiveness in vitro while knockdown of drebrin in U87 cells by small interfering RNA (siRNA) decreases invasion and migration. In addition, we show that depletion of drebrin by siRNA alters glioma cell morphology in A172 GBM cell line. Our results suggest that drebrin contributes to the maintenance of cell shape, and may play an important role in glioma cell motility.

 

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[275]

TÍTULO / TITLE:  - Peptide-based glioma-targeted drug delivery vector gHoPe2.

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

REVISTA / JOURNAL:  - Bioconjug Chem. 2013 Jan 28.

            ●● Enlace al texto completo (gratuito o de pago) 1021/bc300370w

AUTORES / AUTHORS:  - Eriste E; Kurrikoff K; Suhorutsenko J; Oskolkov N; Copolovici DM; Jones S; Howl J; Laakkonen P; Langel U

RESUMEN / SUMMARY:  - Gliomas are therapeutically challenging cancers with poor patient prognosis. New  drug delivery strategies are needed to achieve more efficient chemotherapy-based  approach against brain tumors. The current paper demonstrates development of a tumor-targeted delivery vector that is based on a cell-penetrating peptide pVEC and a novel glioma-targeting peptide sequence gHo. The unique tumor-homing peptide gHo was identified using in vitro phage display technology. The novel delivery vector, which we designated as gHoPe2, was constructed by a covalent conjugation of pVEC, gHo and a cargo; the latter could be either a labeling moiety (such as a fluorescent marker) or a cytostatic entity. Using a fluorescent marker, we demonstrate efficient uptake of the vector in glioma cells and selective labeling of glioma xenograft tumors in a mouse model. This is the first time that we know where in vitro phage display has yielded an efficient, in vivo  working vector. We also demonstrate anti-tumor efficacy of the delivery vector gHoPe2 using a well-characterized chemotherapeutic drug doxorubicin. Vectorized doxorubicin proved to be more efficient than the free drug in a mouse glioma xenograft model after systemic administration of the drugs. In conclusion, we have characterized a novel glioma-homing peptide gHo, demonstrated development of a new and potential glioma-targeted drug delivery vector gHoPe2, and demonstrated the general feasibility of the current approach for constructing cell-penetrating peptide-based targeted delivery systems.

 

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[276]

TÍTULO / TITLE:  - The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.10.JNS12895

AUTORES / AUTHORS:  - Seidel K; Beck J; Stieglitz L; Schucht P; Raabe A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Inselspital, Bern University Hospital, Bern, Switzerland.

RESUMEN / SUMMARY:  - Object Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. Methods A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration  500 musec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively. Results The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months,  5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or  showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75%  of patients with irreversible DCS-MEP loss had permanent motor deficits. Conclusions Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

 

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[277]

TÍTULO / TITLE:  - Risk Factors of Central Nervous System Relapse In Mantle Cell Lymphoma.

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

REVISTA / JOURNAL:  - Leuk Lymphoma. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.767454

AUTORES / AUTHORS:  - Conconi A; Franceschetti S; Lobetti-Bodoni C; Stathis A; Casaluci GM; Ramponi A; Mazzucchelli L; Bertoni F; Ghielmini M; Gaidano G; Cavalli F; Zucca E

RESUMEN / SUMMARY:  - ABSTRACT Central nervous system (CNS) relapse has not been extensively studied in mantle cell lymphoma (MCL). We retrospectively analysed the risk factors and pattern of CNS relapse in consecutive MCL patients. We identified 142 cases of MCL treated from 1980 to 2011. Median age at diagnosis was 68 years; 82% of patients had advanced stage; extranodal disease was reported in 89% of cases, high serum lactate dehydrogenase (LDH) in 40%. Fourteen patients (10%) did not receive treatment at diagnosis. Chemotherapy was administered to 125 patients (88%), in 21 cases (15%) including drugs penetrating into the CNS or given intrathecally, 49 patients (35%) had rituximab. Ten patients had front-line autologous transplantation. After median follow-up of 7.9 years, CNS relapse occurred in 11 cases (7.8%) at a median of 13.8 months. Actuarial risk of CNS relapse was higher in patients with elevated LDH (P=0.002), higher International  Prognostic Index (IPI) scores (P=0.018) and blastoid histology (P<0.0001). Blastoid histology retained significance at multivariate analysis. Median survival after CNS relapse was 6.3 months. No front-line treatment reduced the risk of CNS relapse. Our analysis confirm the poor outcome of MCL after CNS relapse and may allow the identification of patients needing prophylaxis of CNS relapse.

 

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[278]

TÍTULO / TITLE:  - Artifacts in magnetic resonance imaging after surgical resection of brain tumors.

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

REVISTA / JOURNAL:  - Magn Reson Imaging. 2013 Jan 17. pii: S0730-725X(12)00430-4. doi: 10.1016/j.mri.2012.11.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.mri.2012.11.001

AUTORES / AUTHORS:  - Bagheri MH; Ahmadloo N; Rezaian S

INSTITUCIÓN / INSTITUTION:  - Medical Imaging Research Center, Namazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; Center for Evidence-Based Imaging, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School. Electronic address: bagherih@sums.ac.ir.

RESUMEN / SUMMARY:  - BACKGROUND: Since the advent of magnetic resonance imaging, metal artifacts have  posed an important diagnostic problem in different fields of medicine. However, this has not been systematically studied in patients undergoing surgery for brain tumors. OBJECTIVE: This study was planned to assess whether metal artifacts can occur in patients undergoing brain surgery without metallic implants. METHODS: Of 40 individuals who could be included because of having a pre- and postoperative MRI and a postoperative computed tomography (CT) scan or a conventional skull X-ray for the detection of metallic artifacts, 26 patients agreed to participate  in this study and gave informed consent. RESULTS: Twenty-six subjects, 12 males and 14 females, with an age range of 12 to 54 years, were included in the study.  Four patients were found to have gross metal particles in their postoperative brain CTs and were excluded. Of the remaining 22 subjects, 7 patients (31.8%) had metallic artifacts. CONCLUSION: Our study showed that simple bone drilling or chiseling during surgical manipulation of skull bones may result in separation of very tiny metal particles which can remain in the surgical site and cause artifacts in postoperative MRIs. This finding appeared to be independent of factors such as age, sex, tumor/incision site, tumor size, pathologic tumor type, total radiation dose, operation-MRI time interval and sequence of MRI.

 

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[279]

TÍTULO / TITLE:  - Accessibility of low-molecular-mass molecules to the median eminence and arcuate  hypothalamic nucleus of adult mouse.

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

REVISTA / JOURNAL:  - Cell Biochem Funct. 2013 Jan 24. doi: 10.1002/cbf.2953.

            ●● Enlace al texto completo (gratuito o de pago) 1002/cbf.2953

AUTORES / AUTHORS:  - Morita S; Miyata S

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy & Neuroscience, Nara Medical University840 Shijyo-cho, Kashihara City, Nara, 634-8521, Japan.

RESUMEN / SUMMARY:  - Blood-derived molecules are able to access to the median eminence (ME) and arcuate hypothalamic nucleus (Arc) due to the lack of the blood-brain barrier. In the present study, we examined the accessibility of low-molecular-mass (LMM) molecules into parenchyma in the ME and Arc of adult mice by administration of Dextran 3000 (Dex3k), Dex10k, Evans blue (EB) and fluorescein isothiocyanate (FITC). In the external zone of the ME, the fluorescence of Dex3k, EB and FITC tracers generated an intensity gradient from fenestrated capillary, but that of Dex10k was detected only between the inner and outer basement membrane of pericapillary space. The fluorescence of FITC in the external zone of the ME was  closely associated with axonal terminals and surrounded by cellular processes of  tanycytes-like cells and astrocytes. In the ependymal/internal zone of the ME and Arc, the fluorescence of all LMM tracers was seen at tanycytes-like cells and neurons. The fluorescence of EB and FITC in these regions was not detected when brains were fixed during or before the administration of tracers. The inhomogeneity of accessibility for fluorescent tracers depended on routes for tracer administration. Thus, the present study indicates that the accessibility of LMM blood-derived molecules to parenchyma depends on fenestration of the capillary in the external zone of the ME and active transport of ependymal cells  in the ependymal/internal zone of the ME and Arc. Copyright © 2013 John Wiley & Sons, Ltd.

 

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[280]

TÍTULO / TITLE:  - Pineal cysts in children: case-based update.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-2011-6

AUTORES / AUTHORS:  - Kahilogullari G; Massimi L; Di Rocco C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Ankara, Ankara, Turkey.

RESUMEN / SUMMARY:  - PURPOSE: Pineal cysts (PC) are found in children as often asymptomatic and without change in their size over the time. However, there are some debatable issues about their evolution and management in the pediatric population. The aim  of the present paper is to update the information regarding pathogenesis, clinical presentation, and management of these lesions. METHODS: All the pertinent literature was reviewed, and a meta-analysis of operated on cases was carried out. An illustrative case regarding the clinical evolution of a 13-year-old girl is also presented. RESULTS AND CONCLUSIONS: PC are often asymptomatic and do not evolve over the time. However, since there is a certain risk of clinical and/or radiological progression, or even sudden and severe clinical onset (apoplexy), both a clinical and radiological follow-up is recommended in the pediatric age. The surgical excision is usually limited to symptomatic patients or to cases with clear radiological evolution.

 

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[281]

TÍTULO / TITLE:  - Paraganglioma of the urinary bladder—clinicopathological, immunohistochemical and electron microscopy analysis—a case report.

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

REVISTA / JOURNAL:  - Coll Antropol. 2012 Sep;36(3):1041-3.

AUTORES / AUTHORS:  - Persec Z; Bukovic D; Persec J; Sovic T; Ljubanovic D; Lambasa S; Radan M; Babic I

INSTITUCIÓN / INSTITUTION:  - University of Zagreb, Dubrava University Hospital, Department of Urology, Zagreb, Croatia. zpersec@net.amis.hr

RESUMEN / SUMMARY:  - Tumors that grow within the adrenal medulla are called pheochromocytoma; when located extra-adrenal, they are called paraganglioma. Paraganglioma of the bladder are very rare, with only 180 reported cases. Less than 30 were malignant. We report a case of a 72-years old man with bladder paraganglioma who presented with painless hematuria. Urgent transurethral resection (TUR) was performed. Definitive pathohistological diagnosis was confirmed to imunohistochemical and electron microscopy. Clinical diagnostic showed normal value of epinephrine and norepinehrine in the urine. Scintigraphy of entire body and targeted pictures of  pelvis where taken 24, 48 and 72 hours after administration of RI. No loci of pathologic accumulation of 131-I MIBG where found. Computer tomography (CT) of pelvis and abdomen were normal. Considering staging and pathohistological analysis, we treated our patient with TUR and longtime follow-up afterworth.

 

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[282]

TÍTULO / TITLE:  - Primary intracranial soft tissue sarcoma in children and adolescents: a cooperative analysis of the European CWS and HIT study groups.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1020-3

AUTORES / AUTHORS:  - Benesch M; von Bueren AO; Dantonello T; von Hoff K; Pietsch T; Leuschner I; Claviez A; Bierbach U; Kropshofer G; Korinthenberg R; Graf N; Suttorp M; Kortmann RD; Friedrich C; von der Weid N; Kaatsch P; Klingebiel T; Koscielniak E; Rutkowski S

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria, martin.benesch@klinikum-graz.at.

RESUMEN / SUMMARY:  - Purely intracranial soft tissue sarcomas (ISTS) are very rare among children. A retrospective database analysis of the Cooperative Weichteilsarkom Studiengruppe  (CWS) and brain tumor (HIT) registries was conducted to describe treatment and long-term outcome of children and adolescents with ISTS. Nineteen patients from Germany, Austria and Switzerland were reported between 1988 and 2009. Median age  at diagnosis was 9.7 years (range, 0.5-17.8). Central pathological review was performed in 17 patients. Eleven patients underwent a total and five a subtotal tumor resection. A biopsy was done in one patient. In two patients no data concerning extent of initial resection was available. Radiotherapy was performed  in 15 patients (first-line, n = 11; following progression, n = 4). All but one patient received chemotherapy (first-line, n = 7, following progression, n = 5; first-line and following progression, n = 6). With a median follow-up of 5.8 years (range, 0.6-19.8) ten patients were alive in either first or second complete remission. Seven patients died due to relapse or progression and two were alive with progressive disease. Estimated progression-free and overall survival at 5 years were 47 % (+/-12 %) and 74 % (+/-10 %), respectively. About 50 % of patients with ISTS remain relapse-free after 5 years. Multimodality treatment including complete tumor resection and radio-/chemotherapy is required  to achieve sustained tumor control in patients with ISTS. Early initiation of postoperative non-surgical treatment seems to be important to prevent recurrence. Due to the intracranial localization local therapy should follow the recommendations used in brain tumors rather than in soft tissue sarcomas, whereas chemotherapy should be guided by histological subtype.

 

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[283]

TÍTULO / TITLE:  - Adult with cerebellar anaplastic pilocytic astrocytoma associated with BRAF V600E mutation and p16 loss.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300564

AUTORES / AUTHORS:  - Yeo YH; Byrne NP; Counelis GJ; Perry A

RESUMEN / SUMMARY:  - Pilocytic astrocytoma (PA) is the most common pediatric tumor, with the vast majority being benign (WHO Grade I). Herein, we present a rare sporadic (not radiation- or NF1-associated) anaplastic PA arising from the cerebellum of an adult patient. The diagnosis was based on the coexistence of classic PA and more  cellular foci, associated with both tumor necrosis and up to 27 mitoses per 10 high power fields. Based on these features, the tumor was felt to be equivalent in biological behavior to that of a WHO Grade III astrocytoma. Additional genetic studies revealed the presence of a BRAF V600E mutation. In comparison to the foci of classic PA, the malignant component showed increased p53 protein expression, decreased p16 protein expression, and hemizygous p16 gene deletion by FISH analysis. This case provides additional support for the concept of anaplastic transformation in PA and further elucidates the possible molecular pathways associated with malignant progression.

 

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[284]

TÍTULO / TITLE:  - Invariant Delineation of Nuclear Architecture in Glioblastoma Multiforme from The Cancer Genome Atlas Cohort.

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

REVISTA / JOURNAL:  - IEEE Trans Med Imaging. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1109/TMI.2012.2231420

AUTORES / AUTHORS:  - Chang H; Han J; Borowsky A; Loss L; Gray J; Spellman P; Parvin B

RESUMEN / SUMMARY:  - Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer  Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E)  stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, Multi-Reference Graph Cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The  proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear  features and their organization have identified (i) statistically significant subtypes based on several morphometric indices, (ii) whether each subtype can be  predictive or not, and (iii) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at:  http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for quality control.

 

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[285]

TÍTULO / TITLE:  - Intracranial phosphaturic mesenchymal tumors.

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

REVISTA / JOURNAL:  - J Neurosurg. 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.JNS12598

AUTORES / AUTHORS:  - Mathis DA; Stehel EJ Jr; Beshay JE; Mickey BE; Folpe AL; Raisanen J

INSTITUCIÓN / INSTITUTION:  - Division of Neuropathology.

RESUMEN / SUMMARY:  - Hypophosphatemia with osteomalacia may be due to a neoplasm that produces fibroblast growth factor 23 (FGF-23), which inhibits phosphate reabsorption in the kidneys. Most of these tumors occur in bone or soft tissue and occasionally in the head, although intracranial occurrence is very rare. This report describes a tumor that caused hypophosphatemia and osteomalacia and was located entirely in the right anterior cranial fossa. Radiologically, the tumor resembled a meningioma; histologically, it was a low-grade phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). After gross-total resection, the patient’s symptoms abated and laboratory values normalized. The authors also studied another PMTMCT initially diagnosed as a hemangiopericytoma that involved  the left anterior cranial fossa and ethmoid sinus, and reviewed reports of 6 other intracranial tumors that induced osteomalacia, 3 entirely in the anterior cranial fossa, 2 involving the anterior cranial fossa and ethmoid sinus, and 1 in the cavernous sinus. In older children or adults who have hypophosphatemia with osteomalacia and no personal or family history of metabolic, renal, or malabsorptive disease, a neoplasm should be suspected and an imaging workup that  includes the brain is warranted, with particular attention to the anterior cranial fossa. Additionally, because there are some overlapping histological features between PMTMCTs and hemangiopericytomas, it may be helpful to assess tumoral FGF-23 expression by reverse transcriptase polymerase chain reaction or immunohistochemical analysis in patients with oncogenic osteomalacia from an intracranial tumor diagnosed as, or resembling, hemangiopericytoma.

 

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[286]

TÍTULO / TITLE:  - Letter to the Editor: Incidental low-grade gliomas.

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

REVISTA / JOURNAL:  - J Neurosurg. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.2.JNS111956

AUTORES / AUTHORS:  - Pallud J; Mandonnet E

INSTITUCIÓN / INSTITUTION:  - Centre Hospitalier Sainte-Anne, Paris, France.

 

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[287]

TÍTULO / TITLE:  - Pre- and post-contrast three-dimensional double inversion-recovery MRI in human glioblastoma.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1057-y

AUTORES / AUTHORS:  - Harris RJ; Cloughesy TF; Pope WB; Godinez S; Natsuaki Y; Nghiemphu PL; Meyer H; Paul D; Behbahanian Y; Lai A; Ellingson BM

INSTITUCIÓN / INSTITUTION:  - Department of Radiological Sciences, David Geffen School of Medicine, University  of California Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA, 90024, USA.

RESUMEN / SUMMARY:  - Fluid attenuated inversion recovery (FLAIR) MRI sequences have become an indispensible tool for defining the malignant boundary in patients with brain tumors by nulling the signal contribution from cerebrospinal fluid allowing both  regions of edema and regions of non-enhancing, infiltrating tumor to become hyperintense on resulting images. In the current study we examined the utility of a three-dimensional double inversion recovery (DIR) sequence that additionally nulls the MR signal associated with white matter, implemented either pre-contrast or post-contrast, in order to determine whether this sequence allows for better differentiation between tumor and normal brain tissue. T1- and T2-weighted, FLAIR, dynamic susceptibility contrast (DSC)-MRI estimates of cerebral blood volume (rCBV), contrast-enhanced T1-weighted images (T1+C), and DIR data (pre- or post-contrast) were acquired in 22 patients with glioblastoma. Contrast-to-noise  (CNR) and tumor volumes were compared between DIR and FLAIR sequences. Line profiles across regions of tumor were generated to evaluate similarities between  image contrasts. Additionally, voxel-wise associations between DIR and other sequences were examined. Results suggested post-contrast DIR images were hyperintense (bright) in regions spatially similar those having FLAIR hyperintensity and hypointense (dark) in regions with contrast-enhancement or elevated rCBV due to the high sensitivity of 3D turbo spin echo sequences to susceptibility differences between different tissues. DIR tumor volumes were statistically smaller than tumor volumes as defined by FLAIR (Paired t test, P =  0.0084), averaging a difference of approximately 14 mL or 24 %. DIR images had approximately 1.5x higher lesion CNR compared with FLAIR images (Paired t test, P = 0.0048). Line profiles across tumor regions and scatter plots of voxel-wise coherence between different contrasts confirmed a positive correlation between DIR and FLAIR signal intensity and a negative correlation between DIR and both post-contrast T1-weighted image signal intensity and rCBV. Additional discrepancies between FLAIR and DIR abnormal regions were also observed, together suggesting DIR may provide additional information beyond that of FLAIR.

 

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[288]

TÍTULO / TITLE:  - Tryptophan PET in pretreatment delineation of newly-diagnosed gliomas: MRI and histopathologic correlates.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1043-4

AUTORES / AUTHORS:  - Kamson DO; Juhasz C; Buth A; Kupsky WJ; Barger GR; Chakraborty PK; Muzik O; Mittal S

INSTITUCIÓN / INSTITUTION:  - PET Center and Translational Imaging Laboratory, Children’s Hospital of Michigan, Detroit, MI, USA.

RESUMEN / SUMMARY:  - Pretreatment delineation of infiltrating glioma volume remains suboptimal with current neuroimaging techniques. Gadolinium-enhanced T1-weighted (T1-Gad) MR images often underestimate the true extent of the tumor, while T2-weighted images preferentially highlight peritumoral edema. Accumulation of alpha-[(11)C]methyl-L-tryptophan (AMT) on positron emission tomography (PET) has  been shown in gliomas. To determine whether increased uptake on AMT-PET would detect tumor-infiltrated brain tissue outside the contrast-enhancing region and differentiate it from peritumoral vasogenic edema, volumes and spatial concordance of T1-Gad and T2 MRI abnormalities as well as AMT-PET abnormalities were analyzed in 28 patients with newly-diagnosed WHO grade II-IV gliomas. AMT-accumulating grade I meningiomas were used to define an AMT uptake cutoff threshold that detects the tumor but excludes peri-meningioma vasogenic edema. Tumor infiltration in AMT-accumulating areas was studied in stereotactically-resected specimens from patients with glioblastoma. In the 28 gliomas, mean AMT-PET-defined tumor volumes were greater than the contrast-enhancing volume, but smaller than T2 abnormalities. Volume of AMT-accumulating tissue outside MRI abnormalities increased with higher tumor proliferative index and was the largest in glioblastomas. Tumor infiltration was  confirmed by histopathology from AMT-positive regions outside contrast-enhancing  glioblastoma mass, while no or minimal tumor cells were found in AMT-negative specimens. These results demonstrate that increased AMT accumulation on PET detects glioma-infiltrated brain tissue extending beyond the contrast-enhanced tumor mass. While tryptophan uptake is low in peritumoral vasogenic edema, AMT-PET can detect tumor-infiltrated brain outside T2-lesions. Thus, AMT-PET may  assist pretreatment delineation of tumor infiltration, particularly in high-grade gliomas.

 

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[289]

TÍTULO / TITLE:  - Glial cell-line derived neurotrophic factor (GDNF) replacement attenuates motor impairments and nigrostriatal dopamine deficits in 12-month-old mice with a partial deletion of GDNF.

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

REVISTA / JOURNAL:  - Pharmacol Biochem Behav. 2013 Jan 2. pii: S0091-3057(12)00356-5. doi: 10.1016/j.pbb.2012.12.022.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pbb.2012.12.022

AUTORES / AUTHORS:  - Littrell OM; Granholm AC; Gerhardt GA; Boger HA

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy and Neurobiology, Parkinson’s Disease Translational Research Center of Excellence, University of Kentucky Medical Center, 306 Davis Mills Bldg., 800 Rose St., Lexington, KY 40536, USA.

RESUMEN / SUMMARY:  - Glial cell-line derived neurotrophic factor (GDNF) has been established as a growth factor for the survival and maintenance of dopamine (DA) neurons. In phase I clinical trials, GDNF treatment in Parkinson’s disease patients led to improved motor function and asGDNF has been found to be down regulated in Parkinson’s disease patients. Studies using GDNF heterozygous (Gdnf(+/-)) mice have demonstrated that a partial reduction of GDNF leads to an age-related accelerated decline in nigrostriatal DA system- and motor-function and increased neuro-inflammation and oxidative stress in the substantia nigra (SN). Therefore,  the purpose of the current studies was to determine if GDNF replacement restores  motor function and functional markers within the nigrostriatal DA system in middle-aged Gdnf(+/-) mice. At 11months of age, male Gdnf(+/-) and wildtype (WT)  mice underwent bilateral intra-striatal injections of GDNF (10mug) or vehicle. Locomotor activity was assessed weekly 1-4weeks after treatment. Four weeks after treatment, their brains were processed for analysis of GDNF levels and various DAergic and oxidative stress markers. An intrastriatal injection of GDNF increased motor activity in Gdnf(+/-) mice to levels comparable to WT mice (1week after injection) and this effect was maintained through the 4-week time point. This increase in locomotion was accompanied by a 40% increase in striatal GDNF protein levels and SN GDNF expression in Gdnf(+/-) mice. Additionally, GDNF treatment significantly increased the number of tyrosine hydroxylase (TH)-positive neurons in the SN of middle-aged Gdnf(+/-) mice, but not WT mice, which was coupled with reduced oxidative stress in the SN. These studies further  support that long-term changes related to the dysfunction of the nigrostriatal pathway are influenced by GDNF expression and add that this dysfunction appears to be responsive to GDNF treatment. Additionally, these studies suggest that long-term GDNF depletion alters the biological and behavioral responses to GDNF treatment.

 

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[290]

TÍTULO / TITLE:  - Hypopituitarism Following Stereotactic Radiosurgery for Pituitary Adenomas.

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

REVISTA / JOURNAL:  - Neurosurgery. 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1227/NEU.0b013e3182846e44

AUTORES / AUTHORS:  - Xu Z; Lee Vance M; Schlesinger D; Sheehan JP

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, (Z.X., J.P.S.), Department of Medicine (M.L.V.), and Department of Radiation Oncology (D.S.), University of Virginia Health Sciences System, Charlottesville, Virginia 22908.

RESUMEN / SUMMARY:  - BACKGROUND:: Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS) -induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. OBJECTIVE:: We investigated the outcomes of SRS  for pituitary adenoma patients with regard to newly developed hypopituitarism. METHODS:: This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately prior to SRS and in regular follow-up. It consisted of  24-hour urine free cortisol (patients with Cushing’s disease), serum ACTH, cortisol, FSH, LH, IGF-1, GH, testosterone (men), PRL, TSH, and free T4. RESULTS:: Endocrine remission occurred in 144 of 199 patients with a functioning  adenoma. Tumor control rate was 89%. Eighty patients experienced at least one axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based upon endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years post-SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior RT, and age at SRS. CONCLUSION:: SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were two independent predictors of SRS-induced hypopituitarism.

 

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[291]

TÍTULO / TITLE:  - Profiling and sequencing of gangliosides from human caudate nucleus by chip-nanoelectrospray mass spectrometry.

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

REVISTA / JOURNAL:  - J Mass Spectrom. 2012 Dec;47(12):1561-70. doi: 10.1002/jms.3116.

            ●● Enlace al texto completo (gratuito o de pago) 1002/jms.3116

AUTORES / AUTHORS:  - Serb AF; Sisu E; Vukelic Z; Zamfir AD

INSTITUCIÓN / INSTITUTION:  - Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Sq. 2A, Timisoara, Romania.

RESUMEN / SUMMARY:  - Gangliosides (GGs), sialic acid-containing glycosphingolipids are involved in many brain functions at the cell and molecular level. Compositional and structural elucidation of GGs in mixtures extracted from human brain is essential for correlating their profile with the specialized function of each brain area in health and disease. As a part of our ongoing study on GG expression and structure in different healthy and diseased brain regions, in this work, a preliminary investigation of GGs in a specimen of human caudate nucleus (CN) was carried out  using an advanced mass spectrometry (MS) technique. By chip-nanoelectrospray MS performed on a NanoMate robot coupled to a high capacity ion trap instrument, 81  GG components were detected in human CN in only 1.5 min of signal acquisition. Although the native GG mixture from CN was found dominated by mono-, di- and trisialylated GGs with a slight dominance of disialylated forms (GD), four tetrasialylated structures (GQ) and two pentasialylated (GP) species were also identified. Additionally, species with unusually long fatty acid chains, exceeding 30 carbon atoms in their ceramide (Cer) composition, and several glycoforms modified by fucosyl (Fuc), O-acetyl (O-Ac) and/or lactonization were discovered. By tandem MS (MS(2) ) using collision-induced dissociation, two atypical mono and disialylated species with long-chain fatty acids in their Cer could be confirmed and structurally characterized. These results may be a starting point for new GG-based approaches in the study of CN functions and ethiopathogenesis of CN-related neurodegenerative disorders. Copyright © 2012 John Wiley & Sons, Ltd.

 

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[292]

TÍTULO / TITLE:  - Outcome of resection of infratemporal fossa tumors.

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

REVISTA / JOURNAL:  - Head Neck. 2013 Jan 16. doi: 10.1002/hed.23186.

            ●● Enlace al texto completo (gratuito o de pago) 1002/hed.23186

AUTORES / AUTHORS:  - Givi B; Liu J; Bilsky M; Mehrara B; Disa J; Pusic A; Cordeiro P; Shah JP; Kraus DH

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology, Head and Neck Surgery, New York University, New York, NY. babak.givi@nyumc.org.

RESUMEN / SUMMARY:  - BACKGROUND: A variety of tumors arise in or extend to the infratemporal fossa. We investigated the outcome of surgical management of these tumors. METHODS: We conducted a retrospective review of a craniofacial approach to resection of infratemporal fossa tumors from 1992 to 2008 in a cancer center. RESULTS: Forty-three patients underwent resection of a infratemporal fossa tumors (68% men). Median age was 46 years (range, 1-81 years). The most common pathology was  sarcoma (13; 30%). Twenty-two tumors (51%) were recurrent. Twenty patients (46%)  underwent resection of tumors from the infratemporal fossa, 5 (12%) required resection of the anterior skull base, and 18 (42%) required orbital exenteration, additionally. Thirty-one patients (72%) required reconstruction with free tissue  transfer. Twenty-seven patients (62.8%) required further treatment with radiation and/or chemotherapy. Complications occurred in 9 patients (21%). Six patients (14%) underwent salvage operations. Median follow-up was 24 months. Median overall survival and 3-year survival were 40 months and 59.6%. CONCLUSION: Tumors involving the infratemporal fossa can be resected with acceptable morbidity and long-term survival. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.

 

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[293]

TÍTULO / TITLE:  - Computer-aided detection of metastatic brain tumors using magnetic resonance black-blood imaging.

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

REVISTA / JOURNAL:  - Invest Radiol. 2013 Feb;48(2):113-9. doi: 10.1097/RLI.0b013e318277f078.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e318277f078

AUTORES / AUTHORS:  - Yang S; Nam Y; Kim MO; Kim EY; Park J; Kim DH

INSTITUCIÓN / INSTITUTION:  - From the *Department of Electrical and Electronic Engineering, Yonsei University, Seoul, Korea; daggerDepartment of Radiology, University Hospital, Cincinnati, OH; and double daggerDepartment of Brain and Cognitive Engineering, Korea University, Seoul, Korea.

RESUMEN / SUMMARY:  - OBJECTIVES: The objective of this study was to develop a computer-aided detection system for automated brain metastases detection using magnetic resonance black-blood imaging and compare its applicability with conventional magnetization-prepared rapid gradient echo (MP-RAGE) imaging. MATERIALS AND METHODS: Twenty-six patients with brain metastases were imaged with a contrast-enhanced, 3-dimensional, whole-brain magnetic resonance black-blood pulse sequence. Approval from the institutional review board and informed consent from the patients were obtained. Preprocessing steps included B1 inhomogeneity correction and brain extraction. The computer-aided detection system used 3-dimensional template matching, which measured normalized cross-correlation coefficient to generate possible metastases candidates. An artificial neural network was used for classification after various volume features were extracted. The same detection procedure was tested with contrast-enhanced MP-RAGE, which was also acquired from the same patients. RESULTS: The performance of the proposed detection method was measured by the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity values. In the black-blood case, detection process displayed an AUROC of 0.9355, a sensitivity value of 81.1%, and a specificity value of 98.2%. Magnetization-prepared rapid gradient echo data showed an AUROC of 0.6508, a sensitivity value of 30.2%, and a specificity value of 99.97%. CONCLUSIONS: The results demonstrate that accurate automated detection of metastatic brain tumors using contrast-enhanced black-blood imaging sequence is possible compared with using conventional contrast-enhanced MP-RAGE sequence.

 

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[294]

TÍTULO / TITLE:  - Marked improvement in opsoclonus and cerebellar ataxia after the surgical removal of a squamous cell carcinoma of the thymus: A case report.

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

REVISTA / JOURNAL:  - J Neurol Sci. 2013 Feb 15;325(1-2):156-9. doi: 10.1016/j.jns.2012.11.011. Epub 2012 Dec 9.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jns.2012.11.011

AUTORES / AUTHORS:  - Yamaguchi Y; Wada M; Tanji H; Kurokawa K; Kawanami T; Ohtake H; Kato T

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan.

RESUMEN / SUMMARY:  - A 69-year-old man with rapidly evolving vertigo and ataxia was admitted to our hospital. He was presented with a dysarthric speech and chaotic eye movements, identified as opsoclonus. Neurological examination revealed limb and truncal ataxias and an inability to stand unless fully assisted. A chest CT scan revealed a mass at the anterior mediastinum, which suggested paraneoplastic neurological syndrome (PNS). However, an extensive search for anti-neuronal antibodies linked  to cerebellar ataxia failed to find any autoantibodies, including cell surface autoantibodies. Subsequently, a total surgical removal of the thymic tumor was performed, leading to marked improvements in his signs and symptoms. The pathological findings by conventional and immunohistochemical examinations confirmed a squamous cell carcinoma of the thymus. Three months after onset his signs and symptoms improved and he was able to walk without support. In contrast  to thymomas, PNS is extremely rare in patients with thymic carcinoma. Previous reports have shown that neurological symptoms, similar to opsoclonus or cerebellar ataxia, deteriorated in cases of thymic carcinoma that could not be controlled. The present report indicates that early diagnosis and total removal of the rare neoplasm may increase the possibility of neurological recovery.

 

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[295]

TÍTULO / TITLE:  - Towards MIB-1 and p53 detection in glioma magnetic resonance image: a novel computational image analysis method.

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

REVISTA / JOURNAL:  - Phys Med Biol. 2012 Dec 21;57(24):8393-404. doi: 10.1088/0031-9155/57/24/8393. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1088/0031-9155/57/24/8393

AUTORES / AUTHORS:  - Liu C; Zhang H; Pan Y; Huang F; Xia S

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China.

RESUMEN / SUMMARY:  - Glioma is the primary tumor in the central nervous system, and poses one of the greatest challenges in clinical treatment. MIB-1 and p53 are the most useful biomarkers for gliomas and could help neurosurgeons establish a therapeutic schedule. However, these biomarkers are commonly detected with the help of immunohistochemistry (IHC), which wastes time and energy and is often influenced  by subjective factors. To reduce the subjective factors and improve the efficiency in the judgment of IHC, a novel magnetic resonance image (MRI) analysis method is proposed in the present study to detect the expression status  of MIB-1 and p53 in IHC. The proposed method includes two kinds of MRI acquisition (FLAIR and T1 FLAIR images), regions of interest (ROIs) selection, texture features (i.e. the gray level gradient co-occurrence matrix (GLGCM), Minkowski functions (MFs), etc) extraction in ROIs, and classification with a support vector machine in a leave-one-out cross validation strategy. By classifying the ROIs, the performance of the method was evaluated by accuracy, area under ROC curve (AUC), etc. A high accuracy (0.7640 +/- 0.0225) and AUC (0.7873 +/- 0.0377) for MIB-I detection were achieved. In terms of the texture features, 0.7621 +/- 0.0199, 0.7666 +/- 0.0365 and 0.7426 +/- 0.0451 AUC can be obtained using only GLCM, RLM or GLGCM for MIB-1 detection, respectively. In all, the experimental results demonstrated that MR image texture features are associated with the expression status of MIB-1 and p53. The proposed method has the potential to realize high accuracy and robust detection for MIB-I expression  status, which makes it promising for clinical glioma diagnosis and prognosis.

 

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[296]

TÍTULO / TITLE:  - Microarray-based analysis of gene regulation by transcription factors and microRNAs in glioma.

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

REVISTA / JOURNAL:  - Neurol Sci. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10072-012-1228-1

AUTORES / AUTHORS:  - Yu J; Cai X; He J; Zhao W; Wang Q; Liu B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Traumatic Brain Injury Center in the Military People’s Liberation Army101 Hospital, Wuxi, Jiangsu, 214000, China.

RESUMEN / SUMMARY:  - Transcription factor (TF) and microRNA (miRNA) are two best characterized gene regulators that have been found to play an important role in gene regulation. However, high throughput screening the interaction relationships between transcription factors, microRNAs, and target genes in gliomas remains rare. Using GSE16666 and GSE13091 datasets downloaded from Gene Expression Omnibus data, we first screened the differentially expressed genes in gliomas. We explored the regulation relationship among TFs, miRNAs and target genes by different algorithms. The underlying molecular mechanisms of these crucial target genes were investigated by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Our study has developed three regulation relationships between two TFs and three miRNAs, including TP53/hsa-mir-155, TP53/hsa-mir-125b, and KLF2/hsa-mir-126. In addition, we also constructed a regulation network of the target genes by transcription factors and miRNAs. Some  of them had been demonstrated to be involved in glioma progression via various pathways. For example, ATP2B2 target gene could be regulated by has-mir-181a to involve in calcium signaling pathway. RB1 could be regulated by has-miR-26a to participate in pathways in cancer. Smad7 could be regulated by has-miR-21 via intracellular TGF-beta signal transduction. We constructed a comprehensive regulatory network which was found to play an important role in gliomas progression.

 

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[297]

TÍTULO / TITLE:  - Occult pigmented ganglioglioma in an adult male with chronic posttraumatic epilepsy.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300550

AUTORES / AUTHORS:  - Plowey ED; Vogel H; Salmi D; Shuer LM

 

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[298]

TÍTULO / TITLE:  - Immediate post-operative MRI suggestive of the site and timing of glioblastoma recurrence after gross total resection: a retrospective longitudinal preliminary  study.

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

REVISTA / JOURNAL:  - Eur Radiol. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00330-012-2762-1

AUTORES / AUTHORS:  - Smets T; Lawson TM; Grandin C; Jankovski A; Raftopoulos C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Cliniques universitaires Saint-Luc, Universite catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium.

RESUMEN / SUMMARY:  - OBJECTIVES: To retrospectively identify morphological and physiological post-operative magnetic resonance imaging (MRI) characteristics predictive of glioblastoma recurrences after gross total resection (gross-TR). METHODS: Resection margins of 24 glioblastoma were analysed immediately post-operatively (MRI </= 2 h) and early post-operatively (24 h </= MRI </= 48 h), and subdivided  into areas with and without subtle contrast enhancement previously considered non-specific. On follow-up MRI, tumour regrowth areas were subdivided according to recurrence extent (focally/extended) and delay (</=6 and >/=12 months). Co-registration of pre-operative, immediately post-operative and early post-operative MRI with the first follow-up MRI demonstrating recurrence authorised their morphological (contrast enhancements) and physiological (rCBV) characterisation. RESULTS: Morphologically, on immediately post-operative MRI, micro-nodular and frayed enhancements correlate significantly with early recurrences (</=6 months). After gross-TR the absence of these enhancements is associated with a significant increase in progression-free survival (61 vs 15 weeks respectively) and overall survival (125 vs 51 weeks respectively). Physiologically, areas with a future focal recurrence have a trend toward higher  rCBV than other areas. CONCLUSION: Immediately post-operative topography of micro-nodular and frayed enhancements is suggestive of recurrence location and delay. Absence of such enhancements is associated with a fourfold increase in progression-free survival and a 2.5-fold increase in overall survival. KEY POINTS : * Immediately post-operative MRI reveals contrast enhancement after glioblastoma gross total resection. * Immediately post-operative micro-nodular and frayed enhancement correlate with early recurrence. * Absence of micro-nodular/frayed enhancement is associated with 61 weeks’ progression-free survival. * Absence of micro-nodular/frayed enhancement is associated with 125 weeks’ overall survival.

 

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[299]

TÍTULO / TITLE:  - Functional characterization of non-metastatic paraganglioma and pheochromocytoma  by (18) F-FDOPA PET: focus on missed lesions.

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

REVISTA / JOURNAL:  - Clin Endocrinol (Oxf). 2012 Dec 11. doi: 10.1111/cen.12126.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cen.12126

AUTORES / AUTHORS:  - Gabriel S; Blanchet EM; Sebag F; Chen CC; Fakhry N; Deveze A; Barlier A; Morange I; Pacak K; Taieb D

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.

RESUMEN / SUMMARY:  - AIMS AND METHODS: To evaluate the clinical value of (18) F-fluorodihydroxyphenylalanine ((18) F-FDOPA) PET in relation to tumour localization and the patient’s genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results. A retrospective study of PGL patients who were investigated with (18) F-FDOPA PET or PET/CT imaging in two academic endocrine tumour centers was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA). RESULTS: One hundred sixteen patients (39.7% harboring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. (18) F-FDOPA PET correctly detected 179 lesions (91.8%) in 107 patients (92.2%). Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98.2% [96.5% for Timone and 100% for NIH], 93.9% [93.8% and 93.9%], and 70.3% [47.1% and 90%], respectively (P<0.001). Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative  (18) F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, p<0.001). By contrast, the risk of negative (18) F-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, p= 0.32). (18) F-FDOPA PET failed to detect 2 head and neck  PGLs (HNPGL), likely due to their small size, while most missed sympathetic PGL were larger and may have exhibited a specific (18) F-FDOPA-negative imaging phenotype. (18) F-FDG PET detected all the missed sympathetic lesions. CONCLUSIONS: (18) F-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on (18) F-FDOPA PET should be tested for SDHx mutations. © 2012 Blackwell Publishing Ltd.

 

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[300]

TÍTULO / TITLE:  - Plasma levels of transforming growth factor-beta 1 before and after removal of low- and high-grade astrocytomas.

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

REVISTA / JOURNAL:  - Cytokine. 2012 Dec 20. pii: S1043-4666(12)00794-6. doi: 10.1016/j.cyto.2012.11.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2012.11.011

AUTORES / AUTHORS:  - Loh JK; Lieu AS; Su YF; Cheng CY; Tsai TH; Lin CL; Lee KS; Hwang SL; Kwan AL; Wang CJ; Hong YR; Chio CC; Howng SL

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung  Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Healthcare  Administration and Medical Informatics, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

RESUMEN / SUMMARY:  - Transforming growth factor-beta 1 (TGF-beta1) has been reported to be a possible  marker for a number of tumors, including brain tumors. The aim of this study was  to measure the plasma levels of TGF-beta1 in patients with low- and high-grade astrocytomas before and after surgery. This prospective study included 14 patients with low-grade astrocytomas and 25 with high-grade astrocytomas who underwent tumor removal and 13 controls (patients who underwent cranioplasty for  skull bone defects). Plasma levels of TGF-beta1 were measured in all subjects using enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis showed that when the level of TGF-beta1 before tumor removal was 2.52ng/ml, astrocytoma was predicted with a sensitivity  of 94.9% and specificity of 100%. The mean plasma level of TGF-beta1 in both the  low-grade and high-grade astrocytoma groups significantly decreased after tumor removal (p<0.05); there was no significant change in TGF-beta1 plasma level of the controls following surgery. Patients with high-grade astrocytomas had a significantly higher mortality rate than patients with low-grade astrocytomas (p=0.019) and significantly shorter survival (p=0.008). A positive correlation between TGF-beta1 level after tumor removal and tumor volume was only found in the high-grade astrocytoma group (gamma=0.597, p=0.002). The findings show that plasma TGF-beta1 level was increased in patients with low-grade and high-grade astrocytoma, and that the levels significantly decreased after tumor removal in both groups. The results provide additional evidence that TGF-beta1 might be useful as a tumor marker for astrocytomas.

 

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[301]

TÍTULO / TITLE:  - Computed tomography and magnetic resonance features of extraventricular neurocytoma: A study of eight cases.

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

REVISTA / JOURNAL:  - Clin Radiol. 2013 Jan 17. pii: S0009-9260(12)00578-8. doi: 10.1016/j.crad.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.crad.2012.11.009

AUTORES / AUTHORS:  - Huang WY; Zhang BY; Geng DY; Zhang J

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - AIM: To present the neuroradiological and clinical findings of extraventricular (central) neurocytomas (EVNs) to increase awareness of this entity. MATERIALS AND METHODS: The computed tomography (CT; n = 6), magnetic resonance imaging (MRI; n  = 8), and clinical presentations of eight patients with pathologically documented EVN were retrospectively analysed. RESULTS: Most tumours were well circumscribed  and occurred in young adults. Six tumours were solid or solid-cystic, five of these showed contrast enhancement and three contained calcifications. Multiple small cysts were present in one solid mass and had a “soap bubble” or spongy appearance on MRI. Two other tumours were predominantly cystic; these demonstrated slight contrast enhancement, which contained calcifications. Of the  six cases assessed using CT, three showed predominantly hyperdensity and three showed hypodensity, with a mean attenuation value of 75 HU. At MRI, eight masses  were isointense (n = 4) or hypointense (n = 4) to grey matter on T1-weighted images and hyperintense (n = 6), isointense (n = 1), or hypointense (n = 1) on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Signal voids  were visible in two cases. Four tumours had mild or moderate peritumoural oedema. CONCLUSION: EVN is a rare neoplasm that can have significant overlap in imaging appearance with other primary brain neoplasms; therefore, it is difficult to make an accurate preoperative diagnosis. However, EVN should be considered in the differential diagnosis when a large cerebral parenchymal mass with cystic change  and calcification is encountered in younger patients.

 

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[302]

TÍTULO / TITLE:  - The decrease of paclitaxel efflux by pretreatment of interferon-gamma and tumor necrosis factor-alpha after intracerebral microinjection.

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

REVISTA / JOURNAL:  - Brain Res. 2013 Jan 9. pii: S0006-8993(13)00030-9. doi: 10.1016/j.brainres.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.brainres.2013.01.005

AUTORES / AUTHORS:  - Lee NY; Kang YS

INSTITUCIÓN / INSTITUTION:  - College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women’s  University, Seoul 140-742, Korea.

RESUMEN / SUMMARY:  - Paclitaxel is highly efficacious in the treatment of patients suffering from a broad spectrum of neoplastic diseases. However, its efficacy against malignant glioma is very moderate. Paclitaxel is known to be a substrate for P-glycoprotein (P-gp), so this transporter may be due to insufficient access of paclitaxel to the brain. First, we investigated the brain-to-blood transport of paclitaxel across the blood-brain barrier (BBB) using the brain efflux index method. [(3)H]Paclitaxel was eliminated from rat brain with an efflux transport rate of 1.87x10(-2)+/-0.16x10(-2)min(-1). The elimination of [(3)H]paclitaxel was inhibited by unlabeled paclitaxel and verapamil, suggesting a carrier-mediated transport process via P-gp. Furthermore, TNF-alpha and IFN-gamma induced significant decrease of paclitaxel efflux 1 and 24h pre-treatment. These results  suggest that P-gp efflux function at the BBB is reduced by TNF-alpha and IFN-gamma. Therefore, the distribution of P-gp dependant drugs including paclitaxel in the central nervous system can be modulated by neurological diseases.

 

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[303]

TÍTULO / TITLE:  - Modulation of paroxysmal activity in focal cortical dysplasia by centromedian thalamic nucleus stimulation.

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

REVISTA / JOURNAL:  - Epilepsy Res. 2012 Dec 12. pii: S0920-1211(12)00323-3. doi: 10.1016/j.eplepsyres.2012.10.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.eplepsyres.2012.10.012

AUTORES / AUTHORS:  - Pasnicu A; Denoyer Y; Haegelen C; Pasqualini E; Biraben A

INSTITUCIÓN / INSTITUTION:  - Electrophysiology Department, Pontchaillou Hospital, Rennes University Hospital,  France. Electronic address: anca.pasnicu@chu-rennes.fr.

RESUMEN / SUMMARY:  - Stimulation of the centromedian thalamic nucleus (CM) was performed during presurgical depth recordings in a patient with drug-resistant partial epilepsy related to premotor focal cortical dysplasia. Low- and high-frequency stimulation of the ipsilateral CM reproducibly suppressed the interictal spikes and fast rhythms. This is the first time that the effects of CM stimulation on interictal  focal paroxysmal activity have been observed in humans using depth recordings. These results need further confirmation, but suggest that the CM is a worthwhile  stimulation target for alternative treatment in selected cases of drug-resistant  nonsurgical epilepsy.

 

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[304]

TÍTULO / TITLE:  - Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):224-34. doi: 10.1093/neuonc/nos292. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos292

AUTORES / AUTHORS:  - Friedrich C; von Bueren AO; von Hoff K; Gerber NU; Ottensmeier H; Deinlein F; Benesch M; Kwiecien R; Pietsch T; Warmuth-Metz M; Faldum A; Kuehl J; Kortmann RD; Rutkowski S

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: S. Rutkowski, MD, Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. s.rutkowski@uke.de.

RESUMEN / SUMMARY:  - Background Especially in young children, primitive neuroectodermal tumors of the  central nervous system (CNS-PNET) and pineoblastomas are associated with an unfavorable outcome, and only a few prospective trials have been conducted thus far. Methods From January 2001 through January 2005, 17 eligible children aged <4 years with CNS-PNET not otherwise specified (n = 8), ependymoblastoma (n = 1), or pineoblastoma (n = 8) confirmed by central review were prospectively treated in the trial HIT 2000. In nonmetastatic disease (n = 11), up to 5 postoperative cycles of HIT-SKK systemic multiagent chemotherapy (8 months duration), followed  by craniospinal radiotherapy (CSI), were given. In metastatic disease (M1-M3, n = 6), treatment consisted of a shorter induction chemotherapy (2-3 months) with carboplatin and etoposide, followed by tandem high-dose chemotherapy (HDCT) in case of good response to induction. During induction and HDCT, patients received  intraventricular methotrexate. CSI was applied to all patients with poor response to induction or residual disease after HDCT and was optional for patients with residual disease before HDCT. Results Five-year event-free survival and overall survival rates +/- standard error for all eligible patients were 24% +/- 10% and  40% +/- 12%, respectively (median follow-up of survivors: 8.3 years). Only one patient with nonmetastatic disease remained free of relapse/progressive disease during induction. Three of 6 patients with metastatic disease responded to induction and received tandem-HDCT, followed by preventive CSI, and remain in continuous complete remission. Conclusions Short intensive induction chemotherapy followed by tandem-HDCT in young children with CNS-PNET/pineoblastomas seems to be superior to the prolonged and less intensive induction regimen.

 

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[305]

TÍTULO / TITLE:  - Application of low-field intraoperative magnetic resonance imaging in transsphenoidal surgery for pituitary adenomas: technical points to improve the visibility of the tumor resection margin.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1608-6

AUTORES / AUTHORS:  - Kim EH; Oh MC; Kim SH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Yonsei Brain Research Institute, Pituitary Tumor Clinic, Yonsei University College of Medicine, 250 Seongsanno, Seodaemoon-gu, Seoul, 120-752, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is proven to be advantageous in transsphenoidal surgery (TSS) for pituitary adenomas. We evaluated the efficacy of low-field iMRI. Also, we described several techniques to enhance the visibility of the tumor resection margin. METHODS: Two hundred twenty-nine patients who underwent TSS using low-field iMRI were analyzed. iMRI was acquired in cases where the tumor removal was thought to meet the surgical goal after the tumor resection cavity had been packed with contrast-soaked cotton pledgets to improve the visibility of the tumor resection margin. Suspicious remnants were localized and explored using updated iMRI-based semi-real-time navigation. A merging technique was adopted for very small tumors. The final outcome was evaluated using postoperative 3-T diagnostic magnetic resonance imaging (MRI). RESULTS: Among 198 patients in whom total resection was attempted, total resection seemed to have been achieved in 184 patients based on iMRI findings. However, immediate postoperative MRI revealed remnant tumors in 4 out of 184 patients (false-negative rate, 2.2 %). The other 31 patients underwent intended subtotal resection of the tumors. Overall, in 47 patients (20.5 %), the  use of iMRI led to further resection. Those patients benefited from the use of iMRI to achieve the planned extent of tumor resection. CONCLUSIONS: iMRI maximizes the extent of resection and minimizes the possibility of unexpected tumor remnants in TSS for pituitary adenomas. It is essential to reduce imaging artifacts and enhance the visibility of the tumor resection margin during the use of low-field iMRI.

 

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[306]

TÍTULO / TITLE:  - Rapamycin inhibits the growth of glioblastoma.

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

REVISTA / JOURNAL:  - Brain Res. 2013 Feb 7;1495:37-51. doi: 10.1016/j.brainres.2012.11.044. Epub 2012  Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.brainres.2012.11.044

AUTORES / AUTHORS:  - Arcella A; Biagioni F; Antonietta Oliva M; Bucci D; Frati A; Esposito V; Cantore G; Giangaspero F; Fornai F

INSTITUCIÓN / INSTITUTION:  - I.R.C.C.S. Neuromed Pozzilli, Italy.

RESUMEN / SUMMARY:  - The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and  disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects  of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These  effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of  10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts  in nude mice rapamycin almost doubled the survival time of mice and inhibited by  more than 95% of tumor volume.

 

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[307]

TÍTULO / TITLE:  - Diagnostic and prognostic markers in gliomas - an update.

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

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2012.752432

AUTORES / AUTHORS:  - Ma R; de Pennington N; Hofer M; Blesing C; Stacey R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, John Radcliffe Hospital , Oxford Racliffe Hospitals Trust, West Wing, Headley Way, Headington , Oxford, UK .

RESUMEN / SUMMARY:  - Gliomas are the most common primary central nervous system tumour seen in adults. There have been many advances over the last two decades as we widen our search for a molecular basis of gliomagenesis. Many biomarkers have been discovered to be important in the management of gliomas, including 1p19q co-deletion, MGMT promoter methylation, BRAF and IDH1 mutations. In this review, we attempt to summarise the available literature on these biomarkers and their use in the diagnosis and management of gliomas. We pay special attention to the recently discovered IDH1 mutation, which is already proving to be a valuable new marker for favourable prognosis and may also indicate a greater response to therapy. 1p19q co-deletions have been shown to delineate a clinically distinct tumour type and are now routinely tested for in certain situations and can help direct treatment. MGMT promoter methylation is one of the most commonly studied biomarkers in gliomas. It has been shown to be a strong positive prognostic marker in gliomas, with positive tumours being more sensitive to chemotherapy. However, a lack of alternatives means that it is not yet a routine mutation tested for clinically. BRAF mutations are new markers found in pilocytic astrocytomas. Although the prognostic value of such mutations is not yet known, they may play a significant role in the diagnosis and treatment of such tumours.  IDH1 mutations are ‘the new kid on the block’ and seem to play a central role in  the pathogenesis of gliomas. They represent an independent and favourable prognostic marker and are a new molecular marker for disease diagnosis. Its role  in determining response to chemotherapy is still controversial but with further study, IDH1 mutations may prove to be an invaluable marker in the management of gliomas.

 

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[308]

TÍTULO / TITLE:  - MEG3: a novel long noncoding potentially tumour-suppressing RNA in meningiomas.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1038-6

AUTORES / AUTHORS:  - Balik V; Srovnal J; Sulla I; Kalita O; Foltanova T; Vaverka M; Hrabalek L; Hajduch M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic, balik.vladimir@gmail.com.

RESUMEN / SUMMARY:  - Meningiomas represent one of the most common types of primary intracranial tumours. However, the specific molecular mechanisms underlying their pathogenesis remain uncertain. Loss of chromosomes 22q, 1p, and 14q have been implicated in most meningiomas. Inactivation of the NF2 gene at 22q12 has been identified as an early event in their pathogenesis, whereas abnormalities of chromosome 14 have been reported in higher-grade as well as recurrent tumours. It has long been supposed that chromosome 14q32 contains a tumour suppressor gene. However, the identity of the potential 14q32 tumour suppressor remained elusive until the Maternally Expressed Gene 3 (MEG3) was recently suggested as an ideal candidate.  MEG3 is an imprinted gene located at 14q32 that encodes a non-coding RNA (ncRNA). In meningiomas, loss of MEG3 expression, its genomic DNA deletion and degree of promoter methylation have been found to be associated with aggressive tumour growth. These findings indicate that MEG3 may have a significant role as a novel  long noncoding RNA tumour suppressor in meningiomas.

 

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[309]

TÍTULO / TITLE:  - Enhanced Resection of Orthotopic Red-fluorescent-Protein-expressing Human Glioma  by Fluorescence-guided Surgery in Nude Mice.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):107-11.

AUTORES / AUTHORS:  - Momiyama M; Hiroshima Y; Suetsugu A; Tome Y; Mii S; Yano S; Bouvet M; Chishima T; Endo I; Hoffman RM

INSTITUCIÓN / INSTITUTION:  - AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, U.S.A. all@anticancer.com.

RESUMEN / SUMMARY:  - Malignant glioma is the most common type of primary central nervous system cancer. Gliomas are very difficult to completely resect due to their invasiveness. In the present study, we compared fluorescence-guided and standard  bright-light resection of a human glioma orthotopically implanted in nude mice. U87 human glioma cells, expressing red fluorescent protein (RFP), were injected stereotactically into the nude mouse brain through a craniotomy open window. Two  weeks after cancer-cell implantation, gliomas were resected under fluorescence guidance or under bright light. U87-RFP tumors were clearly visualized with a long-working distance fluorescence microscope. Almost all cancer cells were removed using fluorescence-guided navigation without damage to the brain tissue.  In contrast, brain tumors were difficult to visualize under bright light and many residual cancer cells remained in the brain after bright-light surgery. Fluorescence-guided surgery significantly extended the survival of the mice compared to those who underwent bright-light surgery. These results suggest that  fluorescence-guided surgery has significant potential for brain cancer treatment.

 

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[310]

TÍTULO / TITLE:  - A Case of Clear Cell Meningioma With Tyrosine-Rich Crystals.

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

REVISTA / JOURNAL:  - Int J Surg Pathol. 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1066896912470165

AUTORES / AUTHORS:  - Schollenberg E; Easton AS

RESUMEN / SUMMARY:  - We present a case of clear cell meningioma with unusual clinical and pathologic features. The patient was a 54-year-old man who underwent laminectomy and durotomy for an intradural tumor in the lumbar spinal canal. Sections showed a predominance of dense collagenous tissue with irregularly shaped and irregularly  sized magenta-colored extracellular deposits. On electron microscopy, these deposits were osmiophilic and “petaloid.” The final diagnosis of clear cell meningioma rested on relatively inconspicuous intervening nests of glycogen-containing clear cells that were positive for epithelial membrane antigen. The unusual extracellular deposits seen in this case have previously been characterized as tyrosine-rich crystals of the type most commonly seen in salivary gland tumors. Recognition of this tumor as a clear cell meningioma, despite misleading clinical features and initially challenging histologic findings, is not only a matter of diagnostic accuracy but also imparts important  prognostic information.

 

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[311]

TÍTULO / TITLE:  - Pleomorphic xanthoastrocytoma: magnetic resonance imaging findings in a series of cases with histopathological confirmation.

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

REVISTA / JOURNAL:  - Arq Neuropsiquiatr. 2013 Jan;71(1):35-9. Epub 2012 Dec 18.

AUTORES / AUTHORS:  - Goncalves VT; Reis F; Queiroz Lde S; Franca M Jr

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Clinics Hospital, UNICAMP, Campinas, SP, Brazil.

RESUMEN / SUMMARY:  - Pleomorphic xanthoastrocytoma (PXA) is a rare glioma. This paper aimed to analyze magnetic resonance imaging (MRI) characteristics in a series of patients diagnosed with PXA. We analyzed MRI findings in 9 patients with histopathologic diagnosis of PXA in our department over the last 12 years. The mean age of patients was 27.3 years. Cortical location was observed in all cases. The lesion  imaging was solid-cystic in six cases. In eight cases, the solid component presented hypo or isointense on T1 and iso or hyperintense on T2. Contrast enhancement in the solid component was observed in eight cases. The observed imaging pattern of PXA was superficial location with leptomeningeal involvement,  solid-cystic pattern and contrast enhancement in the solid component. We should consider that the association between PXA and other cortical tumors may occur, particularly, with gangliogliomas, which tend to be the main differential diagnosis in MRI.

 

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[312]

TÍTULO / TITLE:  - The fate of a macroporous hydroxyapatite cranioplasty four years after implantation: Macroscopical and microscopical findings in a case of recurrent atypical meningioma.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2012 Dec 26. pii: S0303-8467(12)00610-5. doi: 10.1016/j.clineuro.2012.11.032.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.11.032

AUTORES / AUTHORS:  - Frassanito P; De Bonis P; Mattogno PP; Mangiola A; Novello M; Brinchi D; Pompucci A; Anile C

INSTITUCIÓN / INSTITUTION:  - Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy.

 

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[313]

TÍTULO / TITLE:  - Cervix carcinoma or Burkitt lymphoma metastases in meningiomas, two case reports.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 11. pii: S0303-8467(12)00622-1. doi: 10.1016/j.clineuro.2012.12.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.012

AUTORES / AUTHORS:  - Vrotsos E; Hirzel A; Kantrowitz A; Nanes M; Sriganeshan V; Castellanos-Sanchez A; Howard L

INSTITUCIÓN / INSTITUTION:  - Mount Sinai Medical Center, Department of Pathology and Laboratory Medicine, Miami Beach, FL, United States. Electronic address: elena.vrotsos@msmc.com.

 

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[314]

TÍTULO / TITLE:  - MicroRNA-107 inhibits glioma cell migration and invasion by modulating Notch2 expression.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1037-7

AUTORES / AUTHORS:  - Chen L; Chen XR; Zhang R; Li P; Liu Y; Yan K; Jiang XD

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

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs), small non-protein-coding RNA molecules, modulate target gene  expression by binding to 3’untranslated regions (UTR) of target mRNA. These molecules are aberrantly expressed in many human cancers, and can function either as tumor suppressors or oncogenes. In the current study, we show that miR-107 is  down-regulated in glioma tissues and cell lines, and its overexpression leads to  inhibition of the migratory and invasive ability of glioma cells via direct targeting of Notch2, which is known to transactivate Tenascin-C and Cox-2. Experiments with Notch2 siRNA further suggest that miR-107 may exerts its anti-invasive activity through Notch2 signaling pathways. Our findings collectively indicate that miR-107 is involved in glioma cell migration and invasion, and support its utility as a potential target for glioma treatment.

 

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[315]

TÍTULO / TITLE:  - Immunohistochemical Expression of PTTG in Brain Tumors.

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

REVISTA / JOURNAL:  - Anticancer Res. 2013 Jan;33(1):119-22.

AUTORES / AUTHORS:  - Salehi F; Scheithauer BW; Sharma S; Kovacs K; Lloyd RV; Cusimano MD; Munoz DG

INSTITUCIÓN / INSTITUTION:  - M.Sc., C/O Dr. Kalman Kovacs, Department of Laboratory Medicine and Pathology, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada. sfateme@gmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: Pituitary tumor-transforming gene (PTTG1) has been implicated in several oncogenic processes. The aim of this study was to determine PTTG expression in brain tumors. MATERIALS AND METHODS: We investigated 88 benign and  malignant brain tumors. PTTG immunoexpression was evaluated using a scale of 0 to 3. PTTG immunoexpression was nuclear and cytoplasmic in most tumors, except for medulloblastomas and hemangiopericytomas. Expression was highest in medulloblastomas. Higher grade gliomas including glioblastoma multiforme (GBM) IV and astrocytoma III had the highest level of PTTG expression, whereas low-grade gliomas had the lowest levels of PTTG expression. Hemangiopericytomas had the lowest levels of PTTG immunoreactivity, with meningiomas and schwannomas exhibiting similarly low PTTG levels. Nuclear PTTG immunoreactivity was higher than cytoplasmic in higher-grade tumors. CONCLUSION: Our results indicate that PTTG immunoexpression is higher in aggressive brain tumors including medulloblastomas, GBM IV, and astrocytoma III, whereas in more benign tumors, PTTG immunoexpression is lower.

 

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[316]

TÍTULO / TITLE:  - Paraneoplastic limbic encephalitis from esophagogastric squamous cell carcinoma successfully managed by radical gastrectomy.

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

REVISTA / JOURNAL:  - Surgery. 2013 Jan 7. pii: S0039-6060(12)00714-3. doi: 10.1016/j.surg.2012.11.014.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.014

AUTORES / AUTHORS:  - Mc Cormack O; Cooney JM; Doherty CP; Muldoon C; Reynolds JV

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, St. James’s Hospital, Dublin, Ireland; Trinity College Dublin, Dublin, Ireland.

 

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[317]

TÍTULO / TITLE:  - pEGFP-N1-mediated BmK CT expression suppresses the migration of glioma.

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

REVISTA / JOURNAL:  - Cytotechnology. 2012 Dec 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10616-012-9518-2

AUTORES / AUTHORS:  - Fu Y; Jiao Y; An N; 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, yjfu@sxu.edu.cn.

RESUMEN / SUMMARY:  - Gliomas can diffuse into the normal brain and this invasion of glioma cells involves modification of receptor-mediated adhesive properties of tumor cells, degradation and remodeling of extracellular matrix by tumor-secreted metalloproteinase (MMPs) such as MMP-2, consequently creating an intercellular space for invasion of glioma cells. BmK CT, one of the key toxins in scorpion Buthus martensii Karsch venom, is a novel blocker of the chloride ion channel and MMP-2. In this report, a recombinant plasmid pEGFP-N1-BmK CT was constructed and  characterized by in vitro studies. The results showed that pEGFP-N1 mediated BmK  CT expression displayed a high activity in suppressing cell migration via MMP-2.  The potential therapeutic effect of pEGFP-N1 mediated BmK CT against rat glioma C6 cells was assessed and its potential mechanism was elucidated. It represented  an approach for developing a novel therapeutic agent-recombinant plasmid pEGFP-N1-BmK CT as an efficient and powerful adjuvant.

 

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[318]

TÍTULO / TITLE:  - A magnetic resonance imaging study of cerebellar volume in tuberous sclerosis complex.

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

REVISTA / JOURNAL:  - Pediatr Neurol. 2013 Feb;48(2):105-10. doi: 10.1016/j.pediatrneurol.2012.10.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pediatrneurol.2012.10.011

AUTORES / AUTHORS:  - Weisenfeld NI; Peters JM; Tsai PT; Prabhu SP; Dies KA; Sahin M; Warfield SK

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts. Electronic address: weisen@crl.med.harvard.edu.

RESUMEN / SUMMARY:  - The cerebellum plays an important role in motor learning and cognition, and structural cerebellar abnormalities have been associated with cognitive impairment. In tuberous sclerosis complex, neurologic outcome is highly variable, and no consistent imaging or pathologic determinant of cognition has been firmly  established. The cerebellum calls for specific attention because mouse models of  tuberous sclerosis complex have demonstrated a loss of cerebellar Purkinje cells, and cases of human histologic data have demonstrated a similar loss in patients.  We hypothesized that there might be a common cerebellar finding in tuberous sclerosis complex that could be measured as morphometric changes with magnetic resonance imaging. Using a robust, automated image analysis procedure, we studied 36 patients with tuberous sclerosis complex and age-matched control subjects and  observed significant volume loss among patients in the cerebellar cortices and vermis. Furthermore, this effect was strongest in a subgroup of 19 patients with  a known, pathogenic mutation of the tuberous sclerosis 2 gene and impacted all cerebellar structures. We conclude that patients with tuberous sclerosis complex  exhibit volume loss in the cerebellum, and this loss is larger and more widespread in patients with a tuberous sclerosis 2 mutation.

 

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[319]

TÍTULO / TITLE:  - P2Y(1) nucleotide receptor silencing and its effect on glioma C6 calcium signaling.

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

REVISTA / JOURNAL:  - Acta Biochim Pol. 2012;59(4):711-7. Epub 2012 Dec 20.

AUTORES / AUTHORS:  - Wypych D; Pomorski P

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Basis of Cell Motility, Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.

RESUMEN / SUMMARY:  - In our earlier studies of the signaling cross-talk between nucleotide receptors in an in vitro glioma model (C6 cell line) under prolonged serum deprivation conditions, a growth arrest of the cells and expression shift from P2Y(1) to P2Y(12) receptors was found. The aim of the present work was to test if siRNA silencing of P2Y(1) receptor changes P2Y(12) expression similarly as following the serum deprivation and which physiological downstream pathways it affects. Here we demonstrate for the first time the efficiency of siRNA technology in silencing P2Y nucleotide receptors in glioma C6 cell line. Moreover, P2Y(12) proved to be insensitive to the P2Y(1) receptor silencing. The effect of the P2Y(1) silencing on calcium signaling was less pronounced then the extent of the  protein change itself, exactly as was the case for the serum starvation experiments. Phosphorylation of ERK and Akt kinases were studied as the downstream effect of P2Y(1)-evoked signaling and similar effects as in the case of serum deprivation were found for ERK, and even stronger ones for Akt phosphorylation.

 

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[320]

TÍTULO / TITLE:  - Detection of paranasal ectopic adrenocorticotropic hormone-secreting pituitary adenoma by Ga-68-DOTANOC positron-emission tomography-computed tomography.

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

REVISTA / JOURNAL:  - Laryngoscope. 2013 Jan 8. doi: 10.1002/lary.23867.

            ●● Enlace al texto completo (gratuito o de pago) 1002/lary.23867

AUTORES / AUTHORS:  - Veit JA; Boehm B; Luster M; Scheuerle A; Rotter N; Rettinger G; Scheithauer M

INSTITUCIÓN / INSTITUTION:  - Department of ENT Surgery, University Hospital Ulm, Ulm, Germany. johannes.veit@uniklinik-ulm.de.

RESUMEN / SUMMARY:  - Ectopic adrenocorticotropic hormone (ACTH)-secreting tumors account for approximately 10% of Cushing’s syndrome (CS). We present an extremely rare case of a patient with CS caused by an ectopic ACTH-secreting pituitary adenoma (EAPA) of the ethmoid sinus. The tumor was identified by positron-emission tomography-computed tomography (PET/CT) using the somatostatin receptor analogue  Ga-68-DOTANOC. Transnasal endoscopic resection was performed and the patient showed significant clinical improvement with normalization of the endocrine pituitary axis. Immunostaining showed a somatostatin receptor 2 and 5-positive ACTH-producing adenoma. In patients with ectopic ACTH secretion, Ga-68-DOTANOC-PET/CT may play an important role in the localization of EAPA. Transnasal endoscopic resection is the therapy of choice. Laryngoscope, 2012.

 

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[321]

TÍTULO / TITLE:  - Real-time multi-modality imaging of glioblastoma tumor resection and recurrence.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan;111(2):153-61. doi: 10.1007/s11060-012-1008-z. Epub 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1008-z

AUTORES / AUTHORS:  - Hingtgen S; Figueiredo JL; Farrar C; Duebgen M; Martinez-Quintanilla J; Bhere D; Shah K

INSTITUCIÓN / INSTITUTION:  - Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

RESUMEN / SUMMARY:  - The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and non-invasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal  non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multi-modality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics.

 

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[322]

TÍTULO / TITLE:  - Relationship between SATB1 expression and prognosis in astrocytoma.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 11. pii: S0967-5868(12)00457-2. doi: 10.1016/j.jocn.2012.05.033.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.05.033

AUTORES / AUTHORS:  - Chu SH; Ma YB; Feng DF; Zhang H; Qiu JH; Zhu ZA; Li ZQ; Jiang PC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, No. 3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 280 Mo He Road, Bao Shan District, Shanghai 201900, China. Electronic address: shenghuachu@126.com.

RESUMEN / SUMMARY:  - Special AT-rich-sequence-binding protein 1 (SATB1), a new type of gene regulator, has been reported to be expressed in various human cancers and may be associated  with malignancy. The aim of this study was to investigate the expression of SATB1 in astrocytoma and to determine its prognostic value for the overall survival of  patients with astrocytoma. The expression of SATB1 protein and messenger RNA (mRNA) in human astrocytoma specimens was examined using immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The relationship between SATB1 expression and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was also investigated. Spearman’s correlation  coefficient was used to describe the association between SATB1 expression and the clinical parameters of astrocytoma patients. SATB1 protein and mRNA were expressed at significant levels in astrocytoma specimens. SATB1 expression was positively correlated with astrocytoma pathological grade but negatively correlated with the life span of astrocytoma patients. SATB1 expression was also  significantly lower in astrocytoma specimens with MGMT promoter methylation than  in those without MGMT promoter methylation. Our findings suggest that SATB1 may have an important role as a positive regulator of astrocytoma development and progression and that SATB1 might be a useful molecular marker for predicting the  prognosis of patients with astrocytoma and could be a novel target for treating astrocytoma.

 

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[323]

TÍTULO / TITLE:  - A role for LRIG1 in the regulation of malignant glioma aggressiveness.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):1081-7. doi: 10.3892/ijo.2013.1776. Epub 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1776

AUTORES / AUTHORS:  - Mao F; Wang B; Xiao Q; Xi G; Sun W; Zhang H; Ye F; Wan F; Guo D; Lei T; Chen X

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery and Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.

RESUMEN / SUMMARY:  - The molecular mechanisms that drive the develop-ment and aggressive progression of malignant astrocytic tumors remain obscure. Recently, in the search for endo-genous negative regulators of EGF receptor, LRIG1 was cloned and characterized as a putative tumor suppressor gene often downregulated in various  human tumors, including astrocytic tumors. Although several studies have implicated the function of LRIG1 in the inhibition of tumorigenesis, its precise  role and potential underlying mechanisms remain obscure. Therefore, we generated  a full-length expression vector to overexpress LRIG1 in the U251 malignant glioma cell line. Introduction of exogenous LRIG1 into glioma cells inhibited cell proliferation manifested by MTT and soft agar clone assay in vitro and subcutaneously tumor xenografts. On the other hand, LRIG1 overexpression inhibited glioma growth by significantly changing the expression pattern of cyclins, resulting in delayed cell cycle. Employing transwell invasion and wound  scratch assay and gelatin zymography, LRIG1 inhibited U-251 MG cell invasion and  migration by attenuating MMP2 and MMP9 production. Under ligand-stimulated conditions, p-ERK levels did not change, whereas p-AKT levels were inhibited in cells with LRIG1 upregulation, indicating that LRIG1 exerts more inhibiting effects on the PI3K/AKT pathway. Our findings suggest that LRIG1 restricted glioma aggressiveness by inhibiting cell proliferation, migration and invasion. Restoration of LRIG1 to glioma cells could offer a novel therapeutic strategy.

 

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[324]

TÍTULO / TITLE:  - Synthetic glycolipids for glioma growth inhibition developed from neurostatin and NF115 compound.

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

REVISTA / JOURNAL:  - Bioorg Med Chem Lett. 2013 Jan 15;23(2):435-9. doi: 10.1016/j.bmcl.2012.11.070. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2012.11.070

AUTORES / AUTHORS:  - Doncel-Perez E; Garcia-Alvarez I; Fernandez-Mayoralas A; Nieto-Sampedro M

INSTITUCIÓN / INSTITUTION:  - Grupo de Quimica Neuro-regenerativa, Unidad Neurologia Experimental, Hospital Nacional de Paraplejicos, Servicio de Salud de Castilla La Mancha (SESCAM), Finca La Peraleda s/n, 45071 Toledo, España. Electronic address: ernestod@sescam.jccm.es.

RESUMEN / SUMMARY:  - Neurostatin, a natural glycosphingolipid, and NF115, a synthetic glycolipid, are  inhibitors of glioma growth. While neurostatin shows high inhibitory activity on  gliomas its abundance is low in mammalian brain. On the contrary NF115 exhibits less inhibitory activity on gliomas, but could be prepared by chemical synthesis. In this study we describe synthetic compounds, structurally related to NF115, capable of inhibiting glioma growth at low micromolar range. We used DNA microarray technology to compare the genes inhibited in U373-MG human glioma cells after treatment with the natural or synthetic inhibitor. New synthetic compounds were developed to interact with the product of Rho GDP dissociation inhibitor alpha gene, which was repressed in both treatments. Compounds that were inhibitors of glioma cell growth in assays for [3H]-thymidine incorporation were  then injected in C6 tumor bearing rats and the tumor size in each animal group were measured. The GC-17, GC-4 and IG-5 are new compounds derived from NF115 and  showed high antiproliferative activity on tumor cell lines. The GC-17 compound inhibited U373-MG glioblastoma cells (3.2muM), the effects was fifty times more potent than NF115, and caused a significant reduction of tumor volume (P<0.05) when tested in Wistar rats allotransplanted with C6 glioma cells.

 

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[325]

TÍTULO / TITLE:  - Biological characteristics of intratumoral [F-18]fluoromisonidazole distribution  in a rodent model of glioma.

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

REVISTA / JOURNAL:  - Int J Oncol. 2013 Mar;42(3):823-30. doi: 10.3892/ijo.2013.1781. Epub 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1781

AUTORES / AUTHORS:  - Hatano T; Zhao S; Zhao Y; Nishijima K; Kuno N; Hanzawa H; Sakamoto T; Tamaki N; Kuge Y

INSTITUCIÓN / INSTITUTION:  - Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.

RESUMEN / SUMMARY:  - Accurate imaging to identify hypoxic regions in tumors is key for radiotherapy planning. [F-18]fluoro-misonidazole ([F-18]-FMISO) is widely used for tumor hypoxia imaging and has the potential to optimize radiotherapy planning. However, the biological characteristics of intratumoral [F-18]-FMISO distribution have not yet been fully investigated. In hypoxic cells, the hypoxia-inducible factor-1 (HIF-1) target proteins that induce cellular proliferation and glucose metabolism, glucose transporter-1 (Glut-1) and hexokinase-II (HK-II), are upregulated. In this study, we determined the intratumoral distribution of [F-18]-FMISO by autoradiography (ARG) and compared it with pimonidazole uptake, expression of Glut-1, tumor proliferative activity (Ki-67 index) and glucose metabolism ([C-14]2-fluoro-2-deoxy-D-glucose uptake; [C-14]-FDG) in a glioma rat  model. Five C6 gliomabearing rats were injected with [F-18]-FMISO and [C-14]-FDG. After 90 min, the rats were injected with pimonidazole and 60 min later, the rats were sacrificed and tumor tissues were sectioned into slices. The adjacent slices were used for ARG and immunohistochemical (IHC) analyses of pimonidazole, Glut-1  and Ki-67. [F-18]-FMISO ARG images were divided into regions of high [F-18]-FMISO uptake (FMISO+) and low [F-18]-FMISO uptake (FMISO-). Pimonidazole and Glut-1 expression levels, Ki-67 index and [C-14]-FDG distribution were evaluated in the  regions of interest (ROIs) placed on FMISO+ and FMISO-. [F-18]-FMISO distribution was generally consistent with pimonidazole distribution. The percentage of positively stained areas (% positive) of Glut-1 in FMISO+ was significantly higher compared to FMISO- (24+/-8% in FMISO+ and 9+/-4% in FMISO-; P<0.05). There were no significant differences in Ki-67 index and [C-14]-FDG uptake between FMISO+ and FMISO- (for Ki-67, 10+/-5% in FMISO+ and 12+/-5% in FMISO-, P = ns; for [C-14]-FDG, 1.4+/-0.3% IDgkg in FMISO+ and 1.3+/-0.3% IDgkg in FMISO-, P = ns). Intratumoral [F-18]-FMISO distribution reflected tumor hypoxia and expression of the hypoxiarelated gene product Glut-1; it did not, however, reflect tumor proliferation or glucose metabolism. Our findings help elucidate the biological characteristics of intratumoral [F-18]-FMISO distribution that are relevant to radiotherapy planning.

 

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[326]

TÍTULO / TITLE:  - Potential of MR spectroscopy for assessment of glioma grading.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Feb;115(2):146-53. doi: 10.1016/j.clineuro.2012.11.002. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.11.002

AUTORES / AUTHORS:  - Bulik M; Jancalek R; Vanicek J; Skoch A; Mechl M

INSTITUCIÓN / INSTITUTION:  - International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech Republic; Department of Diagnostic Imaging, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic.

RESUMEN / SUMMARY:  - BACKGROUND: Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including  N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. METHODS: In this review, we describe potential of MRS for grading of gliomas. RESULTS: Low-grade gliomas are generally characterized by a relatively high concentration  of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions  with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. CONCLUSIONS: Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.

 

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[327]

TÍTULO / TITLE:  - Indocyanine green videoangiography (ICGV)-guided surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS).

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1617-5

AUTORES / AUTHORS:  - d’Avella E; Volpin F; Manara R; Scienza R; Della Puppa A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital of Padua, Via Giustiniani, 2, 35128, Padua, Italy.

RESUMEN / SUMMARY:  - BACKGROUND: Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in  brain tumor surgery for the identification of vessels. The aim of this study was  to investigate the role of ICGV in surgery of parasagittal meningiomas occluding  the superior sagittal sinus (SSS). METHOD: In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGV assisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure. RESULTS: Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved  in four cases. Surgery was uneventful in all cases. CONCLUSIONS: Despite the small number of patients, our study shows that ICG videoangiography could play a  crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.

 

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[328]

TÍTULO / TITLE:  - Differentiation of glioblastoma and primary CNS lymphomas using susceptibility weighted imaging.

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

REVISTA / JOURNAL:  - Eur J Radiol. 2012 Dec 10. pii: S0720-048X(12)00542-6. doi: 10.1016/j.ejrad.2012.11.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.11.002

AUTORES / AUTHORS:  - Radbruch A; Wiestler B; Kramp L; Lutz K; Baumer P; Weiler M; Roethke M; Sahm F; Schlemmer HP; Wick W; Heiland S; Bendszus M

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, University of Heidelberg Medical Center, INF 400, 69120 Heidelberg, Germany; Department of Radiology, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany. Electronic address: alexander.radbruch@med.uni-heidelberg.de.

RESUMEN / SUMMARY:  - INTRODUCTION: Reliable differentiation between glioblastoma and primary CNS lymphoma (PCNSL) using conventional MR imaging is challenging, since both entities may show similar appearance on structural MR imaging. Here we analyzed if the appearance of intratumoural susceptibility signals (ITSS) on susceptibility weighted imaging (SWI) may differentiate between both entities. METHODS AND MATERIALS: SWI and contrast enhanced T1-weighted images were acquired from 15 patients with newly diagnosed PCNSL (14 B-cell PCNSL, 1 T-cell PCNSL) and 117 patients with newly diagnosed glioblastoma with a 3Tesla MR. Additional phase images were available in 8 patients with PCNSL and 88 patients with glioblastoma. Appearance of ITSS was assessed by two readers on SWI and the size of the enhancing lesions on contrast enhanced T1-weighted images were measured. Furthermore it was assessed if ITSS displayed more clearly on SWI or on phase images. RESULTS: ITSS were detected in 106 (reader 1) and 109 (reader 2) glioblastoma, respectively. Both readers identified ITSS within the T-cell PCNSL  while both readers did not identify any ITSS within the 14 Bcell PCNSL. Interrarter variability as determined by Cohen kappa was excellent for glioblastoma (kappa=0.938) and for PCNSL (kappa=1). The medium size of the enhancing lesion of the glioblastoma that did not harbour ITSS was significantly  smaller than the size of the glioblastoma exhibiting ITSS (p<0.008). All identified ITSS displayed more clearly on SWI than on phase images. CONCLUSION: Presence of ITSS differentiates reliably between glioblastoma and B-cell PCNSL and provides a fast bases for the clinical decision without causing any postprocessing work.

 

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[329]

TÍTULO / TITLE:  - Involvement of N-cadherin in the protective effect of glial cell line-derived neurotrophic factor on dopaminergic neuron damage.

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

REVISTA / JOURNAL:  - Int J Mol Med. 2013 Mar;31(3):561-8. doi: 10.3892/ijmm.2013.1226. Epub 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1226

AUTORES / AUTHORS:  - Zuo T; Qin JY; Chen J; Shi Z; Liu M; Gao X; Gao D

INSTITUCIÓN / INSTITUTION:  - Department of Neurobiology, Xuzhou Medical College, Jiangsu, P.R. China.

RESUMEN / SUMMARY:  - The aim of this study was to further confirm that glial cell line-derived neurotrophic factor (GDNF) exerts a neuro-protective effect on dopaminergic neurons (DAs) and to investigate the protective mechanism. Cadherins are calcium-dependent adhesion proteins, and N-cadherins are found in neurons. Our study attempted to ascertain whether GDNF activates the PI3K/Akt signaling pathway through the mediation of N-cadherin to confer a protective effect on DAs. Flow cytometry and Hoechst 33258 staining results indicated that the apoptosis rate of damaged neurocytes increased following interference of N-cadherin expression. Immunoblotting results demonstrated that the amount of phosphorylated Akt (p-Akt) in the cytoplasm decreased, while the total Akt quantity remained unchanged following interference of N-cadherin expression. The immunohistochemical staining results demonstrated that the levels of total N-cadherin, phosphorylated N-cadherin (Tyr860) and p-Akt decreased; however, the  amount of total Akt remained unchanged. In addition, we also demonstrated that Tyr860 and p-Akt levels were reduced in a GDNF dose-dependent manner with the phosphorylation level peaking at GDNF dose of 50 ng/ml (in vitro) and 50 ng/4 microl (in vivo), and also in a time-dependent manner with the phosphorylation level peaking at 15 min (in vitro) and 30 min (in vivo). Statistical analysis also showed that changes in the phosphorylation levels of Tyr860 and p-Akt demonstrated a positive correlation. Collectively, GDNF activates the PI3K/Akt pathway via N-cadherin to protect DAs.

 

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[330]

TÍTULO / TITLE:  - Tumefactive cerebral amyloid angiopathy mimicking CNS neoplasm.

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

REVISTA / JOURNAL:  - AJR Am J Roentgenol. 2013 Jan;200(1):50-6. doi: 10.2214/AJR.12.8500.

            ●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8500

AUTORES / AUTHORS:  - Kotsenas AL; Morris JM; Wald JT; Parisi JE; Campeau NG

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

RESUMEN / SUMMARY:  - OBJECTIVE: The tumefactive variant of cerebral amyloid angiopathy (CAA) is rare.  In this article we describe imaging findings associated with this entity and evaluate the role of susceptibility MRI sequences in its diagnosis. CONCLUSION: Our findings suggest that in elderly patients, susceptibility sequences should be part of prebiopsy MRI for tumefactive lesions. Identification of characteristic diffuse microhemorrhages should prompt inclusion of CAA in the differential diagnosis, targeted biopsy of the cortex and leptomeninges, and pathologic staining for CAA.

 

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[331]

TÍTULO / TITLE:  - Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-2013-4

AUTORES / AUTHORS:  - Aguilera D; Mazewski C; Fangusaro J; Macdonald TJ; McNall-Knapp RY; Hayes LL; Kim S; Castellino RC

INSTITUCIÓN / INSTITUTION:  - Aflac Cancer & Blood Disorders Center, Children’s Healthcare of Atlanta, Emory University School of Medicine, 5455 Meridian Mark Rd., N.E., Suite 400, Atlanta,  GA, 30342, USA.

RESUMEN / SUMMARY:  - PURPOSE: Chemotherapy for relapsed medulloblastoma has been inadequate, and most  patients succumb to disease. METHODS: We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, +/- temozolomide.  Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125-150 mg/m(2) irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m(2) orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m(2) irinotecan orally for five consecutive days, 100 mg/m(2)/day temozolomide IV for 5 days, and 1.5 mg/m(2) vincristine IV, each administered every 21 days. RESULTS: Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive  with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea. CONCLUSIONS: The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy  of this strategy.

 

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[332]

TÍTULO / TITLE:  - Retropharyngeal Ganglioneuroma: A Case Report.

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

REVISTA / JOURNAL:  - J Neuroimaging. 2012 Dec 28. doi: 10.1111/j.1552-6569.2012.00765.x.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1552-6569.2012.00765.x

AUTORES / AUTHORS:  - Yang AI; Ozsvath J; Shukla P; Fatterpekar GM

INSTITUCIÓN / INSTITUTION:  - From the Department of Radiology, New York University School of Medicine, New York, NY (AIY, JO, GMF); and Department of Pathology, New York University School  of Medicine, New York, NY (PS).

RESUMEN / SUMMARY:  - Ganglioneuromas are uncommon, benign, and highly differentiated tumors arising from sympathetic ganglia. Common sites for these tumors include the paraspinal region of the retroperitoneum and posterior mediastinum. We report a case of a retropharyngeal ganglioneuroma, a rare occurrence, emphasizing its key imaging characteristics.

 

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[333]

TÍTULO / TITLE:  - Gab2 expression in glioma and its implications for tumor invasion.

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

REVISTA / JOURNAL:  - Acta Oncol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.750032

AUTORES / AUTHORS:  - Shi L; Sun X; Zhang J; Zhao C; Li H; Liu Z; Fang C; Wang X; Zhao C; Zhang X; Zhou F; Lu S; Luo R; Zhang B

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Nanfang Hospital of Southern Medical University , Guangzhou , PR China.

RESUMEN / SUMMARY:  - Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it  is not known whether Gab2 has any role in the migration and invasion of gliomas.  This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and  their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma  cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be  a useful prognostic marker for gliomas and a novel therapeutic target for glioma  invasion intervention.

 

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[334]

TÍTULO / TITLE:  - Epithelial-to-mesenchymal(-like) transition as a relevant molecular event in malignant gliomas.

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

REVISTA / JOURNAL:  - Cancer Lett. 2012 Dec 23. pii: S0304-3835(12)00727-6. doi: 10.1016/j.canlet.2012.12.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.12.010

AUTORES / AUTHORS:  - Kahlert UD; Nikkhah G; Maciaczyk J

INSTITUCIÓN / INSTITUTION:  - Department of General Neurosurgery, Section of Stereotactic Neurosurgery, University Medical Center Freiburg, Germany.

RESUMEN / SUMMARY:  - Tumor dissemination and metastatic behavior account for the vast majority of cancer associated mortality. Epithelial tumors achieve this progressive state via epithelial-to-mesenchymal transition (EMT); however, the importance of this process in the neuroepithelial context is currently very controversially discussed. The review describes the current research status concerning EMT-like changes in malignant gliomas including the role of TWIST1, ZEB1/ZEB2 and SNAIl1/SNAIl2 as inducers for cell-invasiveness in GBMs. Furthermore, WNT/beta-catenin signaling with its key-component FRIZZLED4 activating an EMT-like program in malignant gliomas and its relationship to the stem-like phenotype as well as discoveries on micro-RNA-level regulating the EMT-like process are discussed.

 

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[335]

TÍTULO / TITLE:  - Erratum to: Delayed development of a rhabdomyosarcoma following radiation for a spinal cord glioma.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1053-2

AUTORES / AUTHORS:  - Marzbani E; Jones RL; Fink J; Chamberlain MC

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Washington, Seattle, WA, USA.

 

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[336]

TÍTULO / TITLE:  - Delayed development of a rhabdomyosarcoma following radiation for a spinal cord glioma.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1042-x

AUTORES / AUTHORS:  - Mazbani E; Jones RL; Fink J; Chamberlain MC

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Washington, Seattle, WA, USA.

RESUMEN / SUMMARY:  - Radiation-induced sarcomas represent a rare delayed-late secondary complication of radiation therapy. Radiation-associated sarcomas are associated with a worse overall prognosis compared to sporadic sarcomas irrespective of histological type. Herein we report a case of a 65-year old man who underwent surgery and radiation therapy for a T4 spinal cord low-grade two astrocytoma in 1965 and presented over 40 years later with spinal cord complex intramedullary tumor involving the thoracic cord with drop metastases in the lumbar spine. Histology from a partial resection of the thoracic spinal tumor revealed a high-grade rhabdomyosarcoma. In addition to the rarity of radiation-induced sarcoma arising  following the treatment of a spinal cord glioma, this case study represents one of the first reports of a spinal cord rhabdomyosarcoma arising in this setting.

 

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[337]

TÍTULO / TITLE:  - Registering pre- and postresection 3-dimensional ultrasound for improved visualization of residual brain tumor.

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

REVISTA / JOURNAL:  - Ultrasound Med Biol. 2013 Jan;39(1):16-29. doi: 10.1016/j.ultrasmedbio.2012.08.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ultrasmedbio.2012.08.004

AUTORES / AUTHORS:  - Mercier L; Araujo D; Haegelen C; Del Maestro RF; Petrecca K; Collins DL

INSTITUCIÓN / INSTITUTION:  - McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.

RESUMEN / SUMMARY:  - The goal of this study was to find a registration technique to improve the alignment of ultrasound images taken before and after brain tumor resection. Validation was performed on 16 tumor cases in 2 ways: (1) manually selected tags  on pre- and postresection ultrasounds were used to compute the mean Euclidean distance between corresponding points in the 2 volumes before and after registration; and (2) the surgeon was asked to rank and rate the quality of the alignment before and after registration. The mean distance was 2.7 mm after a rigid registration and 1.7 mm after a nonlinear registration. Of 16 cases, the surgeon determined that initially only 2 were satisfactorily aligned; after the rigid registration, 5 were satisfactory, and after the nonlinear registration, 13 were satisfactory. According to both the distance and the ranking metrics, the nonlinear registration approach significantly improved the alignment of the ultrasound images.

 

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[338]

TÍTULO / TITLE:  - Visualization of Experimental Glioma C6 by MRI with Magnetic Nanoparticles Conjugated with Monoclonal Antibodies to Vascular Endothelial Growth Factor.

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

REVISTA / JOURNAL:  - Bull Exp Biol Med. 2012 Nov;154(2):274-277.

AUTORES / AUTHORS:  - Abakumov MA; Shein SA; Vishvasrao H; Nukolova NV; Sokol’ski-Papkov M; Sandalova TO; Gubskii IL; Grinenko NF; Kabanov AV; Chekhonin VP

INSTITUCIÓN / INSTITUTION:  - Department of Medical Nanobiotechnologies, N. I. Pirogov Russian National Research Medical University, Moscow; Faculty of Pharmacology, Center for Drug Delivery and Nanomedicine, Medical Center of the University of Nebraska, Omaha, USA; Department of Basic and Applied Neurobiology, V. P. Serbskii Center of Social and Forensic Psychiatry, Ministry of Health Care and Social Development of the Russian Federation, Moscow; Laboratory of Chemical Design of Bionanomaterials, Chemical Faculty, M. V. Lomonosov Moscow State University, Russia. abakumov1988@gmail.com.

RESUMEN / SUMMARY:  - We developed a method for obtaining iron oxide nanoparticles and their conjugation with monoclonal antibodies to vascular endothelial growth factor. The resultant vector nanoparticles were low-toxic and the antibodies retained their immunochemical activity after conjugation. The study was carried out on rats with intracranial glioma C6 on day 14 after its implantation. The intravenously injected nanoparticles visualized the brain tumor in contrast to nanoparticles conjugated with nonspecific immunoglobulins that did not accumulate in the tumor.

 

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[339]

TÍTULO / TITLE:  - Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

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

REVISTA / JOURNAL:  - Acta Neurochir (Wien). 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00701-012-1580-1

AUTORES / AUTHORS:  - Vassal F; Schneider F; Sontheimer A; Lemaire JJ; Nuti C

INSTITUCIÓN / INSTITUTION:  - Neurosurgery Service, Hopital Nord, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France, francoisvassal@wanadoo.fr.

RESUMEN / SUMMARY:  - BACKGROUND: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). METHODS AND MATERIALS: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. RESULTS: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 +/- 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. CONCLUSION: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

 

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[340]

TÍTULO / TITLE:  - Expression of integrins alphavbeta3 and alphavbeta5 and their ligands in primary  and secondary central nervous system neoplasms.

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

REVISTA / JOURNAL:  - Histol Histopathol. 2012 Dec 3.

AUTORES / AUTHORS:  - Mittelbronn M; Warth A; Meyermann R; Goodman S; Weller M

INSTITUCIÓN / INSTITUTION:  - Institute of Brain Research, University of Tubingen, Tubingen, Germany. michel.mittelbronn@kgu.de.

RESUMEN / SUMMARY:  - Aims: To study the expression of integrins alphavbeta3 and alphavbeta5 and their  ligands in tumour, stroma and endothelial cells from human glioblastoma and CNS metastases from breast, lung and skin tumours. Methods and results: Integrin and  integrin ligand expression was quantified in frozen tumour surgical specimens (15 glioblastomas and breast carcinoma metastases as well as 16 lung carcinoma and melanoma metastases) using immunohistochemistry. Gene expression profiles were evaluated in glioblastomas (n=424) and in normal brain (n=11). Overall, alphavbeta3 expression was more common than alphavbeta5 except in tumours derived from lung. alphavbeta3 expression was most frequent in glioblastomas and melanoma metastases. Most lung-derived tumours expressed alphavbeta5 but expression was less frequent in other tumours; about 20% of breast-derived tumours strongly expressed alphavbeta5. Melanoma-derived tumours did not express alphavbeta5. Expression of integrin ligands vitronectin, fibrinogen, fibronectin and osteopontin was variable between tumours, although most tumours expressed the ligands to some extent. Marked alphavbeta3, but not alphavbeta5, expression was common in stroma of CNS metastases. In blood vessels, alphavbeta3 expression was  more frequent than alphavbeta5 and more pronounced in CNS metastases than in glioblastomas. Integrin ligand expression occurred in blood vessels in most tumours. In glioblastomas, mRNA expression of alphavbeta3, alphavbeta5, osteopontin and fibronectin were significantly upregulated over normal brain. Conclusions: Overall, we report distinct and heterogeneous patterns of integrin expression in primary and secondary brain tumours that may be relevant to the future development of integrin-targeting therapeutic approaches to brain tumours.

 

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[341]

TÍTULO / TITLE:  - Viability screen on pediatric low grade glioma cell lines unveils a novel anti-cancer drug of the steroid biosynthesis inhibitor family.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Mar 1;330(1):96-105. doi: 10.1016/j.canlet.2012.11.034. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.11.034

AUTORES / AUTHORS:  - Ajeawung NF; Maltais R; Jones C; Poirier D; Kamnasaran D

INSTITUCIÓN / INSTITUTION:  - Pediatrics Research Unit, CHUQ (CHUL) - Research Centre, Quebec, QC, Canada G1V 4G2.

RESUMEN / SUMMARY:  - Pediatric low grade gliomas are the most common central nervous system tumors and are still incurable among a subset of patients despite current treatment modalities. Steroid biosynthesis occurs in a wide variety of organs including the brain, to mediate an assortment of functions, including a proposed role in the growth of gliomas. Hence, targeting steroid biosynthesis and/or their signaling pathways, is anticipated as an effective approach for treating gliomas. In this study, we investigated whether our chemical library of steroid inhibitors can modulate the growth of pediatric low grade glioma cell lines (Res186, Res259, R286), and subsequently identified a potent inhibitor of 17beta-hydroxysteroid dehydrogenase type 3, referred to as DK16, which functions by attenuating cell viability, proliferation, migration/invasion and anchorage independent growth and conversely induces apoptosis and cell cycle arrest in a dose and duration dependent manner. Further investigations into the mechanisms of how DK16 functions showed that this drug increased the BAX/BCL2 expression ratio, induced  phosphatidylserine externalization, and mitochondrial membrane depolarizations culminating to the release and nuclear translocation of AIF. In addition, treatments of low grade glioma cell lines with DK16 increased the expression of pro-apoptotic mediators including CDK2 and CTSL1, and with the converse diminished expression of pro-survival and migratory/invasion genes like PRKCA, TERT, MAPK8, MMP1 and MMP2. Our findings collectively demonstrate the potent anti-neoplastic properties of DK16, a steroid biosynthesis inhibitor, on the growth of pediatric low grade gliomas.

 

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[342]

TÍTULO / TITLE:  - Preservation of olfaction in surgery of olfactory groove meningiomas.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 9. pii: S0303-8467(12)00614-2. doi: 10.1016/j.clineuro.2012.12.004.

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

AUTORES / AUTHORS:  - Jang WY; Jung S; Jung TY; Moon KS; Kim IY

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Gwangju, South Korea.

RESUMEN / SUMMARY:  - INTRODUCTION: Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. METHODS: Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of “Sniffin’Sticks” test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient’s age, and gender were analyzed with attention to the post-operative olfactory function. RESULTS: Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size <4cm and 42.3% in size >4cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). CONCLUSIONS: If the tumor was smaller than 4cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing  the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction.

 

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[343]

TÍTULO / TITLE:  - Semi-automatic Segmentation of Brain Tumors Using Population and Individual Information.

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

REVISTA / JOURNAL:  - J Digit Imaging. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10278-012-9568-1

AUTORES / AUTHORS:  - Wu Y; Yang W; Jiang J; Li S; Feng Q; Chen W

INSTITUCIÓN / INSTITUTION:  - School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, China.

RESUMEN / SUMMARY:  - Efficient segmentation of tumors in medical images is of great practical importance in early diagnosis and radiation plan. This paper proposes a novel semi-automatic segmentation method based on population and individual statistical information to segment brain tumors in magnetic resonance (MR) images. First, high-dimensional image features are extracted. Neighborhood components analysis is proposed to learn two optimal distance metrics, which contain population and patient-specific information, respectively. The probability of each pixel belonging to the foreground (tumor) and the background is estimated by the k-nearest neighborhood classifier under the learned optimal distance metrics. A cost function for segmentation is constructed through these probabilities and is  optimized using graph cuts. Finally, some morphological operations are performed  to improve the achieved segmentation results. Our dataset consists of 137 brain MR images, including 68 for training and 69 for testing. The proposed method overcomes segmentation difficulties caused by the uneven gray level distribution  of the tumors and even can get satisfactory results if the tumors have fuzzy edges. Experimental results demonstrate that the proposed method is robust to brain tumor segmentation.

 

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[344]

TÍTULO / TITLE:  - Cilary Body Medulloepithelioma in an Adult.

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

REVISTA / JOURNAL:  - Surv Ophthalmol. 2012 Dec 5. pii: S0039-6257(12)00186-5. doi: 10.1016/j.survophthal.2012.08.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.survophthal.2012.08.006

AUTORES / AUTHORS:  - Ali MJ; Honavar SG; Vemuganti GK

INSTITUCIÓN / INSTITUTION:  - Ocular Oncology Services, LV Prasad Eye Institute, Hyderabad, India.

RESUMEN / SUMMARY:  - A 67-year-old woman presented with complaints of poor vision and persistent redness in the right eye of 4 months duration. She had undergone an uncomplicated cataract surgery in the same eye 2 years ago and had regained visual acuity of 20/20 with a then otherwise unremarkable eye examination. She had only light perception in the affected right eye with an intraocular pressure of 42 mm Hg. There were dilated episcleral vessels inferotemporally. Powdery white material was dispersed over the corneal endothelium and in the anterior chamber. There was diffuse iris neovascularization and a large yellowish white, fluffy, ciliary body mass. A metastasis was suspected, but systemic evaluation failed to reveal a primary. In view of the neovascular glaucoma, poor visual potential, and suspicion of a malignancy, the eye was enucleated. Histopathological examination  revealed malignant nonteratoid ciliary body medulloepithelioma. Although ciliary  body medulloepithelioma is predominantly a pediatric tumor, this case emphasizes  the need to include it in the differential diagnosis of ciliary body tumors in adults.

 

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[345]

TÍTULO / TITLE:  - CDKN2A deletion in pediatric versus adult glioblastomas and predictive value of p16 immunohistochemistry.

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

REVISTA / JOURNAL:  - Neuropathology. 2013 Jan 14. doi: 10.1111/neup.12014.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12014

AUTORES / AUTHORS:  - Purkait S; Jha P; Sharma MC; Suri V; Sharma M; Kale SS; Sarkar C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

RESUMEN / SUMMARY:  - Cell cycle regulator genes are major target of mutation in many human malignancies including glioblastomas (GBMs). CDKN2A is one such tumor suppressor  gene which encodes p16INK4a protein and serves as an inhibitor of cell cycle progression. Very few studies are available regarding the association of CDKN2A deletion with p16 protein expression in GBMs. There is limited data on the frequency of CDKN2A deletion in different age groups. The aim of the present study was to analyze the frequency of CDKN2A gene deletions in GBM and correlate  CDKN2A deletional status with (i) age of the patient (ii) p16 protein expression  and (iii) other genetic alterations, namely EGFR amplification and TP53 mutation. A combined retrospective and prospective study was conducted. Sixty seven cases were included. The patients were grouped into pediatric (</=18 years), young adults (19-40 years) and older adults (>40 years). CDKN2A and EGFR status were assessed by Fluorescence in situ Hybridization.TP53 mutation was analyzed by PCR  based method. p16 expression was assessed using immunohistochemistry. CDKN2A deletion was noted in 40.3% cases of GBM with majority being homozygous deletion  (74%). It was commoner in primary GBMs (65.8%) and cases with EGFR amplification  (50%). A variable frequency of CDKN2A was observed in older adults (42.3%), young adults (44%), and pediatric patients (31.25%). The difference however was not statistically significant. There was statistically significant association between CDKN2A deletion and p16 immunonegativity with a high negative predictive  value of immunohistochemistry.

 

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[346]

TÍTULO / TITLE:  - miRNA-mediated tumor specific delivery of TRAIL reduced glioma growth.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1033-y

AUTORES / AUTHORS:  - Bo Y; Guo G; Yao W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China, drylbo@yahoo.com.cn.

RESUMEN / SUMMARY:  - As an aggressive cancer with high morbidity, malignant glioma always has a poor prognosis even after surgery, chemotherapy and radiotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including glioma. However  so far, TRAIL delivery mediated by adenoviral vectors lacks tumor specificity and thus has cytotoxicity to normal cells. To improve the tumor-specificity of adenovirus-mediated TRAIL delivery, we utilized miR-124, miR-128, miR-146b and miR-218 to restrict its expression to within glioma cells. qPCR assay showed that expression of these four miRNAs was greatly downregulated in glioma in comparison with normal brain tissue. Luciferase reporter assay confirmed that miR-124, miR-128, miR-146b and miR-218 conferred exogenous gene expression with glioma-specificity. By inserting miRNA response elements (MREs) of these miRNAs into the downstream of TRAIL on adenoviral vectors, TRAIL was highly expressed in glioma cells, but not in normal brain cells. Cell viability and immunoblotting assays and FACS analysis showed that cytotoxicity and apoptosis elicited by TRAIL was only observed in glioma cells, rather than normal brain cells. Animal experiments also showed that MREs-regulated TRAIL delivery reduced the growth of  glioma xenograft. In this study, we proved that miRNA-mediated tumor specific delivery of TRAIL was able to inhibit the survival of glioma cells and reduce the growth of glioma in vivo.

 

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[347]

TÍTULO / TITLE:  - Inhibition of GSH synthesis potentiates temozolomide-induced bystander effect in  glioblastoma.

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

REVISTA / JOURNAL:  - Cancer Lett. 2012 Dec 12. pii: S0304-3835(12)00722-7. doi: 10.1016/j.canlet.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2012.12.005

AUTORES / AUTHORS:  - Kohsaka S; Takahashi K; Wang L; Tanino M; Kimura T; Nishihara H; Tanaka S

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Pathology, Hokkaido University Graduate School of Medicine,  N15, W7, Kita-ku, Sapporo 060-8638, Japan.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor prognosis. Current standard treatment includes chemotherapy using DNA alkylating agent temozolomide (TMZ) concomitant with surgical resection and/or irradiation. However, GBM patients exhibit various levels of the elevated expression of DNA repair enzyme, due to MGMT causing resistance to TMZ. Determination of the MGMT-positive population of primary tumor is important to evaluate the therapeutic efficacy of TMZ. Here we generated TMZ-resistant GBM cells by introducing MGMT into TMZ-sensitive GBM cell line KMG4, and established  a model to assess the TMZ-induced bystander effect on TMZ-resistant cells. By mixing TMZ-resistant and -sensitive cells, GBM tumors with MGMT positivity as 50%, 10%, and 1% were generated in vivo. We could not observe any bystander effect of TMZ-induced cell death in tumor with 50% MGMT positivity. Although the  bystander effect was observed within 20days in the case of tumor with 1% MGMT positivity, final tumor size at day 28 was the same as control without sensitive  cells. This bystander effect was observed in vitro using conditioned medium of TMZ-damaged GBM cells, and PCR array analysis indicated that the conditioned medium stimulated stress and toxicity pathway and upregulated anti-oxidants genes expression such as catalase and SOD2 in TMZ-resistant cells. In addition, the reduction of the activity of anti-stress mechanism by using inhibitor of GSH synthesis potentiated TMZ-induced bystander effect. These results suggest that GSH inhibitor might be one of the candidates for combination therapy with TMZ for TMZ-resistant GBM patients.

 

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[348]

TÍTULO / TITLE:  - Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma.

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

REVISTA / JOURNAL:  - Am J Clin Oncol. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318271ae03

AUTORES / AUTHORS:  - Paulsson AK; McMullen KP; Peiffer AM; Hinson WH; Kearns WT; Johnson AJ; Lesser GJ; Ellis TL; Tatter SB; Debinski W; Shaw EG; Chan MD

INSTITUCIÓN / INSTITUTION:  - Departments of *Radiation Oncology section signNeurosurgery double daggerMedicine (Hematology & Oncology) daggerRadiology parallelBrain Tumor Center of Excellence, Wake Forest University, Winston-Salem, NC.

RESUMEN / SUMMARY:  - OBJECTIVE:: We investigate the patterns of failure in the treatment of glioblastoma (GBM) based on clinical target volume (CTV) margin size, dose delivered to the site of initial failure, and the use of temozolomide and intensity-modulated radiotherapy (IMRT). METHODS:: Between August 2000 and May 2010, 161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide. Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique. Patterns of failure and time to progression and overall survival were compared based on CTV margin, use of temozolomide, and use of IMRT. Kaplan Meier analysis was used to estimate survival times, and chi test was used for comparison of cohorts. RESULTS:: For patients treated with 5-, 10-, and 15- to 20-mm CTV, 79%, 77%, and 86% experienced failures in the 60 Gy volume, respectively. Forty-eight percent, 55%, and 66% of patients with 5-, 10-, and 15- to 20-mm CTV experienced failures in the 46 Gy volume, respectively. There was no statistical difference between patients treated with 5-, 10-, 15- to 20-mm margins with regard to 60 Gy failure  (P=0.76), 46 Gy failure (P=0.51), or marginal failure (P=0.73). Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume. There was no increased likelihood of marginal failures in patients receiving IMRT (P=0.97). CONCLUSIONS:: Modern treatment techniques including use of concurrent temozolmide, limited CTV margin size, and IMRT have not greatly changed the patterns of failure of GBM.

 

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[349]

TÍTULO / TITLE:  - Measurements of heterogeneity in gliomas on computed tomography relationship to tumour grade.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan;111(2):213-9. doi: 10.1007/s11060-012-1010-5. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1010-5

AUTORES / AUTHORS:  - Skogen K; Ganeshan B; Good C; Critchley G; Miles K

INSTITUCIÓN / INSTITUTION:  - Brighton and Sussex Medical School, Brighton, UK, karolineskogen@hotmail.com.

RESUMEN / SUMMARY:  - To undertake a preliminary study that uses CT texture analysis (CTTA) to quantify heterogeneity in gliomas on contrast-enhanced CT and to assess the relationship between tumour heterogeneity and grade. Retrospective analysis of contrast enhanced CT images was performed in 44 patients with histologically proven cerebral glioma between 2007 and 2010. 11 tumours were low grade (Grade I = 3; Grade II, = 8) and 33 high grade (Grade III = 10, Grade IV = 23). CTTA assessment of tumour heterogeneity was performed using a proprietary software algorithm (TexRAD) that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features). Heterogeneity was quantified as standard deviation (SD) with or without filtration. Tumour heterogeneity, size and attenuation were correlated with tumour grade. For each parameter, receiver operating characteristics characterised the diagnostic performance for discrimination of high grade from low grade glioma and of grade III tumours from grade IV. Further the CTTA was compared to the radiological diagnosis. Tumour heterogeneity correlated significantly with grade (SD without filtration rs = 0.664, p < 0.001, SD with coarse filtration (rs = 0.714, p < 0.001). Tumour size and attenuation showed only moderate correlations with tumour grade (rs = 0.426, p = 0.004 and rs = 0.447, p = 0.002 respectively). Coarse texture was the best discriminator between high and low grade tumours (AUC 0.832, p < 0.0001) and between grade III and grade IV gliomas (AUC = 0.878 p = 0.0001). Compared to the radiological diagnosis, CTTA further characterised the indetermined cases. By quantifying tumour heterogeneity, CTTA has the potential to provide a marker of tumour grade  for patients with cerebral glioma. By differentiating between high and low grade  tumours, CTTA could possibly assist clinical management.

 

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[350]

TÍTULO / TITLE:  - CD133 is essential for glioblastoma stem cell maintenance.

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

REVISTA / JOURNAL:  - Stem Cells. 2013 Jan 10. doi: 10.1002/stem.1317.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1317

AUTORES / AUTHORS:  - Paola B; Barbara O; Lorenzo F; Daniel L; Giovanni B; Giuliana P

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy.

RESUMEN / SUMMARY:  - The role of the cell surface CD133 as a cancer stem cell marker in glioblastoma has been widely investigated, since it identifies cells able to initiate neurosphere growth and form heterogeneous tumors when transplanted in immune-compromised mice. However, evidences of CD133-negative cells exhibiting similar properties have also been reported. Moreover, the functional role of CD133 in cancer stem/progenitor cells remains poorly understood. We studied the biological effects of CD133 down-regulation in glioblastoma patient-derived neurospheres. Our results indicate that there is not a hierarchical relation between CD133-positive and CD133-negative cells composing the neurospheres. Indeed, CD133 appears in an interconvertible state, changing its subcellular localization between the cytoplasm and the plasmamembrane of neurosphere cells. Silencing of CD133 in human glioblastoma neurospheres using lentivirus mediated short hairpin RNA, impairs the self-renewal and tumorigenic capacity of neurosphere cells. These results imply that CD133 could be used as a therapeutic  target in glioblastomas.

 

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[351]

TÍTULO / TITLE:  - Tumor-specific Activation of the c-JUN/MELK Pathway Regulates Glioma Stem Cell Growth in a p53-dependent Manner.

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

REVISTA / JOURNAL:  - Stem Cells. 2013 Jan 17. doi: 10.1002/stem.1322.

            ●● Enlace al texto completo (gratuito o de pago) 1002/stem.1322

AUTORES / AUTHORS:  - Gu C; Banasavadi-Siddegowda YK; Joshi K; Nakamura Y; Kurt H; Gupta S; Nakano I

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, The Ohio State University, Columbus, OH, 43210.

RESUMEN / SUMMARY:  - Accumulated evidence suggests that glioma stem cells (GSCs) may contribute to therapy resistance in high grade glioma (HGG). Although recent studies have shown that the serine/threonine kinase MELK is abundantly expressed in various cancers, the function and mechanism of MELK remain elusive. Here, we demonstrate that MELK depletion by shRNA diminishes the growth of GSC-derived mouse intracranial tumors in vivo, induces GFAP (+) glial differentiation of GSCs leading to decreased malignancy of the resulting tumors, and prolongs survival periods of tumor-bearing mice. Tissue microarray analysis with 91 HGG tumors demonstrates that the proportion of MELK (+) cells is a statistically significant indicator of post-surgical survival periods. Mechanistically, MELK is regulated by the JNK signaling and forms a complex with the oncoprotein c-JUN in GSCs but not in normal progenitors. MELK silencing induces p53 expression, whereas p53 inhibition induces MELK expression, indicating that MELK and p53 expression are mutually exclusive. Additionally, MELK silencing-mediated GSC apoptosis is partially rescued by both pharmacological p53 inhibition and p53 gene silencing, indicating that MELK action in GSCs is p53 dependent. Furthermore, irradiation of GSCs markedly elevates MELK mRNA and protein expression both in vitro and in vivo. Clinically, recurrent HGG tumors following the failure of radiation and chemotherapy exhibit a statistically significant elevation of MELK protein compared with untreated newly-diagnosed HGG tumors. Together, our data indicate that GSCs, but not normal cells, depend on JNK-driven MELK/c-JUN signaling to regulate their survival, maintain GSCs in an immature state, and facilitate tumor radioresistance in a p53-dependent manner.

 

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[352]

TÍTULO / TITLE:  - Multiple mucosal neuromas in the larynx as part of a multiple endocrine neoplasia type 2B.

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

REVISTA / JOURNAL:  - Acta Otorrinolaringol Esp. 2012 Dec 3. pii: S0001-6519(12)00225-7. doi: 10.1016/j.otorri.2012.09.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.otorri.2012.09.008

AUTORES / AUTHORS:  - Soroa-Ruiz F; Lara-Sanchez H; Ramirez Anguiano J; Cordova-Ramon JC

INSTITUCIÓN / INSTITUTION:  - Servicio de Otorrinolaringologia y Cirugia de Cabeza y Cuello, Instituto Nacional de Ciencias Medicas y Nutricion <<Salvador Zubiran>>, Mexico, DF, Mexico. Electronic address: pacosoroa@yahoo.com.

 

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[353]

TÍTULO / TITLE:  - Epidermoid cyst mimicking an intrinsic brainstem tumor.

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

REVISTA / JOURNAL:  - Neurocirugia (Astur). 2012 Dec 7. pii: S1130-1473(12)00187-X. doi: 10.1016/j.neucir.2012.09.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.neucir.2012.09.007

AUTORES / AUTHORS:  - Volpon Santos M; Lopes Furlanetti L; Jeanne Bezerra MD; Santos de Oliveira R

INSTITUCIÓN / INSTITUTION:  - Division of Pediatric Neurosurgery, Department of Surgery and Anatomy, Ribeirao Preto School of Medicine, University of Sao Paulo; Hospital Infantil Varela Santiago, Natal, Brazil. Electronic address: marcelovolpon@yahoo.com.

RESUMEN / SUMMARY:  - OBJECTIVE: To describe an atypical clinical and radiological presentation of a brainstem epidermoid cyst in a child and to provide a review of the medical literature on brainstem epidermoid cysts in children. MATERIAL AND METHOD: Review of medical records and operative notes of an unusual case of a patient with a brainstem epidermoid cyst. MEDLINE literature search using the terms brainstem, epidermoid cyst and children. RESULTS: Gross total resection of the cyst was achieved. The patient had an uneventful recovery. CONCLUSION: Epidermoid cysts are rare tumors of the brain and children. The management of these tumors can be  quite challenging. A good clinical and neuroradiological evaluation pre-operatively is fundamental for a successful surgical treatment. Surgical resection should be as radical as possible without putting the patient’s neurological status into risk.

 

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[354]

TÍTULO / TITLE:  - Clear Cell Ependymoma in a Dog.

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

REVISTA / JOURNAL:  - J Comp Pathol. 2012 Dec 27. pii: S0021-9975(12)00424-0. doi: 10.1016/j.jcpa.2012.11.236.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jcpa.2012.11.236

AUTORES / AUTHORS:  - Traslavina RP; Kent MS; Mohr FC; Dickinson PJ; Vernau KM; Bollen AW; Higgins RJ

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, USA. Electronic address: traslavina@gmail.com.

RESUMEN / SUMMARY:  - A 13-year-old, mixed breed dog presented with a 1-month history of seizures. Magnetic resonance imaging of the brain revealed a 2.2 x 1.0 x 0.9 cm ovoid and elongate cystic mass within the white matter of the left frontal lobe extending caudally from the cribriform plate to the rostral left lateral ventricle. Three fractions of stereotactic radiotherapy were administered and resulted in reduction of the volume of the tumour; however, the clinical signs failed to improve. On post-mortem examination, a single mass 1.5 x 0.3 x 1 cm was found within the left frontal lobe. It consisted of gelatinous, grey, friable tissue bordering a central empty cavity. Microscopical evaluation revealed polygonal neoplastic cells with distinct cytoplasmic borders and one or more intracytoplasmic solid, brightly eosinophilic, sharply defined globules. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein and S100 but were negative for pan cytokeratin, vimentin, olig-2 and synaptophysin. Ultrastructurally, neoplastic cells had dense whorls of intracytoplasmic intermediate filaments and were connected by multiple intermittent long zonula adherens-type junctions. Based on these findings, a diagnosis of clear cell ependymoma was made. This is the first report of this subtype in the dog.

 

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[355]

TÍTULO / TITLE:  - The incidence and significance of multiple lesions in glioblastoma.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1030-1

AUTORES / AUTHORS:  - Thomas RP; Xu LW; Lober RM; Li G; Nagpal S

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Stanford University Hospital, 300 Pasteur Drive, Room A343, Palo Alto, CA, 94304-5235, USA, Reenat@stanford.edu.

RESUMEN / SUMMARY:  - The location and distribution of glioblastoma (GBM) within the brain parenchyma plays an important role in surgical and radiation planning. Prior studies have reported incidences of multiple lesions at the time of diagnosis ranging from 0.5 to 20 %. Multiple lesions can be further categorized as multifocal (multiple areas involved, but with a clear path of spread from one lesion to another) or multicentric (multiple lesions, no clear path of spread). In this retrospective study, we reviewed our experience with GBM and found the incidence of multiple lesions at time of diagnosis was 35 %, much higher than previously suggested in the literature. Patients with single lesions had an improved overall survival when compared to patients with multiple lesions (18 vs. 10 months). Patients with multicentric lesions fared the worst, with average survival of 3 months. However, the difference between single and multiple lesions (multifocal or multicentric) was no longer significant when taking into consideration age, Karnofsky performance score (KPS) and extent of resection by multivariate analysis. Age, KPS, gross total resection, and MGMT status were independent predictors of outcome. Multiple lesions did not independently confer a worse outcome, but were  associated with lower KPS scores and inability to perform gross total resection.  These findings suggest that single, multiple and multicentric imaging exams represent a spectrum of presentations of a single disease. The rate of multiple lesions reported here may be the result of improved imaging technology, suggesting that incidence of multiple lesions will continue to increase as imaging technology advances.

 

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[356]

TÍTULO / TITLE:  - PRDM1 is directly targeted by miR-30a-5p and modulates the Wnt/beta-catenin pathway in a Dkk1-dependent manner during glioma growth.

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

REVISTA / JOURNAL:  - Cancer Lett. 2013 Jan 21. pii: S0304-3835(13)00025-6. doi: 10.1016/j.canlet.2013.01.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.005

AUTORES / AUTHORS:  - Wang X; Wang K; Han L; Zhang A; Shi Z; Zhang K; Zhang H; Yang S; Pu P; Shen C; Yu C; Kang C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.

RESUMEN / SUMMARY:  - The transcriptional regulator PRDM1 controls cell-fate decisions and has been implicated in human tumorigenesis as a tumor suppressor. However, its pathological role in glioma remains elusive. In this study, we showed that PRDM1  protein levels were inversely correlated with the pathological grade of gliomas and were predictive of patient survival in a retrospective analysis. Restored expression of PRDM1 inhibited proliferation and suppressed invasion by glioma cells. Mechanistic investigation revealed that PRDM1 attenuated glioma malignancy by negatively modulating Wnt/beta-catenin signaling and this modulation was dependent on the Wnt inhibitor Dkk1. Using bioinformatics and biological approaches, we found that PRDM1 was a direct target of miR-30a-5p, and PRDM1 dysfunction was attributable to miR-30a-5p-mediated repression. Our results provide evidence that PRDM1 deficiency contributes to the phenotype maintenance and pathogenesis of gliomas.

 

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[357]

TÍTULO / TITLE:  - Expression and Significance of E-Cadherin and beta-Catenins in Pituitary Adenoma.

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

REVISTA / JOURNAL:  - Int J Surg Pathol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1066896912471850

AUTORES / AUTHORS:  - Zhou K; Jin H; Luo Y

RESUMEN / SUMMARY:  - This study used immunohistochemical methods for detecting the expression of E-cadherin and beta-catenin in pituitary adenoma. Specimens were collected from 91 cases. EnVision was used for immunohistochemical staining. The results were graded depending on the staining intensity and range. Associations between E-cadherin and beta-catenin expression and tumor subtype, invasiveness, and postoperative recurrence were investigated. There was a significant downregulation of E-cadherin and beta-catenin in growth hormone (GH)-type tumors  when compared with prolactin-type tumors (u© = 2.693 and 2.109, respectively; P < .05). E-cadherin and beta-catenin were downregulated in invasive pituitary adenomas (u© = 3.563 and 4.166, respectively; P < .05) and in clinically recurring pituitary adenomas (u© = 2.871 and 3.866, respectively; P < .05). There was no difference in the percentage of invasive prolactin and GH secreting  tumors (28.57% and 22.86%, respectively; P > .05). The expression of E-cadherin and beta-catenin in pituitary adenoma was significantly downregulated and related to subtype, invasiveness, and postoperative recurrence.

 

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[358]

TÍTULO / TITLE:  - Pilocytic astrocytoma: A retrospective study of 32 cases.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2012 Dec 19. pii: S0303-8467(12)00587-2. doi: 10.1016/j.clineuro.2012.11.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.11.009

AUTORES / AUTHORS:  - Cyrine S; Sonia Z; Mounir T; Badderedine S; Kalthoum T; Hedi K; Moncef M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University Hospital Farhat Hached, 4000 Sousse, Tunisia.

RESUMEN / SUMMARY:  - Pilocytic astrocytoma (PA) is a neoplasia which is considered as a grade I astrocytoma by the World Health Organization (WHO). Its most common location is the cerebellum and it develops during the first two decades of life. Prognosis is mostly excellent if gross-total resection can be achieved, with 10-year survival  rates of up to 95%. In rare cases, however, the patient has a bad outcome. Our aims were to retrospectively describe the clinicopathological features of 32 PAs, and identify factors that may be associated with aggressive behavior. The study included 21 males and 11 females with a median age of 10.5 years. Tumors demonstrated predilection for infratentorial location (74.9%), especially the cerebellum (59.3%), followed by cerebral ventricles (15.6%), supratentorial location (12.5%) and optic pathway (3.12%). Gross total resection was achieved in 14 tumors only. On histopathology, moderate cellularity (68.7%), microcystic changes (71.9%), Rosenthal fibers (62.5%) and eosinophilic granular bodies (53.2%) were present in the majority of cases. Atypia was present in 62.5% of cases, while endothelial proliferation and necrosis was noted in 3 and 2 cases, respectively. Median follow-up for all patients was 24 months. Four patients died in the postoperative period, one of whom was 62-year-old men and two others had brainstem location or invasion. Recurrence was observed in a 56-year-old patient  whom first tumor was locally invasive. The patient died after the second surgery  and anaplastic features was found in the recurrent tumor without previous radiotherapy. PA is a benign tumor, but some clinicopathological factors, such as partial resection, brainstem location and adult age have a worse prognosis.

 

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[359]

TÍTULO / TITLE:  - Eps8 promotes cellular growth of human malignant gliomas.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Feb;29(2):697-703. doi: 10.3892/or.2012.2160. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2012.2160

AUTORES / AUTHORS:  - Ding X; Zhou F; Wang F; Yang Z; Zhou C; Zhou J; Zhang B; Yang J; Wang G; Wei Z; Hu X; Xiang S; Zhang J

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Protein Chemistry and Developmental Biology of the State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, PR China.

RESUMEN / SUMMARY:  - Eps8 was initially identified as a substrate of the epidermal growth factor receptor. Overexpression of Eps8 leads to increased mitogenic signaling and malignant transformation. However, little is known concerning the importance of Eps8 in human gliomas. In this study, we found that Eps8 was overexpressed in 56.6% of human gliomas (WHO grades III and IV) compared with adjacent normal brain tissues by immunohistochemical analysis. The U251 human glioma cell line stably expressing Eps8 was established by G418 screening, and the ectopic expression of Eps8 enhanced U251 glioma cell growth and survival by cell survival, MTT and liquid colony formation assays. By contrast, the lentiviral expression of Eps8 siRNA in SHG-44 cells resulted in a significant reduction in cellular growth and proliferation. Furthermore, Eps8 modulated the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), phosphorylated serine-threonine protein kinase Akt and beta-catenin expression in glioma cell lines and tissues. These results suggest that Eps8 is overexpressed in human gliomas, and affects glioma cell growth possibly by regulating ERK and Akt/beta-catenin signaling. Therefore, Eps8 may represent a novel potential target in human glioma therapy.

 

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[360]

TÍTULO / TITLE:  - Textiloma resembling anaplastic progression of an isocitrate dehydrogenase 1 (IDH1) mutant, low grade glioma.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1013-2

AUTORES / AUTHORS:  - Anderson MD; Raghunathan A; Gilbert MR

INSTITUCIÓN / INSTITUTION:  - The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 431, Houston, TX, 77030, USA, mdanderson2@mdanderson.org.

 

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[361]

TÍTULO / TITLE:  - Right frontal lobe glioma presenting as anorexia nervosa: Further evidence implicating dorsal anterior cingulate as an area of dysfunction.

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

REVISTA / JOURNAL:  - Int J Eat Disord. 2012 Dec 26. doi: 10.1002/eat.22072.

            ●● Enlace al texto completo (gratuito o de pago) 1002/eat.22072

AUTORES / AUTHORS:  - Goddard E; Ashkan K; Farrimond S; Bunnage M; Treasure J

INSTITUCIÓN / INSTITUTION:  - Section of Eating Disorders, Department of Psychological Medicine, King’s College London, Institute of Psychiatry, London, United Kingdom.

RESUMEN / SUMMARY:  - OBJECTIVE: The association of anorexia nervosa (AN) with organic brain lesions may offer insight into underlying illness neuropathology. A systematic review reported an association between AN and lesions located in the right frontal lobe. To date, no studies have studied such a case longitudinally. A case of a male presenting with AN and a frontal lobe glioma is described. METHOD: The clinical symptoms and subsequent medical and neuropsychological investigations before and  after surgery are reviewed. RESULTS: The remission of ED symptoms is observed at  2 year post-surgery follow up. DISCUSSION: The features of this case are set into the context of recent conceptualizations of AN and the clinical implications for  identifying individuals with underlying organic causes. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012).

 

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[362]

TÍTULO / TITLE:  - A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1041-y

AUTORES / AUTHORS:  - Satge D; Stiller CA; Rutkowski S; von Bueren AO; Lacour B; Sommelet D; Nishi M; Massimino M; Garre ML; Moreno F; Hasle H; Jakab Z; Greenberg M; von der Weid N; Kuehni C; Zurriaga O; Vicente ML; Peris-Bonet R; Benesch M; Vekemans M; Sullivan SG; Rickert C

INSTITUCIÓN / INSTITUTION:  - Epidemiology and Biostatistics Department, EA 2415, University Institute for Clinical Research IURC, Montpellier 1 University, 34093, Montpellier, France, danielsatge@orange.fr.

RESUMEN / SUMMARY:  - Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the  total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell  embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS.  Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

 

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[363]

TÍTULO / TITLE:  - Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy.

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

REVISTA / JOURNAL:  - J Neurooncol. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1028-8

AUTORES / AUTHORS:  - Neidert MC; Schoor O; Trautwein C; Trautwein N; Christ L; Melms A; Honegger J; Rammensee HG; Herold-Mende C; Dietrich PY; Stevanovic S

INSTITUCIÓN / INSTITUTION:  - Department of Immunology, Institute for Cell Biology, University of Tubingen, Auf der Morgenstelle 15, 72076, Tubingen, Germany.

RESUMEN / SUMMARY:  - Glioblastoma multiforme is the most frequent and most malignant primary brain tumor with poor prognosis despite surgical removal and radio-chemotherapy. In this setting, immunotherapeutical strategies have great potential, but the reported repertoire of tumor associated antigens is only for HLA-A*02 positive tumors. We describe the first analysis of HLA-peptide presentation patterns in HLA-A*02 negative glioma tissue combined with gene expression profiling of the tumor samples by oligonucleotide microarrays. We identified numerous candidate peptides for immunotherapy. These are peptides derived from proteins with a well-described role in glioma tumor biology and suitable gene expression profiles such as PTPRZ1, EGFR, SEC61G and TNC. Information obtained from complementary analyses of HLA-A*02 negative tumors not only contributes to the discovery of novel shared glioma antigens, but most importantly provides the opportunity to tailor a patient-individual cocktail of tumor-associated peptides for a personalized, targeted immunotherapeutic approach in HLA-A*02 negative patients.

 

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[364]

TÍTULO / TITLE:  - Superior cerebellar hyperintense sign on FLAIR-weighted magnetic resonance imaging in paraneoplastic cerebellar degeneration.

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

REVISTA / JOURNAL:  - Arq Neuropsiquiatr. 2012 Dec;70(12):967.

AUTORES / AUTHORS:  - Aragao Mde M; Pedroso JL; Albuquerque MV; Dutra LA; Barsottini OG

INSTITUCIÓN / INSTITUTION:  - Ataxia Unit, Department of Neurology, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.

 

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[365]

TÍTULO / TITLE:  - Posterior clinoid process meningioma.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 10. pii: S0303-8467(12)00617-8. doi: 10.1016/j.clineuro.2012.12.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.007

AUTORES / AUTHORS:  - Shukla D; Gangadharan J; Kakati A; Devi BI

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, NIMHANS, Bangalore, India. Electronic address: neurodhaval@rediffmail.com.

 

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[366]

TÍTULO / TITLE:  - Glial cell line-derived neurotrophic factor: Characterization of mammalian posttranslational modifications.

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

REVISTA / JOURNAL:  - Ann Med. 2013 Feb;45(1):66-73. doi: 10.3109/07853890.2012.663927. Epub 2012 Mar 9.

            ●● Enlace al texto completo (gratuito o de pago) 3109/07853890.2012.663927

AUTORES / AUTHORS:  - Piccinini E; Kalkkinen N; Saarma M; Runeberg-Roos P

INSTITUCIÓN / INSTITUTION:  - Institute of Biotechnology, University of Helsinki , PB 56 (Viikinkaari 9), SF-00014, University of Helsinki , Finland.

RESUMEN / SUMMARY:  - Introduction. Although glial cell line-derived neurotrophic factor (GDNF) has a strong clinical potential, little is known of how the posttranslational modifications of GDNF affect its biological activity and therapeutic potential. In mammalian cells GDNF is synthesized as a preproprotein. During secretion GDNF  dimerizes, folds with -S-S- bonds, is modified by N-linked glycosylation, and undergoes proteolytic processing. After production in E. coli, unglycosylated GDNF is renaturated in vitro. Nevertheless, GDNF from E. coli was used in Parkinson’s disease-related clinical trials. Material and methods. Constructs encoding variants of human GDNF were generated and expressed in mammalian cells.  The proteins were analysed by SDS-PAGE, Western blotting, RET-phosphorylation assays, and N-terminal sequencing. The stability of mammalian GDNF was compared to commercial GDNF produced in E. coli. Results. Posttranslational processing of  mammalian GDNF depends on the expression conditions. Two forms of GDNF with different N-termini are formed. GDNF without a prosequence is secreted and biologically active. GDNF is modified by N-linked glycosylation at one (Asn(49))  out of two consensus sites. N-linked glycosylation aids proteolytic processing of GDNF. Both glycosylated and unglycosylated GDNF from mammalian cells are more stable than GDNF from E. coli. Discussion. Posttranslational modifications of GDNF influence its stability, which may be critical for its clinical use.

 

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[367]

TÍTULO / TITLE:  - Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas.

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

REVISTA / JOURNAL:  - Arq Neuropsiquiatr. 2013 Jan;71(1):31-4. Epub 2013 Jan 8.

AUTORES / AUTHORS:  - Bianco Ade M; Miura FK; Clara C; Almeida JR; Silva CC; Teixeira MJ; Marie SK

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors  in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

 

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[368]

TÍTULO / TITLE:  - Synchronization regulation in a model of coupled neural masses.

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

REVISTA / JOURNAL:  - Biol Cybern. 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00422-012-0541-3

AUTORES / AUTHORS:  - Ma Z; Zhou W; Geng S; Yuan Q; Li X

INSTITUCIÓN / INSTITUTION:  - School of Information Science and Engineering, Shandong University, 27 Shanda Road, Jinan, 250100, People’s Republic of China.

RESUMEN / SUMMARY:  - A model of coupled neural masses can generate seizure-like events and dynamics similar to those observed during interictal to ictal transitions and thus can be  used for theoretical study of the control of epileptic seizures. In an effort to  understand the mechanisms underlying epileptic seizures and how to avoid them, we added a control input to this model. Epileptic seizures are always accompanied by hypersynchronous firing of neurons, so research on synchronization among cortical areas is significant for seizure control. In this study, principal component analysis (PCA) was used to identify synchronization clusters composed of several  neural masses. A method for calculating the synchronization cluster strength and  participation rate is presented. The synchronization cluster strength can be used to identify synchronization clusters and the participation rate can be employed to identify neural masses that participate in the clusters. Each synchronization  cluster is controlled as a whole using a proportional-integral-derivative (PID) controller. We illustrate these points using coupled neural mass models of synchronization to show their responses to increased (between node) coupling with and without control. Experiment results indicated that PID control can effectively regulate synchronization between neural masses and has the potential  for seizure prevention.

 

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[369]

TÍTULO / TITLE:  - Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma.

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

REVISTA / JOURNAL:  - Oncol Rep. 2013 Jan 17. doi: 10.3892/or.2013.2240.

            ●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2240

AUTORES / AUTHORS:  - Wang Z; Sun J; Li X; Yang S; Yue S; Zhang J; Yang X; Zhu T; Jiang R; Yang W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin  300052, P.R. China.

RESUMEN / SUMMARY:  - Src is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor  growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic  effect of temozolomide through AKT supression in glioma.

 

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[370]

TÍTULO / TITLE:  - Chromosomal heterogeneity and instability characterize pediatric medulloblastoma  cell lines and affect neoplastic phenotype.

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

REVISTA / JOURNAL:  - Cytotechnology. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10616-012-9529-z

AUTORES / AUTHORS:  - Castro-Gamero AM; Borges KS; Lira RC; Andrade AF; Fedatto PF; Cruzeiro GA; Silva RB; Fontes AM; Valera ET; Bobola M; Scrideli CA; Tone LG

INSTITUCIÓN / INSTITUTION:  - Department of Genetics, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil, amcgen@gmail.com.

RESUMEN / SUMMARY:  - Chromosomal heterogeneity is a hallmark of most tumors and it can drive critical  events as growth advantages, survival advantages, progression and karyotypic evolution. Medulloblastoma (MB) is the most common malignant central nervous system tumor in children. This work attempted to investigate chromosomal heterogeneity and instability profiles of two MB pediatric cell lines and their relationship with cell phenotype. We performed GTG-banding and cytokinesis-block  micronucleus cytome assays, as well as morphological characterization, cell population doubling time, colony-forming efficiency, and chemo-sensitivity assays in two pediatric MB cell lines (UW402 and UW473). Both MB cells showed a high chromosomal heterogeneity. UW473 cells showed ~2 fold higher both clonal- and non-clonal chromosomal alterations than UW402 cells. Besides, UW473 showed two clonal-groups well-differentiated by ploidy level (<2n> and <4n>) and also presented a significantly higher number of chromosomal instability biomarkers. These results were associated with high morphological heterogeneity and survival  advantages for UW473 and proliferation advantages for UW402 cells. Moreover, UW473 was significantly more sensitive to methotrexate, temozolomide and cisplatin while UW402 cells were more sensitive to doxorubicin. These data suggest that distinct different degrees of karyotypic heterogeneity and instability may affect neoplasic phenotype of MB cells. These findings bring new  insights into cell and tumor biology.

 

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[371]

TÍTULO / TITLE:  - Primary central nervous system diffuse large B cell lymphoma transformed from orbital mucosa-associated lymphoid tissue lymphoma: complete response to combined intrathecal and systemic rituximab.

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

REVISTA / JOURNAL:  - Ann Hematol. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00277-012-1651-7

AUTORES / AUTHORS:  - Huang HC; Cheng AL; Lin CW; Kuo SH

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Yun-Lin Branch, National Taiwan University Hospital, Yun-Lin, Taiwan.

 

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[372]

TÍTULO / TITLE:  - Double pituitary adenomas.

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

REVISTA / JOURNAL:  - Endocrine. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9876-3

AUTORES / AUTHORS:  - Iacovazzo D; Bianchi A; Lugli F; Milardi D; Giampietro A; Lucci-Cordisco E; Doglietto F; Lauriola L; De Marinis L

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Catholic University, Policlinico “A. Gemelli”, Largo A. Gemelli, 8, 00168, Rome, Italy, donatoiacovazzo@gmail.com.

RESUMEN / SUMMARY:  - Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing’s disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing’s disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient’s clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to  a prolactin secreting microadenoma although not confirmed histologically, shrunk  by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done.

 

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[373]

TÍTULO / TITLE:  - EGF signalling and rapamycin-mediated mTOR inhibition in glioblastoma multiforme  evaluated by phospho-specific flow cytometry.

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

REVISTA / JOURNAL:  - J Neurooncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-012-1035-9

AUTORES / AUTHORS:  - Cornez I; Joel M; Tasken K; Langmoen IA; Glover JC; Berge T

INSTITUCIÓN / INSTITUTION:  - The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Gaustadalleen 21, 0349, Oslo, Norway.

RESUMEN / SUMMARY:  - Development of novel patient stratification tools for cancer is a challenge that  require advanced molecular screening and a detailed understanding of tumour signalling networks. Here, we apply phospho-specific flow cytometry for signal profiling of primary glioblastoma tumours after preservation of single-cell phosphorylation status as a strategy for evaluation of tumour signalling potential and assessment of rapamycin-mediated mTOR inhibition. The method has already enhanced insight into cancers and disorders of the immune system, and our study demonstrate a great potential to improve the understanding of aberrant signalling in glioblastoma and other solid tumours.

 

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[374]

TÍTULO / TITLE:  - Glioma infiltration of the corpus callosum: early signs detected by DTI.

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

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

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1049-y

AUTORES / AUTHORS:  - Kallenberg K; Goldmann T; Menke J; Strik H; Bock HC; Stockhammer F; Buhk JH; Frahm J; Dechent P; Knauth M

INSTITUCIÓN / INSTITUTION:  - Neuroradiology, Universitatsmedizin, Georg-August-University Gottingen, Robert-Koch-Str. 40, 37099, Gottingen, Germany, kai.kallenberg@med.uni-goettingen.de.

RESUMEN / SUMMARY:  - The most frequent primary brain tumors, anaplastic astrocytomas (AA) and glioblastomas (GBM): tend to invasion of the surrounding brain. Histopathological studies found malignant cells in macroscopically unsuspicious brain parenchyma remote from the primary tumor, even affecting the contralateral hemisphere. In early stages, diffuse interneural infiltration with changes of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) is suspected. The purpose of this study was to investigate the value of DTI as a possible instrument of depicting evidence of tumor invasion into the corpus callosum (CC). Preoperatively, 31 patients with high-grade brain tumors (8 AA and 23 GBM) were examined by MRI at 3 T, applying a high-resolution diffusion tensor imaging (DTI) sequence. ADC- and FA-values were analyzed in the tumor-associated area of the CC as identified by fiber tracking, and were compared to matched healthy controls. In (MR-)morphologically normal appearing CC the ADC values were elevated in the tumor patients (n = 22; 0.978 x 10(-3) mm(2)/s) compared to matched controls (0.917 x 10(-3) mm(2)/s, p < 0.05), and the corresponding relative FA was reduced (rFA: 88 %, p < 0.01). The effect was pronounced in case of affection of the CC visible on MRI (n = 9; 0.978 x 10(-3) mm(2)/s, p < 0.05; rFA: 72 %, p < 0.01). Changes in diffusivity and anisotropy in the CC can be interpreted as an indicator of tumor spread into the contralateral hemisphere not visible on conventional MRI.

 

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[375]

TÍTULO / TITLE:  - Pseudoprogression in high-grade glioma.

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

REVISTA / JOURNAL:  - Acta Neurol Scand Suppl. 2013;(196):31-7. doi: 10.1111/ane.12047.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ane.12047

AUTORES / AUTHORS:  - Knudsen-Baas KM; Moen G; Fluge O; Storstein A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Haukeland University Hospital, Bergen, Norway. kristin.marie.knudsen-baas@helse-bergen.no

RESUMEN / SUMMARY:  - Pseudoprogression is a treatment-related effect seen on imaging in high-grade glioma. Enhancement of gadolinium contrast on control MRI can be misinterpreted as tumor recurrence and is also difficult to distinguish from radiation necrosis. Pseudoprogression is seen in up to 30% after standard treatment for glioblastoma  multiforme (GBM), which is radiotherapy concurrent with chemotherapy with temozolomide (TMZ) and adjuvant cycles of TMZ. In this article, the current literature on pseudoprogression in high-grade glioma is reviewed by searches in PubMed. We also present two clinical cases, one of which had medullary pseudoprogression. No articles on this subentity of pseudoprogression were found  in PubMed. Standard MRI with gadolinium contrast cannot differentiate between pseudoprogression, tumor recurrence and radiation necrosis. More advanced imaging techniques are often not available. Pseudoprogression seems to be related to methylated promoter of the O(6)--methyl-guanine methyl transferase (MGMT) gene, which is associated with improved treatment effect. Discontinuation or change of  therapy on the basis of misinterpretation of MRI as disease progression is thus unfortunate. MRI should be interpreted with caution the first 6 months after standard treatment of high-grade glioma. In a GBM patient with contrast enhancement on MRI but few or no new symptoms and/or stable steroid doses, treatment should be continued and control imaging performed after 2-3 months.

 

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[376]

TÍTULO / TITLE:  - Intraosseous traumatic neuroma of the lumbar spine: a previously unrecognized form of vertebral pseudotumor.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300568

AUTORES / AUTHORS:  - Guevara C; Seidel U; Hewer E; Vajtai I

 

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[377]

TÍTULO / TITLE:  - Glioblastoma with the appearance of arteriovenous malformation: Pitfalls in diagnosis.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2013 Jan 2. pii: S0303-8467(12)00619-1. doi: 10.1016/j.clineuro.2012.12.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.12.009

AUTORES / AUTHORS:  - Gmeiner M; Sonnberger M; Wurm G; Weis S

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Landes-Nervenklinik Wagner-Jauregg, Linz, Austria. Electronic address: matthias.gmeiner@gespag.at.

RESUMEN / SUMMARY:  - OBJECTIVES: Very few cases of arteriovenous malformations (AVMs) associated with  gliomas were reported so far in the literature. METHODS: Here, we report a rare case of a glioblastoma with an AVM-like lesion and review the existing literature. RESULTS: We report an unusual case of a 72-year old woman, who presented with a progressive history of aphasia, memory deficit, and headache. Initial MRI imaging was suggestive of a high-grade glioma for which a pterional craniotomy was performed. Intraoperatively, the lesion resembled a vascular malformation. Total extirpation of the lesion was verified by intraoperative MR imaging. Initial histopathological analysis revealed an AVM. Due to the discrepancy between the radiologic and histopathologic findings, the patient was  monitored at close intervals. Two month later, multiple lesions were visible on MRI imaging, thus, supporting the diagnosis of malignant glioma. Therefore, after reinvestigating the histopathological sections and cutting the paraffin block in  additional serial sections, in only 5% of the section a glioblastoma was discerned which was surrounded by an AVM-like lesion. CONCLUSION: Gliomas are rarely found in association with AVMs and require accurate diagnostic evaluation  and interpretation for adequate therapeutic interventions.

 

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[378]

TÍTULO / TITLE:  - Choroid plexus papilloma arising in a mature cystic teratoma of a 32-year-old female.

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

REVISTA / JOURNAL:  - Pathology. 2013 Jan;45(1):88-9. doi: 10.1097/PAT.0b013e32835b6855.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAT.0b013e32835b6855

AUTORES / AUTHORS:  - Dessauvagie BF; Ruba S; Robbins PD

INSTITUCIÓN / INSTITUTION:  - *Histopathology Department, PathWest, King Edward Memorial Hospital, Subiaco daggerDivision of Tissue Pathology, PathWest, QEII Medical Centre, Nedlands, WA,  Australia.

 

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[379]

TÍTULO / TITLE:  - Characteristics of sequential targeting of brain glioma for transferrin-modified  cisplatin liposome.

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

REVISTA / JOURNAL:  - Int J Pharm. 2013 Jan 21. pii: S0378-5173(13)00052-5. doi: 10.1016/j.ijpharm.2013.01.025.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ijpharm.2013.01.025

AUTORES / AUTHORS:  - Lv Q; Li LM; Han M; Tang XJ; Yao JN; Ying XY; Li FZ; Gao JQ

INSTITUCIÓN / INSTITUTION:  - Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, P.R.China; College of Pharmaceutical Science, Zhejiang Chinese Medical University, China.

RESUMEN / SUMMARY:  - Methods on how to improve the sequential targeting of glioma subsequent to passing of drug through the blood-brain barrier (BBB) have been occasionally reported. However, the characteristics involved are poorly understood. In the present study, cisplatin (Cis) liposome (lipo) was modified with transferrin(Tf)  to investigate the characteristics of potential sequential targeting to glioma. In bEnd3/C6 co-culture BBB models, higher transport efficiency across the BBB and cytotoxicity in basal C6 cells induced by Cis-lipo(Tf) than Cis-lipo and Cis-solution, suggest its sequential targeting effect. Interestingly, similar liposomal morphology as that of donor compartment was first demonstrated in the receptor solution of BBB models. Meanwhile, a greater acquisition in the lysosome of bEnd3, distribution sequentially into the nucleus of C6 cells were found for the Cis-lipo(Tf). Pre-incubation of chlorpromazine and Tf inhibited this process, indicating that a clathrin-dependent endocytosis is involved in the transport of  Cis-lipo(Tf) across the BBB (Graphical Abstract Fig. 8).

 

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[380]

TÍTULO / TITLE:  - Molecular diagnostics in paediatric glial tumours.

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

REVISTA / JOURNAL:  - Lancet Oncol. 2013 Jan;14(1):e19-27. doi: 10.1016/S1470-2045(12)70577-6.

            ●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(12)70577-6

AUTORES / AUTHORS:  - Kim JH; Huse JT; Huang Y; Lyden D; Greenfield JP

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Weill Cornell Medical College, New York, NY,  USA.

RESUMEN / SUMMARY:  - Glial tumours in children have distinct patterns of epigenetic alteration, chromosomal structure, and gene and protein expression that differentiate them from their histological counterparts in adults. Understanding paediatric gliomas  at the molecular level provides important prognostic and therapeutic insights, such as which genetic alterations confer a favourable response to adjuvant therapy, or which signalling pathways might be amenable to specific molecularly targeted agents. For clinicians, the ultimate goal is to individualise therapeutic regimens on the basis of the molecular fingerprint of a particular tumour and the prognosis conferred by this profile. In this Review, we examine a  series of studies of molecular and genomic analysis of glial tumours in children, and discuss the many clinical insights that these molecular features provide.

 

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[381]

TÍTULO / TITLE:  - Gliosarcoma arising from an oligodendroglioma (oligosarcoma).

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300577

AUTORES / AUTHORS:  - Hiniker A; Hagenkord JM; Powers MP; Aghi MK; Prados MD; Perry A

RESUMEN / SUMMARY:  - Gliosarcoma, a biphasic tumor with both mesenchymal and glial elements, is typically considered a variant of astrocytoma (glioblastoma), WHO Grade IV. A 57-year-old man presented with altered mental status and was found to have a large right frontal mass. Biopsy and subsequent subtotal resection revealed a WHO Grade II oligodendroglioma with classic histological features, expression of IDH1 R132H mutant protein, and chromosome 1p19q co-deletion. Fifteen months later, the patient developed recurrent tumor composed of intersecting fascicles of spindled  cells with necrosis and a high mitotic index. The recurrent tumor stained for both mesenchymal and glial elements, consistent with the diagnosis of gliosarcoma, and showed retained IDH1 R132H expression. By FISH analysis, the gliosarcoma showed no evidence of 1p19q co-deletion. We performed SNP arrays and  detailed SNP analysis of both the oligodendroglioma and the gliosarcoma. This demonstrated loss of heterozygosity (LOH) of chromosomes 1 and 19 in the gliosarcoma with retention of the same full-length chromosomes 1 and 19 found intact in the oligodendroglioma. Not surprisingly, the gliosarcoma harbored multiple additional alterations, consistent with clonal evolution. There have been only rare reports of sarcomatous transformation of oligodendroglioma (“oligosarcoma”) and most were published prior to the development of modern genetic modalities. Here we present a case with detailed genetic evidence that suggests that mesenchymal metaplasia sarcomatous transformation is possible in classic oligodendrogliomas with 1p19q codeletions.

 

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[382]

TÍTULO / TITLE:  - Ependymal cyst of the midbrain.

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

REVISTA / JOURNAL:  - Clin Neuropathol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 5414/NP300563

AUTORES / AUTHORS:  - Prieto R; Subhi-Issa I; Pascual JM

RESUMEN / SUMMARY:  - We present the case of a 30-year-old man who developed an acute hydrocephalus secondary to an obstruction of the cerebral aqueduct by a midbrain cystic lesion. After a ventriculo-peritoneal shunt was placed to relief symptoms of intracranial hypertension, the patient underwent a neuronavigation-assisted endoscopic fenestration of the cyst. A careful immunohistochemical staining confirmed the diagnosis of an ependymal cyst. An extensive review of the literature has revealed that this is the first report of a periaqueductal ependymal cyst with definite histological diagnosis. This is a rare cause of acute non-communicating  hydrocephalus but an important entity in the differential diagnosis.

 

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[383]

TÍTULO / TITLE:  - Cerebral Fat Embolisms Secondary to Rupture of a Tarlov Cyst.

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

REVISTA / JOURNAL:  - J Neuroimaging. 2013 Jan 14. doi: 10.1111/j.1552-6569.2012.00782.x.

            ●● Enlace al texto completo (gratuito o de pago) 1111/j.1552-6569.2012.00782.x

AUTORES / AUTHORS:  - Zubizarreta IK; Menoyo JL; Ojeda JR; Olabarria IV; Carra JC

INSTITUCIÓN / INSTITUTION:  - From the Department of Neurology, Hospital de Galdakao-Usansolo, Barrio Labeaga s.n., 48960 Galdakao (Bizkaia), España (IKZ, JLSM, JRO, JCG-MC); OSATEK. de Galdakao. Barrio Labeaga s.n., 48960 Galdakao (Bizkaia), España (IVO).

 

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[384]

TÍTULO / TITLE:  - Levodopa/Carbidopa to Improve Motor Function Subsequent to Brain Tumor Excision.

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

REVISTA / JOURNAL:  - Am J Phys Med Rehabil. 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PHM.0b013e318278dc20

AUTORES / AUTHORS:  - Ennis JD; Harvey D; Ho E; Chari V; Graham A; Nesathurai S

INSTITUCIÓN / INSTITUTION:  - From the Physical Medicine and Rehabilitation Training Program, Department of Postgraduate Medicine, McMaster University, Hamilton, Canada (JE, DH, EH, VC, SN); Division of Physical Medicine and Rehabilitation, Department of Medicine, Hamilton Health Sciences, Hamilton, Canada (DH, VC, AG, SN); and Division of Physical Medicine and Rehabilitation, Department of Medicine, Saint Joseph’s Healthcare, Hamilton, Canada (SN).

RESUMEN / SUMMARY:  - OBJECTIVE: The aim of this study was to evaluate the role of levodopa/carbidopa as an augmenting agent to improve motor recovery after brain tumor excision. DESIGN: This case report is structured as an n-of-1 style trial. The study patient was an outpatient with residual hemiparesis secondary to removal of benign oligoastrocytoma seen in an outpatient physiatry practice at an academic center. The study intervention was levodopa/carbidopa vs. placebo, combined with  a structured 6-wk physiotherapy regimen. Outcomes were measured using the motor subscale of the Fugl-Meyer Assessment to assess for motor recovery. RESULTS: The  mean motor Fugl-Meyer Assessment score for the levodopa/carbidopa weeks was 6.90  points greater than the mean score for placebo. The results were significant at P < 0.05. CONCLUSIONS: Levodopa/carbidopa may have a beneficial effect on improving motor recovery after sustaining a brain injury as a result of tumor excision.

 

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[385]

TÍTULO / TITLE:  - Benign cutaneous neural tumors.

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

REVISTA / JOURNAL:  - Semin Diagn Pathol. 2013 Feb;30(1):45-57. doi: 10.1053/j.semdp.2012.01.008.

            ●● Enlace al texto completo (gratuito o de pago) 1053/j.semdp.2012.01.008

AUTORES / AUTHORS:  - Rodriguez-Peralto JL; Riveiro-Falkenbach E; Carrillo R

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Hospital Universitario 12 de Octubre, Instituto de Investigacion i+12, Universidad Complutense, Madrid, España. Electronic address: jrodriguezp.hdoc@salud.madrid.org.

RESUMEN / SUMMARY:  - Benign cutaneous neural neoplasms are one of the most frequent benign mesenchymal tumors in the skin. Because peripheral sheath nerve is composed of different cells, the tumors raised in these structures are varied and usually contain many  of these cells. Most of these tumors are easy to diagnose, as usually present characteristic features well-recognized and express -specific immunohistochemical proteins. However, there are so many infrequent variants that many times require  distinction from others spindle-cell tumors including melanoma. The tumors differ from one another by displaying a different proportion and arrangement of the various constituents of a peripheral nerve. In this article, we present the most  characteristic clinical and histopathological features of many of these frequent  benign cutaneous neural tumors including their uncommon variants.

 

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[386]

TÍTULO / TITLE:  - PF-8380 and Closely Related Analogs: Synthesis and Structure-Activity Relationship towards Autotaxin Inhibition and Glioma Cell Viability.

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

REVISTA / JOURNAL:  - Arch Pharm (Weinheim). 2013 Jan 8. doi: 10.1002/ardp.201200395.

            ●● Enlace al texto completo (gratuito o de pago) 1002/ardp.201200395

AUTORES / AUTHORS:  - St-Coeur PD; Ferguson D; Morin PJ; Touaibia M

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry and Biochemistry, Universite de Moncton, Moncton, NB, Canada.

RESUMEN / SUMMARY:  - A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).

 

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[387]

TÍTULO / TITLE:  - Cutaneous and leptomeningeal hemangiomas with impressive benign evolution.

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

REVISTA / JOURNAL:  - Pediatr Neurol. 2013 Jan;48(1):73-5. doi: 10.1016/j.pediatrneurol.2012.09.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pediatrneurol.2012.09.001

AUTORES / AUTHORS:  - Falsaperla R; Pavone P; Ruggieri M; Pavone L

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics and Pediatric Emergencies, University Hospital Policlinico-Vittorio Emanuele, Catania, Italy.

RESUMEN / SUMMARY:  - We describe an infant with cutaneous and leptomeningeal diffuse hemangiomata. Clinical facial anomalies were evident at birth. Routine transfontanellar ultrasonography revealed very diffuse leptomeningeal hemangioma. Magnetic resonance imaging during the first days of age confirmed vascular lesions. The patient was otherwise normal, and was monitored at ages 3.5, 9, and 18 months. Rapid resolution of the hemangioma occurred within 1 year. The infant did not present with persistent embryonic arteries, a posterior fossa, or other malformations typically reported in Pascual-Castroviejo type II syndrome. However, the characteristic skin color, leptomeningeal hemangioma, and rapid involution prompted the diagnosis of Pascual-Castroviejo II syndrome in its wider, benign spectrum.

 

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[388]

TÍTULO / TITLE:  - Characterization of microglia/macrophages in gliomas developed in S-100beta-v-erbB transgenic rats.

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

REVISTA / JOURNAL:  - Neuropathology. 2013 Jan 20. doi: 10.1111/neup.12015.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12015

AUTORES / AUTHORS:  - Sasaki A; Yokoo H; Tanaka Y; Homma T; Nakazato Y; Ohgaki H

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Saitama Medical University, Saitama.

RESUMEN / SUMMARY:  - Glioma-infiltrating microglia/macrophages are referred to as tumor-associated macrophages (TAMs). Transgenic (TG) rats expressing v-erbB, which is a viral form of the epidermal growth factor receptor, under transcriptional regulation by the  S100-beta promoter, develop brain tumors. This study was designed to clarify the  pathological characteristics of TAMs in these experimental tumors. We carried out immunohistochemical and morphometrical analyses of microglia/macrophages in brain tumors (5 malignant glioma, 4 anaplastic oligodendroglioma, 4 astrocytoma) that developed in TG rats. TAMs with ionized calcium-binding adaptor molecule 1 (Iba1) positivity and morphology of activated, non-phagocytic microglia increased within and around the tumors in malignant gliomas and anaplastic astrocytomas. The Iba1-positive TAMs of the tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal anaplastic oligodendrogliomas. Iba1 expression showed a significant positive correlation to Ki-67 expression in all the gliomas. Most TAMs showed no or little expression against CD68, CD163 or CD204, although CD204-positive TAMs were observed in necrosis as well as in the proliferating vascular wall. In conclusion, S-100beta-v-erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2  phenotype remains unclear.

 

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[389]

TÍTULO / TITLE:  - Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1.

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

REVISTA / JOURNAL:  - Cardiovasc Pathol. 2012 Dec 3. pii: S1054-8807(12)00133-0. doi: 10.1016/j.carpath.2012.10.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.carpath.2012.10.006

AUTORES / AUTHORS:  - Muller H; Renner M; Bergmann F; Mechtersheimer G; Weiss C; Poeschl J; Helmke BM; Mollenhauer J

INSTITUCIÓN / INSTITUTION:  - Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany. Electronic address: Hanna.Mueller@med.uni-heidelberg.de.

RESUMEN / SUMMARY:  - BACKGROUND: Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement  system, in different types of cardiac amyloidosis. METHODS: Expression of DMBT1 and of the complement proteins C1q, C3d and C4d in cardiac specimens of patients  with different types of amyloidosis were determined by immunohistochemistry and correlated with amyloid deposits stained by Congo red dye. RESULTS: Strong DMBT1  staining adjacent to amyloid deposits was detected in different amyloidosis types, depending on the extent of the deposits. DMBT1 is localized in the endomysium and perimysium, in the endocardium, in the myocytes and in endothelial cells of affected transmural vessels. C1q, C3d and C4d were detected in the amyloid deposits but also in the endomysium and perimysium, in some myocytes, in  endothelial cells, in the endocardium, and around the amyloid deposits. CONCLUSIONS: Up-regulated DMBT1 and complement activation in cardiac amyloidosis  may be part of the activated pathways induced by protein aggregation and the consecutive inflammatory reaction.

 

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[390]

TÍTULO / TITLE:  - Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):242-50. doi: 10.1093/neuonc/nos295. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos295

AUTORES / AUTHORS:  - Omuro A; Chan TA; Abrey LE; Khasraw M; Reiner AS; Kaley TJ; Deangelis LM; Lassman AB; Nolan CP; Gavrilovic IT; Hormigo A; Salvant C; Heguy A; Kaufman A; Huse JT; Panageas KS; Hottinger AF; Mellinghoff I

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Antonio Omuro, MD, Memorial Sloan-Kettering Cancer Center,  1275 York Avenue, New York, NY 10065. omuroa@mskcc.org.

RESUMEN / SUMMARY:  - Background In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs). Methods Eligible patients received daily temozolomide (50 mg/m(2)) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially “drugable” mutations in patients entering recurrent MG clinical trials. Results Among glioblastoma patients, median age was 56 y; median Karnofsky Performance Score (KPS) was 80; 62% of patients had been treated for >/=2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had  lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were  found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1). Conclusions In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in  bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG. Clinical trials.gov identifier NCT00498927 (available at http://clinicaltrials.gov/ct2/show/NCT00498927).

 

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[391]

TÍTULO / TITLE:  - Delta-like ligand 4 correlates with endothelial proliferation and vessel maturation in human malignant glioma.

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

REVISTA / JOURNAL:  - Onkologie. 2012;35(12):763-8. doi: 10.1159/000345116. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345116

AUTORES / AUTHORS:  - Li ZQ; Gong LL; Wen ZH; Wang J; Xu CS; Huang XD

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.  lifenzhi@yahoo.com.cn

RESUMEN / SUMMARY:  - AIM: To investigate the role of delta-like ligand 4 (DLL4) in the angiogenesis of high-grade malignant glioma. MATERIALS AND METHODS: DLL4 expression and microvessel density (MVD) were detected by immunohistochemistry in 51 human high-grade malignant glioma tissue samples. The vessel maturation index (VMI) was calculated as the percentage of a-smooth muscle actin (a-SMA)-positive vessels in relation to the amount of CD31-positive vessels. Double fluorescent immunostaining for CD31 and EphrinB2 or EphB4 was performed to identify the arterial (EphrinB2) or venous (EphB4) origins of glioma microvessels. RESULTS: Strong immunostaining of DLL4 and a positive correlation of DLL4 with the MVD were observed in high-grade malignant gliomas. The VMI of the DLL4-positive group was significantly higher than that of the DLL4-negative group. However, no significant association was found between DLL4 and EphrinB2 or EphB4 in high-grade gliomas. CONCLUSION: DLL4 may be an important regulator for vessel proliferation and maturation in human high-grade malignant gliomas.

 

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[392]

TÍTULO / TITLE:  - Role of Fentanyl in Supratentorial Tumor: Can it Change the Requirement of Propofol?

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

REVISTA / JOURNAL:  - J Neurosurg Anesthesiol. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1097/ANA.0b013e31827de29f

AUTORES / AUTHORS:  - Chowdhury T; Cappellani RB

INSTITUCIÓN / INSTITUTION:  - Department of Anesthesiology Health Sciences Center University of Manitoba, Winnipeg, MB.

 

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[393]

TÍTULO / TITLE:  - Juvenile-onset Hereditary Pheochromocytoma-paraganglioma Syndrome.

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

REVISTA / JOURNAL:  - Intern Med. 2013;52(2):281-4. Epub 2013 Jan 15.

AUTORES / AUTHORS:  - Sugisawa C; Okada Y; Arao T; Mori H; Nishida K; Isobe K; Takekoshi K; Tanaka Y

INSTITUCIÓN / INSTITUTION:  - The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.

RESUMEN / SUMMARY:  - It is insufficient to distinguish benign tumors from malignant pheochromocytoma using histological analyses of resected tissue alone. We experienced an 18-year-old woman who complained of severe headaches in whom hypertension was revealed. She was suspected of having a malignant tumor based on her clinical characteristics, despite showing no evidence of metastatic lesions. The patient was diagnosed with an aggressive form of hereditary pheochromocytoma-paraganglioma syndrome (HPPS) based on immunohistochemical analyses and genetic testing. The present case indicates that conducting genetic  testing, including SDHB mutation analyses, is required to determine the prognosis in patients highly suspected of having HPPS.

 

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[394]

TÍTULO / TITLE:  - Overlap syndrome comprised of systemic sclerosis and systemic lupus erythematosus associated with spinocerebellar ataxia type 6 and MALT lymphoma.

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

REVISTA / JOURNAL:  - Eur J Dermatol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1684/ejd.2012.1902

AUTORES / AUTHORS:  - Tsuruta D; Ohzono A; Ishii N; Ono F; Hamada T; Dainichi T; Ohata C; Furumura M; Noda K; Hashimoto T

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology.

 

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[395]

TÍTULO / TITLE:  - Bone Metastases in Medulloblastoma -Single Institution Experience.

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

REVISTA / JOURNAL:  - Pediatr Hematol Oncol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 3109/08880018.2012.752888

AUTORES / AUTHORS:  - Marina N; Jelena B; Lejla P; Ivana G; Danica G; Jelena S

INSTITUCIÓN / INSTITUTION:  - Clinic for Radiation Oncology, Institute for Oncology and Radiology of Serbia (IORS) , Belgrade , Serbia.

RESUMEN / SUMMARY:  - Background: Medulloblastoma has one of the highest rates of metastasis outside the central nervous system (CNS). Bone metastases are the most common lesions, although lymph node and visceral spread have also been reported. Objective: To present patients with bone metastasis in medulloblastoma and discuss their radiologic appearances and treatment approach. Patients and methods: From 1993 to 2008, 82 patients diagnosed with medulloblastoma were treated at the Institute for Oncology and Radiology of Serbia. Three (3.6%) developed extraneural metastasis (ENM). In primary treatment, patients were treated with surgery, craniospinal radiotherapy with local boost to tumor bed, and adjuvant chemotherapy [lomustine (CCNU) and vincristine]. Of the three patients with ENM,  all developed bone metastases at the time of relapse. Relapse occurred within 17  to 42 months of initial diagnosis. Patients received secondary chemotherapy and palliative radiotherapy to the affected bone in two cases. Results: Among these three patients, case 1 had initially a solitary lytic lesion. Case 2 had diffuse  blastic lesions and also bone marrow involvement. Case 3 had multiple mixed lytic-sclerotic lesions but later developed lymph node metastasis and metastases  to both breasts, as well. All patients were without concurrent CNS involvement at the time of ENM. Unfortunately, after initial partial response, the three patients died at 24, 13, and 18 months after detection of metastases, respectively. Conclusion: With prolonged survival times in children with medulloblastoma, more emphasis should be placed on the possibility of systemic involvement. A greater understanding of the pathogenesis of the systemic metastases may be valuable in designing future, more aggressive multimodal therapy.

 

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[396]

TÍTULO / TITLE:  - Segmentation of pituitary adenoma: A graph-based method vs. a balloon inflation method.

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

REVISTA / JOURNAL:  - Comput Methods Programs Biomed. 2012 Dec 21. pii: S0169-2607(12)00308-2. doi: 10.1016/j.cmpb.2012.11.010.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cmpb.2012.11.010

AUTORES / AUTHORS:  - Egger J; Zukic D; Freisleben B; Kolb A; Nimsky C

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Marburg, Marburg, Germany; Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany; Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: egger@med.uni-marburg.de.

RESUMEN / SUMMARY:  - Among all abnormal growths inside the skull, the percentage of tumors in sellar region is approximately 10-15%, and the pituitary adenoma is the most common sellar lesion. A time-consuming process that can be shortened by using adequate algorithms is the manual segmentation of pituitary adenomas. In this contribution, two methods for pituitary adenoma segmentation in the human brain are presented and compared using magnetic resonance imaging (MRI) patient data from the clinical routine: Method A is a graph-based method that sets up a directed and weighted graph and performs a min-cut for optimal segmentation results: Method B is a balloon inflation method that uses balloon inflation forces to detect the pituitary adenoma boundaries. The ground truth of the pituitary adenoma boundaries - for the evaluation of the methods - are manually extracted by neurosurgeons. Comparison is done using the Dice Similarity Coefficient (DSC), a measure for spatial overlap of different segmentation results. The average DSC for all data sets is 77.5+/-4.5% for the graph-based method and 75.9+/-7.2% for the balloon inflation method showing no significant difference. The overall segmentation time of the implemented approaches was less  than 4s - compared with a manual segmentation that took, on the average, 3.9+/-0.5min.

 

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[397]

TÍTULO / TITLE:  - Institutional experience of endoscopic suprasellar arachnoid cyst fenestration.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-013-2032-9

AUTORES / AUTHORS:  - Rizk E; Chern JJ; Tagayun C; Tubbs RS; Hankinson T; Rozzelle C; Oakes WJ; Blount JP; Wellons JC

INSTITUCIÓN / INSTITUTION:  - Pediatric Neurosurgery, Children’s Hospital, 1600 7th Avenue South ACC 400, Birmingham, AL, USA.

RESUMEN / SUMMARY:  - INTRODUCTION: Suprasellar arachnoid cysts can differ from other arachnoid cysts in several ways, making a separate analysis of these cysts worthwhile. Herein, we present the outcome and perform volumetric analysis of six children with suprasellar arachnoid cysts treated with endoscopic ventriculocystocisternostomy  in order to evaluate the long-term outcomes. PATIENTS AND METHODS: Operative and  postoperative data were retrospectively reviewed for six patients harboring suprasellar arachnoid cysts. Imaging was then used to follow success of surgical  intervention. RESULTS: Six patients with suprasellar arachnoid cysts underwent ventriculocystocisternostomy. Presenting symptoms were headaches in three patients, developmental delay in another, and an incidental finding in the remaining patients. All patients had enlarged lateral and third ventricles on initial imaging. Average age at presentation was 145.7 months (65.4-250.2). Follow-up was an average of 46.5 months (3-84). The average cyst size was 153.96  cm(3) (42.98-369.20) preoperatively and an average of 39.92 cm(3) (3.20-101.47) at follow-up. CONCLUSIONS: Based on our experience, suprasellar arachnoid cyst treatment with ventriculocystocisternostomy is an adequate surgical intervention. Suprasellar and third ventricular size does respond to the surgical intervention  at long-term follow-up.

 

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[398]

TÍTULO / TITLE:  - Occurrence and distribution of pilomyxoid astrocytoma.

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

REVISTA / JOURNAL:  - Br J Neurosurg. 2013 Jan 3.

            ●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2012.752430

AUTORES / AUTHORS:  - Bhargava D; Sinha P; Chumas P; Al-Tamimi Y; Shivane A; Chakrabarty A; Surash S; Novegno F; Crimmins D; Tyagi AK

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Leeds General Infirmary , Leeds , UK.

RESUMEN / SUMMARY:  - Purpose. To know the occurrence and distribution of Pilomyxoid Astrocytomas amongst tumours previously diagnosed histologically as Pilocytic Astrocytoma and  to assess the clinical impact of this new entity. Methods. Retrospective Diagnostic review of all cases histologically diagnosed as WHO Grade I Astrocytoma at a single Neurosurgical unit between 1990 and 2003. Results. Of a total of 91 cases identified, 9 were found to have Pilomyxoid histology. Of these, 8 were children (mean age 3.33 years) and 1 adult. 6 tumours were hypothalamochiasmatic in location. The clinical course of Pilomyxoid tumours was  aggressive marked by maturation, multiple recurrences and disease control was rarely achieved with single treatment modality as opposed to typical pilocytics.  The overall survival of the pilomyxoid group was not statistically different from the pilocytic tumours. Conclusions. Encompassing all age-groups and locations, Pilomyxoid Astrocytomas constitute about 10% of all tumours previously diagnosed  as Pilocytic Astrocytoma. Nearly two-thirds are hypothalamo-chiasmatic in location. Knowledge of this entity is essential for appropriate aggressive treatment and follow-up.

 

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[399]

TÍTULO / TITLE:  - Medial posterior choroidal artery territory infarction associated with tumor removal in the pineal/tectum/thalamus region through the occipital transtentorial approach.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2012 Dec 19. pii: S0303-8467(12)00598-7. doi: 10.1016/j.clineuro.2012.11.020.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.11.020

AUTORES / AUTHORS:  - Saito R; Kumabe T; Kanamori M; Sonoda Y; Mugikura S; Takahashi S; Tominaga T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

RESUMEN / SUMMARY:  - OBJECT: Damage to the deep venous system, occipital lobe, and/or corpus callosum  is well known to cause complications associated with the occipital transtentorial approach (OTA), but ischemic complications are not well documented. The authors investigated the high incidences of ischemic complications associated with removal of pineal/tectal/thalamic tumors through the OTA. METHODS: Clinical records of 29 patients who underwent 31 surgeries using the OTA from December 2001 to May 2011 were retrospectively studied. Tumor locations were the pineal/tectal/thalamic region for 19, cerebellum for 7, and medial temporal lobe  for 3. RESULTS: Postoperative diffusion-weighted magnetic resonance images obtained within 72h after surgery detected infarction in the tectal/splenial/thalamic region, presumably representing the medial posterior choroidal artery (MPChA) territory, in 10 patients. All these patients had tumor  in the pineal/tectal/thalamic region. Deteriorated or newly developed eye symptoms including vertical gaze palsy tended to persist in these patients compared to those without ischemic complications. CONCLUSIONS: A relatively high  incidence of MPChA territory infarction was associated with removal of tumors in  the pineal/tectal/thalamic region through the OTA. Eye symptoms often occurred post-surgery and tended to persist in these patients. Neurosurgeons must be aware of the possibility of MPChA territory infarction to further increase the safety of the OTA.

 

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[400]

TÍTULO / TITLE:  - Trimodality approach for ceruminous mucoepidermoid carcinoma of the external auditory canal.

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

REVISTA / JOURNAL:  - J Laryngol Otol. 2013 Jan 15:1-4.

            ●● Enlace al texto completo (gratuito o de pago) 1017/S0022215112003015

AUTORES / AUTHORS:  - Mourad WF; Hu KS; Shourbaji RA; Harrison LB

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Beth Israel Medical Center, New York, USA.

RESUMEN / SUMMARY:  - Background: Ceruminous mucoepidermoid carcinoma of the external auditory canal is extremely rare. This paper highlights the impact of concurrent chemoradiotherapy  on the outcomes of this disease. Case report: A 47-year-old female presented with a 2-month history of otalgia and a mass in her right ear. Biopsy revealed high grade ceruminous mucoepidermoid carcinoma. She underwent surgical excision of the right external auditory canal and right upper neck dissection. Pathological analysis of tumour-node-metastasis staging revealed a T2 N0 (stage II) tumour. One year later, computed tomography scanning of the temporal bone showed tumour recurrence. Biopsy revealed recurrent ceruminous mucoepidermoid carcinoma. The patient underwent salvage resection. Pathology revealed that the tumour was diffusely invading nearby structures, with perineural invasion, lymphatic spread  and extracapsular extension. Pathological analysis of tumour-node-metastasis staging revealed a T3 N1 M0 (recurrent stage IV) tumour. Results: The patient subsequently received concurrent chemoradiotherapy. There was no evidence of disease at 37 months’ follow up. Conclusion: The trimodality approach, using surgery plus concurrent chemoradiotherapy, provided reasonable loco-regional control with tolerable toxicity. Further detailed case reports are warranted to optimise the management of this rare malignancy.

 

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[401]

TÍTULO / TITLE:  - An update on the management of pseudotumor cerebri.

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

REVISTA / JOURNAL:  - Clin Neurol Neurosurg. 2012 Dec 19. pii: S0303-8467(12)00596-3. doi: 10.1016/j.clineuro.2012.11.018.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clineuro.2012.11.018

AUTORES / AUTHORS:  - Galgano MA; Deshaies EM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, USA.

RESUMEN / SUMMARY:  - Pseudotumor cerebri, or benign intracranial hypertension, is characterized by intracranial hypertension of unknown etiology typically in obese women <45 years  of age, and can be disabling secondary to headaches and visual disturbances. Medical management includes pharmaceuticals that reduce cerebrospinal fluid (CSF) production and lumbar punctures that reduce the CSF volume, both aimed at reducing intracranial pressure. When medical management fails, surgical CSF diverting procedures are indicated. Recently it has been demonstrated that dural  sinus stenosis or thrombosis can be responsible for this disease and treated with endovascular venous stent placement. The intent of this educational manuscript is to review the clinical presentation of pseudotumor cerebri patients and discuss the medical, surgical, and endovascular treatment options for this disease. After reading this paper, the reader should be able to: (1) understand the pathophysiological basis of pseudotumor cerebri, (2) describe its presenting signs and symptoms, and (3) discuss the medical, surgical, and endovascular treatment options.

 

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[402]

TÍTULO / TITLE:  - Pilocytic astrocytoma with leptomeningeal dissemination.

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

REVISTA / JOURNAL:  - Childs Nerv Syst. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00381-012-1970-y

AUTORES / AUTHORS:  - Bian SX; McAleer MF; Vats TS; Mahajan A; Grosshans DR

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

RESUMEN / SUMMARY:  - PURPOSE: Pilocytic astrocytoma (PA) is a common pediatric glioma that is generally characterized by indolent growth. However, there are reports of PA disseminating throughout the central nervous system. Given the rarity of dissemination, the appropriate treatment for these patients is poorly defined. In this case series, we describe the clinical characteristics and treatment outcomes of six children treated for disseminated PA at our institution and review the current published literature. METHODS: Six cases of disseminated PA treated at the University of Texas MD Anderson Cancer Center were identified. Demographics,  disease characteristics, and follow-up data were compiled. Fifty-three reported cases were identified in the published literature. RESULTS: Our cohort’s mean age at presentation was 7 years, and the mean time to identification of disseminated  disease was 12 months after initial diagnosis. Two patients underwent chemotherapy, and all underwent proton beam radiation therapy to all or part of the craniospinal axis. With a median follow-up of 24 months after radiation therapy, five of six patients were alive, four with stable disease and one with progressive disease. CONCLUSIONS: Treatment of disseminated PA is frequently multi-modal, including surgical resection, chemotherapy, and radiation therapy. On the basis of early clinical data, extended-field radiation therapy is a viable option for treating disseminated PA.

 

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[403]

TÍTULO / TITLE:  - Evaluation of Quantitative Criteria for Glioma Grading With Static and Dynamic 18F-FDopa PET/CT.

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

REVISTA / JOURNAL:  - Clin Nucl Med. 2013 Feb;38(2):81-7. doi: 10.1097/RLU.0b013e318279fd5a.

            ●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279fd5a

AUTORES / AUTHORS:  - Nioche C; Soret M; Gontier E; Lahutte M; Dutertre G; Dulou R; Capelle L; Guillevin R; Foehrenbach H; Buvat I

INSTITUCIÓN / INSTITUTION:  - From the *Hopital d’Instruction des Armees du Val-de-Grace 74, bd du Port Royal;  daggerUMR 678 INSERM AP-HP Groupe Hospitalier Pitie-Salpetriere, Paris; and double daggerUMR 8165 CNRS Imagerie et Modelisation en Neurobiologie et Cancerologie Orsay, France.

RESUMEN / SUMMARY:  - PURPOSE: The aim of this study was to compare various acquisition and processing  protocols for noninvasive glioma grading using either static or dynamic F-FDopa PET. METHODS: Dynamic studies were performed in 33 patients. Based on histopathological analysis, 18 patients had a high-grade (HG) tumor and 15 patients had a low-grade (LG) tumor. For static imaging, SUVmean and SUVmax were  calculated for different acquisition time ranges after injection. For dynamic imaging, the transport rate constant k1 was calculated according to a compartmental kinetic analysis using an image-derived input function. RESULTS: With the use of a 5-minute static imaging protocol starting at 38 minutes after injection, newly diagnosed HG tumors could be distinguished from LG tumors with a sensitivity of 70% and a specificity of 90% with a threshold of SUVmean of 2.5. In recurrent tumors, a sensitivity of 100% and a specificity of 80% for identifying HG tumors were obtained with a threshold set to 1.8. Dynamic imaging  only slightly, but nonsignificantly, improved differential diagnosis. CONCLUSIONS: Static and dynamic imaging without blood sampling can discriminate between LG and HG for both newly diagnosed and recurrent gliomas. In dynamic imaging, excellent discrimination was obtained by considering the transport rate  constant k1 of tumors. In static imaging, the best discrimination based on SUV was obtained for SUVmean calculated from a 5-minute acquisition started at 38 minutes after injection.

 

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[404]

TÍTULO / TITLE:  - Organizing hematoma mimicking brain tumor.

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

REVISTA / JOURNAL:  - Clin Imaging. 2013 Jan-Feb;37(1):143-6. doi: 10.1016/j.clinimag.2012.04.006. Epub 2012 Jun 8.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.04.006

AUTORES / AUTHORS:  - Ilica AT; Rodrigues F; Maluf F; Aygun N

INSTITUCIÓN / INSTITUTION:  - The Russell H. Morgan Department of Radiology, The Johns Hopkins Medical Institutions, Phipps B-100F, Baltimore, MD 21287, USA. ailica1@jhmi.edu

RESUMEN / SUMMARY:  - A 64-year-old man was referred to our hospital with progressive loss of function  in his right upper and lower extremities. Unenhanced computed tomographic showed  a high-density nodular lesion in the left basal ganglion with surrounding hypoattenuation. Brain magnetic resonance imaging demonstrated a predominantly cystic mass with multiple internal septa and an eccentric solid component showing enhancement. Histological examination revealed organizing blood clot and piloid gliosis. This unusual appearance of a mass-like organizing blood clot should be considered in the differential diagnosis when an encapsulated cystic mass with nodular component following the signal characteristics of old blood on MRI is encountered.

 

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[405]

TÍTULO / TITLE:  - Radiologic findings of thoracic scoliosis due to giant ganglioneuroma.

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

REVISTA / JOURNAL:  - Clin Imaging. 2013 Jan 9. pii: S0899-7071(12)00337-3. doi: 10.1016/j.clinimag.2012.11.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.11.003

AUTORES / AUTHORS:  - Kara T; Oztunali C

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey. Electronic address: taylankara@gmail.com.

RESUMEN / SUMMARY:  - A 28-year-old male with scoliosis presented with complaints of dyspnea and vomiting. His medical history revealed a mediastinal ganglioneuroma resection at  the age of 2. After the surgery, he had not been followed up until his admission  to our hospital. Computed tomography and MRI showed severe scoliosis of the thoracic spine and a paravertebral mass extending from the upper thoracic level to the level of renal arteries. Based on its radiological findings and the patient’s history, the tumor was considered to be a recurrent ganglioneuroma. Paravertebral ganglioneuromas may cause progressive scoliosis, and a careful examination for patients with progressive scoliosis is mandatory.

 

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[406]

TÍTULO / TITLE:  - Brain tumor immunotherapy: seeing the brain in the body.

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

REVISTA / JOURNAL:  - Drug Discov Today. 2012 Nov 27. pii: S1359-6446(12)00393-5. doi: 10.1016/j.drudis.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.drudis.2012.11.007

AUTORES / AUTHORS:  - Lampson LA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brigham and Women’s Hospital and Harvard Medical School, United States. Electronic address: LoisLampson@hotmail.com.

RESUMEN / SUMMARY:  - Brain tumor immunotherapy is often interpreted in terms of immune privilege and the blood-brain barrier (BBB), but a broader view is warranted. The delicate regulatory balance of the immune system is relevant at any site, as are the heterogeneity and plasticity of tumor growth. Criteria for tumor antigens, and often the antigens themselves, cut across tumor types. Here, this broader view, complemented by current understanding of privilege and the BBB, provides the context for review. Future success is likely to exploit simplified methods, used  in combination; and similarities - more than differences - between the brain and  other sites.

 

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[407]

TÍTULO / TITLE:  - mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing  their Morphopathological Features.

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

REVISTA / JOURNAL:  - Endocr Pathol. 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12022-012-9230-y

AUTORES / AUTHORS:  - Sajjad EA; Zielinski G; Maksymowicz M; Hutnik L; Bednarczuk T; Wlodarski P

INSTITUCIÓN / INSTITUTION:  - Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chalubinskiego 5, 02-004, Warszawa, Poland.

RESUMEN / SUMMARY:  - Initiating factors and mechanisms of tumor formation are poorly understood in nonfamilial pituitary adenomas. Alteration of intracellular pathways is an underlying event in numerous neoplasms. Among them, excessive activation of mammalian target of rapamycin (mTOR) pathway and its two main regulators, Akt and Erk, has been detected frequently in solid tumors. This study tests the activation of mTOR pathway in pituitary adenomas and its influence on their morphopathological features. Fifty-three pituitary adenomas were fresh frozen after surgery and analyzed by western blotting using phospho-specific antibodies. The impact of Akt and Erk activation on mTOR pathway was assessed in five primary cultures derived from the excised adenomas using selective kinase inhibitors. Statistical correlations of size, volume, Ki-67 %, Knosp’s grading, and somatostatin receptor (SSTR) expression with the activation of mentioned kinases  was performed. GHomas showed the highest frequency (71 %) and level of mTOR pathway activity comparing to other adenomas (33 %). No significant correlation was found between mTOR activation and any of the morphopathological features in the studied samples. mTOR kinase phosphorylation was independent of Erk and Akt in primary cultures. Erk activity was significant in all types of adenomas but was the highest in control samples. Its phosphorylation correlated inversely with the Knosp’s grading in nonfunctional pituitary adenomas and directly with somatostatin receptor subtype 2 A expression in GHomas. Presented data point to the noteworthy mTOR activity in GHomas. However, the lack of correlation with morphopathological features, its independence of Erk and Akt phosphorylation, and high level of Erk activity in control pituitary necessitate further research for  clarifying the role of these pathways in pituitary adenomas.

 

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[408]

TÍTULO / TITLE:  - Paediatric germ cell tumours of the central nervous system: Results and experience from a tertiary-referral paediatric institution in Australia.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 11. pii: S0967-5868(12)00450-X. doi: 10.1016/j.jocn.2012.04.017.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.04.017

AUTORES / AUTHORS:  - Carlos Chung KH; Owler BK; Dexter M; Chaseling R

INSTITUCIÓN / INSTITUTION:  - T. Y. Nelson Department of Neurology and Neurosurgery, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia. Electronic address: carloschung@me.com.

RESUMEN / SUMMARY:  - A retrospective analysis was conducted on consecutive patients with intracranial  germ cell tumours diagnosed and treated from 1 January 1997 to 31 December 2007 to assess and determine demographic factors and treatment outcomes of children with these tumours treated in a major paediatric referral hospital in Australia.  In this study, intracranial germ cell tumours represented 4.8% of paediatric brain tumours seen. Of the 21 patients identified, 15 (71.4%) were diagnosed with pure germinoma and six (28.6%) with non-germinomatous germ cell tumours (NGGCT) or mixed tumours. One patient received chemotherapy alone, two patients were treated with radiation alone and the remaining 18 received a combination of chemotherapy and radiotherapy. A total of 33 neurosurgical operations were performed with 15 biopsies via open, endoscopic or transphenoidal means; nine open resections; and nine procedures for hydrocephalus comprising seven third ventriculostomies and two ventriculoperitoneal shunts. For patients with pure germinomas, the 5-year disease-free rate (DFS) was 93.3%, and overall survival (OS) rate was 100% compared to NGGCT or mixed tumours (DFS 50%; OS 50%) (DFS p=0.019, OS p=0.004). The data presented show that pure germinomas carry a favourable prognosis. The data also support that treatment with induction chemotherapy followed by dose-attenuated radiotherapy is an effective alternative with results comparable to historical controls treated with craniospinal irradiation. Although chemoradiotherapy has become the mainstay of treatment in intracranial germ cell tumours, surgery remains integral to the management of this condition. Surgery remains important in establishing the histological diagnosis, as well as in the treatment of hydrocephalus. Furthermore, debulking procedures may be advocated in NGGCT as they are often resistant to chemotherapy.

 

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[409]

TÍTULO / TITLE:  - Infiltration of the Optic Chiasm, Nerve, and Disc by Gliomatosis Cerebri.

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

REVISTA / JOURNAL:  - J Neuroophthalmol. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 1097/WNO.0b013e31827912d7

AUTORES / AUTHORS:  - Traynis I; Singer S; Winterkorn J; Rosenblum M; Dinkin M

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology (IT, JW, MD), Weill Cornell Medical Center, New York, New York; and the Department of Neurology (SS, MR), Memorial Sloan-Kettering Cancer Center, New York, New York.

RESUMEN / SUMMARY:  - ABSTRACT:: An 18-year-old man with gliomatosis cerebri (GC) developed tumor infiltration of the optic chiasm and right optic nerve including the optic disc.  Although papilledema often is seen with GC, tumor invasion of the optic nerve head is observed.

 

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[410]

TÍTULO / TITLE:  - Growth pattern of tumor recurrence following bis-chloroethylnitrosourea (BCNU) wafer implantation in malignant glioma.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2013 Jan 10. pii: S0967-5868(12)00440-7. doi: 10.1016/j.jocn.2012.01.060.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.01.060

AUTORES / AUTHORS:  - Dorner L; Mustafa A; Rohr A; Mehdorn HM; Nabavi A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Universitatsklinikum Schleswig-Holstein Campus, Kiel, Germany. Electronic address: doerner@medbaltic.de.

RESUMEN / SUMMARY:  - Bis-chloroethylnitrosourea (BCNU; Gliadel, Eisai, Tokyo, Japan) is the only therapeutic agent for local chemotherapy of malignant gliomas approved by the US  Food and Drug Administration and the European Medicines Agency. In a small patient cohort, it has previously been shown that glioblastomas recur locally despite treatment with BCNU. This raises concern about local treatment with BCNU  as a stand-alone measure. The goal of this study was to analyze the growth pattern of tumor recurrence in a larger patient group: 41 patients were included  in this study. Tumor recurrences were morphologically categorized as: local, diffuse, distant or multilocular. Thirty-three of the tumors (80%) that recurred  were local or diffuse. These results show that BCNU implantation does not provide lasting local tumor control. Our data support the need to incorporate BCNU in to  multimodal therapy schemes. The improved survival rates of patients who receive concomitant local and systemic adjuvant treatment support using local therapy to  bridge the therapy-free interval of the initial postoperative phase.

 

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[411]

TÍTULO / TITLE:  - A cystic haemorrhagic lesion located in the cerebellopontine angle cistern. Cavernous angioma.

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

REVISTA / JOURNAL:  - J Clin Neurosci. 2012 Nov;19(11):1551, 1608.

AUTORES / AUTHORS:  - Otani N; Wada K; Sakakibara F; Takeuchi S; Nagatani K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. naotani@ndmc.ac.jp

 

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[412]

TÍTULO / TITLE:  - Epstein-Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma.

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

REVISTA / JOURNAL:  - Neuropathology. 2012 Dec 21. doi: 10.1111/neup.12005.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12005

AUTORES / AUTHORS:  - Ogura R; Aoki H; Natsumeda M; Shimizu H; Kobayashi T; Saito T; Takizawa J; Okamoto K; Hasegawa G; Umezu H; Ohshima K; Takahashi H; Fujii Y; Kakita A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Niigata, Niigata, Japan.

RESUMEN / SUMMARY:  - Primary central nervous system lymphoma (PCNSL) expressing T-cell markers is rare, among which nasal-type extranodal NK/T-cell lymphoma is an extremely rare subtype associated with Epstein-Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV-associated PCNSL showing a cytotoxic  T-cell phenotype. The patient, a 73-year-old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1-weighted images, hyperintense on T2-weighted and fluid-attenuated inversion recovery images, and slightly hyperintense on diffusion-weighted images. Biopsy specimens from the temporal region showed many medium-sized anaplastic lymphocytic cells with perivascular and angio-invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T-cell-restricted intracellular antigen-1 (TIA-1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV-encoded RNAs in the tumor cell nuclei. A rearrangement study showed T-cell receptor gamma-chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery,  and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T-cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV-associated T-cell lymphoma.

 

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[413]

TÍTULO / TITLE:  - Recurrent left frontal lobe cystic tumor in a 49-year-old woman.

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

REVISTA / JOURNAL:  - Neuropathology. 2013 Jan 16. doi: 10.1111/neup.12011.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12011

AUTORES / AUTHORS:  - Sugita Y; Nakashima S; Nakamura Y; Ohshima K; Terasaki M; Maruiwa H

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

 

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[414]

TÍTULO / TITLE:  - Whole-exome sequencing of a unique brain malformation with periventricular heterotopia, cingulate polymicrogyria and midbrain tectal hyperplasia.

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

REVISTA / JOURNAL:  - Neuropathology. 2012 Dec 13. doi: 10.1111/neup.12007.

            ●● Enlace al texto completo (gratuito o de pago) 1111/neup.12007

AUTORES / AUTHORS:  - Okumura A; Hayashi M; Shimojima K; Ikeno M; Uchida T; Takanashi JI; Okamoto N; Hisata K; Shoji H; Saito A; Furukawa T; Kishida T; Shimizu T; Yamamoto T

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.

RESUMEN / SUMMARY:  - We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included  a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR-based sequencing. Whole-exome sequencing confirmed the presence of novel gene variants for filamin  B (FLNB), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X-linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.

 

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[415]

TÍTULO / TITLE:  - Risk of thromboembolic events in patients with prolactinomas compared with patients with nonfunctional pituitary adenomas.

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

REVISTA / JOURNAL:  - Pituitary. 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-012-0450-4

AUTORES / AUTHORS:  - Mon SY; Alkabbani A; Hamrahian A; Thorton JN; Kennedy L; Weil R; Olansky L; Doshi K; Makin V; Hatipoglu B

INSTITUCIÓN / INSTITUTION:  - Medicine Institute, Cleveland, OH, USA.

RESUMEN / SUMMARY:  - Prolactin has been proposed as a potent coactivator of platelet aggregation, possibly contributing to thromboembolic events. The objective of the study was to evaluate the relationship between prolactinoma and deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accident (CVA). Subjects were identified from a prospectively maintained pituitary database at the Cleveland Clinic. We retrospectively reviewed the charts of 544 subjects: 347 patients with prolactinomas (prolactinoma group) and 197 patients with nonfunctional pituitary  adenomas (control group). Main outcome measures were DVT, PE and CVA. We found that 19 (5.5 %) patients in the prolactinoma group and five (2.5 %) patients in the control group had documented DVT, PE, or CVA, but this difference was not significant (p = 0.109). However, the mean initial prolactin level was higher at  the time of diagnosis among prolactinoma patients than among controls (815.23 ng/ml vs. 15.90 ng/ml; p < 0.001). Among prolactinoma patients, 15 (5.5 %) of 275 patients who underwent medical treatment (with cabergoline, bromocriptine, pergolide and/or other drug) and 4 (5.6 %) of 72 patients who underwent transsphenoidal surgery had documented DVT, PE, or CVA, which suggests that dopaminergic therapy did not influence the risk of thromboembolic events. Hyperprolactinemia per se does not appear to predispose to a hypercoagulable state.

 

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[416]

TÍTULO / TITLE:  - Screening for psychological distress in neurosurgical brain tumor patients using  the Patient Health Questionnaire-2.

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

REVISTA / JOURNAL:  - Psychooncology. 2012 Dec 12. doi: 10.1002/pon.3237.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pon.3237

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

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Lithuanian University of Health Sciences, Kaunas, Lithuania; Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.

RESUMEN / SUMMARY:  - OBJECTIVE: Psychological distress is highly prevalent but often undiagnosed in brain tumor patients. We evaluated the psychometric properties of the Patient Health Questionnaire-2 (PHQ-2) for screening of distressed neurosurgical brain tumor patients. METHODS: A total of 226 (69% women; mean age 55.6 +/- 14.7 years) consecutive patients on admission for elective brain tumor surgery were evaluated for psychological distress using the PHQ-2, the Hospital Anxiety and Depression Scale (HADS; n = 206), and the Beck Depression Inventory-II (BDI-II; n = 196). At discharge, the patients were reevaluated using the PHQ-2 and HADS. RESULTS: On admission, 43% and 18% of patients had moderate-severe psychological distress according to the HADS (HADS depression or anxiety score >/=11) and BDI-II (score  >/=20), respectively. At discharge, there was a significant decrease in psychological distress among patients according to the PHQ-2 (p = 0.04) and HADS  (p < 0.001) screening results. The PHQ-2 had marginal internal consistency (Cronbach’s coefficient alpha = 0.68) and suboptimal test-retest reliability (intraclass correlation coefficient = 0.51). The PHQ-2 had acceptable psychometric properties for identifying patients with moderate-severe psychological distress according to the HADS (sensitivity = 74%, specificity = 68%, and positive predictive value (PPV) = 40%) and BDI-II (sensitivity = 71%, specificity = 65%, and PPV = 30%). Psychometric properties of the PHQ-2 were inferior for mild-severe psychological distress. Greater number of PHQ-2 depressive symptoms was associated with greater scores on the HADS and BDI-II (all ps < 0.001). CONCLUSIONS: Psychological distress is prevalent in brain tumor patients and can be successfully identified using the PHQ-2. The PHQ-2 has moderate internal consistency. The PHQ-2 should be considered for routine use in  brain tumor patients for psychological distress screening purposes. Copyright © 2012 John Wiley & Sons, Ltd.

 

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[417]

TÍTULO / TITLE:  - Hypoxia-related molecules HIF-1alpha, CA9, and osteopontin : Predictors of survival in patients with high-grade glioma.

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

REVISTA / JOURNAL:  - Strahlenther Onkol. 2013 Feb;189(2):147-154. Epub 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00066-012-0262-5

AUTORES / AUTHORS:  - Erpolat OP; Gocun PU; Akmansu M; Ozgun G; Akyol G

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Medical School of Gazi University, Ahmet Taner  Kislali Mah, Konutkent 2 sitesi, A8 Blok, No: 62 Cayyolu, Ankara, Turkey, petektater@yahoo.com.

RESUMEN / SUMMARY:  - PURPOSE: A high expression of hypoxia-inducible factor-1 alpha (HIF)-1alpha, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas. PATIENTS AND METHODS: HIF-1alpha, CA9, and osteopontin levels in tissue  specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry. RESULTS: Patients with a high expression of cytoplasmic and nuclear HIF-1alpha, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1alpha, CA9, and osteopontin) was the only  independent negative prognostic factor for survival (p = 0.028). CONCLUSION: Our  results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

 

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[418]

TÍTULO / TITLE:  - Genetic analysis in young patients with sporadic pituitary macroadenomas:Beside AIP don’t forget MEN1 genetic analysis.

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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-0763

AUTORES / AUTHORS:  - Cuny T; Pertuit M; Sahnoun-Fathallah M; Daly AF; Occhi G; Odou MF; Tabarin A; Nunes ML; Delemer B; Rohmer V; Desailloud R; Kerlan V; Chabre O; Sadoul JL; Cogne M; Caron P; Cortet C; Lienhardt-Roussie A; Raingeard I; Guedj AM; Brue T; Beckers A; Weryha G; Enjalbert A; Barlier A

INSTITUCIÓN / INSTITUTION:  - T Cuny, Endocrinology, University Hospital of Nancy Brabois, Vandoeuvre-Les-Nancy, France.

RESUMEN / SUMMARY:  - CONTEXT: germline mutations in the AIP gene have been identified in young patients (age </= 30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of MEN1 mutations in such population. OBJECTIVE: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age </= 30  years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. DESIGN: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. PATIENTS AND SETTINGS: 174 patients from Endocrinology Departments of 15 French University Hospital Centers were eligible  for this study. RESULTS: 21/174(12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6,  3.4%) mutations. In pediatric patients (age </= 18 years old), AIP/MEN1 mutation  frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were respectively identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients; they each accounted for 4/74 (5.4%) prolactinoma patients with mutations. Half of patients  (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the 8 corticotroph-adenomas and a single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. CONCLUSION: mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly prolactinomas, and together with AIP, we suggest genetic analysis of MEN1 in such population.

 

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[419]

TÍTULO / TITLE:  - Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO).

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan;15(1):112-21. doi: 10.1093/neuonc/nos283. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos283

AUTORES / AUTHORS:  - Leibetseder A; Ackerl M; Flechl B; Wohrer A; Widhalm G; Dieckmann K; Kreinecker SS; Pichler J; Hainfellner J; Preusser M; Marosi C

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Christine Marosi, MD, Department of Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20 1090 Vienna, Austria. christine.marosi@meduniwien.ac.at.

RESUMEN / SUMMARY:  - Background Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers. Patients and Methods Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed. All patients were treated with standard first-line therapy. The primary end points were overall survival (OS) and time to progression (TTP). IDH1-R132H mutation status was analyzed using immunohistochemistry, and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction. Results We included 70 patients (36 men and 34 women) with a median age of 33 years. IDH1-R132H mutations were detected in 22 (39.3%) of 56 cases and MGMT promoter methylation in 33 (61.1%) of 54 cases with available tissue samples. In  patients with wild-type IDH, median TTP was 8.2 months and median OS was 24 months, compared with 18 months and 44 months, respectively, observed in patients with mutated IDH. Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS. Of note, the social and economical situation of the young patients with GBM was alarming, because only 17% succeeded in staying employed after receiving the diagnosis. Conclusions We found a high frequency of  IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age. The social and economic coverage of patients with glioma remains  an unsolved socio-ethical problem.

 

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[420]

TÍTULO / TITLE:  - Patients with recurrent glioblastoma multiforme. Initial experience with p-[131I]iodo-L-phenylalanine and external beam radiation therapy.

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

REVISTA / JOURNAL:  - Nuklearmedizin. 2013 Jan 10;52(1).

            ●● Enlace al texto completo (gratuito o de pago) 3413/Nukmed-0510-12-06

AUTORES / AUTHORS:  - Verburg FA; Sweeney R; Hanscheid H; Diessl S; Israel I; Lohr M; Vince GH; Flentje M; Reiners C; Samnick S

INSTITUCIÓN / INSTITUTION:  - Frederik A. Verburg, MD, PhD, RWTH Aachen University Hospital, Department of Nuclear Medicine, Pauwelsstr. 30, 52074 Aachen, Germany, Tel. +49/(0)241/803 66 19, Fax +49/(0)241/808 25 20, E-mail: fverburg@ukaachen.de.

RESUMEN / SUMMARY:  - Aim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[131I]iodo-L-phenylalanine (131IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme  (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a  positive O-(2-[18F]Fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by 131  IPA-SPECT up to six days after radiotracer administration. After 131 IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of 131 IPA, resulting in radiation absorbed doses to the blood of 0.80-1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first  two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from 131 IPA were low (</= 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with 131IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by  the animal studies.

 

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[421]

TÍTULO / TITLE:  - DARPP32, STAT5 and STAT3 mRNA Expression Ratios in Glioblastomas are Associated with Patient Outcome.

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

REVISTA / JOURNAL:  - Pathol Oncol Res. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9588-7

AUTORES / AUTHORS:  - Televantou D; Karkavelas G; Hytiroglou P; Lampaki S; Iliadis G; Selviaridis P; Polyzoidis KS; Fountzilas G; Kotoula V

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, University Campus, 54006, Thessaloniki, Greece.

RESUMEN / SUMMARY:  - Based on recent developments in glioblastoma subtyping, we examined DARPP32 (PPP1R1B), a neuronal marker against STAT5 and STAT3 that are pro-oncogenic in glioblastoma. mRNA ratios of DARPP32, STAT1, STAT3, STAT5A and STAT5B were assessed in routinely diagnosed gliomas s including a series of glioblastomas from patients (n = 67) treated with chemoradiotherapy (temozolomide), out of which 88 % had sequencing validated IDH-negative disease. DARPP32/STAT1 (p = 0.0007), DARPP32/STAT3 (p = 0.0004) and DARPP32/STAT5B (p = 0.0039) ratios were significantly higher in grade II and III as compared to grade IV tumours. The same high ratios were also associated with absence of immunohistochemically assessed AKT/PKB phosphorylation and survivin protein expression. High DARPP32/STAT3, DARPP32/STAT5B, and STAT5B/STAT3 ratios were associated with longer patient progression free (PFS) and overall survival (OS). Upon multivariate analysis, total/subtotal removal of the tumour (HR:0.431; 95%CI:0.241-0.771, Wald p = 0.005), high DARPP32/STAT5B (HR:0.341; 95%CI:0.169-0.690; Wald p = 0.003) and STAT5B/STAT3 mRNA ratios (HR:0.480; 95%CI:0.280-0.824; Wald p = 0.008) were independent favorable parameters for prolonged PFS. Extent of surgery (HR:0.198; 95%CI:0.101-0.390; p < 0.001) and high DARPP32/STAT5A ratios (HR:0.320; 95%CI:0.160-0.638, p = 0.001) were independently predictive for longer OS. The presented approach is applicable for  prospective validation and appears promising towards an effective glioblastoma patient stratification in addition to IDH mutations. These data may contribute to understanding the biology of gliomas with respect to their potential neuronal characteristics and justify STAT-inhibiting therapeutic interventions in the same tumour system.

 

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[422]

TÍTULO / TITLE:  - On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):198-207. doi: 10.1093/neuonc/nos302. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos302

AUTORES / AUTHORS:  - Stechishin OD; Luchman HA; Ruan Y; Blough MD; Nguyen SA; Kelly JJ; Cairncross JG; Weiss S

INSTITUCIÓN / INSTITUTION:  - Corresponding author: Dr. Samuel Weiss, PhD, Room 1A10 HRIC, 3330 Hospital Dr. NW, Calgary, AB, Canada, T2N 4N1. weiss@ucalgary.ca.

RESUMEN / SUMMARY:  - Background Glioblastoma multiforme (GBM) is characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity. GBM-derived brain tumor stem cells (BTSCs) closely model this molecular heterogeneity and likely have a key role in tumor recurrence and therapeutic resistance. Emerging evidence indicates that Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 is an important mediator of tumor cell survival, growth, and invasion in a large group of GBM. Here, we used  a large set of molecularly heterogeneous BTSCs to evaluate the translational potential of JAK2/STAT3 therapeutics. Methods BTSCs were cultured from GBM patients and MGMT promoter methylation, and the mutation statuses of EGFR, PTEN,  and TP53 were determined. Endogenous JAK2/STAT3 activity was assessed in human GBM tissue, BTSCs, and orthotopic xenografts by immunohistochemistry and Western  blotting. STAT3 short hairpin (sh)RNA, cucurbitacin-I, and WP1066 were used to inhibit JAK2/STAT3 activity in vitro and in vivo. Results The JAK2/STAT3 pathway  was demonstrated to be highly activated in human GBM, molecularly heterogeneous BTSCs derived from these tumors, and BTSC xenografts. STAT3 shRNA knockdown or cucurbitacin-I and WP1066 administration resulted in on-target JAK2/STAT3 inhibition and dramatically reduced BTSC survival regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. BTSC orthotopic xenografts maintained the high levels of activated JAK2/STAT3 seen in their parent human tumors. Intraperitoneal WP1066 reduced intratumoral JAK2/STAT3 activity and prolonged animal survival. Conclusion Our study demonstrates the in  vitro and in vivo efficacy of on-target JAK2/STAT3 inhibition in heterogeneous BTSC lines that closely emulate the genomic and tumorigenic characteristics of human GBM.

 

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[423]

TÍTULO / TITLE:  - Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy  and autologous stem cell transplantation in patients with high-risk medulloblastoma.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos304

AUTORES / AUTHORS:  - Sung KW; Lim DH; Son MH; Lee SH; Yoo KH; Koo HH; Kim JH; Suh YL; Joung YS; Shin HJ

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School  of Medicine, Seoul, Republic of Korea (K.W.S., M.H.S., S.H.L., K.H.Y., H.H.K.); Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (J.H.K.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (Y.S.); Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School  of Medicine, Seoul, Republic of Korea (Y.S.J.); and Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (H.J.S.).

RESUMEN / SUMMARY:  - BackgroundWe assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).MethodsFrom October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm(2)) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.ResultsOf 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm(2) without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23-82) from diagnosis. The probability of 5-year event-free survival was 70.0% +/- 10.3% for all patients and 70.6% +/- 11.1% for  patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12-68) after tandem HDCT/autoSCT were acceptable.ConclusionsIn children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.

 

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[424]

TÍTULO / TITLE:  - NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos322

AUTORES / AUTHORS:  - Peereboom DM; Ahluwalia MS; Ye X; Supko JG; Hilderbrand SL; Phuphanich S; Nabors LB; Rosenfeld MR; Mikkelsen T; Grossman SA

INSTITUCIÓN / INSTITUTION:  - Cleveland Clinic, Cleveland, Ohio (D.M.P., M.S.A.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland (X.Y., S.A.G.); Massachusetts General Hospital, Boston, Massachusetts (J.G.S., S.L.H.); Cedars-Sinai Medical Center, Los Angeles, California (S.P.); University of Alabama, Birmingham, Alabama (L.B.N.); Hospital Clinic/IDIBAPS, Barcelona, España  (M.R.R.); Henry Ford Hospital, Detroit, Michigan (T.M.).

RESUMEN / SUMMARY:  - BackgroundThe signal transduction pathways of epidermal growth factor receptor and Ras are both important in the growth of glioblastoma multiforme (GBM). We hypothesized that inhibition of both pathways would improve the survival time of  patients with recurrent GBM.MethodsPatients with recurrent/progressive GBM with 0-2 prior chemotherapy regimens received erlotinib 150 mg once daily and sorafenib 400 mg twice daily until progression. The primary endpoint was overall  survival. Pharmacokinetic sampling was performed during cycle 1.ResultsThe median overall survival was 5.7 months. Progression-free survival at 6 months was 14%. Toxicity was manageable. Clearance of erlotinib was markedly enhanced by sorafenib.ConclusionThe study did not meet its objective of a 30% increase in overall survival time compared with historical controls. Erlotinib and sorafenib  have significant pharmacokinetic interactions that may negatively impact the efficacy of the combination regimen.

 

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[425]

TÍTULO / TITLE:  - Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening.

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

REVISTA / JOURNAL:  - Pituitary. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0462-8

AUTORES / AUTHORS:  - Nunes VS; Souza GL; Perone D; Conde SJ; Nogueira CR

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Biology, Department of Internal Medicine, Botucatu Medical School, UNESP, Univ Estadual Paulista, Botucatu, Brazil, vsnunes@fmb.unesp.br.

RESUMEN / SUMMARY:  - The purpose of this study it was to evaluate the frequency of Multiple Endocrine  Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP-Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005-2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly  asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed.

 

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[426]

TÍTULO / TITLE:  - Predicting outcomes of vocational rehabilitation in patients with brain tumours.

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

REVISTA / JOURNAL:  - Psychooncology. 2013 Jan 27. doi: 10.1002/pon.3241.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pon.3241

AUTORES / AUTHORS:  - Rusbridge SL; Walmsley NC; Griffiths SB; Wilford PA; Rees JH

INSTITUCIÓN / INSTITUTION:  - Therapy and Rehabilitation Services, National Hospital for Neurology and Neurosurgery, London, UK.

RESUMEN / SUMMARY:  - OBJECTIVE: The aim of this study was to examine the outcome of a vocational rehabilitation programme for patients with brain tumours and to determine whether the outcome could be predicted at point of referral to the service. METHODS: Data was collected for 34 patients with brain tumours referred to the Macmillan vocational rehabilitation service. Work status at baseline (time of referral) and at discharge was compared. Logistic regression analyses were computed to identify which variables (demographic, tumour and treatment, functional and vocational) predicted work status at discharge from the service. RESULTS: Significantly, more patients were working at discharge from the service than at baseline. Having at least some physical disability decreased the likelihood of being in work at discharge from the service. CONCLUSIONS: The vocational rehabilitation programme  for brain tumour survivors showed significant improvement over time. Functional ability affected the likelihood of working to some extent. Vocational rehabilitation services should be available to patients with brain tumours and should focus on supporting patients wishing to return to or maintain their current work. However, more support for brain tumour patients with physical impairments is needed. Copyright © 2013 John Wiley & Sons, Ltd.

 

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[427]

TÍTULO / TITLE:  - MGMT promoter methylation status and MGMT and CD133 immunohistochemical expression as prognostic markers in glioblastoma patients treated with temozolomide plus radiotherapy.

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

REVISTA / JOURNAL:  - J Transl Med. 2012 Dec 17;10:250. doi: 10.1186/1479-5876-10-250.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-10-250

AUTORES / AUTHORS:  - Melguizo C; Prados J; Gonzalez B; Ortiz R; Concha A; Alvarez PJ; Madeddu R; Perazzoli G; Oliver JA; Lopez R; Rodriguez-Serrano F; Aranega A

INSTITUCIÓN / INSTITUTION:  - Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, España. jcprados@ugr.es.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The CD133 antigen is a marker of radio- and chemo-resistant stem cell populations in glioblastoma (GBM). The O6-methylguanine DNA methyltransferase (MGMT) enzyme is related with temozolomide (TMZ) resistance. Our propose is to analyze the prognostic significance of the CD133 antigen and promoter methylation and protein expression of MGMT in a homogenous group of GBM  patients uniformly treated with radiotherapy and TMZ. The possible connection between these GBM markers was also investigated. METHODS: Seventy-eight patients  with GBM treated with radiotherapy combined with concomitant and adjuvant TMZ were analyzed for MGMT and CD133. MGMT gene promoter methylation was determined by methylation-specific polymerase chain reaction after bisulfite treatment. MGMT and CD133 expression was assessed immunohistochemically using an automatic quantification system. Overall and progression-free survival was calculated according to the Kaplan-Meier method. RESULTS: The MGMT gene promoter was found to be methylated in 34 patients (44.7%) and unmethylated in 42 patients (55.3%).  A significant correlation was observed between MGMT promoter methylation and patients’ survival. Among the unmethylated tumors, 52.4% showed low expression of MGMT and 47.6% showed high-expression. Among methylated tumors, 58.8% showed low-expression of MGMT and 41.2% showed high-expression. No correlation was found between MGMT promoter methylation and MGMT expression, or MGMT expression and survival. In contrast with recent results, CD133 expression was not a predictive  marker in GBM patients. Analyses of possible correlation between CD133 expression and MGMT protein expression or MGMT promoter methylation were negative. CONCLUSIONS: Our results support the hypothesis that MGMT promoter methylation status but not MGMT expression may be a predictive biomarker in the treatment of  patients with GBM. In addition, CD133 should not be used for prognostic evaluation of these patients. Future studies will be necessary to determine its clinical utility.

 

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[428]

TÍTULO / TITLE:  - Upregulation of DLX2 confers a poor prognosis in glioblastoma patients by inducing a proliferative phenotype.

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

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Yan ZH; Bao ZS; Yan W; Liu YW; Zhang CB; Wang HJ; Feng Y; Wang YZ; Zhang W; You G; Zhang QG; Jiang T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, No. 6 Tiantan Xili, Dongcheng District, Beijing 100050, China. taojiang1964@yahoo.com.cn.

RESUMEN / SUMMARY:  - The human Distal-less Homeobox (DLX) gene family encodes homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis, which is primarily expressed in embryonic development. Recently, DLX gene family was reported to have essential roles in carcinogenesis. We have profiled whole genome expressed genes in 83 glioblastoma multiforme (GBM) patients from the Chinese Glioma Genome Atlas (CGGA) Group. Two major groups of samples were identified in  mRNA expression profiles (referred to as Group 1 (G1) and Group 2 (G2)). We identified 7 out of the top 10 Gene Ontology terms in the G1 group were associated with differentiation and development of neuronal cell. The most significant prognostic gene was DLX2 (P<0.001, OR=1.744); overexpression of DLX2  indicated poor survival in the 83 GBM patients (low DLX2 vs. high DLX2, 77.6 vs.  44.7 weeks, P<0.001). Annotation of mRNA profiling data on GBM from The Cancer Genome Atlas and MD Anderson Cancer Center showed the proneural and neural subtypes highly correlated with low and high DLX2 expression, respectively. Knocking down of DLX2 in GBM cell line-LN229 results in decreased cyclin D1 expression and cell proliferation. Collectively, these data identified high expression of DLX2 as a poor prognostic marker to GBM patients.

 

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[429]

TÍTULO / TITLE:  - Erratum for “Detection of 2-hydroxyglutaric acid in vivo by proton magnetic resonance spectroscopy in U87 glioma cells overexpressing isocitrate dehydrogenase-1 mutation”.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan;15(1):133. doi: 10.1093/neuonc/nos332.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos332

 

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[430]

TÍTULO / TITLE:  - 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. 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0127-8

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.

RESUMEN / SUMMARY:  - Tumorigenic activity of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the production of prostaglandins (PGs), has been proved for some types of cancer, including brain tumors. We evaluated expression of COX-2 in meningioma, one of the most common intracranial tumors in adults which accounts for 24-30 % of intracranial tumors. We performed immunostaining for COX-2 in 76 cases of meningioma consisting of 44 cases of low-grade (WHO Grade I) and 32 cases of high-grade (29 cases of Grade II and 3 cases of Grade III) meningioma, and evaluated COX-2 expression levels on the basis of staining intensity and proportion in tumor cells. The expression level of COX-2 in meningioma cells was  significantly correlated with WHO grade (P = 0.0153). In addition, COX-2 expression was significantly correlated with MIB-1 labeling index for all 76 cases of meningioma (P = 0.0075), suggesting tumor promotion by COX-2 in meningioma progression. Our results may indicate the therapeutic value of non-steroidal anti-inflammatory drugs against meningioma, especially for patients with elevated proliferation, to regulate the tumorigenic activity of COX-2 in meningioma cells.

 

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[431]

TÍTULO / TITLE:  - Glioblastoma Tumor Initiating Cells: Therapeutic Strategies Targeting Apoptosis and MicroRNA Pathways.

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

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Liu J; Albrecht AM; Ni X; Yang J; Li M

INSTITUCIÓN / INSTITUTION:  - The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Min.Li@uth.tmc.edu.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is a highly malignant primary brain tumor known for its invasiveness and aggressive resistance to standard treatment. It is currently the most common primary brain tumor which is associated with a high mortality rate. Tumor initiating cells (TICs) are a subpopulation of GBM stem cells which are capable of self-renewal and apoptotic resistance, and are thought to account for  GBMs aggressive nature. Recent efforts have focused on therapies which target key intracellular apoptotic pathways which may confer tumor resistance, such as Akt,  p53, Bcl-2 family proteins, caspase family proteases, and more recently microRNAs. Research into microRNA’s role in GBM has shown that microRNAs play a key regulatory role in the GBM apoptotic pathway, making it a potential therapeutic target. In this review we summarized the molecular mechanisms involved in the signaling pathways of human GBM TIC apoptosis and microRNAs, the  contemporary treatments involving different members of the signaling cascade, and the future direction of GBM treatment strategies.

 

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[432]

TÍTULO / TITLE:  - The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

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

REVISTA / JOURNAL:  - Oncologist. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1634/theoncologist.2012-0247

AUTORES / AUTHORS:  - Sizoo EM; Taphoorn MJ; Uitdehaag B; Heimans JJ; Deliens L; Reijneveld JC; Pasman HR

INSTITUCIÓN / INSTITUTION:  - Department of Neurology.

RESUMEN / SUMMARY:  - Background. In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient’s personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients.Methods. We approached relatives of a cohort of 155  deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity.Results. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate  analysis identified satisfaction with the physician, the ability to communicate,  and the absence of transitions between settings as most predictive of a dignified death.Conclusions. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

 

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[433]

TÍTULO / TITLE:  - Levetiracetam improves verbal memory in high-grade glioma patients.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):216-23. doi: 10.1093/neuonc/nos288. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos288

AUTORES / AUTHORS:  - de Groot M; Douw L; Sizoo EM; Bosma I; Froklage FE; Heimans JJ; Postma TJ; Klein M; Reijneveld JC

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Marjolein de Groot, MD, Department of Neurology, VU University Medical Center, PO Box 7057 1007 MB Amsterdam, The Netherlands. marjolein.degroot@vumc.nl.

RESUMEN / SUMMARY:  - Background Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration.  The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of older and newer AEDs on cognitive performance in postoperative HGG patients. Methods We selected  HGG patients from 3 separate cohorts for use of older, newer, or no AEDs, as they represented distinct treatment eras and provided the opportunity to compare older and newer AEDs. In all 3 cohorts, patients were included within 6 weeks following neurosurgery before the start of postoperative treatment. Cognitive functioning was evaluated by an extensive neuropsychological assessment, executed in 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed). Results One hundred seventeen patients met the inclusion criteria; 44 patients used no AED, 35 were on monotherapy with a newer AED (all levetiracetam), and 38 were on monotherapy with an older AED (valproic acid or phenytoin). Patients on older and newer AEDs performed equally well as patients not on an AED, and patients on levetiracetam performed even better on verbal memory tests than patients not on an AED. Post-hoc analyses revealed that within the group using older AEDs, patients on valproic acid performed better than patients on phenytoin. Conclusions Neither levetiracetam nor valproic acid was associated with additional cognitive deficits in HGG patients. Both AEDs even appeared to have a  beneficial effect on verbal memory in these patients.

 

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[434]

TÍTULO / TITLE:  - Quantitative Analysis of the Fate of Gold Nanocages In Vitro and In Vivo after Uptake by U87-MG Tumor Cells.

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

REVISTA / JOURNAL:  - Angew Chem Int Ed Engl. 2013 Jan 21;52(4):1152-5. doi: 10.1002/anie.201208096. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1002/anie.201208096

AUTORES / AUTHORS:  - Cho EC; Zhang Y; Cai X; Moran CM; Wang LV; Xia Y

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Engineering, Washington University, St. Louis, MO 63130  (USA); Current address: Department of Chemical Engineering, Division of Chemical  and Bioengineering, Hanyang University, Seoul, 133-791 (Korea).

RESUMEN / SUMMARY:  - Not always equal: When a mother cell that contains Au nanocages divides, the nanoparticles are unequally distributed between the two daughter cells. This unequal distribution of nanoparticles as well as their clearance from the cells is quantitatively analyzed both in vitro and in vivo using two-photon microscopy  and photoacoustic microscopy, respectively.

 

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[435]

TÍTULO / TITLE:  - Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients.

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

REVISTA / JOURNAL:  - J Transl Med. 2013 Jan 9;11:10. doi: 10.1186/1479-5876-11-10.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-10

AUTORES / AUTHORS:  - Qiu S; Lin S; Hu D; Feng Y; Tan Y; Peng Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. docpengy@yahoo.com.cn.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs) is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. METHODS: Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA) dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS) and progression-free survival (PFS) associated with interested miRNAs and miRNA-interactions were performed by  Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. RESULTS: In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high  miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP). More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model together with clinicopathological factors: Age, Gender and Recurrence. Plus, the availability and rationality of the miRNA-interaction as predictors for survival were further supported by analysis of network, biological processes, KEGG pathway and correlation analysis  with gene markers. CONCLUSIONS: Our results demonstrates that miR-326, miR-130a,  miR-155, miR-210 and the 4 miRNA-interactions could serve as prognostic and predictive markers for survival of GBM patients, suggesting a potential application in improvement of prognostic tools and treatments.

 

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[436]

TÍTULO / TITLE:  - Bevacizumab-based therapy in relapsed glioblastoma: rationale and clinical experience to date.

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

REVISTA / JOURNAL:  - Expert Rev Anticancer Ther. 2012 Nov;12(11):1413-27. doi: 10.1586/era.12.128.

            ●● Enlace al texto completo (gratuito o de pago) 1586/era.12.128

AUTORES / AUTHORS:  - Chinot OL

INSTITUCIÓN / INSTITUTION:  - Aix-Marseille University, Assistance Publique-Hopitaux de Marseille, Centre Hospitalo-Universitaire Timone, Service de Neuro-Oncologie, 13008 Marseille, France. olivier.chinot@ap-hm.fr.

RESUMEN / SUMMARY:  - Relapsed glioblastoma (GBM) has an extremely poor prognosis and remains an invariably fatal disease, with a median overall survival of 6-7 months. Despite numerous clinical trials over the past 20-30 years, treatment options for relapsed GBM remain limited. In recent years, significant research efforts have focused on the use of antiangiogenic therapies for the treatment of GBM. Bevacizumab is a humanized monoclonal antibody that specifically inhibits the proangiogenic VEGF, with well-established clinical efficacy in a number of solid  malignancies, which is now under investigation for the treatment of GBM. In this  review, we discuss the available data regarding bevacizumab-based therapy in relapsed GBM, highlighting its potential and ongoing challenges in this difficult-to-treat disease.

 

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[437]

TÍTULO / TITLE:  - The DNA repair protein ALKBH2 mediates temozolomide resistance in human glioblastoma cells.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos301

AUTORES / AUTHORS:  - Johannessen TC; Prestegarden L; Grudic A; Hegi ME; Tysnes BB; Bjerkvig R

INSTITUCIÓN / INSTITUTION:  - NorLux Neuro-Oncology, Department of Biomedicine, University of Bergen, Bergen, Norway (T.-C.A.J., L.P., A.G., B.B.T., R.B.); Department of Dermatology, Haukeland University Hospital, Bergen, Norway (L.P.); Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland (M.E.H.); NorLux Neuro-Oncology, Oncology Department, Centre de Recherche Public de la Sante, Luxembourg, Luxembourg (R.B.).

RESUMEN / SUMMARY:  - IntroductionGlioblastoma multiforme (GBM; World Health Organization astrocytoma grade IV) is the most frequent and most malignant primary brain tumor in adults.  Despite multimodal therapy, all such tumors practically recur during the course of therapy, causing a median survival of only 14.6 months in patients with newly  diagnosed GBM. The present study was aimed at examining the expression of the DNA repair protein AlkB homolog 2 (ALKBH2) in human GBM and determining whether it could promote resistance to temozolomide chemotherapy.MethodsALKBH2 expression in GBM cell lines and in human GBM was determined by quantitative real-time PCR (qRT-PCR) and gene expression analysis, respectively. Drug sensitivity was assessed in GBM cells overexpressing ALKBH2 and in cells in which ALKBH2 expression was silenced by small-interfering (si)RNA. ALKBH2 expression following activation of the p53 pathway was examined by western blotting and qRT-PCR.ResultsALKBH2 was abundantly expressed in established GBM cell lines and  human GBM, and temozolomide exposure increased cellular ALKBH2 expression levels. Overexpression of ALKBH2 in the U87 and U251 GBM cell lines enhanced resistance to the methylating agents temozolomide and methyl methanesulfonate but not to the nonmethylating agent doxorubicin. Conversely, siRNA-mediated knockdown of ALKBH2  increased sensitivity of GBM cells to temozolomide and methyl methanesulfonate but not to doxorubicin or cisplatin. Nongenotoxic activation of the p53 pathway by the selective murine double minute 2 antagonist nutlin-3 caused a significant  decrease in cellular ALKBH2 transcription levels.ConclusionOur findings identify  ALKBH2 as a novel mediator of temozolomide resistance in human GBM cells. Furthermore, we place ALKBH2 into a new cellular context by showing its regulation by the p53 pathway.

 

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[438]

TÍTULO / TITLE:  - Calcifying pseudoneoplasm of the neuraxis with single nerve rootlet involvement.

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

REVISTA / JOURNAL:  - Can J Neurol Sci. 2012 Nov;39(6):840-2.

AUTORES / AUTHORS:  - Jentoft ME; Scheithauer BW; Bertoni F; Abood C; Chang HT

INSTITUCIÓN / INSTITUTION:  - Department of Laboratory Medicine and Pathology, 200 First Street, SW, Rochester, MN, 55905, USA. jentoft.mark@mayo.edu

 

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[439]

TÍTULO / TITLE:  - Tumor treating fields therapy for recurrent glioblastoma.

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

REVISTA / JOURNAL:  - Manag Care. 2012 Dec;21(12):43-4.

 

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[440]

TÍTULO / TITLE:  - Nanofiber-mediated inhibition of focal adhesion kinase sensitizes glioma stemlike cells to epidermal growth factor receptor inhibition.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos316

AUTORES / AUTHORS:  - Srikanth M; Das S; Berns EJ; Kim J; Stupp SI; Kessler JA

INSTITUCIÓN / INSTITUTION:  - Department of Neurology (M.S., J.K., J.A.K.); Department of Neurosurgery (S.D.),  Northwestern University, Chicago, Illinois; Department of Biomedical Engineering  (E.J.B.); Department of Chemistry and Department of Material Science and Engineering, Northwestern University, Evanston, Illinois (S.I.S.).

RESUMEN / SUMMARY:  - BackgroundGlioblastoma multiforme is the most common glioma in adults and carries a poor prognosis, due to tumor recurrence despite aggressive treatment. Such relapse has been attributed to the persistence of glioma stemlike cells (GSCs), a subpopulation of glioma cells with stem cell properties. Thus, targeting these cells will be critical to achieving meaningful improvement in glioblastoma multiforme survival. We investigated the role of beta1-integrin signaling as one  such potential target.MethodsWe used GSCs isolated from primary human gliomas and maintained in stem cell conditions. We manipulated beta1-integrin signaling using a self-assembling peptide amphiphile (PA) displaying the IKVAV (isoleucine-lysine-valine-alanine-valine) epitope as well as lentiviral overexpression, and we assayed the effects on downstream effectors and apoptosis  using immunofluorescence.ResultsWe show that beta1-integrin expression correlates with decreased survival in glioma patients and that beta1-integrin is highly expressed by GSCs. The IKVAV PA potently increases immobilized beta1-integrin at  the GSC membrane, activating integrin-linked kinase while inhibiting focal adhesion kinase (FAK). The IKVAV PA induces striking apoptosis in GSCs via this FAK inhibition, which is enhanced in combination with inhibition of epidermal growth factor receptor (EGFR). Conversely, lentiviral overexpression of beta1-integrin renders GSCs resistant to EGFR inhibition, which was overcome by FAK inhibition.ConclusionsThese observations reveal a role for beta1-integrin signaling through FAK in GSC treatment resistance and introduce self-assembling PAs as a novel new therapeutic approach for overcoming this resistance.

 

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[441]

TÍTULO / TITLE:  - Survivin Expression in Medulloblastoma: A Possible Marker for Survival.

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

REVISTA / JOURNAL:  - Pathol Oncol Res. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9594-9

AUTORES / AUTHORS:  - Abdel-Aziz A; Mohamed MA; Akl FM; Taha AN

INSTITUCIÓN / INSTITUTION:  - Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt,  azza3a@yahoo.com.

RESUMEN / SUMMARY:  - Medulloblastomas are highly invasive tumors which are generally disseminated at the time of diagnosis. High and continued morbidity and mortality have prompted the search for new biologic markers that might be used for targeted therapy to minimise treatment related side effects. In this work, we studied the positive expression of survivin in medulloblastoma and investigated its relation to clinical, pathologic data and survival. Tumor tissue specimens from 47 patients with medulloblastoma who underwent primary surgical treatment from June 2002 to June 2006 at the Mansoura university hospital, Egypt were collected. Paraffin sections of all samples were submitted for immunohistochemistry using anti-survivin antibody. The relation between the percentage of positive survivin  cells with clinical, pathological and survival data was evaluated Results: In 47  cancer tissue specimens, one case large-cell-anaplastic (1.12 %), tweleve cases desmoplastic (25.53 %) and 34 cases classic medulloblastomas (72.34 %). The immunohistochemical expression of survivin was nulear with moderate intensity. It does not correlate with either age or sex. There was a significant negative correlation of survivin expression with survival (p < 0.001), where negative survivin immunostaining was associated with prolonged overall and disease free survival, while survivin expression was associated with shortened survival. Conclusion: Survivin expression correlate with the clinical outcome with poor prognosis and could be a potential predictive factor for recurrence or metastasis.

 

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[442]

TÍTULO / TITLE:  - Combined analysis of O6-methylguanine-DNA methyltransferase protein expression and promoter methylation provides optimized prognostication of glioblastoma outcome.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos308

AUTORES / AUTHORS:  - Lalezari S; Chou AP; Tran A; Solis OE; Khanlou N; Chen W; Li S; Carrillo JA; Chowdhury R; Selfridge J; Sanchez DE; Wilson RW; Zurayk M; Lalezari J; Lou JJ; Ormiston L; Ancheta K; Hanna R; Miller P; Piccioni D; Ellingson BM; Buchanan C; Mischel PS; Nghiemphu PL; Green R; Wang HJ; Pope WB; Liau LM; Elashoff RM; Cloughesy TF; Yong WH; Lai A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology (S.L., A.T., W.C., S.L., R.C., J.S., M.Z., J.L., J.J.L.,  L.O., K.A., R.H., P.M., D.P., P.L.N., T.F.C., A.L.), Department of Neurosurgery (A.P.C., C.B., L.M.L.), and Department of Pathology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California (O.E.S., N.K., D.E.S., R.W.W. P.S.M. W.H.Y.); Department of Neurology, UC Irvine School of Medicine, University of California, Irvine, California (J.A.C.); Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California (B.M.E., W.B.P.); Kaiser Permanente Southern  California (R.G.); and Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California (H.-J.W., R.M.E.).

RESUMEN / SUMMARY:  - BackgroundPromoter methylation of the DNA repair gene, O-6-methylguanine-DNA methyltransferase (MGMT), is associated with improved treatment outcome for newly diagnosed glioblastoma (GBM) treated with standard chemoradiation. To determine the prognostic significance of MGMT protein expression as assessed by immunohistochemistry (IHC) and its relationship with methylation, we analyzed MGMT expression and promoter methylation with survival in a retrospective patient cohort.MethodsWe identified 418 patients with newly diagnosed GBM at University of California Los Angeles Kaiser Permanente Los Angeles, nearly all of whom received chemoradiation, and determined MGMT expression by IHC, and MGMT promoter methylation by methylation-specific PCR (MSP) and bisulfite sequencing (BiSEQ) of 24 neighboring CpG sites.ResultsWith use of the median percentage of cells staining by IHC as the threshold, patients with <30% staining had progression-free survival (PFS) of 10.9 months and overall survival (OS) of 20.5  months, compared with PFS of 7.8 months (P < .0001) and OS of 16.7 months (P < .0001) among patients with >/=30% staining. Inter- and intrareader correlation of IHC staining was high. Promoter methylation status by MSP was correlated with IHC staining. However, low IHC staining was frequently observed in the absence of promoter methylation. Increased methylation density determined by BiSEQ correlated with both decreased IHC staining and increased survival, providing a practical semiquantitative alternative to MSP. On the basis of multivariate analysis validated by bootstrap analysis, patients with tandem promoter methylation and low expression demonstrated improved OS and PFS, compared with the other combinations.ConclusionsOptimal assessment of MGMT status as a prognostic biomarker for patients with newly diagnosed GBM treated with chemoradiation requires determination of both promoter methylation and IHC protein expression.

 

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[443]

TÍTULO / TITLE:  - YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context.

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

REVISTA / JOURNAL:  - Mol Cancer Ther. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0901

AUTORES / AUTHORS:  - Jane EP; Premkumar DR; Didomenico JD; Hu B; Cheng SY; Pollack IF

INSTITUCIÓN / INSTITUTION:  - 1Neurosurgery, University of Pittsburgh.

RESUMEN / SUMMARY:  - Antiapoptotic proteins are commonly overexpressed in gliomas, contributing to therapeutic resistance. We recently reported that clinically achievable concentrations of the Bcl-2/Bcl-xL inhibitor ABT-737 failed to induce apoptosis in glioma cells, with persistent expression of survivin and Mcl-1. To address the role of these mediators in glioma apoptosis resistance, we analyzed the effects of YM-155, a survivin suppressant, on survival on a panel of glioma cell lines. YM-155 inhibited growth, and downregulated survivin and Mcl-1 in a dose- and cell line-dependent manner. Whereas U373, LN18, LNZ428, T98G, LN229, and LNZ308 cells  exhibited an IC50 of 10-75 nM, A172 cells were resistant (IC50 ~ 250 nM). No correlation was found between sensitivity to YM-155 and baseline expression of survivin or cIAP-1/cIAP-2/XIAP. However, strong correlation was observed between  EGFR activation levels and YM-155 response, which was confirmed using EGFR-transduced versus wild-type cells. Because we postulated that decreasing Mcl-1 expression may enhance glioma sensitivity to ABT-737, we examined whether cotreatment with YM-155 promoted ABT-737 efficacy. YM-155 synergistically enhanced ABT-737-induced cytotoxicity and caspase-dependent apoptosis. Down-regulation of Mcl-1 using shRNA also enhanced ABT-737-inducing killing, confirming an important role for Mcl-1 in mediating synergism between ABT-737 and YM-155. As with YM-155 alone, sensitivity to YM-155 and ABT-737 inversely correlated with EGFR activation status. However, sensitivity could be restored in highly resistant U87-EGFRvIII cells by inhibition of EGFR or its downstream pathways, highlighting the impact of EGFR signaling on Mcl-1 expression and the relevance of combined targeted therapies to overcome the multiple resistance mechanisms of these aggressive tumors.

 

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[444]

TÍTULO / TITLE:  - Treatment, prognostic factors, and outcomes in spinal cord astrocytomas.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos309

AUTORES / AUTHORS:  - Fakhreddine MH; Mahajan A; Penas-Prado M; Weinberg J; McCutcheon IE; Puduvalli V; Brown PD

INSTITUCIÓN / INSTITUTION:  - Baylor College of Medicine, Waco, Texas (M.H.F.); Department of Radiation Oncology (A.M., P.D.B.); Department of Neuro-oncology (M.P.-P., V.P); and Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (J.W., I.E.M.).

RESUMEN / SUMMARY:  - BackgroundSpinal astrocytomas are rare intramedullary CNS tumors for which there  is limited consensus on treatment; the importance of the extent of resection (EOR), postoperative radiotherapy, and chemotherapy remains poorly understood. We report on outcomes associated with surgery, postoperative radiotherapy, and chemotherapy in a series of patients treated at M. D. Anderson Cancer Center (MDACC) with the aim of elucidating the role of these treatments in spinal astrocytomas.MethodsWe retrospectively reviewed charts from a series of 83 patients with histologically confirmed spinal astrocytoma treated at MDACC during 1990-2011. Data collected included patient demographic characteristics, prognostic indicators, and treatment modality at diagnosis. We analyzed overall survival (OS) and progression-free survival (PFS) for pilocytic (World Health Organization [WHO] grade I) and infiltrative (WHO grades II, III, and IV) astrocytomas, separately. Multivariate analysis was performed for the infiltrative patients but not the pilocytic patients because of a limited number  of cases.ResultsHigher WHO grade among all patients was associated with worse OS  (P < .0001) and PFS (P = .0003). Among patients with infiltrative tumors, neither EOR nor radiotherapy was associated with a difference in outcomes in multivariate analysis; however, among patients with infiltrative astrocytomas, chemotherapy was significantly associated with improved PFS (hazard ratio = .22, P = .0075) but not OS (hazard ratio = .89, P = .83) in multivariate analysis.ConclusionWHO grade was the strongest prognostic indicator in patients with spinal cord astrocytomas. Our results also show that chemotherapy improved PFS in infiltrative astrocytomas in multivariate analysis, but neither EOR nor radiation therapy influenced outcomes in this group.

 

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[445]

TÍTULO / TITLE:  - The miR-183/96/182 Cluster Regulates Oxidative Apoptosis and Sensitizes Cells to  Chemotherapy in Gliomas.

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

REVISTA / JOURNAL:  - Curr Cancer Drug Targets. 2012 Dec 13.

AUTORES / AUTHORS:  - Tang H; Bian Y; Tu C; Wang Z; Yu Z; Liu Q; Xu G; Wu M; Li G

INSTITUCIÓN / INSTITUTION:  - Cancer Research Institute, Central South University, Changsha, Hunan, China.

RESUMEN / SUMMARY:  - Many microRNAs reside in clusters in the genome, are generally similar in sequence, are transcribed in the same direction, and usually function synergistically. The miR-183/96/182 cluster is composed of 3 miRNA genes, and increased expression of miR-183, 96 and 182 are implicated in glioma carcinogenesis. Knockdown of individual components or of the entire miR-183/96/182 cluster inhibits the survival of glioma cells by regulating the ROS-induced apoptosis pathway. Furthermore, inhibition of the miR-183/96/182 cluster induced ROS-mediated AKT/survival independent of three target genes FGF9, CPEB1, and FOXO1, and inhibition of the miRNA cluster induced p53/apoptosis signaling, which was dependent on these same genes. In addition, knockdown of the miR-183/96/182 cluster enhanced the anticancer effect of Temozolomide on glioma cells by the ROS-mediated apoptosis pathway. Therefore, the miR-183/96/182 cluster may be a pleiotropic target for glioma therapy.

 

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[446]

TÍTULO / TITLE:  - The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas.

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

REVISTA / JOURNAL:  - Cancer Cell. 2012 Dec 11;22(6):765-80. doi: 10.1016/j.ccr.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2012.11.005

AUTORES / AUTHORS:  - Binda E; Visioli A; Giani F; Lamorte G; Copetti M; Pitter KL; Huse JT; Cajola L; Zanetti N; DiMeco F; De Filippis L; Mangiola A; Maira G; Anile C; De Bonis P; Reynolds BA; Pasquale EB; Vescovi AL

INSTITUCIÓN / INSTITUTION:  - Department of Biotechnology and Biosciences, University of Milan Bicocca, 20126 Milan, Italy. elena.binda@unimib.it

RESUMEN / SUMMARY:  - In human glioblastomas (hGBMs), tumor-propagating cells with stem-like characteristics (TPCs) represent a key therapeutic target. We found that the EphA2 receptor tyrosine kinase is overexpressed in hGBM TPCs. Cytofluorimetric sorting into EphA2(High) and EphA2(Low) populations demonstrated that EphA2 expression correlates with the size and tumor-propagating ability of the TPC pool in hGBMs. Both ephrinA1-Fc, which caused EphA2 downregulation in TPCs, and siRNA-mediated knockdown of EPHA2 expression suppressed TPCs self-renewal ex vivo and intracranial tumorigenicity, pointing to EphA2 downregulation as a causal event in the loss of TPCs tumorigenicity. Infusion of ephrinA1-Fc into intracranial xenografts elicited strong tumor-suppressing effects, suggestive of  therapeutic applications.

 

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[447]

TÍTULO / TITLE:  - Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized 13C magnetic resonance spectroscopic imaging.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos319

AUTORES / AUTHORS:  - Park JM; Recht LD; Josan S; Merchant M; Jang T; Yen YF; Hurd RE; Spielman DM; Mayer D

INSTITUCIÓN / INSTITUTION:  - Department of Radiology (J.M.P., S.J., D.M.S., D.M.); Department of Electrical Engineering (J.M.P., D.M.S.); Department of Neurology and Neurological Sciences,  Stanford University, Stanford, California (L.D.R., M.M., T.J.); SRI International, Neuroscience Program, Menlo Park, California (S.J., D.M.); Applied Science Laboratory, GE Healthcare, Menlo Park, California (Y.F.Y., R.E.H.).

RESUMEN / SUMMARY:  - BackgroundThe metabolic phenotype that derives disproportionate energy via glycolysis in solid tumors, including glioma, leads to elevated lactate labeling  in metabolic imaging using hyperpolarized [1-(13)C]pyruvate. Although the pyruvate dehydrogenase (PDH)-mediated flux from pyruvate to acetyl coenzyme A can be indirectly measured through the detection of carbon-13 ((13)C)-labeled bicarbonate, it has proven difficult to visualize (13)C-bicarbonate at high enough levels from injected [1-(13)C]pyruvate for quantitative analysis in brain. The aim of this study is to improve the detection of (13)C-labeled metabolites, in particular bicarbonate, in glioma and normal brain in vivo and to measure the  metabolic response to dichloroacetate, which upregulates PDH activity.MethodsAn optimized protocol for chemical shift imaging and high concentration of hyperpolarized [1-(13)C]pyruvate were used to improve measurements of lactate and bicarbonate in C6 glioma-transplanted rat brains. Hyperpolarized [1-(13)C]pyruvate was injected before and 45 min after dichloroacetate infusion.  Metabolite ratios of lactate to bicarbonate were calculated to provide improved metrics for characterizing tumor metabolism.ResultsGlioma and normal brain were well differentiated by lactate-to-bicarbonate ratio (P = .002, n = 5) as well as  bicarbonate (P = .0002) and lactate (P = .001), and a stronger response to dichloroacetate was observed in glioma than in normal brain.ConclusionOur results clearly demonstrate for the first time the feasibility of quantitatively detecting (13)C-bicarbonate in tumor-bearing rat brain in vivo, permitting the measurement of dichloroacetate-modulated changes in PDH flux. The simultaneous detection of lactate and bicarbonate provides a tool for a more comprehensive analysis of glioma metabolism and the assessment of metabolic agents as anti-brain cancer drugs.

 

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[448]

TÍTULO / TITLE:  - Case of the month #180: atypical thalamic and mesencephalic neurocytoma-a rare neoplasm in children.

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

REVISTA / JOURNAL:  - Can Assoc Radiol J. 2013 Feb;64(1):74-6. doi: 10.1016/j.carj.2010.09.006.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.carj.2010.09.006

AUTORES / AUTHORS:  - Shuster A; Midia M

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Imaging, Hamilton General Hospital, Hamilton Health Science, McMaster University, Hamilton, Ontario, Canada. Electronic address: tshuster2000@yahoo.com.

 

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[449]

TÍTULO / TITLE:  - Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):172-88. doi: 10.1093/neuonc/nos298. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos298

AUTORES / AUTHORS:  - Miranda-Goncalves V; Honavar M; Pinheiro C; Martinho O; Pires MM; Pinheiro C; Cordeiro M; Bebiano G; Costa P; Palmeirim I; Reis RM; Baltazar F

INSTITUCIÓN / INSTITUTION:  - Corresponding Authors: Fatima Baltazar, PhD, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. fbaltazar@ecsaude.uminho.pt); Rui M. Reis, PhD, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal (rreis@ecsaude.uminho.pt.

RESUMEN / SUMMARY:  - Background Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples.  The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results MCT1, MCT4, and CD147 were overexpressed in  the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.

 

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[450]

TÍTULO / TITLE:  - Longitudinal in vivo monitoring of rodent glioma models through thinned skull using laser speckle contrast imaging.

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

REVISTA / JOURNAL:  - J Biomed Opt. 2012 Dec;17(12):126017. doi: 10.1117/1.JBO.17.12.126017.

            ●● Enlace al texto completo (gratuito o de pago) 1117/1.JBO.17.12.126017

AUTORES / AUTHORS:  - Rege A; Seifert AC; Schlattman D; Ouyang Y; Li KW; Basaldella L; Brem H; Tyler BM; Thakor NV

INSTITUCIÓN / INSTITUTION:  - Johns Hopkins University, Department of Biomedical Engineering, Baltimore, Maryland, USA.

RESUMEN / SUMMARY:  - Laser speckle contrast imaging (LSCI) is a contrast agent free imaging technique  suited for longitudinal assessment of vascular remodeling that accompanies brain  tumor growth. We report the use of LSCI to monitor vascular changes in a rodent glioma model. Ten rats are inoculated with 9L gliosarcoma cells, and the angiogenic response is monitored five times over two weeks through a thinned skull imaging window. We are able to visualize neovascularization and measure the number of vessels per unit area to assess quantitatively the microvessel density  (MVD). Spatial spread of MVD reveals regions of high MVD that may correspond to tumor location. Whole-field average MVD values increase with time in the tumor group but are fairly stable in the control groups. Statistical analysis shows significant differences in MVD values between the tumor group and both saline-receiving and unperturbed control groups over the two-week period (p<0.05). In conclusion, LSCI is suitable for investigation of tumor angiogenesis in rodent models. In addition, the statistical difference (p<0.02) between MVD values of the tumor (24.40 +/- 1.41) and control groups (15.40 +/- 1.60) on the 14th day after inoculation suggests a potential use of LSCI in the clinic in distinguishing tumor environments from normal vasculature.

 

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[451]

TÍTULO / TITLE:  - In vivo metabolism of tryptophan in meningiomas is mediated by indoleamine 2,3-dioxygenase 1.

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

REVISTA / JOURNAL:  - Cancer Biol Ther. 2013 Jan 28;14(4).

AUTORES / AUTHORS:  - Zitron IM; Kamson D; Kiousis S; Juhasz C; Mittal S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery; Wayne State University; Detroit, MI USA; Karmanos Cancer Institute; Detroit, MI USA.

RESUMEN / SUMMARY:  - Expression and activity of indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting step of the kynurenine pathway of tryptophan catabolism, can enable tumor cells to effectively evade the host’s immune response. The potential role of this system was investigated in meningiomas. Surgical specimens from 22 patients with meningiomas were used for cellular, immunological and molecular techniques (immunofluorescence, western blotting, RT-PCR and biochemical assay of enzyme activity) to investigate the expression and activity of IDO. In addition,  PET imaging was obtained preoperatively in 10 patients using the tracer alpha-[ ( 11) C]methyl-L-tryptophan (AMT) which interrogates the uptake and metabolism of tryptophan. Strong AMT accumulation was noted in all meningiomas by PET imaging indicating in vivo tryptophan uptake. Freshly-resected meningiomas expressed both LAT1, the tryptophan transporter system and IDO, demonstrating an active kynurenine pathway. Dissociated meningioma cells lost IDO expression. Following exposure to interferon-gamma (IFN-gamma), IDO expression was reinduced and could  be blocked by a selective IDO1 inhibitor. IDO activity may represent an element of local self-protection by meningiomas and could be targeted by emerging IDO1 inhibitors.

 

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[452]

TÍTULO / TITLE:  - Wnt/beta-catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):161-71. doi: 10.1093/neuonc/nos299. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos299

AUTORES / AUTHORS:  - Kim KH; Seol HJ; Kim EH; Rheey J; Jin HJ; Lee Y; Joo KM; Lee J; Nam DH

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Do-Hyun Nam, MD, PhD, Department of Neurosurgery, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, South Korea. nsnam@skku.edu); Jeongwu Lee, PhD, Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (leej7@ccf.org.

RESUMEN / SUMMARY:  - Background Glioblastoma (GBM) is the most lethal and common type of primary brain tumor. Recent evidence suggests that a subpopulation of GBM cells (glioblastoma stem cells [GSCs]) is critical for tumor progression, invasion, and therapeutic resistance. We and others have demonstrated that MET, a receptor tyrosine kinase, positively regulates the stemness phenotype and radioresistance of GSCs. Here, we interrogated the downstream effector pathways of MET signaling in GSCs. Methods We have established a series of GSCs and xenograft tumors derived from freshly dissociated specimens from patients with GBM and characterized a subpopulation enriched with MET activation (MET(high/+)). Through global expression profiling and subsequent pathways analysis, we identified signaling pathways that are enriched in MET(high/+) populations, one of which is Wnt/beta-catenin signaling pathway. To determine molecular interaction and the biological consequences of MET and Wnt/beta-catenin signaling, we used pharmacological and shRNA-mediated genetic inhibition and performed various molecular and cellular analyses, including flow cytometry, immunohistochemistry, and clonogenicity assays. Results We found that Wnt/beta-catenin signaling is highly active in MET(high/+) cells, compared with bulk tumor cells. We also showed that Wnt/beta-catenin signaling activities in GBM are directly modulated by the addition of ligand-mediated MET activation or MET inhibition. Furthermore, the ectopic expression of active-beta-catenin (S37A and S45Y) rescued the phenotypic effects caused by MET  inhibition. Conclusion These data suggest that Wnt/beta-catenin signaling is a key downstream effector of MET signaling and contributes to the maintenance of GSC and GBM malignancy.

 

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[453]

TÍTULO / TITLE:  - Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):189-97. doi: 10.1093/neuonc/nos305. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos305

AUTORES / AUTHORS:  - Chen PY; Ozawa T; Drummond DC; Kalra A; Fitzgerald JB; Kirpotin DB; Wei KC; Butowski N; Prados MD; Berger MS; Forsayeth JR; Bankiewicz K; James CD

INSTITUCIÓN / INSTITUTION:  - Corresponding author: C. David James, PhD, Department of Neurological Surgery, University of California San Francisco, 1450 Third Street, Room HD-283, San Francisco, CA, 94158. david.james@ucsf.edu.

RESUMEN / SUMMARY:  - Background Liposomal drug packaging is well established as an effective means for increasing drug half-life, sustaining drug activity, and increasing drug efficacy, whether administered locally or distally to the site of disease. However, information regarding the relative effectiveness of peripheral (distal)  versus local administration of liposomal therapeutics is limited. This issue is of importance with respect to the treatment of central nervous system cancer, for which the blood-brain barrier presents a significant challenge in achieving sufficient drug concentration in tumors to provide treatment benefit for patients. Methods We compared the anti-tumor activity and efficacy of a nanoliposomal formulation of irinotecan when delivered peripherally by vascular route with intratumoral administration by convection-enhanced delivery (CED) for  treating intracranial glioblastoma xenografts in athymic mice. Results Our results show significantly greater anti-tumor activity and survival benefit from  CED of nanoliposomal irinotecan. In 2 of 3 efficacy experiments, there were animal subjects that experienced apparent cure of tumor from local administration of therapy, as indicated by a lack of detectable intracranial tumor through bioluminescence imaging and histopathologic analysis. Results from investigating  the effectiveness of combination therapy with nanoliposomal irinotecan plus radiation revealed that CED administration of irinotecan plus radiation conferred greater survival benefit than did irinotecan or radiation monotherapy and also when compared with radiation plus vascularly administered irinotecan. Conclusions Our results indicate that liposomal formulation plus direct intratumoral administration of therapeutic are important for maximizing the anti-tumor effects of irinotecan and support clinical trial evaluation of this therapeutic plus route of administration combination.

 

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[454]

TÍTULO / TITLE:  - Demyelination after primary central nervous system lymphoma; reversed ‘sentinel’.

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

REVISTA / JOURNAL:  - Can J Neurol Sci. 2012 Nov;39(6):843-4.

AUTORES / AUTHORS:  - Barun B; Kinda S; Aurer I; Zarkovic K; Adamec I; Habek M

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, University Department of Neurology, University Hospital  Center Zagreb, Kispaticeva 12, HR-10000 Zagreb, Croatia.

 

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[455]

TÍTULO / TITLE:  - Suppression of Autophagy Enhanced Growth Inhibition and Apoptosis of Interferon-beta in Human Glioma Cells.

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

REVISTA / JOURNAL:  - Mol Neurobiol. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12035-013-8403-0

AUTORES / AUTHORS:  - Li Y; Zhu H; Zeng X; Fan J; Qian X; Wang S; Wang Z; Sun Y; Wang X; Wang W; Ju D

INSTITUCIÓN / INSTITUTION:  - Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai, 201203, China.

RESUMEN / SUMMARY:  - Interferon-beta (IFN-beta) is a cytokine with anti-viral, anti-proliferative, and immunomodulatory effects. In this study, we investigated the effects of IFN-beta  on the induction of autophagy and the relationships among autophagy, growth inhibition, and apoptosis induced by IFN-beta in human glioma cells. We found that IFN-beta induced autophagosome formation and conversion of microtubule associated protein 1 light chain 3 (LC3) protein, whereas it inhibited cell growth through caspase-dependent cell apoptosis. The Akt/mTOR signaling pathway was involved in autophagy induced by IFN-beta. A dose- and time-dependent increase of p-ERK ½ expression was also observed in human glioma cells treated  with IFN-beta. Autophagy induced by IFN-beta was suppressed when p-ERK1/2 was impaired by treatment with U0126. We also demonstrated that suppression of autophagy significantly enhanced growth inhibition and cell apoptosis induced by  IFN-beta, whereas inhibition of caspase-dependent cell apoptosis impaired autophagy induced by IFN-beta. Collectively, these findings indicated that autophagy induced by IFN-beta was associated with the Akt/mTOR and ERK ½ signaling pathways, and inhibition of autophagy could enhance the growth inhibitory effects of IFN-beta and increase apoptosis in human glioma cells. Together, these findings support the possibility that autophagy inhibitors may improve IFN-beta therapy for gliomas.

 

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[456]

TÍTULO / TITLE:  - MiR-218 sensitizes glioma cells to apoptosis and inhibits tumorigenicity by regulating ECOP-mediated suppression of NF-kappaB activity.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos296

AUTORES / AUTHORS:  - Xia H; Yan Y; Hu M; Wang Y; Wang Y; Dai Y; Chen J; Di G; Chen X; Jiang X

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China (H.X., M.H., Y.D., J.C., G.D., X.J.); Department of Neurology, Huzhou Central Hospital, Huzhou, China (Y.Y., Y.W.); Department of Respiratory Medicine, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China (Y.W.); Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China (X.C.).

RESUMEN / SUMMARY:  - IntroductionMalignant gliomas are the most common and deadly primary brain tumors in adults. Increasing evidence has indicated that microRNAs (miRNAs) have an influence on the regulation of apoptotic cell signaling. Downregulation of miRNA  218 (miR-218) has been indicated in human glioma specimens. Here, we investigate  the function of miR-218 in apoptosis and tumor growth of glioma cells.MethodsThe  expression of miR-218 was detected by real-time quantitative reverse transcriptase PCR. The effects of miR-218 on glioma cell proliferation and tumorigenicity were investigated by in vitro clonogenicity and in vivo xenograft  assay. Apoptosis was evaluated by flow cytometric analysis and assay by terminal  deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. The downstream targets of miR-218 were identified by bioinformatics analysis and further validated by Western blot and luciferase reporter assay.ResultsOverexpression of miR-218 induces glioma cell apoptosis and inhibits glioma cell viability, proliferation, and tumorigenicity. Epidermal growth factor receptor-coamplified and overexpressed protein (ECOP) was identified as a functional downstream target of miR-218, which can regulate transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and associated with apoptotic response. Ectopic expression of ECOP rescued the glioma cells from miR-218-induced apoptosis and increased NF-kappaB activity.ConclusionThese results suggest that miR-218 sensitizes glioma cells to  apoptosis by regulating ECOP-mediated suppression of NF-kappaB activity, which may provide novel opportunities for glioma therapy.

 

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[457]

TÍTULO / TITLE:  - Quantitative probabilistic functional diffusion mapping in newly diagnosed glioblastoma treated with radiochemotherapy.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos314

AUTORES / AUTHORS:  - Ellingson BM; Cloughesy TF; Lai A; Nghiemphu PL; Liau LM; Pope WB

INSTITUCIÓN / INSTITUTION:  - Department of Radiological Sciences (B.M.E., W.B.P.), Department of Biomedical Physics (B.M.E.), Department of Biomedical Engineering (B.M.E.), Department of Neurology (T.F.C., A.L., P.L.N.), and Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California (L.M.L.).

RESUMEN / SUMMARY:  - BackgroundFunctional diffusion mapping (fDM) is a cancer imaging technique that uses voxel-wise changes in apparent diffusion coefficients (ADC) to evaluate response to treatment. Despite promising initial results, uncertainty in image registration remains the largest barrier to widespread clinical application. The  current study introduces a probabilistic approach to fDM quantification to overcome some of these limitations.MethodsA total of 143 patients with newly diagnosed glioblastoma who were undergoing standard radiochemotherapy were enrolled in this retrospective study. Traditional and probabilistic fDMs were calculated using ADC maps acquired before and after therapy. Probabilistic fDMs were calculated by applying random, finite translational, and rotational perturbations to both pre-and posttherapy ADC maps, then repeating calculation of fDMs reflecting changes after treatment, resulting in probabilistic fDMs showing  the voxel-wise probability of fDM classification. Probabilistic fDMs were then compared with traditional fDMs in their ability to predict progression-free survival (PFS) and overall survival (OS).ResultsProbabilistic fDMs applied to patients with newly diagnosed glioblastoma treated with radiochemotherapy demonstrated shortened PFS and OS among patients with a large volume of tumor with decreasing ADC evaluated at the posttreatment time with respect to the baseline scans. Alternatively, patients with a large volume of tumor with increasing ADC evaluated at the posttreatment time with respect to baseline scans were more likely to progress later and live longer. Probabilistic fDMs performed  better than traditional fDMs at predicting 12-month PFS and 24-month OS with use  of receiver-operator characteristic analysis. Univariate log-rank analysis on Kaplan-Meier data also revealed that probabilistic fDMs could better separate patients on the basis of PFS and OS, compared with traditional fDMs.ConclusionsResults suggest that probabilistic fDMs are a more predictive biomarker in terms of 12-month PFS and 24-month OS in newly diagnosed glioblastoma, compared with traditional fDM analysis.

 

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[458]

TÍTULO / TITLE:  - Lack of BRAF V600E Protein Expression in Primary Central Nervous System Lymphoma.

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

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e3182688e59

AUTORES / AUTHORS:  - Berghoff AS; Capper D; Preusser M

INSTITUCIÓN / INSTITUTION:  - *Department of Neuropathology, Institute of Neurology daggerComprehensive Cancer  Center parallelDepartment of Medicine I, Medical University of Vienna, Vienna, Austria double daggerDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universitat Heidelberg section signClinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

RESUMEN / SUMMARY:  - BACKGROUND:: Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF), most commonly of the V600E type, are present in a variety of human malignancies including malignant melanoma, papillary thyroid cancers, and hairy-cell leukemia and specific therapeutically active BRAF inhibitors exist. We aimed to investigate BRAF V600E protein expression in primary central nervous system lymphoma (PCNSL). METHODS:: We investigated BRAF V600E expression in formalin-fixed and paraffin-embedded surgical tissue specimens of 20 immunocompetent patients with PCNSL using the mutation-specific monoclonal mouse  antibody VE1. RESULTS:: Ten male and 10 female patients with a median age of 60 years (range, 44 to 71 y) at time of operation were included. All cases were qualified as diffuse large B-cell lymphomas. None of the investigated cases demonstrated specific immunoreactivity for BRAF V600E mutation. CONCLUSIONS:: Our data provide evidence that the BRAF V600E mutation is not pathobiologically relevant in PCNSL and as a consequence is not a feasible drug target in this tumor type.

 

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[459]

TÍTULO / TITLE:  - Acute presentation of craniopharyngioma in children and adults in a Danish national cohort.

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

REVISTA / JOURNAL:  - Pituitary. 2012 Dec 8.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-012-0451-3

AUTORES / AUTHORS:  - Nielsen EH; Jorgensen JO; Bjerre P; Andersen M; Andersen C; Feldt-Rasmussen U; Poulsgaard L; Kristensen LO; Astrup J; Jorgensen J; Laurberg P

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Aalborg Hospital, Aarhus University Hospital, 9000,  Aalborg, Denmark, ehn@rn.dk.

RESUMEN / SUMMARY:  - We aimed to study the occurrence of acute-onset symptoms at initial presentation  in a national Danish cohort of patients with childhood- or adult-onset craniopharyngioma, and to investigate potential risk factors for acute presentation. Medical records of 189 consecutive patients (39 children, 150 adults) presenting with craniopharyngioma during the period 1985-2004 were reviewed, and data regarding initial symptoms, neuroimaging results, vision and pituitary function were systematically collected. Acute symptoms preceding hospital admission were noted. Subgroup analyses were based on age, gender and calendar year period. Potential risk factors for acute presentation were analysed through uni- and multivariate analyses. Acute symptoms were reported in 24 (13 %) patients. Acute visual symptoms, headache, nausea or vomiting were most frequently reported, and acute symptoms were more frequent among children (28 %)  than among adults (9 %) (P < 0.01). There were no differences according to sex or calendar year period. Hydrocephalus was present in half of childhood cases and one-fifth of adult patients (P < 0.001). Intra-tumour haemorrhage was seen in two cases. Acute symptoms were more frequent among patients with tumours occupying the third ventricle (P < 0.01), radiologic signs of calcification (P < 0.05) or hydrocephalus (P < 0.01). In multivariate analysis, however, only childhood onset (P < 0.05) and calcification (P < 0.05) were independent risk factors for acute presentation. Craniopharyngioma presented with acute symptoms in 13 % of patients. Childhood onset and radiologic signs of calcification were independent  risk factors for acute presentation. Intra-tumour haemorrhage was rare.

 

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[460]

TÍTULO / TITLE:  - Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos313

AUTORES / AUTHORS:  - Drucker KL; Paulsen AR; Giannini C; Decker PA; Blaber SI; Blaber M; Uhm JH; O’Neill BP; Jenkins RB; Scarisbrick IA

INSTITUCIÓN / INSTITUTION:  - Department of Physical Medicine and Rehabilitation (K.L.D., I.A.S.); Neurobiology of Disease Program (K.L.D., A.R.P., I.A.S.); Department of Laboratory Medicine and Pathology (C.G., R.B.J.); Biomedical Statistics and Informatics, Mayo Medical and Graduate School, Mayo Clinic, Rochester, Minnesota (P.A.D.); Department of Biomedical Sciences, Florida State University, Tallahassee, Florida (S.I.B., M.B.); Department of Neurology, Mayo Clinic, Rochester, Minnesota (J.H.U., B.P.O., I.A.S.).

RESUMEN / SUMMARY:  - BackgroundKallikreins have prognostic value in specific malignancies, but few studies have addressed their clinical significance to glioblastoma multiforme (GBM). Kallikrein 6 (KLK6) is of potential high relevance to GBM, since it is upregulated at sites of CNS pathology and linked to reactive astrogliosis. Here we examine the clinical value of KLK6 as a prognostic indicator of GBM patient survival and its activity in promoting resistance to cytotoxic agents.MethodsThe  association between patient survival and levels of KLK6 immunoreactivity were investigated in 60 grade IV astrocytoma tumor specimens. Levels of KLK6 RNA were  also evaluated in a separate set of GBM patient tumors (n = 23). Recombinant KLK6 or enforced KLK6 overexpression in GBM cell lines was used to evaluate effects on astrocytoma cell survival.ResultsA range of KLK6 expression was observed across grade IV tumors, with higher levels a poor prognostic indicator of patient survival (P = .02) even after adjusting for gender and Eastern Cooperative Oncology Group performance scores (P = .01). KLK6 reduced the sensitivity of GBM  cell lines to cytotoxic agents, including staurosporine and cisplatin, and to the current standard of patient care: radiotherapy or temozolomide alone or in combination. The ability of KLK6 to promote resistance to apoptosis was dependent on activation of the thrombin receptor, protease activated receptor 1.ConclusionsTaken together, these results indicate that elevated levels of KLK6  in GBM are likely to promote the resistance of tumor cells to cytotoxic agents and are an indicator of reduced patient postsurgical survival times.

 

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[461]

TÍTULO / TITLE:  - Endoscopic treatment of a third ventricle choroid plexus cyst.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12332.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12332

AUTORES / AUTHORS:  - de Lara D; Ditzel Filho LF; Muto J; Prevedello DM

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, The Ohio State University, Columbus, Ohio.

RESUMEN / SUMMARY:  - Choroid plexus cysts are frequent benign intraventricular lesions that infrequently cause symptoms, usually in the form of obstructive hydrocephalus. These instances are even less common in the adult population. When warranted, treatment seeks to reestablish cerebrospinal fluid flow and does not necessarily  require resection of the cyst itself. Hence, endoscopic exploration of the ventricles with subsequent cyst ablation is the current treatment of choice for these lesions. Herein we present the case of a 25-year-old female patient with a  3-week history of intermittent headaches. Investigation with computerized tomography (CT) of the head detected supratentorial hydrocephalus, with enlargement of the lateral and third ventricles. Magnetic resonance imaging revealed a homogeneous cystic lesion in the third ventricle. A right-sided, pre-coronal burr hole was carried out, followed by endoscopic exploration of the  ventricular system. A third-ventriclostomy was performed. With the aid of the 30-degrees endoscope, a cyst arising from the choroid plexus was visualized along the posterior portion of the third ventricle, obstructing the aqueduct opening. The cyst was cauterized until significant reduction of its dimensions was achieved and the aqueduct opening was liberated. Postoperative recovery was without incident and resolution of the hydrocephalus was confirmed by CT imaging. The patient reports complete improvement of her headaches and has been uneventfully followed since surgery. The video can be found here: http://youtu.be/XBtj_SqY07Q .

 

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[462]

TÍTULO / TITLE:  - On a Minimal Model for Hemodynamics and Metabolism of Lactate: Application to Low Grade Glioma and Therapeutic Strategies.

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

REVISTA / JOURNAL:  - Acta Biotheor. 2013 Jan 20.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10441-013-9174-8

AUTORES / AUTHORS:  - Lahutte-Auboin M; Guillevin R; Francoise JP; Vallee JN; Costalat R

INSTITUCIÓN / INSTITUTION:  - Groupe URM-IRM, Paris, France, marionlahutte@gmail.com.

RESUMEN / SUMMARY:  - WHO II low grade glioma evolves inevitably to anaplastic transformation. Magnetic resonance imaging is a good non-invasive way to watch it, by hemodynamic and metabolic modifications, thanks to multinuclear spectroscopy (1)H/(31)P. In this  work we study a multi-scale minimal model of hemodynamics and metabolism applied  to the study of gliomas. This mathematical analysis leads us to a fast-slow system. The control of the position of the stationary point brings to the concept of domain of viability. Starting from this system, the equations bring to light the parameters that push glioma cells out of their domain of viability. Four fundamental factors are highlighted. The first two are cerebral blood flow and the rate of lactate transport through monocarboxylate transporters, which must be reduced in order to push glioma out of its domain of viability. Another factor is the intra arterial lactate, which must be increased. The last factor is pH, indeed a decrease of intra cellular pH could interfere with glioma growth. These  reflections suggest that these four parameters could lead to new therapeutic strategies for the management of low grade gliomas.

 

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[463]

TÍTULO / TITLE:  - Treatment modalities for intractable epilepsy in hypothalamic hamartoma.

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

REVISTA / JOURNAL:  - Adv Tech Stand Neurosurg. 2012;39:117-30. doi: 10.1007/978-3-7091-1360-8_5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/978-3-7091-1360-8_5

AUTORES / AUTHORS:  - Choi JU; Kim DS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Sungnam,  Gyeonggi-do, Korea, juchoi@cha.ac.kr.

RESUMEN / SUMMARY:  - Hypothalamic hamartoma (HH) is usually associated with refractory epilepsy, cognitive impairment, and behavioral disturbance. There is now increasing evidence that HH can be treated effectively with a variety of neurosurgical approaches. Treatment options for intractable gelastic seizure in HH patients include direct open surgery with craniotomy, endoscopic surgery, radiosurgery with gamma knife (GKS) and stereotactic radiofrequency thermocoagulation. Selection of treatment modalities depends on type and size of the HH and the surgeon’s preference. Two surgical techniques, resection and disconnection, had been described with favorable outcomes. Pretreatment evaluation, patient selection, surgical techniques, complications, and possible selection of treatment are discussed in this chapter.

 

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[464]

TÍTULO / TITLE:  - Treatment of Paraneoplastic Cerebellar Degeneration.

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

REVISTA / JOURNAL:  - Curr Treat Options Neurol. 2013 Jan 13.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11940-012-0215-4

AUTORES / AUTHORS:  - Greenlee JE

INSTITUCIÓN / INSTITUTION:  - Clinical Neuroscience Center, University of Utah, 175 North Medical Drive East, Salt Lake City, UT, 84132, USA, john.greenlee@hsc.utah.edu.

RESUMEN / SUMMARY:  - OPINION STATEMENT: Paraneoplastic cerebellar degeneration is an uncommon autoimmune disorder characterized clinically by progressive, ultimately incapacitating ataxia and pathologically by destruction of cerebellar Purkinje cells, with variable loss of other cell populations. The disorder is most commonly associated with gynecological and breast carcinomas, small cell carcinoma of the lung, and Hodgkin’s disease and in most cases comes on prior to  identification of the underlying neoplasm. The hallmark of paraneoplastic cerebellar degeneration is the presence of an immune response reactive with intracellular proteins of Purkinje or other neurons or, less commonly, against neuronal surface antigens. Evidence-based treatment strategies for paraneoplastic cerebellar degeneration do not exist; and approaches to therapy are thus speculative. Diagnosis and treatment of the underlying neoplasm is critical, and  characterization of the antibody response involved may assist in tumor diagnosis. Most investigators have initiated treatment with corticosteroids, plasma exchange, or intravenous immunoglobulin G. Cyclophosphamide, tacrolimus, rituximab, or possibly mycophenolate mofetil may warrant consideration in patients who fail to stabilize or improve on less aggressive therapies. Plasma exchange has been of questionable benefit when used alone but should be considered at initiation of treatment to achieve rapid lowering of circulating paraneoplastic autoantibodies. Because the course of illness is one of relentless neuronal destruction, time is of the essence in initiating treatment. Likelihood  of clinical improvement in patients with longstanding symptoms and extensive neuronal loss is poor.

 

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[465]

TÍTULO / TITLE:  - Optic pathway gliomas in adolescence—time to challenge treatment choices?

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos312

AUTORES / AUTHORS:  - Lee Chong A; Pole JD; Scheinemann K; Hukin J; Tabori U; Huang A; Bouffet E; Bartels U

INSTITUCIÓN / INSTITUTION:  - Division of Haematology/Oncology, Paediatric Brain Tumour Program, The Hospital for Sick Children (A.L.C., U.T., A.H., E.B., U.B.); Pediatric Oncology Group of Ontario, Toronto, Canada (A.L.C., J.D.P.); Division of Haematology/Oncology, McMaster Children’s Hospital, Hamilton, Ontario, Canada (K.S.); Division of Haematology/Oncology, BC Children’s Hospital, Vancouver, British Columbia, Canada (J.H.).

RESUMEN / SUMMARY:  - BackgroundOptimal management of optic pathway/hypothalamic glioma (OPHG) remains  an ongoing challenge. Little is known about the natural history, management strategies, and outcomes in adolescents. Carboplatin-based chemotherapy is a useful modality in younger children, delaying radiation to their immature brains. National trials have focused on younger children and excluded adolescents from studies evaluating the role of chemotherapy.MethodsThis retrospective study describes clinical characteristics, treatment regimens, and outcomes in adolescents (aged >/=10 years) with OPHG (diagnosis during 1990-2006). Progression-free survival was compared with that in a cohort of younger children  (aged <10 years).ResultsThirty-three adolescents (19 females, 6 with neurofibromatosis type 1) with OPHG were identified within 2 Canadian pediatric oncology institutions. The majority presented with visual symptoms (82%). More than 55% (18 of 33) involved the posterior tract and/or hypothalamus (modified Dodge classification ¾). Seventeen were initially observed; 8 remained progression free. Of the 25 of 33 adolescents who required active treatment, 9 (36%) needed second-line therapy. The progression-free survival for any first active treatment at age <10 years (52 of 102) or >/=10 years (25 of 33) was similar (46.9 vs 46.8 months; P = .60). In those who received chemotherapy as first-line treatment or after prior nonchemotherapy treatment failure, the progression-free survival trend was superior (62.9 vs 38.9 months) in those aged  >/=10 years although not statistically significant (P = .16).ConclusionsChemotherapy is a valuable treatment modality for the achievement of disease control even in adolescents; their progression-free survival compares  favorably with that in younger children. We propose that chemotherapy be considered as a first-line modality in adolescents, avoiding potential radiation-associated morbidities.

 

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[466]

TÍTULO / TITLE:  - Anaplastic Oligodendroglioma: Advances and Treatment Options.

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

REVISTA / JOURNAL:  - Curr Treat Options Neurol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11940-013-0218-9

AUTORES / AUTHORS:  - McNamara MG; Sahebjam S; Mason WP

INSTITUCIÓN / INSTITUTION:  - Pencer Brain Tumor Centre, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.

RESUMEN / SUMMARY:  - OPINION STATEMENT: The optimal treatment strategy for anaplastic oligodendroglial (AO) tumors is evolving. Molecular profiling of oligodendrogliomas have shown distinctive genetic patterns characterized by combined deletions of chromosome arms 1p and 19q, O(6)-methylguanine methyltransferase (MGMT) methylation, and isocitrate dehydrogenase 1 (IDH1) mutations; they are all prognostic factors for  patients with AO. In addition, a strong association has also been found between the CpG island hypermethylation phenotype (CIMP) status and MGMT promoter methylation. Long term follow up data of the Radiation Therapy Oncology Group (RTOG) 9402 and the European Organisation for Research and Treatment of Cancer (EORTC) 26951 studies demonstrate clear evidence that for patients with codeleted 1p19q AO, early chemotherapy with radiation offers a significant improvement in overall survival compared with early radiation, even with salvage chemotherapy at tumor relapse, and thus establishes the 1p19q allelic loss as a predictive marker distinct from tumors without the chromosome change. Radiotherapy alone is no longer considered an adequate treatment for this patient population. In cases with no 1p19q deletion, most neuro-oncologists recommend incorporating radiotherapy into the upfront treatment strategy. However, there are still unanswered questions regarding whether upfront chemotherapy, omitting/deferring radiotherapy, in the desire to avoid late neurocognitive toxicity of radiotherapy should be the initial therapy for AO tumors with codeleted 1p19q, or whether temozolomide, an oral agent with a better toxicity profile, can be substituted for procarbazine, lomustine, and vincristine (PCV). Further studies are warranted and the increasing understanding of molecular pathways involved may lead to more  selective therapeutic targets in the future.

 

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[467]

TÍTULO / TITLE:  - Recent therapeutic advances and insights of recurrent glioblastoma multiforme .

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

REVISTA / JOURNAL:  - Front Biosci. 2013 Jan 1;18:676-84.

AUTORES / AUTHORS:  - Chen J; Xu T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, China, 200003.

RESUMEN / SUMMARY:  - Despite recent therapeutic advances, most patients with glioblastoma multiforme (GBM) experience disease recurrence, with very poor prognosis. Much work still needs to done to improve the treatment efficacy. The optimal management of patients with recurrent GBM is still controversial. This article summarizes the current status of therapeutic strategies in recurrent glioblastoma patients, with an emphasis on more novel approaches and important recent progress. The clinical  evidence of current treatment strategies were collected and reviewed. Patients still need comprehensive treatment for recurrent GBM. Surgery may be useful as adjuvant treatment for patients with symptoms due to the effect of the mass or for patients requiring definitive histopathology, but it generally should be combined with another treatment modality; high-precision re-irradiation such as stereotactic radiosurgery or gamma knife is another option. Chemotherapy like fotemustine, or a metronomic schedule of temozolomide regimens and anti-angiogenic agents like bevacizumab could also be considered. Other targeted  molecular inhibitors or anti-angiogenic therapies, and immunotherapies are still  under investigation and their efficacy needs to be evaluated further in the future.

 

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[468]

TÍTULO / TITLE:  - Evaluation of 3’-deoxy-3’-[(18)F]-fluorothymidine ( (18)F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2013 Jan;40(2):175-85. doi: 10.1007/s00259-012-2275-9. Epub 2012 Nov 15.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2275-9

AUTORES / AUTHORS:  - Shinomiya A; Kawai N; Okada M; Miyake K; Nakamura T; Kushida Y; Haba R; Kudomi N; Yamamoto Y; Tokuda M; Tamiya T

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Kagawa University Faculty of Medicine, 1750-1 Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

RESUMEN / SUMMARY:  - PURPOSE: The thymidine analog 3’-deoxy-3’-[(18)F]fluorothymidine ((18)F-FLT) has  been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of (18)F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood-brain  barrier (BBB) breakdown in human brain gliomas. METHODS: A total of 21 patients with newly diagnosed gliomas were examined by (18)F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of (18)F-FLT in the tumor and (18)F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. RESULTS: (18)F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K (1); P = 0.001 and P < 0.001, respectively), but not with the phosphorylation rate constant (k (3)). IHC and real-time PCR studies demonstrated a significant correlation between K (1) and TK-1 mRNA expression (P = 0.001), but not between k (3) and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K (1) and the Ki-67 index (P  = 0.003), but not between k (3) and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). (18)F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast  enhancement in MR images (P = 0.003 and P = 0.011, respectively). CONCLUSION: These results indicate that (18)F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation rate constant k (3) determined by (18)F-FLT PET kinetic analysis does not accurately reflect TK-1 expression in the tissue and should not be used as a surrogate biomarker of cell proliferation activity in human brain gliomas.

 

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[469]

TÍTULO / TITLE:  - Use of mobile phones and cordless phones is associated with increased risk for glioma and acoustic neuroma.

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

REVISTA / JOURNAL:  - Pathophysiology. 2012 Dec 20. pii: S0928-4680(12)00110-1. doi: 10.1016/j.pathophys.2012.11.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.pathophys.2012.11.001

AUTORES / AUTHORS:  - Hardell L; Carlberg M; Hansson Mild K

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, University Hospital, SE-701 85 Orebro, Sweden. Electronic address: lennart.hardell@orebroll.se.

RESUMEN / SUMMARY:  - The International Agency for Research on Cancer (IARC) at WHO evaluation of the carcinogenic effect of RF-EMF on humans took place during a 24-31 May 2011 meeting at Lyon in France. The Working Group consisted of 30 scientists and categorised the radiofrequency electromagnetic fields from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields (RF-EMF), as Group 2B, i.e., a ‘possible’, human carcinogen. The decision on mobile phones was based mainly on the Hardell group of studies from Sweden and the IARC Interphone study. We give an overview of current epidemiological evidence for an increased risk for brain tumours including a meta-analysis of the Hardell group and Interphone results for mobile phone use. Results for cordless phones are lacking in Interphone. The meta-analysis gave for glioma in the most exposed part of the brain, the temporal lobe, odds ratio (OR)=1.71, 95% confidence interval (CI)=1.04-2.81 in the >/=10 years (>10 years in the Hardell group) latency group. Ipsilateral mobile phone use >/=1640h in total gave OR=2.29, 95% CI=1.56-3.37. The results for meningioma were OR=1.25, 95% CI=0.31-4.98 and OR=1.35, 95% CI=0.81-2.23, respectively. Regarding acoustic neuroma ipsilateral mobile phone use in the latency group >/=10 years gave OR=1.81, 95% CI=0.73-4.45. For ipsilateral cumulative use >/=1640h OR=2.55, 95% CI=1.50-4.40 was obtained. Also use of cordless phones increased the risk for glioma and acoustic neuroma in the Hardell group studies. Survival of patients with glioma was analysed in the Hardell group studies yielding in the >10 years latency period hazard ratio (HR)=1.2, 95% CI=1.002-1.5 for use of wireless phones. This increased HR was based on results for astrocytoma WHO grade IV (glioblastoma multiforme). Decreased HR was found for low-grade astrocytoma, WHO  grades I-II, which might be caused by RF-EMF exposure leading to tumour-associated symptoms and earlier detection and surgery with better prognosis. Some studies show increasing incidence of brain tumours whereas other  studies do not. It is concluded that one should be careful using incidence data to dismiss results in analytical epidemiology. The IARC carcinogenic classification does not seem to have had any significant impact on governments’ perceptions of their responsibilities to protect public health from this widespread source of radiation.

 

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[470]

TÍTULO / TITLE:  - Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan;15(1):122-9. doi: 10.1093/neuonc/nos282. Epub 2012 Dec 9.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos282

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

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Dr. Alasdair Rooney, MBChB, BMSc, Edinburgh Centre for Neuro-Oncology, Western General Hospital, Edinburgh, UK. a.rooney@nhs.net.

RESUMEN / SUMMARY:  - No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire-9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We  conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or “watchful waiting.” At each of 3 interviews over a 6-month period,  patients completed the screening questionnaires and received a structured clinical interview to diagnose MDD. Internal consistency, area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value, and positive likelihood ratio were calculated. A maximum of 154 patients completed the DT, 133 completed the HAD-D, and 129 completed the PHQ-9.  The HAD-D and PHQ-9 showed good internal consistency (alpha >/= 0.77 at all timepoints). Median AUCs were 0.931 +/- 0.074 for the HAD-D and 0.915 +/- 0.055 for the PHQ-9. The optimal threshold was 7+ for the HAD-D, but 8+ had similar operating characteristics. There was no consistently optimal PHQ-9 threshold, but 10+ was optimal in the largest sample. The DT was inferior to the multi-item instruments. Clinicians can screen for depression in well-functioning glioma patients using the HAD-D at the existing recommended lower threshold of 8+, or the PHQ-9 at a threshold of 10+. Due to a modest positive predictive value of either instrument, patients scoring above these thresholds need a clinical assessment to diagnose or exclude depression.

 

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[471]

TÍTULO / TITLE:  - Genetic and pathologic evolution of early secondary gliosarcoma.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0132-y

AUTORES / AUTHORS:  - Codispoti KE; Mosier S; Ramsey R; Lin MT; Rodriguez FJ

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Johns Hopkins University, Baltimore, USA.

RESUMEN / SUMMARY:  - Gliosarcoma is a subset of glioblastoma with glial and mesenchymal components. True secondary gliosarcomas (i.e. progressing from lower-grade precursors) in the absence of radiation therapy are very rare. We report the unique case of a 61-year-old male who developed a fibrillary astrocytoma (WHO grade II). In the absence of adjuvant therapy the tumor recurred 3 years later as a gliosarcoma comprising an infiltrating glial component and a curious, early high-grade sarcomatous component surrounding intratumoral vessels. DNA was extracted from formalin fixed paraffin-embedded tissues from the precursor low-grade glioma and  from the glioma and sarcomatous components at progression. Samples were hybridized separately to a 300 k Illumina SNP array. IDH1(R132H) mutant protein immunohistochemistry was positive in all tissue components. Alterations identified in all samples included dup(1)(q21q41), del(1)(q41qter), del(2)(q31.1), del(2)(q36.3qter), del(4)(q35.1qter), dup(7)(q22.2q36.3), del(7)(q36.3qter), del(9)(p21.3pter), dup(10)(p13pter), del(10)(q26.13q26.3), dup(17) (q12qter), and copy neutral LOH(20)(p11.23p11.21). The recurrent tumor had additional alterations, including del(3)(p21.31q13.31), del(18)(q21.2qter), and a homozygous del(9)(p21.3)(CDKN2A locus) and the sarcoma component had, in addition, del(4)(p14pter), del(6)(q12qter), del(11)(q24.3qter), and del(16)(p11.2pter). In conclusion, unique copy number alterations were identified during tumor progression from a low-grade glioma to gliosarcoma. A subset of alterations developed specifically in the sarcomatous component.

 

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[472]

TÍTULO / TITLE:  - Children’s Oncology Group’s 2013 blueprint for research: Central nervous system tumors.

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

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2012 Dec 19. doi: 10.1002/pbc.24427.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24427

AUTORES / AUTHORS:  - Gajjar A; Packer RJ; Foreman NK; Cohen K; Haas-Kogan D; Merchant TE

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee. amar.gajjar@stjude.org.

RESUMEN / SUMMARY:  - In the US, approximately 2,500 children are diagnosed annually with brain tumors. Their survival ranges from >90% to <10%. For children with medulloblastoma, the most common malignant brain tumor, 5-year survival ranges from >80% (standard-risk) to 60% (high-risk). For those with high-grade gliomas (HGGs) including diffuse intrinsic pontine gliomas, 5-year survival remains <10%. Sixty-five percent patients with ependymoma are cured after surgery and radiation therapy depending on the degree of resection and histopathology of the tumor. Phase II trials for brain tumors will investigate agents that act on cMET, PDGFRA, or EZH2 in HGG, DIPG, or medulloblastoma, respectively. Phase III trials  will explore risk-based therapy stratification guided by molecular and clinical traits of children with medulloblastoma or ependymoma. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

 

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[473]

TÍTULO / TITLE:  - DNA methylation profiling of medulloblastoma allows robust subclassification and  improved outcome prediction using formalin-fixed biopsies.

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

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Jan 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-012-1077-2

AUTORES / AUTHORS:  - Schwalbe EC; Williamson D; Lindsey JC; Hamilton D; Ryan SL; Megahed H; Garami M; Hauser P; Dembowska-Baginska B; Perek D; Northcott PA; Taylor MD; Taylor RE; Ellison DW; Bailey S; Clifford SC

INSTITUCIÓN / INSTITUTION:  - Northern Institute for Cancer Research, Newcastle University, Sir James Spence Institute Level 5, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.

RESUMEN / SUMMARY:  - Molecular subclassification is rapidly informing the clinical management of medulloblastoma. However, the disease remains associated with poor outcomes and therapy-associated late effects, and the majority of patients are not characterized by a validated prognostic biomarker. Here, we investigated the potential of epigenetic DNA methylation for disease subclassification, particularly in formalin-fixed biopsies, and to identify biomarkers for improved  therapeutic individualization. Tumor DNA methylation profiles were assessed, alongside molecular and clinical disease features, in 230 patients primarily from the SIOP-UKCCSG PNET3 clinical trial. We demonstrate by cross-validation in frozen training and formalin-fixed test sets that medulloblastoma comprises four  robust DNA methylation subgroups (termed WNT, SHH, G3 and G4), highly related to  their transcriptomic counterparts, and which display distinct molecular, clinical and pathological disease characteristics. WNT patients displayed an expected favorable prognosis, while outcomes for SHH, G3 and G4 were equivalent in our cohort. MXI1 and IL8 methylation were identified as novel independent high-risk biomarkers in cross-validated survival models of non-WNT patients, and were validated using non-array methods. Incorporation of MXI1 and IL8 into current survival models significantly improved the assignment of disease risk; 46 % of patients could be classified as ‘favorable risk’ (>90 % survival) compared to 13  % using current models, while the high-risk group was reduced from 30 to 16 %. DNA methylation profiling enables the robust subclassification of four disease subgroups in frozen and routinely collected/archival formalin-fixed biopsy material, and the incorporation of DNA methylation biomarkers can significantly improve disease-risk stratification. These findings have important implications for future risk-adapted clinical disease management.

 

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[474]

TÍTULO / TITLE:  - Personalized Medicine for Glioblastoma: Current Challenges and Future Opportunities.

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

REVISTA / JOURNAL:  - Curr Mol Med. 2013 Jan 15.

AUTORES / AUTHORS:  - Zhu JJ; Wong ET

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Center & Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. ewong@bidmc.harvard.edu.

RESUMEN / SUMMARY:  - The failure to control glioblastoma progression is a major challenge for neuro-oncologists. Emerging data indicate that genetic and epigenetic heterogeneities within tumor cells play a dominant role in the development of resistant disease. These heterogeneities develop because driver mutations enable  the proliferation of certain clones of transformed cells within the tumor microenvironment while pre-existing passenger or secondary mutations emerge from  the clonal selection process during treatment. In addition, epigenetic changes provide another means of modifying the existing heterogeneous genetic background  of tumor cells. These cumulative changes create challenges for the detection, characterization and treatment of glioblastomas, but new opportunities allow the  development of advanced diagnostic modalities and individualized therapies. Furthermore, mutations in the epidermal growth factor receptor (EGFR) alter binding capability to targeted agents like erlotinib, rendering it inactive to block EGFR signaling. Receptor class switching and tyrosine kinase decoupling from cell cycle machineries are also mechanisms that can render tumor cells resistant to EGFR blockade. Therefore, effective therapy most likely requires the combination of personalized medicine treatment offered by targeted drugs and less specific therapies that aim at other processes within the tumor microenvironment. The goal is to take advantage of the specificity offered by targeted drugs to block proliferation of tumor cells harboring driver mutations while less specific treatments can be used against cells with passenger mutations.

 

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[475]

TÍTULO / TITLE:  - Erratum for “Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma”.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan;15(1):131. doi: 10.1093/neuonc/nos311.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos311

 

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[476]

TÍTULO / TITLE:  - Prevalence and incidence of pituitary adenomas: a population based study in Malta.

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

REVISTA / JOURNAL:  - Pituitary. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-012-0454-0

AUTORES / AUTHORS:  - Gruppetta M; Mercieca C; Vassallo J

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, Msida, MSD2090, Malta.

RESUMEN / SUMMARY:  - Epidemiological data is important to correctly quantify the extent of disease and needed health care resources. The aim of the study was to establish the prevalence and incidence of pituitary adenomas (PAs) in the same well defined population, with in-depth analysis of the various subtypes. The design involved a retrospective cross-sectional analysis of PA patients diagnosed prior to 31 July  2011 for prevalence estimates and those diagnosed between July 2000 and July 2011 for incidence estimation. A thorough search for patients with PAs was carried out in central hospital registries including outpatients departments, surgical registries, radiological department and specialty clinic databases. Prevalence rates/100,000 and Standardised incidence ratios (SIR)/100,000/year were worked out. The respective prevalence rates and SIR for PAs overall were 75.7/100,000, and 4.27/100,000/year, for Prolactinomas 35.0/100,000 and 2.05/100,000/year, for  nonfunctioning PA 25.9/100,000 and 1.79/100,000/year and for GH-secreting PAs 12.5/100,000 and 0.31/100,000/year. The overall prevalence for macroadenomas was  32.8/100,000 and SIR was 1.49/100,000/year. The prevalence rate in males for PAs  overall was 46.3/100,000 and SIR was 2.08/100,000/year and in females 104.8/100,000 and SIR was 6.58/100,000/year. Females had a lower proportion of macroadenomas than males (29.5 vs. 75.0 %; P < 0.001) and macroadenomas tended to present at a later age compared to microadenomas (48 vs. 34.5; P < 0.001). The highest SIR was reached in the 30-39 age group at 7.42/100,000/year. Our data confirm the considerable disease burden that PAs bear on health care resources. Males and females have similar prevalence and SIR rates for macroadenomas but there is a significant increase in SIR in females of child bearing age compared to males. These observations may have important implications in terms of the economic burden and need for early intervention.

 

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[477]

TÍTULO / TITLE:  - Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

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

REVISTA / JOURNAL:  - J Biomed Opt. 2012 Dec;17(12):126004. doi: 10.1117/1.JBO.17.12.126004.

            ●● Enlace al texto completo (gratuito o de pago) 1117/1.JBO.17.12.126004

AUTORES / AUTHORS:  - Fortin PY; Genevois C; Koenig A; Heinrich E; Texier I; Couillaud F

INSTITUCIÓN / INSTITUTION:  - Universite Bordeaux Segalen, Laboratoire IMF, CNRS/UMR 5231, Universite Bordeaux  2, France.

RESUMEN / SUMMARY:  - Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to  localize tumors in mice using fluorescent nanoparticles as a blood pool contrast  agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice  bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using  bioluminescent imaging, and tumor localization is further determined by magnetic  resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

 

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[478]

TÍTULO / TITLE:  - Management of children with brain tumors in Paraguay.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):235-41. doi: 10.1093/neuonc/nos291. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos291

AUTORES / AUTHORS:  - Baskin JL; Lezcano E; Kim BS; Figueredo D; Lassaletta A; Perez-Martinez A; Madero L; Caniza MA; Howard SC; Samudio A; Finlay JL

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Jacquelyn Baskin, MD, 4650 Sunset Blvd, MS #54, Los Angeles, CA 90027. jbaskin@chla.usc.edu.

RESUMEN / SUMMARY:  - Background Cure rates among children with brain tumors differ between low-income  and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country. Methods Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asuncion and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death. Results All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities. Conclusions National and center-specific deficiencies in resources to manage pediatric brain  tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain  tumor programs in other low- and middle-income countries.

 

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[479]

TÍTULO / TITLE:  - Pituitary adenomas in childhood and adolescence with a focus on intratumoral hemorrhage.

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

REVISTA / JOURNAL:  - Pituitary. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-012-0456-y

AUTORES / AUTHORS:  - Kinoshita Y; Tominaga A; Usui S; Arita K; Sakoguchi T; Sugiyama K; 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.

RESUMEN / SUMMARY:  - Pituitary adenomas in childhood and adolescence are relatively rare. In the present study we investigated intratumoral hemorrhage in pituitary adenomas and examined cases of intratumoral hemorrhage using adult patients for comparison. From 1975 to 2012, 38 consecutive patients operated for pituitary adenoma and one patient treated with medication alone, were enrolled in this study. Their ages were less than 18 years old at the initial diagnosis (mean age 15.3 +/- 2.9 years). The comparison group consisted of 209 consecutive adult patients (>18 years old). The incidence and characteristics of intratumoral hemorrhage in pituitary adenomas were evaluated, based on magnetic resonance imaging (MRI) findings (28 cases) and on operative findings. The incidence of pituitary adenomas in childhood and adolescence was 38/1,073 (3.5 %) patients operated. Functioning pituitary adenomas (82.1 %) were common and non-functioning pituitary adenomas (17.9 %) were rare. Although no significant difference in tumor size was found and Knosp grade did not differ between young (</=18 years old) and adult (>18 years old) patients, indications of intratumoral hemorrhage on MRI was common in young patients (42.9 %). Based on both MRI and operative findings, intratumoral hemorrhage was significantly more likely to occur in young patients, compared with adult patients.

 

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[480]

TÍTULO / TITLE:  - Erratum for “Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma—a Pediatric Brain Tumor Consortium study”.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan;15(1):132. doi: 10.1093/neuonc/nos318.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos318

 

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[481]

TÍTULO / TITLE:  - CRX/OTX3: A Useful Marker in the Differential Diagnosis of Tumors of the Pineal Region and Indicator of Photoreceptor Differentiation in Medulloblastomas and Atypical Teratoid Rhabdoid Tumors.

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

REVISTA / JOURNAL:  - Appl Immunohistochem Mol Morphol. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e3182649dad

AUTORES / AUTHORS:  - Gielen GH; Gessi M; Denkhaus D; Pietsch T

INSTITUCIÓN / INSTITUTION:  - Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.

RESUMEN / SUMMARY:  - CRX (OTX3) is a transcription factor of the OTX homeobox family, whose expression and function is essential for the development and differentiation of retinal and  pineal cells. Among human cancers, CRX seems to be selectively expressed only by  retinoblastomas and pineal tumors. In our immunohistochemical analysis, performed on 89 primary and metastatic central nervous system tumors, we found that CRX is  strongly expressed by normal pineal tissue as well as by pineal parenchymal tumors. Other than pineal tumors, we observed CRX positivity not only in a few medulloblastomas but also in atypical teratoid/rhabdoid tumors and in small cell  lung carcinoma metastasis, in which photoreceptor differentiation has not been reported so far. In conclusion, CRX could represent a potential routine immunohistochemical marker in surgical neuropathology for the differential diagnosis of tumors of the pineal region. However, owing to the significant percentage of negative cells in some pineal tumors of our series, CRX negativity  does not definitively rule out the diagnosis of a pineal parenchymal tumor, particularly in case of small biopsy specimens.

 

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[482]

TÍTULO / TITLE:  - WEE1 Kinase Inhibition Enhances the Radiation Response of Diffuse Intrinsic Pontine Gliomas.

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

REVISTA / JOURNAL:  - Mol Cancer Ther. 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0735

AUTORES / AUTHORS:  - Caretti V; Hiddingh L; Lagerweij T; Schellen P; Koken PW; Hulleman E; van Vuurden DG; Vandertop WP; Kaspers GJ; Noske DP; Wurdinger T

INSTITUCIÓN / INSTITUTION:  - 1Neurosurgery, VU University Medical Center-Cancer Center Amsterdam.

RESUMEN / SUMMARY:  - Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric disease. Thus far no therapeutic agent has proven beneficial in the treatment of this malignancy. Hence, conventional DNA-damaging radiotherapy (RT) remains the standard treatment, providing transient neurological improvement without improving probability of overall survival. During RT, WEE1 kinase controls the G2 cell cycle checkpoint allowing for repair of irradiation (IR)-induced DNA damage. Here we show that WEE1 kinase is one of the highest overexpressed kinases in primary DIPG tissues as compared to matching non-neoplastic brain tissues. Inhibition of  WEE1 by MK-1775 treatment of DIPG cells inhibited the IR-induced WEE1-mediated phosphorylation of CDC2, resulting in reduced G2/M arrest and decreased cell viability. Finally, we demonstrate that MK-1775 enhances the radiation response of E98-Fluc-mCherry DIPG mouse xenografts. Altogether, these results show that inhibition of WEE1 kinase in conjunction with RT holds potential as a therapeutic approach for the treatment of DIPG.

 

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[483]

TÍTULO / TITLE:  - Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum,  and thalamus of the rat.

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

REVISTA / JOURNAL:  - Anal Bioanal Chem. 2013 Jan 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00216-012-6638-7

AUTORES / AUTHORS:  - Kaplan KA; Chiu VM; Lukus PA; Zhang X; Siems WF; Schenk JO; Hill HH Jr

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry, Washington State University, Pullman, WA, 99164, USA, kim.kaplan@email.wsu.edu.

RESUMEN / SUMMARY:  - We report results of studies of global and targeted neuronal metabolomes by ambient pressure ion mobility mass spectrometry. The rat frontal cortex, striatum, and thalamus were sampled from control nontreated rats and those treated with acute cocaine or pargyline. Quantitative evaluations were made by standard additions or isotopic dilution. The mass detection limit was approximately 100 pmol varying with the analyte. Targeted metabolites of dopamine, serotonin, and glucose followed the rank order of distribution expected between the anatomical areas. Data was evaluated by principal component analysis  on 764 common metabolites (identified by m/z and reduced mobility). Differences between anatomical areas and treatment groups were observed for 53 % of these metabolites using principal component analysis. Global and targeted metabolic differences were observed between the three anatomical areas with contralateral differences between some areas. Following drug treatments, global and targeted metabolomes were found to shift relative to controls and still maintained anatomical differences. Pargyline reduced 3,4-dihydroxyphenylacetic acid below detection limits, and 5-HIAA varied between anatomical regions. Notable findings  were: (1) global metabolomes were different between anatomical areas and were altered by acute cocaine providing a broad but targeted window of discovery for metabolic changes produced by drugs of abuse; (2) quantitative analysis was demonstrated using isotope dilution and standard addition; (3) cocaine changed glucose and biogenic amine metabolism in the anatomical areas tested; and (4) the largest effect of cocaine was on the glycolysis metabolome in the thalamus confirming inferences from previous positron emission tomography studies using 2-deoxyglucose.

 

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[484]

TÍTULO / TITLE:  - Local Perspective On A Rare Brain Tumour: Adult Medulloblastoma.

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

REVISTA / JOURNAL:  - Intern Med J. 2012 Dec 24. doi: 10.1111/imj.12060.

            ●● Enlace al texto completo (gratuito o de pago) 1111/imj.12060

AUTORES / AUTHORS:  - Wong SF; Mak G; Rosenthal MA; Cher L; Gan H

INSTITUCIÓN / INSTITUTION:  - Royal Melbourne Hospital.

RESUMEN / SUMMARY:  - BACKGROUND: Little contemporary data is available regarding Australian patterns of care in adult medulloblastoma. It is unclear whether treatment, extrapolated from paediatric protocols despite known differences between the two groups, results in comparable efficacy. AIMS: To perform a retrospective review of patterns of care in adult medulloblastoma, especially with respect to adjuvant chemotherapy, in Australian patients. METHODS: All medulloblastoma patients aged  15 years or older, at two neuro-oncology institutions, were identified from January 1995 - May 2011. Patients with supratentorial or peripheral tumours were  excluded. Standardised data were extracted from each institution regarding symptoms, disease staging, treatments received, toxicities and survival outcomes. RESULTS: Seventeen eligible patients were identified. Median age was 37 years (range 20 - 67 years). All had good performance status (ECOG 0-1). There were 11  standard-risk de novo patients, three high-risk de novo patients and three patients with recurrent disease. Median overall survival (OS) had not been reached for standard-risk patients with median follow up of 58 months. The median OS for high-risk de novo patients was 21 months whilst the median OS was 15 months for patients with recurrent disease. Treatment was well tolerated, with haematological toxicities being most common. CONCLUSIONS: Combined modality therapy (surgery followed by post-operative radiotherapy and adjuvant chemotherapy) was well tolerated and associated with good outcomes in standard-risk de novo patients. High-risk and recurrent disease patients do extremely poorly regardless of treatment and better treatment strategies are needed in these patients.

 

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[485]

TÍTULO / TITLE:  - Microsurgical resection of giant intraventricular meningioma.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12352.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12352

AUTORES / AUTHORS:  - Liu JK

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and Otolaryngology-Head and Neck Surgery, Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey.

RESUMEN / SUMMARY:  - Intraventricular meningiomas are rare tumors, accounting for approximately 0.5 to 3% of all intracranial meningiomas. The majority arise in the atrium of the lateral ventricle. The surgical management of these tumors remains a considerable challenge because of their deep location and proximity to critical structures. Complete resection, if safely possible, should be the goal of surgery since this  results in the best rates of local control. Although various approaches exist to  access the lateral ventricular system, selection of the optimal approach should be individualized to the patient based upon the location of the tumor within the  ventricle, the tumor size, the origin of the vascular supply to the tumor, and the relationship to neighboring neurovascular structures at risk. In this operative video manuscript, the author demonstrates an illustrative step-by-step  technique for microsurgical resection of a giant intraventricular meningioma of the left atrium via a transcortical parieto-occipital approach. The patient illustrated in this video presented with a large recurrent meningioma (> 5 cm) approximately 10 years after the initial resection. The tumor had grown around a  pre-existing shunt catheter and resulted in loculated hydrocephalus. A complete resection and shunt revision were both performed at the same sitting. The operative technique and surgical nuances, including the surgical approach, intradural tumor removal, closure, and management of hydrocephalus are illustrated in this video atlas. The video can be found here: http://youtu.be/vpdmZ1ccWSM .

 

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[486]

TÍTULO / TITLE:  - Relationship of 14-3-3zeta (zeta), HIF-1alpha, and VEGF expression in human brain gliomas.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-013-0135-3

AUTORES / AUTHORS:  - Cao WD; Kawai N; Miyake K; Zhang X; Fei Z; Tamiya T

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

RESUMEN / SUMMARY:  - Accumulating evidence suggests that tissue hypoxia and apoptosis play important roles in the malignant progression of brain tumors. We investigated the relationship of 14-3-3zeta (an apoptosis-related protein), HIF-1alpha, and VEGF immunohistochemistry, and evaluated the prognostic value of their expression in human brain gliomas. A semiquantitative analysis of the immunoreactivity scores (IRSs) of the 14-3-3zeta, HIF-1alpha, and VEGF proteins was performed in 27 patients with various grades of gliomas. The IRS of 14-3-3zeta increased with tumor grade, with grade IV gliomas having the highest score (P < 0.05). Similar results were found for the IRSs of HIF-1alpha and VEGF (P < 0.05). A significant  positive correlation was found between the IRSs of 14-3-3zeta and HIF-1alpha, 14-3-3zeta and VEGF, and HIF-1alpha and VEGF (P < 0.001 for all). The survival time of HIF-1alpha in grade III and grade IV glioma patients with low IRSs (0-6)  was significantly longer than that in such glioma patients with high IRSs (8-12)  (P < 0.05). These data indicate that 14-3-3zeta, HIF-1alpha, and VEGF are involved in the same cascade of the malignant progression of gliomas. Further studies will elucidate their detailed role in the malignant progression of glioma, and will contribute to the development of a new treatment strategy for this lethal disease.

 

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[487]

TÍTULO / TITLE:  - Coexpression of glial and neuronal markers in the neurocytic rosettes of rosette-forming glioneuronal tumors.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0133-x

AUTORES / AUTHORS:  - Matsumura N; Wang Y; Nakazato Y

INSTITUCIÓN / INSTITUTION:  - Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan, nozomim@med.gunma-u.ac.jp.

RESUMEN / SUMMARY:  - Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) is a new entity in the WHO 2007 Classification of Tumors of the Central Nervous System. RGNT has  two components: neurocytic rosettes and low-grade gliomas. Neurocytic rosettes are conventionally described as consisting of uniform neurocytes. However, some studies have reported rosette-forming tumor cells that expressed glial markers such as Olig2. We indicated the expression of glial markers including Olig2, cyclinD1, glial fibrillary acidic protein (GFAP), and platelet-derived growth factor receptor alpha (PDGFRalpha) in the neurocytic rosettes in our previous study, and we suggested that these tumor cells had a heterogeneous nature. In this study, we used double and triple immunostaining to demonstrate that these tumor cells have both glial and neuronal characteristics. We found that rosette-forming tumor cells coexpressed Olig2/cyclinD1 and synaptophysin. Furthermore, the cores of the rosettes coexpressed GFAP/PDGFRalpha in the peripheral zone and synaptophysin in the central zone. These findings imply that  rosette-forming tumor cells have a similar nature to neuronal-glial progenitor cells, and we believe that the nomination “neurocytic rosette” may be unsuitable  given their heterogeneous nature. Our study appears to clarify some of the properties of RGNT tumor cells and may help elucidate the histogenesis of RGNT.

 

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[488]

TÍTULO / TITLE:  - Bladder paraganglioma. A case report.

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

REVISTA / JOURNAL:  - J Med Liban. 2012 Jul-Sep;60(3):182-4.

AUTORES / AUTHORS:  - El Khoury F; Jour I; Malaeb B; Assaf G

INSTITUCIÓN / INSTITUTION:  - Urology Department, Saint George Hospital University Medical Center, University of Balamand, Beirut, Lebanon.

RESUMEN / SUMMARY:  - This is a report of a 32-year-old man who presented with dyspnea upon micturition. He was found to have hematuria. Pelvic ultrasound and CT scan of the abdomen and pelvis revealed a left bladder wall polyp confirmed by cystoscopy to  be a submucosal pulsating mass. Plasma free metanephrines were elevated in favor  of a bladder paraganlioma while urinary metanephrines, catecholamines and MIBG scan were normal. Patient was managed by partial cystectomy with disappearance of symptoms thereafter. Pathology showed a completely excised paraganglioma. The assessment, diagnosis and treatment are illustrated.

 

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[489]

TÍTULO / TITLE:  - Intradural extramedullary spinal nerve sheath myxoma: a report of two cases.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0131-z

AUTORES / AUTHORS:  - Yamato M; Ikota H; Hanakita J; Iizuka Y; Nakazato Y

INSTITUCIÓN / INSTITUTION:  - Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

RESUMEN / SUMMARY:  - Nerve sheath myxoma, a myxoid variant of schwannoma, is a dermal tumor that usually occurs in the upper extremities, head and neck region, or trunk; occasionally, however, it has also been reported to develop in the spinal canal.  Here, we describe two cases of intraspinal nerve sheath myxoma. Case 1 was a 74-year-old man with left hypochondrial pain. Gadolinium-enhanced magnetic resonance imaging (MRI) of his spine revealed a well-demarcated intradural extramedullary tumor with peripheral enhancement at the Th8 level. Case 2 was a 58-year-old man with lower back and left buttock pain. Gadolinium-enhanced MRI revealed a well-demarcated intradural extramedullary tumor with peripheral enhancement at the Th12-L1 level. Both cases were clinically diagnosed as schwannoma. Histological studies revealed characteristic myxoid lobules which were separated by fibrous septa or bands of more compact cellular area. The tumor cells were diffusely positive for S-100 and focally positive for Schwann/2E, which reacts with Schwann cells and myelin in the peripheral nervous system. The  positive reaction to Schwann/2E confirmed the occurrence of peripheral nerve sheath differentiation. Nerve sheath myxoma should be included in differential diagnosis of spinal canal tumors.

 

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[490]

TÍTULO / TITLE:  - In human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencing.

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

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1081-1

AUTORES / AUTHORS:  - Kreth S; Limbeck E; Hinske LC; Schutz SV; Thon N; Hoefig K; Egensperger R; Kreth FW

INSTITUCIÓN / INSTITUTION:  - Research Group Molecular Medicine, Department of Anesthesiology, University of Munich (LMU), Marchioninistrasse 15, 81337, Munich, Germany, simone.kreth@med.uni-muenchen.de.

RESUMEN / SUMMARY:  - Favorable outcome after chemotherapy of glioblastomas cannot unequivocally be linked to promoter hypermethylation of the O (6)-methylguanine-DNA methyltransferase (MGMT) gene encoding a DNA repair enzyme associated with resistance to alkylating agents. This indicates that molecular mechanisms determining MGMT expression have not yet been fully elucidated. We here show that glioblastomas are capable to downregulate MGMT expression independently of promoter methylation by elongation of the 3’-UTR of the mRNA, rendering the alternatively polyadenylated transcript susceptible to miRNA-mediated suppression. While the elongated transcript is poorly expressed in normal brain,  its abundance in human glioblastoma specimens is inversely correlated with MGMT mRNA expression. Using a bioinformatically guided experimental approach, we identified miR-181d, miR-767-3p, and miR-648 as significant post-transcriptional  regulators of MGMT in glioblastomas; the first two miRNAs induce MGMT mRNA degradation, the latter affects MGMT protein translation. A regression model including the two miRNAs influencing MGMT mRNA expression and the MGMT methylation status reliably predicts The Cancer Genome Atlas MGMT expression data. Responsivity of MGMT expressing T98G glioma cells to temozolomide was significantly enhanced after transfection of miR-181d, miR-767-3p, and miR-648. Taken together, our results uncovered alternative polyadenylation of the MGMT 3’-UTR and miRNA targeting as new mechanisms of MGMT silencing.

 

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[491]

TÍTULO / TITLE:  - Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial.

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

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 6;12:581. doi: 10.1186/1471-2407-12-581.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-581

AUTORES / AUTHORS:  - de Ruiter MA; Schouten-Van Meeteren AY; van Mourik R; Janssen TW; Greidanus JE; Oosterlaan J; Grootenhuis MA

INSTITUCIÓN / INSTITUTION:  - Psychosocial Department, Emma Children’s Hospital AMC, room A3-241, Meibergdreef  9, Amsterdam 1105 AZ, The Netherlands. m.a.deruiter@amc.nl

RESUMEN / SUMMARY:  - BACKGROUND: Neurotoxicity caused by treatment for a brain tumor is a major cause  of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. METHODS/DESIGN: Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off  treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as  well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. DISCUSSION: If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT00961922.

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[492]

TÍTULO / TITLE:  - Extracranial expansion of a feline meningioma.

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

REVISTA / JOURNAL:  - J Feline Med Surg. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1098612X12472175

AUTORES / AUTHORS:  - Karli P; Gorgas D; Oevermann A; Forterre F

INSTITUCIÓN / INSTITUTION:  - 1Small Animal Hospital, Department of Clinical Neurology, Vetsuisse Faculty, University of Berne, Switzerland.

RESUMEN / SUMMARY:  - Meningioma is the most frequently observed primary brain tumour in cats. Usually, it is associated with an intracranial expansion with consequent brain compression, oedema and brain herniation. Typical features of feline intracranial meningiomas are hyperostosis of the adjacent bone and intratumoral mineralisation. We describe a 13-year-old male neutered cat with a 1-year history of behavioural change. At clinical and neurological examination the cat showed signs consistent with right-sided forebrain lesion. Magnetic resonance images showed a right-sided extra-axial contrast enhancing mass in the region of the frontotemporal lobe. The overlying bone of the calvarium showed a marked defect with extracranial expansion of the tissue. Surgery was performed and the tumour could be exposed by a right-sided temporal approach. After extension of the bony  defect the mass could be removed properly. The cat recovered well from surgery and a 12-month follow-up showed no persistent neurological deficits. Histopathological assessment of the tumour revealed a transitional grade 1 meningioma. Despite osteolysis and extracranial expansion of the tumour differentials should include menigioma in feline intracranial neoplasms.

 

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[493]

TÍTULO / TITLE:  - Ectopic meningioma of the orbit.

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

REVISTA / JOURNAL:  - Int Ophthalmol. 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10792-012-9708-0

AUTORES / AUTHORS:  - Pushker N; Shrey D; Kashyap S; Sen S; Khurana S; Sharma S

INSTITUCIÓN / INSTITUTION:  - Oculoplasty, Orbit & Tumors Services, All India Institute of Medical Sciences, New Delhi, India.

RESUMEN / SUMMARY:  - Ectopic meningiomas within the orbit are very rare. Most of the previously reported cases were located along the medial wall. Here we report on three cases  of ectopic meningiomas presenting as superomedial orbital masses along with their radiological and histopathological features. All three patients underwent surgical excision of the tumor via anterior orbitotomy.

 

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[494]

TÍTULO / TITLE:  - Hypoglossal nerve tumor: A rare primary extracranial meningioma of the neck.

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

REVISTA / JOURNAL:  - Ear Nose Throat J. 2012 Nov;91(11):E26-9.

AUTORES / AUTHORS:  - Zulkiflee AB; Prepageran N; Rahmat O; Jayalaskhmi P; Sharizal T

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, University of Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia. ab_zulkiflee@yahoo.com.

RESUMEN / SUMMARY:  - We report a case of primary extracranial meningioma arising from the hypoglossal  nerve in a 54-year-old man who presented with a 9-month history of hoarseness and progressive dysphagia. He had also noticed that his tongue was deviated to the left and, as a result, he was having difficulty pronouncing words. Examination revealed fasciculation and muscle wasting on the left side of the tongue. Other cranial nerve functions were normal. Contrast-enhanced computed tomography detected a heterogeneous mass that had arisen above the bifurcation of the left common carotid artery and had extended to near the skull base. Transcervical excision of the tumor was performed, and histopathology identified it as a meningioma of the hypoglossal nerve. The patient recovered uneventfully, and he was without recurrence at more than 2 years of follow-up. A primary extracranial  meningioma is extremely rare, and its presentation may be subtle. A thorough investigation is necessary to avoid fatal compressive symptoms.

 

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[495]

TÍTULO / TITLE:  - Value of (11)C-methionine PET in imaging brain tumours and metastases.

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

REVISTA / JOURNAL:  - Eur J Nucl Med Mol Imaging. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00259-012-2295-5

AUTORES / AUTHORS:  - Glaudemans AW; Enting RH; Heesters MA; Dierckx RA; van Rheenen RW; Walenkamp AM; Slart RH

INSTITUCIÓN / INSTITUTION:  - Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO 9700 RB, Groningen, The Netherlands, a.w.j.m.glaudemans@umcg.nl.

RESUMEN / SUMMARY:  - (11)C-methionine (MET) is the most popular amino acid tracer used in PET imaging  of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses  on the role of MET PET in imaging cerebral gliomas. The Introduction provides a clinical overview of what is important in primary brain tumours, recurrent brain  tumours and brain metastases. The indications for radiotherapy and the results and problems arising after chemoradiotherapy in relation to imaging (pseudoprogression or radionecrosis) are discussed. The working mechanism, scan interpretation and quantification possibilities of MET PET are then explained. A  literature overview is given of the role of MET PET in primary gliomas (diagnostic accuracy, grading, prognosis, assessment of tumour extent, biopsy and radiotherapy planning), in brain metastases, and in the differentiation between tumour recurrence and radiation necrosis. Finally, MET PET is compared to other nuclear imaging possibilities in brain tumour imaging.

 

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[496]

TÍTULO / TITLE:  - Pharmacotherapeutic Management of Pediatric Gliomas : Current and Upcoming Strategies.

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

REVISTA / JOURNAL:  - Paediatr Drugs. 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s40272-012-0002-4

AUTORES / AUTHORS:  - Hummel TR; Chow LM; Fouladi M; Franz D

INSTITUCIÓN / INSTITUTION:  - Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s  Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH, 45229, USA, trent.hummel@cchmc.org.

RESUMEN / SUMMARY:  - Primary glial brain tumors account for the majority of primary brain tumors in children. They are classified as low-grade gliomas (LGG) or high-grade gliomas (HGG), based on specific pathologic characteristics of the tumor, resulting in disparate clinical prognoses. Surgery is a mainstay of treatment for HGG, although it is not curative, and adjuvant therapy is required. Temozolomide, an oral imidazotetrazine prodrug, while considered standard of care for adult HGG, has not shown the same degree of benefit in the treatment of pediatric HGG. There are significant biologic differences that exist between adult and pediatric HGG,  and targets specifically aimed at the biology in the pediatric population are required. Novel and specific therapies currently being investigated for pediatric HGG include small molecule inhibitors of epidermal growth factor receptor, platelet-derived growth factor receptor, histone deacetylase, the RAS/AKT pathway, telomerase, integrin, insulin-like growth factor receptor, and gamma-secretase. Surgery is also the mainstay for LGG. There are defined front-line, multiagent chemotherapy regimens, but there are few proven second-line chemotherapy options for refractory patients. Approaches such as the  inhibition of the mammalian target of rapamycin pathway, inhibition of MEK1 and 2, as well as BRAF, are discussed. Further research is required to understand the biology of pediatric gliomas as well as the use of molecularly targeted agents, especially in patients with surgically unresectable tumors.

 

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[497]

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos300

AUTORES / AUTHORS:  - Hutterer M; Nowosielski M; Putzer D; Jansen NL; Seiz M; Schocke M; McCoy M; Gobel G; la Fougere C; Virgolini IJ; Trinka E; Jacobs AH; Stockhammer G

INSTITUCIÓN / INSTITUTION:  - Department of Neurology (M.H., M.N., G.S.); Department of Nuclear Medicine (D.P., I.J.V.); Department of Radiology (M.S.); Department of Neurosurgery (M.S.);

RESUMEN / SUMMARY:  - BackgroundTo assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.MethodsWe retrospectively evaluated (18)F-FET  PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET  PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).ResultsSensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 +/- 0.72) and low-grade brain tumors (LBR, 1.52 +/- 0.70; P < .001), as well as among inflammatory (LBR, 1.66 +/- 0.33; P = .056) and other brain lesions (LBR, 1.10 +/- 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade  III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.Conclusions(18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

 

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[498]

TÍTULO / TITLE:  - ADAM 12: A putative marker of oligodendrogliomas?

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

REVISTA / JOURNAL:  - Dis Markers. 2013 Jan 2.

            ●● Enlace al texto completo (gratuito o de pago) 3233/DMA-120953

AUTORES / AUTHORS:  - Kanakis D; Lendeckel U; Theodosiou P; Dobrowolny H; Mawrin C; Keilhoff G; Bukowska A; Dietzmann K; Bogerts B; Bernstein HG

INSTITUCIÓN / INSTITUTION:  - Department of Psychiatry, Otto-von-Guericke-University, Magdeburg, Germany.

RESUMEN / SUMMARY:  - ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell  fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-,  colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is  known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of  normal human brain as well as in neoplastic oligodendroglia and minigemistocytes  arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry  are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA)  showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry  may be a helpful tool in the diagnosis of brain tumours.

 

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[499]

TÍTULO / TITLE:  - Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos337

AUTORES / AUTHORS:  - Towner RA; Gillespie DL; Schwager A; Saunders DG; Smith N; Njoku CE; Krysiak RS 3rd; Larabee C; Iqbal H; Floyd RA; Bourne DW; Abdullah O; Hsu EW; Jensen RL

INSTITUCIÓN / INSTITUTION:  - Advanced Magnetic Resonance Center (R.A.T., D.G.S., N.S., C.E.N., R.S.K., C.L., H.I.) and Experimental Therapeutics Laboratory, Oklahoma Medical Research Foundation (R.A.F.), and Department of Pharmaceutical Sciences, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (D.W.A.B.); Huntsman Cancer Institute, University of Utah Health Sciences Center (D.L.G., R.L.J.), Interdepartmental Program in Neuroscience (A.S.), Department of Bioengineering (O.A., E.W.H.), and Departments of Neurosurgery, Radiation Oncology, Oncological  Sciences, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah (R.L.J.).

RESUMEN / SUMMARY:  - BackgroundGlioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitrone compound OKN-007, a disulfonyl derivative of alpha-phenyl-tert-butyl  nitrone.MethodsMRI was used to assess tumor volumes in F98 and U87 gliomas, and bioluminescence imaging was used to measure tumor volumes in F98 gliomas encoded  with the luciferase gene (F98(luc)). Immunohistochemistry was used to assess angiogenesis (vascular endothelial growth factor [VEGF] and microvessel density [MVD]), cell differentiation (carbonic anhydrase IX [CA-IX]), hypoxia (hypoxia-inducible factor-1alpha [HIF-1alpha]), cell proliferation (glucose transporter 1 [Glut-1] and MIB-1), proliferation index, and apoptosis (cleaved caspase 3) markers in F98 gliomas. VEGF, CA-IX, Glut-1, HIF-1alpha, and cleaved caspase 3 were assessed in U87 gliomas.ResultsAnimal survival was found to be significantly increased (P < .001 for F98, P < .01 for U87) in the group that received OKN-007 treatment compared with the untreated groups. After MRI detection of F98 gliomas, OKN-007, administered orally, was found to decrease tumor growth (P < .05). U87 glioma volumes were found to significantly decrease (P < .05) after OKN-007 treatment, compared with untreated animals. OKN-007 administration resulted in significant decreases in tumor hypoxia (HIF-1alpha [P  < .05] in both F98 and U87), angiogenesis (MVD [P < .05], but not VEGF, in F98 or U87), and cell proliferation (Glut-1 [P < .05 in F98, P < .01 in U87] and MIB-1 [P < .01] in F98) and caused a significant increase in apoptosis (cleaved caspase 3 [P < .001 in F98, P < .05 in U87]), compared with untreated animals.ConclusionsOKN-007 may be considered as a promising therapeutic addition  or alternative for the treatment of aggressive human gliomas.

 

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[500]

TÍTULO / TITLE:  - Pharmacological blockade of FAK autophosphorylation decreases human glioblastoma  tumor growth and synergizes with temozolomide.

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

REVISTA / JOURNAL:  - Mol Cancer Ther. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0701

AUTORES / AUTHORS:  - Golubovskaya V; Huang G; Ho B; Yemma M; Morrison CD; Lee J; Eliceiri B; Cance WG

INSTITUCIÓN / INSTITUTION:  - 1Surgical Oncology, Roswell Park Cancer Institute.

RESUMEN / SUMMARY:  - Malignant gliomas are characterized by aggressive tumor growth with a mean survival of 15-18 months and frequently developed resistance to temozolomide. Therefore, strategies that sensitize glioma cells to temozolomide have a high translational impact. We have studied focal adhesion kinase (FAK), a tyrosine kinase and emerging therapeutic target that is known to be highly expressed and activated in glioma. In this report we tested the FAK autophosphorylation inhibitor, Y15 in DBTRG and U87 glioblastoma cells. Y15 significantly decreased viability and clonogenicity in a dose-dependent manner, increased detachment in a dose and time-dependent manner, caused apoptosis and inhibited cell invasion in both cell lines. In addition, Y15 treatment decreased autophosphorylation of FAK  in a dose-dependent manner and changed cell morphology by causing cell rounding in DBTRG and U87 cells. Administration of Y15 significantly decreased subcutaneous DBTRG tumor growth with decreased Y397-FAK autophosphorylation, activated caspase-3 and PARP. Y15 was administered in an orthotopic glioma model, leading to an increase in mouse survival. The combination of Y15 with temozolomide was more effective than either agent alone in decreasing viability and activating caspase-8 in DBTRG and U87 cells in vitro. In addition, the combination of Y15 and temozolomide synergistically blocked U87 brain tumor growth in vivo. Thus, pharmacologic blockade of FAK autophosphorylation with the  oral administration of a small molecule inhibitor Y15 has a potential to be an effective therapy approach for glioblastoma either alone or in combination with chemotherapy agents such as temozolomide.

 

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[501]

TÍTULO / TITLE:  - The impact of fluorescence guidance on spinal intradural tumour surgery.

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

REVISTA / JOURNAL:  - Eur Spine J. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00586-013-2657-0

AUTORES / AUTHORS:  - Eicker SO; Floeth FW; Kamp M; Steiger HJ; Hanggi D

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Heinrich-Heine-University, Moorenstrasse 5, 40225, Dusseldorf, Germany, eicker.s@mac.com.

RESUMEN / SUMMARY:  - PURPOSE: 5-Aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was shown to be beneficial for cerebral malignant gliomas. Extension of this technique for resection of meningiomas and cerebral metastasis has been recently  evaluated. Aim of the present study is to evaluate the impact of fluorescence-guided surgery in spinal tumor surgery. METHODS: Twenty-six patients with intradural spinal tumors were included in the study. 5-ALA was administered  orally prior to the induction of anesthesia. Intraoperative, 440 nm fluorescence  was applied after exploration of the tumor and, if positive, periodically during  and at the end of resection to detect tumor-infiltrated sites. RESULTS: Tumors of WHO grade III and IV were found in five patients. In detail intra- or perimedullary metastasis of malignant cerebral gliomas was found including glioblastoma WHO grade IV (n = 2), anaplastic astrocytoma WHO grade III (n = 1),  anaplastic oligoastrocytoma WHO grade III (n = 1). In addition, one patient suffered from a spinal drop metastasis of a cerebellar medulloblastoma WHO grade  IV. Tumors of WHO grade I were diagnosed in 18 patients: Eight cases of meningioma (two recurrences), six cases of neurinoma, one neurofibroma, two ependymoma and one plexus papilloma. At least, benign pathologies were histologically proven in three patients. All four spinal metastasis of malignant  glioma (100 %), seven of eight meningiomas (87.5 %) and one of two ependymoma (50 %) were found to be ALA-positive. CONCLUSION: The present study demonstrates that spinal intramedullary gliomas and the majority of spinal intradural meningiomas are 5-ALA positive. As a surgical consequence, especially in intramedullary gliomas, the use of 5-ALA fluorescence seems to be beneficial.

 

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[502]

TÍTULO / TITLE:  - Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos306

AUTORES / AUTHORS:  - Zhang JX; Zhang J; Yan W; Wang YY; Han L; Yue X; Liu N; You YP; Jiang T; Pu PY; Kang CS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, 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, China (J.-X.Z., L.H., X.Y., P.-Y.P., C.-S.K.); Laboratory of Disease Genomics and Individualized Medicine, Center in Computational Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China (J. Z.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (W.Y., T.J.); Department of  Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China (J.-X.Z.,Y.-Y.W, N.L., Y.-P.Y); Chinese Glioma Cooperative Group (CGCG) (J.-X.Z., W.Y., Y.-Y.W, L.H., N.L., Y.-P.Y., P.-Y.P., C.-S.K.).

RESUMEN / SUMMARY:  - BackgroundAberrant activation of beta-catenin/TCF4 and STAT3 signaling in glioblastoma multiforme (GBM) has been reported. However, the molecular mechanisms related to this process are still poorly understood.MethodsGenome-wide screening of the binding characteristics of the transcription factors TCF4 and STAT3 in GBM cells was performed by chromatin immunoprecipitation sequencing (ChIP-seq) assay. Hierarchical clustering was used to analyze the association of  TCF4 and STAT3 coregulated genes with The Cancer Genome Atlas (TCGA) GBM subtypes (classical, mesenchymal, neural, and proneural). New molecular classification of  GBM was proposed and validated in Western and Asian populations.ResultsWe identified 1250 overlapping putative target genes that were coregulated by TCF4 and STAT3. Further, the coregulated genes had the potential to guide TCGA GBM subtypes. Finally, we proposed a new molecular classification of GBM into 2 subtypes (proneural-like and mesenchymal-like) and showed that the new classification could be applied to both Western and Asian populations. In addition, the GBM response to temozolomide therapy differed depending on its subtype; mesenchymal-like GBM benefited, while there was no benefit for proneural-like GBM.ConclusionsThis is the first comprehensive study to combine a  ChIP-seq assay of TCF4 and STAT3 and data mining of patient cohorts to derive molecular subtypes of GBM.

 

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[503]

TÍTULO / TITLE:  - PKC signaling in glioblastoma.

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

REVISTA / JOURNAL:  - Cancer Biol Ther. 2013 Jan 28;14(4).

AUTORES / AUTHORS:  - do Carmo A; Balca-Silva J; Matias D; Lopes MC

INSTITUCIÓN / INSTITUTION:  - Centre for Neuroscience and Cell Biology; University of Coimbra; Coimbra, Portugal; University School of Vasco da Gama; Coimbra, Portugal.

RESUMEN / SUMMARY:  - Glioblastoma Multiforme (GBM) is the most aggressive brain tumor characterized by intratumoral heterogeneity at cytopathological, genomic and transcriptional levels. Despite the efforts to develop new therapeutic strategies the median survival of GBM patients is 12-14 mo. Results from large-scale gene expression profile studies confirmed that the genetic alterations in GBM affect pathways controlling cell cycle progression, cellular proliferation and survival and invasion ability which may explain the difficulty to treat GBM patients. One of the signaling pathways that contribute to the aggressive behavior of glioma cells is the protein kinase C (PKC) pathway. PKC is a family of serine/threonine-specific protein kinases organized into three groups according the activating domains. Due to the variability of actions controlled by PKC isoforms, its contribution to the development of GBM is poorly understood. This review intends to highlight the contribution of PKC isoforms to proliferation, survival and invasive ability of glioma cells.

 

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[504]

TÍTULO / TITLE:  - Optical coherence tomography of retinal astrocytic hamartomas in a 4-year-old boy affected by tuberous sclerosis.

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

REVISTA / JOURNAL:  - Int Ophthalmol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10792-013-9724-8

AUTORES / AUTHORS:  - Spinucci G; Restivo L; Paroli MP; Cava ML

INSTITUCIÓN / INSTITUTION:  - Dipartimento di Scienze Oftalmologiche, Sapienza University of Rome, Policlinico  Umberto I, Viale del Policlinico 155, 00161, Rome, Italy, giospinucci@libero.it.

 

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[505]

TÍTULO / TITLE:  - Adjuvant radiotherapy delays recurrence following subtotal resection of spinal cord ependymomas.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Feb;15(2):208-15. doi: 10.1093/neuonc/nos286. Epub 2012 Dec 9.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos286

AUTORES / AUTHORS:  - Oh MC; Ivan ME; Sun MZ; Kaur G; Safaee M; Kim JM; Sayegh ET; Aranda D; Parsa AT

INSTITUCIÓN / INSTITUTION:  - Corresponding Author: Andrew T. Parsa, MD, PhD, Department of Neurological Surgery, University of California at San Francisco, 505 Parnassus Ave, San Francisco, CA 94117. pparsaaa@nneurosurg.ucsfucsf.edu.

RESUMEN / SUMMARY:  - Background Ependymoma is the most common glial tumor of the adult spinal cord. Current consensus recommends surgical resection with gross total resection (GTR)  whenever possible. We performed a comprehensive review of the literature to evaluate whether adjuvant radiotherapy after subtotal resection (STR) has any benefit. Methods A PubMed search was performed to identify adult patients with spinal cord ependymoma who underwent surgical resection. Only patients who had clearly defined extent of resection with or without adjuvant radiotherapy were included for analysis. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of adjuvant radiotherapy on progression-free survival (PFS) and overall survival (OS). Results A total of 348 patients underwent surgical resection of spinal cord ependymomas, where GTR was obtained in 77.0% (268/348) of patients. Among those who received STR, 58.8% (47/80) received adjuvant radiotherapy. PFS was significantly prolonged among those who received adjuvant radiotherapy after STR (log rank; P < .001). This prolonged PFS with adjuvant radiotherapy remained significant in multivariate Cox regression analysis (STR versus STR + RT group; hazard ratio (HR) = 2.26, P = .047). By contrast, improved OS was only associated with GTR (GTR versus STR + RT group; HR = 0.07, P = .001) and benign ependymomas (HR = 0.16, P = .001). Conclusions Surgery remains the mainstay treatment for spinal cord ependymomas, where GTR provides optimal outcomes with longest PFS and OS. Adjuvant radiotherapy prolongs PFS after STR significantly, and OS is improved by GTR and  benign tumor grade only.

 

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[506]

TÍTULO / TITLE:  - The role of radiotherapy and chemotherapy in the treatment of primary adult high  grade gliomas: assessment of patients for these treatment approaches and the common immediate side effects.

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

REVISTA / JOURNAL:  - ISRN Oncol. 2012;2012:902178. doi: 10.5402/2012/902178. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 5402/2012/902178

AUTORES / AUTHORS:  - Philip-Ephraim EE; Eyong KI; Williams UE; Ephraim RP

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, College of Medical Sciences, University of Calabar, PMB 1278, Nigeria.

RESUMEN / SUMMARY:  - Gliomas are the commonest primary brain tumours in adults. They are usually classified and graded according to the criteria by the World Health Organisation. High-grade gliomas are the most malignant primary brain tumours. Conventional therapies include surgery, radiotherapy, and chemotherapy. The tumours often demonstrate high levels of resistance to these conventional therapies, and in spite of treatment advances the prognosis remains poor.

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[507]

TÍTULO / TITLE:  - Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos324

AUTORES / AUTHORS:  - Rice T; Zheng S; Decker PA; Walsh KM; Bracci P; Xiao Y; McCoy LS; Smirnov I; Patoka JS; Hansen HM; Hsuang G; Wiemels JL; Tihan T; Pico AR; Prados MD; Chang SM; Berger MS; Caron A; Fink S; Kollmeyer T; Rynearson A; Voss J; Kosel ML; Fridley BL; Lachance DH; Eckel-Passow JE; Sicotte H; O’Neill BP; Giannini C; Wiencke JK; Jenkins RB; Wrensch MR

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of California, San Francisco, San  Francisco, California (T.R., S.Z., K.M.W., L.S.M., I.S., J.S.P., H.M.H., G.H., M.D.P., S.M.C., M.S.B., J.K.W., M.R.W.); Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota (P.A.D., M.L.K., B.L.F., J.E.E-P., H.S.); Program in Cancer Genetics, Helen Diller Family  Comprehensive Cancer Center (K.M.W.), Department of Epidemiology and Biostatistics (P.B., Y.X., J.L.W.), Institute of Human Genetics (J.L.W., J.K.W.,  M.R.W.), and Department of Pathology, University of California, San Francisco, San Francisco, California (T.T.); Gladstone Institutes, San Francisco, California (A.R.P.); Department of Laboratory Medicine and Pathology (A.C., S.F., T.K., A.R., J.V., D.H.L., C.G., R.B.R.), and Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota (D.H.L., B.P.O.).

RESUMEN / SUMMARY:  - IntroductionRecent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this  variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas.MethodsWe tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele.ResultsThe 11q23 glioma risk locus was associated  with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but  not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele.ConclusionA variant at the 11q23 locus increases risk for IDH-mutated but  not IDH-wild-type gliomas, regardless of grade or histology.

 

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[508]

TÍTULO / TITLE:  - Interhemispheric transcallosal approach for resection of intraventricular central neurocytoma.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12353.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12353

AUTORES / AUTHORS:  - Liu JK

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and Otolaryngology-Head and Neck Surgery, Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey.

RESUMEN / SUMMARY:  - The interhemispheric transcallosal approach is a versatile approach to access intraventricular tumors of the lateral and third ventricles. The advantages of using a transcallosal approach over a classical transcortical approach include a  direct midline orientation with symmetrical access to both lateral ventricles and both walls of the third ventricle. In addition, violation of the cerebral cortex  and the risk of postoperative seizures can be avoided. Central neurocytomas are rare benign tumors that represent approximately 0.1 to 0.5% of all primary brain  tumors. They are typically located in the lateral ventricles and tend to present  clinically with hydrocephalus. Currently, surgical removal with a gross-total resection is the treatment of choice. In this operative video manuscript, the author demonstrates an illustrative step-by-step technique for microsurgical resection of a large central neurocytoma involving both lateral ventricles in a patient with hydrocephalus using the interhemispheric transcallosal approach. A complete removal was performed without the need for permanent shunting. The operative technique and surgical nuances, including the surgical approach, intraventricular tumor removal, and closure are illustrated in this video atlas.  The video can be found here: http://youtu.be/KzC8QYsTKeg .

 

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[509]

TÍTULO / TITLE:  - Transcortical-transforaminal microscopic approach for purely intraventricular craniopharyngioma.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12347.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12347

AUTORES / AUTHORS:  - Chamoun R; Couldwell WT

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Utah, Salt Lake City, Utah.

RESUMEN / SUMMARY:  - Purely intraventricular craniopharyngiomas are rare and pose particular surgical  challenges. The two main surgical approaches to these lesions based in the anterior third ventricle are the frontal transventricular approach (through a transcortical or transcallosal approach) and the trans-lamina terminalis approach. The authors note that the pituitary stalk in many of these cases is located in a normal position, which suggests that the third ventricular floor is  intact. In such cases, the senior author chooses an approach to avoid disruption  of the floor of the third ventricle. Specifically, a traditional frontotemporal approach is not used; we have found that in such cases, a frontal transventricular approach through the usually dilated foramen of Monro provides an optimal visualization of the tumor while minimizing the risks of injury to the hypothalamus and pituitary stalk. The endoscope can be very helpful in exploring  blind angles, hidden from the microscopic view. Recognition of this rare location variant of craniopharyngioma is helpful in preoperative planning in an effort to  reduce hypothalamic pituitary axis damage. Two patients presenting with craniopharyngiomas that were entirely intraventricular are shown in the video. The patients underwent removal of their tumors without incurring new long-term endocrine deficits. The video can be found here: http://youtu.be/VFlhm_lsrGY .

 

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[510]

TÍTULO / TITLE:  - Surgical management of craniopharyngioma with third ventricle involvement.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12330.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12330

AUTORES / AUTHORS:  - de Lara D; Ditzel Filho LF; Muto J; Otto BA; Carrau RL; Prevedello DM; M D

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Craniopharyngiomas are notorious for their ability to invade the hypothalamus and third ventricle. Although several transcranial approaches have been proposed for  their treatment, the endonasal route provides direct access to the tumor with no  need for cerebral retraction or manipulation of the optic apparatus. After the lesion is debulked, the unique angle of approach achieved with this technique enables the surgeon to perform an extra-capsular dissection and visualize the walls of the third ventricle, the foramina of Monro, and the anterior comissure.  Moreover, the enhanced magnification and lighting afforded by the endoscope facilitate safe tumor removal, particularly in areas where there is loss of clear lesion delimitation and greater infiltration of the surrounding structures. Herein we present the case of a 68-year-old female patient with a 3-month history of visual deterioration accompanied by worsening headaches. Investigation with magnetic resonance imaging revealed a heterogeneous mass in the suprasellar region, extending into the third ventricle and displacing the pituitary gland and stalk inferiorly. Hormonal profile was within expected range for her age. An endonasal, fully endoscopic, transplanum transtuberculum approach was performed.  Gross-total removal was achieved and pathology confirmed the diagnosis of craniopharyngioma. Postoperative recovery was marked by transient diabetes insipidus. Closure was achieved with a pedicled nasoseptal flap; despite exploration of the third ventricle, there was no cerebrospinal fluid leakage. Pituitary function was preserved. Visual function has fully recovered and the patient has been uneventfully followed since surgery. The video can be found here: http://youtu.be/it5mpofZl0Q .

 

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[511]

TÍTULO / TITLE:  - Anaplastic oligodendroglioma in an adolescent with lynch syndrome.

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

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2012 Dec 19. doi: 10.1002/pbc.24424.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24424

AUTORES / AUTHORS:  - Heath JA; Ng J; Beshay V; Coleman L; Lo P; Amor DJ

INSTITUCIÓN / INSTITUTION:  - Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; School of Population Health, University of Melbourne, Melbourne, Victoria, Australia. john.heath@rch.org.au.

RESUMEN / SUMMARY:  - Lynch syndrome (hereditary non-polyposis colorectal cancer; HNPCC) is an autosomal dominant cancer predisposition syndrome with high penetrance. It is caused by heterozygous germline mutations in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. Carriers are at high-risk for developing colorectal carcinomas, as well as various extracolonic malignancies. This case report describes a 15 year-old male with a confirmed germline mutation of MSH2 and early onset anaplastic oligodendroglioma. The patient’s tumor showed loss of  expression of MSH2 and MSH6 proteins with normal microsatellite stability. The immunohistochemical staining pattern provided strong evidence to support the inclusion of anaplastic oligodendroglioma as part of the spectrum of tumors found in Lynch syndrome. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

 

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[512]

TÍTULO / TITLE:  - Glioma is formed by active Akt1 alone and promoted by active Rac1 in transgenic zebrafish.

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

REVISTA / JOURNAL:  - Neuro Oncol. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos387

AUTORES / AUTHORS:  - Jung IH; Leem GL; Jung DE; Kim MH; Kim EY; Kim SH; Park HC; Park SW

INSTITUCIÓN / INSTITUTION:  - Postgraduate School of National Core Research Center for Nanomedical Technology (I.H.J.); Severance Hospital (G.L.L.); Brain Korea 21 Project for Medical Science (D.E.J.); Department of Internal Medicine (M.H.K., E.Y.K., S.W.P.); and Department of Pathology, Yonsei University College of Medicine, Seoul (S.H.K.); and Graduate School of Medicine, Korea University, Ansan, Gyeonggido, Korea (H.C.P.).

RESUMEN / SUMMARY:  - BackgroundOngoing characterization of glioma has revealed that Akt signaling plays a crucial role in gliomagenesis. In mouse models, however, Akt alone was not sufficient to induce glioma.MethodsWe established transgenic zebrafish that overexpressed dominant-active (DA) human Akt1 or Rac1(G12V) (DARac1) at ptf1a domain and investigated transgenic phenotypes and mechanisms leading to gliomagenesis.ResultsTransgene expressions were spatiotemporally restricted without any developmental abnormality of embryos and persisted at cerebellum and  medulla in adult zebrafish. DAAkt1 alone induced glioma (with visible bumps at the head), with incidences of 36.6% and 49% at 6 and 9 months, respectively. Histologically, gliomas showed various histologic grades, increased proliferation, and frequent invasion into the fourth ventricle. Preferential location of small tumors at periventricular area and coexpression of Her4 suggested that tumors originated from Ptf1a- and Her4-positive progenitor cells at ventricular zone. Gliomagenesis was principally mediated by activation of survival pathway through upregulation of survivin genes. Although DARac1 alone was incapable of gliomagenesis, when coexpressed with DAAkt1, gliomagenesis was accelerated, showing higher tumor incidences (62.0% and 73.3% at 6 and 9 months,  respectively), advanced histologic grade, invasiveness, and shortened survival. DARac1 upregulated survivin2, cyclin D1, beta-catenin, and snail1a but downregulated E-cadherin, indicating that DARac1 promotes gliomagenesis by enhancing proliferation, survival, and epithelial-to-mesenchymal transition. On pharmacologic tests, only Akt1/2 inhibitor effectively suppressed gliomagenesis,  inhibited cellular proliferation, and induced apoptosis in established gliomas.ConclusionsThe zebrafish model reinforces the pivotal role of Akt signaling in gliomagenesis and suggests Rac1 as an important protein involved in  progression.

 

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[513]

TÍTULO / TITLE:  - Modified one-piece extended transbasal approach for translamina terminalis resection of retrochiasmatic third ventricular craniopharyngioma.

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

REVISTA / JOURNAL:  - Neurosurg Focus. 2013 Jan;34(1):1. doi: 10.3171/2013.V1.FOCUS12354.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2013.V1.FOCUS12354

AUTORES / AUTHORS:  - Liu JK

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and Otolaryngology-Head and Neck Surgery, Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey.

RESUMEN / SUMMARY:  - Retrochiasmatic third ventricular craniopharyngiomas are formidable tumors to remove surgically. Access to the third ventricle can be achieved through the lamina terminalis corridor. A skull base approach to the lamina terminalis can be performed using either an anterolateral approach (orbitozygomatic, pterional, supraorbital) or a midline approach (extended transbasal, subfrontal). The major  disadvantage of an anterolateral approach is the lack of visualization of the ipsilateral wall of the third ventricle and hypothalamus. However, a midline transbasal approach eliminates this blind spot thereby providing direct visualization of both ependymal walls for safe dissection of the tumor. In this operative video manuscript, the author demonstrates an illustrative step-by-step  technique for translamina terminalis resection of a retrochiasmatic retroinfundibular craniopharyngioma within the third ventricle via a modified one-piece extended transbasal approach. This approach uses the standard bifrontal craniotomy and incorporates the anterior wall of the frontal sinus as a one-piece flap. The inferior limit of the osteotomy is based along the coronal contour of the anterior skull base which eliminates any bony overhang that can obstruct the  line of sight to the lamina terminalis. Additional removal of the supraorbital bar is not necessary. The operative technique for this skull base approach and surgical nuances for craniopharyngioma resection are illustrated in this video atlas. The video can be found here: http://youtu.be/E3Bsp6dUdAE .

 

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[514]

TÍTULO / TITLE:  - TGF-beta1 enhances tumor-induced angiogenesis via JNK pathway and macrophage infiltration in an improved zebrafish embryo/xenograft glioma model.

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

REVISTA / JOURNAL:  - Int Immunopharmacol. 2012 Dec 21;15(2):191-198. doi: 10.1016/j.intimp.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.intimp.2012.12.002

AUTORES / AUTHORS:  - Yang XJ; Chen GL; Yu SC; Xu C; Xin YH; Li TT; Shi Y; Gu A; Duan JJ; Qian C; Cui YH; Zhang X; Bian XW

INSTITUCIÓN / INSTITUTION:  - Key Laboratory of Tumor Immunopathology, Third Military Medical University, Ministry of Education of China, China; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing,  China.

RESUMEN / SUMMARY:  - Angiogenesis plays a crucial role at the early stage of tumorigenesis and tumor progression. A suitable model will be useful not only for the clarification of the underlying molecular mechanisms, but also for high-throughput identification  of novel anti-angiogenesis compounds. Here, we established a zebrafish model for  the purpose to investigate angiogenesis and screen anti-angiogenic compounds. Glioma U87 cells expressing red fluorescent protein (RFP) were transplanted in fli:GFP transgenic zebrafish embryos where significant angiogenesis was observed. TGF-beta1 enhanced glioma-induced angiogenesis, which was inhibited by JNK inhibitor SP600125 but not p38 MAPK inhibitor SB202190, ERK inhibitor PD98059, or PI3K inhibitor LY294002, indicating the important role of TGF-beta1 and JNK pathways in this process. Moreover, the glioma-induced angiogenesis was associated with macrophage infiltration that was further enhanced by TGF-beta1. Therefore, our zebrafish model provides a powerful in vivo tool for the investigation of tumor-induced angiogenesis, and a cost-effective system for high-throughput screening of anti-angiogenic compounds.

 

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[515]

TÍTULO / TITLE:  - Hypothalamus-referenced classification for craniopharyngiomas: evidence provided  by the endoscopic endonasal approach.

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

REVISTA / JOURNAL:  - Neurosurg Rev. 2012 Dec 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10143-012-0439-5

AUTORES / AUTHORS:  - Pascual JM; Prieto R; Dufourny IC; Simoes RG; Carrasco R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, La Princesa University Hospital, C/ Diego de Leon 62, 28006, Madrid, España, jmpasncj@hotmail.com.

 

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[516]

TÍTULO / TITLE:  - A catalogue of glioblastoma and brain MicroRNAs identified by deep sequencing.

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

REVISTA / JOURNAL:  - OMICS. 2012 Dec;16(12):690-9. doi: 10.1089/omi.2012.0069.

            ●● Enlace al texto completo (gratuito o de pago) 1089/omi.2012.0069

AUTORES / AUTHORS:  - Hua D; Mo F; Ding D; Li L; Han X; Zhao N; Foltz G; Lin B; Lan Q; Huang Q

INSTITUCIÓN / INSTITUTION:  - Systems Biology Division, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, China.

RESUMEN / SUMMARY:  - Glioblastoma is the most common and aggressive primary brain tumor. MicroRNAs (miRNAs) are a set of noncoding RNA of about 20 approximately 22 nt in length and they play regulatory roles such as regulating the expression of proteins. Altered miRNA expression is related to cancers, including glioblastoma. In this report, we used deep sequencing to explore the miRNA profiles of glioblastoma and normal  brain tissues. We found 875 and 811 known miRNA and miRNA* in glioblastoma and normal brain tissue, respectively, representing the largest characterization of the miRNAs in GBM so far. 33 of them were upregulated in glioblastoma, including  miR-21, which is well known as an oncomir, while 40 of them were downregulated. Using miR-10b, miR-124, miR-433, and miR-92b as examples, we verified the data by quantitative RT-PCR, suggesting that deep sequencing was able to capture the expression profiles of miRNAs. In addition, we found 18 novel miRNA and 16 new miRNA* in glioblastoma and normal brain tissues. This report provides a useful resource for future studies of the roles of miRNAs in the pathogenesis and early  detection of glioblastoma.

 

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[517]

TÍTULO / TITLE:  - Mature posterior fossa teratoma mimicking dermoid cyst.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0129-6

AUTORES / AUTHORS:  - Bohara M; Yonezawa H; Karki P; Bakhtiar Y; Hirano H; Kitazono I; Matsuyama N; Arita K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan, bohara_manoj@hotmail.com.

RESUMEN / SUMMARY:  - We describe a very rare case of mature posterior fossa teratoma in an adult who presented with clinico-radiological findings consistent with a dermoid cyst. A computed tomography scan showed a hypodense mass in the cistern magna with calcification and a sinus tract in the occipital bone. Magnetic resonance imaging revealed a hypo- to hyperintense mass without contrast enhancement. The intraoperative picture showed a dermal sinus and a cyst containing lipid, keratin and hair. Histopathological examination showed a tumor with components of all the three germ layers; thereby, a diagnosis of mature teratoma was made. The histopathological differentiation between teratoma and dermoid cyst is very valuable for ruling out the presence of immature/malignant or germinomatous components that would require further adjuvant therapies. Thus, we here present a rare case of posterior fossa teratoma mimicking dermoid cyst and emphasize the importance of histopathological differentiation between these entities.

 

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[518]

TÍTULO / TITLE:  - Chronic encapsulated expanding hematoma in nonfunctioning pituitary adenoma.

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

REVISTA / JOURNAL:  - Neurosurg Rev. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10143-013-0449-y

AUTORES / AUTHORS:  - Sugawara T; Aoyagi M; Tanaka Y; Tamaki M; Kobayashi D; Ohno K

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima,  Bunkyo-ku, Tokyo, 113-8519, Japan, sugawara.nsrg@tmd.ac.jp.

RESUMEN / SUMMARY:  - The diagnosis and treatment of pituitary macroadenomas with entire hematoma fluid accumulation are problematic. Such lesions are often difficult to completely resect, and recurrence is not uncommon. We present five cases of pituitary macroadenomas entirely composed of hematoma fluid and investigated their histopathology to clarify the mechanism of the hematoma fluid accumulation. Five  patients with pituitary adenoma and significant intra-tumor hematoma underwent transsphenoidal resection and were retrospectively reviewed for their clinical status, findings on magnetic resonance imaging (MRI), intraoperative findings, and histopathology. The specific surgical techniques used to address these cases  were also reviewed. All patients were diagnosed with nonfunctioning pituitary adenomas by histopathological examination. MRI showed all tumors extended to the  cavernous sinus. Histopathology showed tumor tissues were located between the thick granulation tissue and the pseudocapsule of the tumor. The thick granulation tissues were composed of collagenous layers, neovascular vessels, and necrotic red blood cells, indicating repeat hemorrhage from the granulation tissues. The boundary between adenoma and normal pituitary gland was identified during surgical removal in four patients and was not identified in the other patient who showed a recurrence 2 years later. Clinical and histopathological findings indicate hematoma fluid accumulation in the present cases is caused by repeat hemorrhage from the reactive granulation tissues and can be regarded as a  chronic encapsulated expanding hematoma. In these cases, the boundary between adenoma and normal pituitary gland should be identified before puncturing the hematoma fluid to minimize the risk of tumor recurrence.

 

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[519]

TÍTULO / TITLE:  - Intracranial germ cell tumors at unusual locations.

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

REVISTA / JOURNAL:  - J Postgrad Med. 2012 Oct;58(4):286-9. doi: 10.4103/0022-3859.105449.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0022-3859.105449

AUTORES / AUTHORS:  - Rana C; Krishnani N; Kumar R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Sanjay Gandhi Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

RESUMEN / SUMMARY:  - Germ cell tumor (GCT) is relatively uncommon in intracranial locations. They constitute ~ 0.3-0.6% of intracranial neoplasms and encompass a wide pathologic range. The majority occurs in young adults and occupies the midline locations like pineal gland followed by suprasellar compartment. These tumors are rare in the cerebral hemisphere, basal ganglia, thalamus and ventricles. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histological confirmation. Germ cell tumors can be divided into  major groups including germinomas and nongerminomatous GCTs (NGGCTs). Their proper identification as well as histopathological typing is important as treatment and prognosis vary greatly between different groups. Germinomas have a  superior prognosis and are more radiosensitive as compared to non-germinomatous germ cell tumors. Standard management is still controversial. In this case series we are presenting three cases of intracranial germ cell tumors arising in two unusual locations, that is intraventricular and thalamic region. Apart from the clinical, radiological, histopathological and surgical details we also discuss the various aspects of intracranial germ cell tumors.

 

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[520]

TÍTULO / TITLE:  - GDNF mediates glioblastoma-induced microglia attraction but not astrogliosis.

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

REVISTA / JOURNAL:  - Acta Neuropathol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00401-013-1079-8

AUTORES / AUTHORS:  - Ku MC; Wolf SA; Respondek D; Matyash V; Pohlmann A; Waiczies S; Waiczies H; Niendorf T; Synowitz M; Glass R; Kettenmann H

INSTITUCIÓN / INSTITUTION:  - Department of Cellular Neuroscience, Max Delbruck Center for Molecular Medicine (MDC), Robert Rossle Str. 10, 13125, Berlin, Germany.

RESUMEN / SUMMARY:  - High-grade gliomas are the most common primary brain tumors. Their malignancy is  promoted by the complex crosstalk between different cell types in the central nervous system. Microglia/brain macrophages infiltrate high-grade gliomas and contribute to their progression. To identify factors that mediate the attraction  of microglia/macrophages to malignant brain tumors, we established a glioma cell  encapsulation model that was applied in vivo. Mouse GL261 glioma cell line and human high-grade glioma cells were seeded into hollow fibers (HF) that allow the  passage of soluble molecules but not cells. The glioma cell containing HF were implanted into one brain hemisphere and simultaneously HF with non-transformed fibroblasts (controls) were introduced into the contralateral hemisphere. Implanted mouse and human glioma- but not fibroblast-containing HF attracted microglia and up-regulated immunoreactivity for GFAP, which is a marker of astrogliosis. In this study, we identified GDNF as an important factor for microglial attraction: (1) GL261 and human glioma cells secret GDNF, (2) reduced  GDNF production by siRNA in GL261 in mouse glioma cells diminished attraction of  microglia, (3) over-expression of GDNF in fibroblasts promoted microglia attraction in our HF assay. In vitro migration assays also showed that GDNF is a  strong chemoattractant for microglia. While GDNF release from human or mouse glioma had a profound effect on microglial attraction, the glioma-induced astrogliosis was not affected. Finally, we could show that injection of GL261 mouse glioma cells with GDNF knockdown by shRNA into mouse brains resulted in reduced tumor expansion and improved survival as compared to injection of control cells.

 

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[521]

TÍTULO / TITLE:  - Precocious puberty produced by an osteolipoma of the tuber cinereum.

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

REVISTA / JOURNAL:  - J Pediatr Endocrinol Metab. 2012;25(11-12):1165-8. doi: 10.1515/jpem-2012-0192.

            ●● Enlace al texto completo (gratuito o de pago) 1515/jpem-2012-0192

AUTORES / AUTHORS:  - Vivanco-Allende A; Garcia-Gonzalez M; Gonzalez-Jimenez D; Perez-Guirado A; Fernandez I; Gomez-Illan R

RESUMEN / SUMMARY:  - Abstract Central precocious puberty (CPP) is fairly common in girls. In most girls, the etiology for the CPP is unknown. Among the more rare causes of CPP in  girls are central nervous system tumors and hamartomas. Osteolipoma of the tuber  cinereum, which is the most commonly diagnosed at autopsy, has been reported as a cause of CPP. We describe an 8-year-old girl with central precocious puberty in whom MRI demonstrated a lesion compatible with osteolipoma. Her symptom was breast development that begun at age 7 years and 9 months. Her case history, laboratory studies and imaging are presented. Her puberty was rapidly progressive. She was treated successfully with a GnRHa (Triptorelin 3.75 mg IM q  4 weeks). Her case brings to the forefront the need to perform an MRI in children with rapidly progressing puberty.

 

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[522]

TÍTULO / TITLE:  - Medulloblastoma.

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

REVISTA / JOURNAL:  - Clin Oncol (R Coll Radiol). 2013 Jan;25(1):36-45. doi: 10.1016/j.clon.2012.09.008. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clon.2012.09.008

AUTORES / AUTHORS:  - Bartlett F; Kortmann R; Saran F

INSTITUCIÓN / INSTITUTION:  - Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.

RESUMEN / SUMMARY:  - Medulloblastomas are primary malignant embryonal tumours of the central nervous system. They are the most common childhood central nervous system tumour, but are rare in the adult population. They arise infratentorially in the cerebellum or fourth ventricle and hence the most common presenting symptoms are those associated with raised intracranial pressure. Several histological subtypes have  been described, although the classical and desmoplastic subtypes account for the  majority. Recent advances in molecular biology and cytogenetics have led to an improved understanding of the genetic abnormalities and alterations in cell signalling pathways associated with medulloblastomas, including how these relate  to patient outcome. The Modified Chang Staging System is still in use, but a number of other factors, including age, completeness of resection, histological subtype and genetic markers now contribute to treatment decisions and prognostication. Patients are currently classified as being either standard or high risk in order to stratify treatment. There has been an improvement in survival of all groups over the past 20 years. A multimodality approach is the cornerstone of treatment and recent trials have concentrated on ascertaining the  most efficacious treatment combinations and timings for each patient group. Advances in surgical techniques have allowed a greater attainment of the two primary surgical goals: restoring normal cerebrospinal fluid (CSF) flow and maximal tumour resection. Radiotherapy to the craniospinal axis with a boost to the posterior fossa has been standard practice, but improvement in radiotherapy techniques and quality control has enabled optimisation of the trade-off between  tumour control and normal tissue late toxicities. Combination chemotherapy is usually given adjuvantly, although it may be used to delay or avoid the use of radiotherapy in infants. In the future, the treatment of medulloblastoma will probably become increasingly individualised, based on patient-specific genetic features. Attention will be focussed not only on improving survival, but also on  maintaining quality of life.

 

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[523]

TÍTULO / TITLE:  - Mitochondrial complex II and genomic imprinting in inheritance of paraganglioma tumors.

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

REVISTA / JOURNAL:  - Biochim Biophys Acta. 2013 Jan 2. pii: S0005-2728(12)01105-X. doi: 10.1016/j.bbabio.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.bbabio.2012.12.005

AUTORES / AUTHORS:  - Baysal BE

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.  Electronic address: bora.baysal@roswellpark.org.

RESUMEN / SUMMARY:  - Germ line heterozygous mutations in the structural subunit genes of mitochondrial complex II (succinate dehydrogenase; SDH) and the regulatory gene SDHAF2 predispose to paraganglioma tumors which show constitutive activation of hypoxia  inducible pathways. Mutations in SDHD and SDHAF2 cause highly penetrant multifocal tumor development after a paternal transmission, whereas maternal transmission rarely, if ever, leads to tumor development. This transmission pattern is consistent with genomic imprinting. Recent molecular evidence supports a model for tissue-specific imprinted regulation of the SDHD gene by a long range epigenetic mechanism. In addition, there is evidence of SDHB mRNA editing in peripheral blood mononuclear cells and long-term balancing selection operating on the SDHA gene. Regulation of SDH subunit expression by diverse epigenetic mechanisms implicates a crucial dosage-dependent role for SDH in oxygen homeostasis. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.

 

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[524]

TÍTULO / TITLE:  - An association of craniopharyngioma in turner syndrome.

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

REVISTA / JOURNAL:  - Pediatr Blood Cancer. 2012 Dec 19. doi: 10.1002/pbc.24411.

            ●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24411

AUTORES / AUTHORS:  - Farooque A; Atapattu N; Amarasena S; Hogler W; English MW; Kirk JM

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, Steelhouse Lane, Birmingham, United Kingdom.

RESUMEN / SUMMARY:  - Turner syndrome (TS) (approximately 1:5,000 births) and craniopharyngioma (CP) (1:50,000 children) are both rare conditions. We present three cases of TS with CP, an association not previously described. Visual failure, poor growth or headache led to MRI diagnosis of CP. Whilst two had evidence of hypopituitarism at diagnosis of CP, they all developed hypopituitarism following surgical debulking. Two required radiotherapy due to regrowth. Whether CP and TS share a similar aetiology is unknown. Clinicians need to be aware of this association, and should perform urgent MRI scanning in TS patients with headache, visual impairment or clinical/biochemical evidence of hypopituitarism. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.

 

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[525]

TÍTULO / TITLE:  - Soluble alpha-Klotho: A novel serum biomarker for the activity of growth hormone  producing pituitary adenomas.

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

REVISTA / JOURNAL:  - Eur J Endocrinol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-1045

AUTORES / AUTHORS:  - Neidert MC; Sze L; Zwimpfer C; Sarnthein J; Seifert B; Frei K; Leske H; Rushing EJ; Schmid C; Bernays R

INSTITUCIÓN / INSTITUTION:  - M Neidert, Department of Neurosurgery, University Hospital Zurich, Zurich, CH-8091, Switzerland.

RESUMEN / SUMMARY:  - OBJECTIVE: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble alpha-Klotho (alphaKL) is released into the circulation. In this study we present baseline alphaKL serum levels of patients with acromegaly compared to controls with other pituitary adenomas, and assess changes following transsphenoidal surgery. DESIGN: Prospective controlled study. METHODS: We measured soluble alphaKL (sandwich ELISA) and IGF-1 (RIA) in sera of 14 patients  (8 females, 6 males) with active acromegaly and in 22 control patients (13 females, 9 males) operated for non GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. RESULTS: Soluble alpha-KL was high in the acromegaly group preoperatively (median 4217 pg/ml, IQR, 1812-6623 pg/ml), and declined after surgery during early follow-up (2-6 days) (median 645 pg/ml, IQR 550-1303 pg/ml) (p<0.001) and during late follow-up (2-3 months postop) (median 902 pg/ml, IQR 497-1340 pg/ml) (p<0.001). In controls, preoperative soluble alphaKL was significantly lower than in acromegalics, 532 pg/ml (400-77 pg/ml) (p<0.001). Following surgery, soluble alphaKL remained low during early and late  follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared  to controls. CONCLUSION: High soluble alphaKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble alphaKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and  acromegalics suggest that the rise in serum alphaKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

 

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[526]

TÍTULO / TITLE:  - Intracystic irradiation for craniopharyngiomas.

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

REVISTA / JOURNAL:  - Pituitary. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11102-012-0442-4

AUTORES / AUTHORS:  - Julow JV

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, St. John’s Hospital, Diosarok ut 1-3, 1125, Budapest, Hungary, h12494jul@ella.hu.

RESUMEN / SUMMARY:  - Data collected over a 36-year period were used to assess the value of stereotactically applied intracystic colloidal yttrium-90 (YTx) for the treatment of recurrent cystic craniopharyngiomas (CRF’s). The article compares data from 95 YTx procedures carried out on 78 patients during the years 1975 and 2011, using a cumulative beta dose of 270 Gy aimed at the inner surface of the cyst wall. After YTx, the initial cyst volumes decreased an average of 74.7 %. In 54 patients, the volume reduction exceeded 80 %. In 32 patients, the cyst disappeared completely within one year. The mean survival rate following YTx was 7.5 years (range 0.7-31 years). The survival rates at 5, 10, 15, 20, 25, and 30 years were 56, 29, 15, 8, 3, and 1 %, respectively. Late complications of YTx were related to the anatomical location of the cyst, either presellar or retrosellar. A presellar, that is, prechiasmatic/suprasellar localization resulted in neuro-ophthalmological complications in 5.1 % of the cases, while internal carotid artery injury accounted for 1.4 % of the complications. The treatment of  retrosellar (retrochiasmatic, suprasellar) tumors may cause hypothalamic, fornix, or pontomesencephalothalamic damage, from untoward radiation to the so-called perforating arteries. This complication occurred in 5.2 % of the cases. In the multimodality management of craniopharyngioma cysts, intracavity YTx irradiation  is a valuable treatment alternative despite sporadic complications arising in some surgical cases. The formula for the calculation of the dynamics of reduction of CRF’s following yttrium-90 colloid brachytherapy was supported by correlating  the collected data. The focus was on our minimally invasive YTx following multiple surgeries of cystic CRFs.

 

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[527]

TÍTULO / TITLE:  - Preoperative endovascular embolization for hemangioblastoma in the posterior fossa.

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

REVISTA / JOURNAL:  - Neurol Med Chir (Tokyo). 2012;52(12):878-84.

AUTORES / AUTHORS:  - Sakamoto N; Ishikawa E; Nakai Y; Akutsu H; Yamamoto T; Nakai K; Shiigai M; Tsurushima H; Isobe T; Takano S; Tsuboi K; Matsumura A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Comprehensive Human Sciences.

RESUMEN / SUMMARY:  - Intracranial hemangioblastomas (HBs) are hypervascular neoplasms mainly located in the posterior fossa of the central nervous system. Preoperative embolization of the feeding arteries is one proposal for reduction of intraoperative hemorrhage, although indications for the procedures should be evaluated carefully due to the potential complications. This retrospective study investigated clinical outcomes and complications of 15 patients with HBs in the posterior fossa to evaluate the safety and effectiveness of endovascular procedures as well as angiographical procedures. Surgical excision without presurgical embolization  was performed in 8 cases, and excision with presurgical embolization was performed in 7 cases, using Guglielmi detachable coils with or without polyvinyl  alcohol (GDC +/- PVA) in 4 cases and only n-butyl 2-cyanoacrylate (NBCA) in 3 cases. The embolization was applied for selected cases in which feeding arteries  were located in a deep site and hard to coagulate surgically. Partial embolization was achieved in 5 cases, and all feeders were successfully embolized in 2 cases. Total removal was achieved in 12 cases, and subtotal/partial removal  was achieved in 3 cases. Subarachnoid hemorrhage with intratumoral hemorrhage occurred in 1 case during the angiographic procedure and in 1 case during the embolization procedures. The mean volume of intraoperative blood loss was clearly less in the NBCA group than in the GDC +/- PVA group. HBs are mainly located in the posterior cranial fossa, so the risk of severe clinical complication may be high if vascular problems occur. In our series, presurgical embolization using NBCA made tumor removal safe and reduced bleeding volume in posterior fossa HBs.

 

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[528]

TÍTULO / TITLE:  - Paraganglioma of the maxillary sinus.

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

REVISTA / JOURNAL:  - Auris Nasus Larynx. 2012 Dec 18. pii: S0385-8146(12)00228-3. doi: 10.1016/j.anl.2012.10.009.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.anl.2012.10.009

AUTORES / AUTHORS:  - Kisser U; Braun T; Mayr D; Leunig A

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich, Germany. Electronic address: Ulrich.Kisser@med.uni-muenchen.de.

RESUMEN / SUMMARY:  - Primary paragangliomas of the paranasal sinuses are very rare conditions with only few cases described in the literature. Paragangliomas are locally aggressive, often recur and can metastasize. Usually, open surgery is used to resect such tumors from the sinonasal tract. Here, a case of a large paraganglioma of the left maxillary sinus and nasal cavity, which was successfully removed using the Onyx(®) embolic agent two days prior to minimally invasive image guided endoscopic sinus surgery, is reported. This case  demonstrates that large vascular tumors of the sinonasal tract can be successfully managed by endoscopic endonasal sinus surgery. The patient has no evidence of recurrence after 12 months of follow-up.

 

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[529]

TÍTULO / TITLE:  - Primary cutaneous CD30-positive anaplastic large-cell lymphoma of the external auditory canal.

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

REVISTA / JOURNAL:  - Ear Nose Throat J. 2012 Dec;91(12):E10-2.

AUTORES / AUTHORS:  - Marcal N; Campelos S; Dias L; Goncalves M; Pereira G; Godinho T

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology, Hospital de Sao Marcos, Sete Fontes, S. Victor 4701-243 Braga, Portugal. nunomarcal.orl@gmail.com.

RESUMEN / SUMMARY:  - Primary cutaneous T-cell lymphoma is rare. Cutaneous lymphoma is defined as primary when there is an absence of nodal or systemic disease during the first 6  months following diagnosis. We report what we believe to be the first documented  case of a primary cutaneous CD30-positive anaplastic large-cell lymphoma of the external auditory canal. The patient was an elderly woman who presented with progressively worsening right otalgia and hypoacusis. Otoscopy revealed an erythematic, ulcerative, nonbleeding, localized lesion in the anterosuperior area of the external auditory canal. The patient underwent an excisional biopsy, and after the diagnosis was established, she underwent 22 sessions of radiotherapy. During follow-up, she exhibited no evidence of recurrence.

 

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[530]

TÍTULO / TITLE:  - Hypothalamic Hamartomas: Neuropathological Features with and without Prior Gamma  Knife Radiosurgery.

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

REVISTA / JOURNAL:  - Stereotact Funct Neurosurg. 2012 Nov 29;91(1):45-55.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000341076

AUTORES / AUTHORS:  - Kerrigan JF; Parsons A; Rice SG; Simeone K; Shetter AG; Abla AA; Prenger E; Coons SW

INSTITUCIÓN / INSTITUTION:  - Hypothalamic Hamartoma Program, Phoenix Children’s Hospital, Phoenix, Ariz.,USA.

RESUMEN / SUMMARY:  - Background: The neuropathological consequences of Gamma Knife radiosurgery (GK) on hypothalamic hamartoma (HH) are unknown. Objective: In a cohort of patients undergoing surgery for treatment-resistant epilepsy, we compared surgically resected HH tissue from patients without (group I; n = 19) and with (group II; n  = 10) a history of GK (median dose 16 Gy to the 50% isodose margin). Methods: Techniques included thick-section stereology for total nucleated and total neuron cell counts, and thin-section immunohistochemistry. Normal human hypothalamus derived from age-matched autopsy material was used as control tissue for CD68 immunohistochemistry. Qualitative scoring of tissue sections was performed by a neuropathologist who was blind to the GK treatment history. Results: GK is associated with decreased total cell density (p < 0.02). A dose-dependent association of GK with decreased total neuron density approached significance (p  = 0.06). Group II HH tissue had significantly more (1) reactive gliosis, (2) thickened capillary endothelium and (3) microglial activation. Degenerative features, including karyorrhexis and pyknotic nuclei, were infrequent in group II and absent in group I HH tissue. Conclusions: Nonnecrotizing doses of GK radiosurgery decrease cell density in human HH tissue. Cell loss resulting from GK may contribute to decreased excitation in the neuronal networks responsible for seizure onset in HH tissue.

 

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[531]

TÍTULO / TITLE:  - Extraventricular neurocytoma of the sellar region with spinal dissemination.

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

REVISTA / JOURNAL:  - Brain Tumor Pathol. 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10014-012-0128-7

AUTORES / AUTHORS:  - Kawaji H; Saito O; Amano S; Kasahara M; Baba S; Namba H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shizuoka Red Cross Hospital, 8-2 Ottecho, Aoi-ku, Shizuoka, 420-0853, Japan.

RESUMEN / SUMMARY:  - Extraventricular neurocytoma (EVN) is a rare tumor that mainly occurs in the cerebral hemispheres and spinal cord. Sellar neurocytoma is extremely rare, with  only two previously reported cases. We report a sellar EVN in a 48-year-old man presenting with visual impairment. This tumor was partially resected. The residual tumor disappeared on MRI with adjuvant radiotherapy. However, 2 years later the tumor recurred with craniospinal dissemination, which is also very rare, with only four previously reported cases. The recurrent tumor showed atypical features with an MIB-1 LI score of 3 %. It is suggested that postoperative adjuvant radiation therapy with long-term follow-up is required for incompletely resected EVN.

 

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[532]

TÍTULO / TITLE:  - Primary extra-cranial meningioma of head and neck: clinical, histopathological and immunohistochemical study of three cases.

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

REVISTA / JOURNAL:  - Acta Otorhinolaryngol Ital. 2012 Oct;32(5):336-8.

AUTORES / AUTHORS:  - Possanzini P; Pipolo C; Romagnoli S; Falleni M; Moneghini L; Braidotti P; Salvatori P; Paradisi S; Felisati G

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, Surgery, Dentistry, University of Milan Medical School, Division of Pathology, AO “San Paolo” and Fondazione IRCCS Policlinico “Mangiagalli and Regina Elena”, Milan, Italy;

RESUMEN / SUMMARY:  - Extracranial meningiomas of the head and neck region are rare neoplasms, the majority being a secondary location of a primary intracranial tumour. We herewith report three rare cases of extracranial meningiomas, located in the temporal muscle, parotid gland and nasal cavity, together with complete pathological, immunohistochemical and ultrastructural studies. Prognosis of this tumour is generally excellent. Surgical excision is the treatment of choice, with no need for further treatment; nevertheless, differential diagnosis must consider other more common tumours of the head and neck and be based on histopathologic examination and relative techniques, including examination of frozen sections. This procedure is particularly useful assessing surgical treatment and should be  performed whenever possible to exclude the malignant nature of the lesion and avoid over-treatment. All three patients underwent surgery and are alive and disease-free.

 

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[533]

TÍTULO / TITLE:  - Rac1+ cells distributed in accordance with CD 133+ cells in glioblastomas and the elevated invasiveness of CD 133+ glioma cells with higher Rac1 activity.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4344-8.

AUTORES / AUTHORS:  - Zhang B; Sun J; Yu SP; Chen C; Liu B; Liu ZF; Ren BC; Ming HL; Yang XJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin  300052, China.

RESUMEN / SUMMARY:  - BACKGROUND: Recent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma (GBM) cells is  also implicated in the failure of current therapies, it is not clear how glioma stem cells (GSCs) are involved in invasiveness. Rac1 activity is necessary for inducing reorganization of actin cytoskeleton and cell movement. In this study, we aimed to investigate the distribution characteristics of CD133+ cells and Rac1+ cells in GBM as well as Rac1 activity in CD133+ GBM cells, and analyze the  migration and invasion potential of these cells. METHODS: A series of 21 patients with GBM were admitted consecutively and received tumor resection in Tianjin Medical University General Hospital during the first half of the year 2011. Tissue specimens were collected both from the peripheral and the central parts for each tumor under magnetic resonance imaging (MRI) navigation guidance. Immunohistochemical staining was used to detect the CD133+ cells and Rac1+ cells  distribution in GBM specimens. Double-labeling immunofluorescence was further used to analyze CD133 and Rac1 co-expression and the relationship between CD133+  cells distribution and Rac1 expression. Serum-free medium culture and magnetic sorting were used to isolate CD133+ cells from U87 cell line. Rac1 activation assay was conducted to assess the activation of Rac1 in CD133+ and CD133 - U87 cells. The migration and invasive ability of CD133+ and CD133 - U87 cells were determined by cell migration and invasion assays in vitro. Student’s t-test and one-way analysis of variance (ANOVA) test were used to determine statistical significance in this study. RESULTS: In the central parts of GBMs, CD133+ cells were found to cluster around necrosis and occasionally cluster around the vessels under the microscope by immunohistological staining. In the peripheral parts of the tumors, CD133+ cells were lined up along the basement membrane of the vessels and myelinated nerve fibers. Rac1 expression was high and diffused in the central parts of the GBMs, and the Rac1+ cells were distributed basically in accordance with CD133+ cells both in the central and peripheral parts of GBMs. In double-labeling immunofluorescence, Rac1 was expressed in (83.14 +/- 4.23)% of CD133+ cells, and CD133 and Rac1 co-expressed cells were located around the vessels in GBMs. Significantly higher amounts of Rac1-GTP were expressed in the CD133+ cells (0.378 +/- 0.007), compared to CD133- cells (0.195 +/- 0.004) (t = 27.81; P < 0.05). CD133+ cells had stronger ability to migrate (74.34 +/- 2.40 vs. 38.72 +/- 2.60, t = 42.71, P < 0.005) and invade (52.00 +/- 2.28 vs. 31.26 +/- 1.82, t = 30.76, P < 0.005), compared to their counterpart CD133- cells in transwell cell migration/invasion assay. CONCLUSIONS: These data suggest that CD133+ GBM cells highly express Rac1 and have greater potential to migrate and invade through activated Rac1-GTP. The accordance of distribution between Rac1+ cells and CD133+ cells in GBMs implies that Rac1 might be an inhibited target to  prevent invasion and migration and to avoid malignant glioma recurrence.

 

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[534]

TÍTULO / TITLE:  - Regulation of HGF Expression by DeltaEGFR-Mediated c-Met Activation in Glioblastoma Cells.

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

REVISTA / JOURNAL:  - Neoplasia. 2013 Jan;15(1):73-84.

AUTORES / AUTHORS:  - Garnett J; Chumbalkar V; Vaillant B; Gururaj AE; Hill KS; Latha K; Yao J; Priebe W; Colman H; Elferink LA; Bogler O

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, TX ; Graduate School of Biomedical Sciences, Cancer Biology Program, University of Texas MD Anderson Cancer Center, Houston, TX.

RESUMEN / SUMMARY:  - The hepatocyte growth factor receptor (c-Met) and a constitutively active mutant  of the epidermal growth factor receptor (DeltaEGFR/EGFRvIII) are frequently overexpressed in glioblastoma (GBM) and promote tumorigenesis. The mechanisms underlying elevated hepatocyte growth factor (HGF) production in GBM are not understood. We found higher, coordinated mRNA expression levels of HGF and c-Met  in mesenchymal (Mes) GBMs, a subtype associated with poor treatment response and  shorter overall survival. In an HGF/c-Met-dependent GBM cell line, HGF expression declined upon silencing of c-Met using RNAi or by inhibiting its activity with SU11274. Silencing c-Met decreased anchorage-independent colony formation and increased the survival of mice bearing intracranial GBM xenografts. Consistent with these findings, c-Met activation by DeltaEGFR also elevated HGF expression,  and the inhibition of DeltaEGFR with AG1478 reduced HGF levels. Interestingly, c-Met expression was required for DeltaEGFR-mediated HGF production, anchorage-independent growth, and in vivo tumorigenicity, suggesting that these pathways are coupled. Using an unbiased mass spectrometry-based screen, we show that signal transducer and activator of transcription 3 (STAT3) Y705 is a downstream target of c-Met signaling. Suppression of STAT3 phosphorylation with WP1193 reduced HGF expression in DeltaEGFR-expressing GBM cells, whereas constitutively active STAT3 partially rescued HGF expression and colony formation in c-Met knockdown cells expressing DeltaEGFR. These results suggest that the c-Met/HGF signaling axis is enhanced by DeltaEGFR through increased STAT3-dependent HGF expression and that targeting c-Met in Mes GBMs may be an important strategy for therapy.

 

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[535]

TÍTULO / TITLE:  - Radiation therapy quality in CCG/POG intergroup 9961: implications for craniospinal irradiation and the posterior fossa boost in future medulloblastoma  trials.

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

REVISTA / JOURNAL:  - Front Oncol. 2012;2:185. doi: 10.3389/fonc.2012.00185. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00185

AUTORES / AUTHORS:  - Donahue B; Marymont MA; Kessel S; Iandoli MK; Fitzgerald T; Holmes E; Kocak M; Boyett JM; Gajjar A; Packer RJ

INSTITUCIÓN / INSTITUTION:  - New York University School of Medicine New York, NY, USA.

RESUMEN / SUMMARY:  - Purpose: Associations of radiation therapy (RT) deviations and outcomes in medulloblastoma have not been defined well, particularly in the era of reduced-dose craniospinal irradiation and chemotherapy. The aim of this study is  to evaluate the quality of RT on Children’s Cancer Group/Pediatric Oncology Group 9961 and analyze associations of RT deviations with outcome. Materials and Methods: Major volume deviations were assessed based on the distance from specified anatomical region to field edge. We investigated associations of RT deviations with progression-free survival (PFS), overall survival (OS), and explored associations with demographics and clinical variables. Results: Of the 308 patients who were evaluable for volume deviations, 101 patients (33%) did not have any. Of the remaining 207 patients, 50% had only minor deviations, 29% had only major deviations, and 21% had both minor and major deviations. Of the patients with major deviations, 73% had a single major deviation. The most common major deviation was in the cribriform plate region, followed by the posterior fossa (PF); PF deviations resulted from treating less than whole PF. There were no significant differences in PFS or OS between patients with deviations and those without. There was no evidence of associations of deviations with patient age. Conclusions: Approximately one-third of patients had major volume deviations. There was no evidence of a significant association between these and  outcome. This lack of correlation likely reflects the current high quality of RT  delivered in Children’s Oncology Group institutions, our strict definition of volume deviations, and the relatively few instances of multiple major deviations  in individual patients. In is noteworthy that the types of PF volume deviations observed in this study were not adversely associated with outcome. As we move forward, quality assurance will continue to play an important role to ensure that deviations on study do not influence study outcome.

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[536]

TÍTULO / TITLE:  - alpha-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial.

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

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 27;12:623. doi: 10.1186/1471-2407-12-623.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-623

AUTORES / AUTHORS:  - Akiyama Y; Oshita C; Kume A; Iizuka A; Miyata H; Komiyama M; Ashizawa T; Yagoto M; Abe Y; Mitsuya K; Watanabe R; Sugino T; Yamaguchi K; Nakasu Y

INSTITUCIÓN / INSTITUTION:  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan. y.akiyama@scchr.jp.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: High-grade gliomas including glioblastoma multiforme (GBM)  are among the most malignant and aggressive of tumors, and have a very poor prognosis despite a temozolomide-based intensive treatment. Therefore, a novel therapeutic approach to controlling recurrence is needed. In the present study, we investigated the effect of activated dendritic cell (DC) (alpha-type-1 polarized DC)-based immunotherapy on high-grade glioma patients with the HLA-A2 or A24 genotype. METHODS: Nine patients with recurrent high-grade gliomas including 7 with GBMs who fulfilled eligibility criteria were enrolled into a phase I study of monocyte-derived DC-based immunotherapy. HLA-genotyping revealed 1 case of HLA-A*0201 and 8 cases of A*2402. Enriched monocytes obtained using OptiPrepTM from leukapheresis products on day1, were incubated with GM-CSF and IL-4 in a closed serum-free system, and activated on day6 with TNF-alpha, IL-1beta, IFN-alpha, IFN-gamma, and poly I/C. After pulsing with a cocktail of 5  synthetic peptides (WT-1, HER2, MAGE-A3, and MAGE-A1 or gp100) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Thawed DCs were injected intradermally in the posterior neck at a dose per cohort of 1.0, 2.0 and 5.0x 107/body. RESULTS: The frequency of CD14+ monocytes increased to 44.6% from  11.9% after gradient centrifugation. After a 7-day-incubation with cytokines, the mean percentage of DCs rated as lin-HLA-DR+ in patients was 56.2 +/- 19.1%. Most  DCs expressed high levels of maturation markers, co-stimulatory molecules and type-1 phenotype (CD11c+HLA-DR+) with a DC1/2 ratio of 35.6. The amount of IL-12  produced from activated DCs was 1025 +/- 443 pg/ml per 105 cells. All 76 DC injections were well tolerated except for transient liver dysfunction with grade  II. Six patients showed positive immunological responses to peptides in an ELISPOT assay, and positive skin tests to peptide-pulsed DC and KLH were recognized in 4 cases. The clinical response to DC injections was as follows :1 SD and 8 PD. Interestingly, the SD patient, given 24 DC injections, showed a long-term recurrence-free and immunological positive response period. CONCLUSIONS: These results indicate peptide cocktail-treated activated alpha-type-1 DC-based immunotherapy to be a potential therapeutic tool against recurrent high-grade glioma with mainly HLA-A*2402. TRIAL REGISTRATION: Current non-randomized investigational trial UMIN-CTR UMIN ID: 000000914.

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[537]

TÍTULO / TITLE:  - Recurrent acute subdural bleeding as a rare complication of a hemorrhagic non malignant meningioma.

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

REVISTA / JOURNAL:  - JBR-BTR. 2012 Sep-Oct;95(5):309-12.

AUTORES / AUTHORS:  - Deprez FC; Finet P; Raftopoulos C; Duprez T

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Cliniques Universitaires St-Luc, Brussels, Belgium. fabrice.deprez@uclouvain.be

RESUMEN / SUMMARY:  - We report the case of a 66-year-old male patient who presented acute and sub-acute subdural hematomas complicating a grade I meningioma. In the absence of trauma, detection of a subdural hematoma necessitates an etiologic research, in particular the exclusion of a vascular anomaly or a tumour. Subdural bleeding as  a complication of a non malignant meningioma is a very rare and threatening situation and requires prompt surgical removal of the tumor.

 

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[538]

TÍTULO / TITLE:  - The impact on quality of life for people with brain tumours of entering a research trial involving new anti-cancer agents.

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

REVISTA / JOURNAL:  - Eur J Oncol Nurs. 2013 Jan 20. pii: S1462-3889(12)00128-7. doi: 10.1016/j.ejon.2012.12.003.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.ejon.2012.12.003

AUTORES / AUTHORS:  - Sutton K

INSTITUCIÓN / INSTITUTION:  - University College London Hospitals NHS Foundation Trust, T14 North Chemotherapy  Office, 235 Euston Road, London NW1 2BU, United Kingdom. Electronic address: katie.sutton@kcl.ac.uk.

RESUMEN / SUMMARY:  - PURPOSE: The intention of this study was to offer an alternative perspective to the quantitative findings of larger randomised controlled trials by using a phenomenological approach to explore the impact on Quality of Life (QoL) for people with brain tumours of entering a research trial involving new anti-cancer  agents. METHOD: Given the subjective nature of the proposed topic, a phenomenological approach was adopted. Sample size was limited to five participants. A semi-structured interview technique was used. Interviews were digitally audio recorded with permission from those involved. In order to guide data analysis for this study, Colaizzi’s framework was utilised. RESULTS: As a result of data analysis, two major themes were identified. These were ‘Hope and optimism’ and ‘The therapeutic relationship’. Three minor themes were also found. These were ‘A complex symptom profile’, ‘The importance of non-medical coping strategies’ and ‘Impressions of the QoL tools used’. CONCLUSIONS: This phenomenological study has highlighted key themes relating to QoL which are not addressed in some of the widely used assessment tools such as the EORTC QLQ C30 and BN20. They generally focus on health status, and do not capture issues identified in this study as being of significant importance to the QoL of participants such as hope and optimism, and the importance of the therapeutic relationship. They also omit reference to coping and management strategies.

 

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[539]

TÍTULO / TITLE:  - Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: A phase II study.

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

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):799-801. Epub 2012 Jul 5.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.788

AUTORES / AUTHORS:  - Santoni M; Paccapelo A; Burattini L; Bianconi M; Cardinali M; Fabbietti L; Trignani R; Rychlicki F; Cascinu S

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology.

RESUMEN / SUMMARY:  - O(6)-alkylguanine-DNA alkyltransferase (AGAT), involved in temozolomide-induced DNA damage repair, plays a key role in the efficacy of temozolomide. AGAT activity may be reduced by protracted temozolomide doses. On the basis of the preclinical findings, we treated patients with a histologically-proven diagnosis  of glioblastoma (GBM) following adjuvant temozolomide failure with a low protracted dose of temozolomide (130 mg/m(2)/day, days 1-7 and 15-21, every 4 weeks). The primary endpoint of the study was 6-month progression-free survival (PFS-6 m). The secondary endpoints were overall survival (OS) from the start of temozolomide alternative schedule and toxicity. Enrolment was ceased at 27 patients due to the lack of effectiveness of this regimen. Results indicate that  our schedule is well-tolerated, but ineffective in patients with GBM and further  strategies are required to improve the outcome of these patients.

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[540]

TÍTULO / TITLE:  - Fractionated stereotactic radiation therapy improves cranial neuropathies in patients with skull base meningiomas: a retrospective cohort study.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2012 Dec 28;7:225. doi: 10.1186/1748-717X-7-225.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-7-225

AUTORES / AUTHORS:  - Shen X; Andrews DW; Sergott RC; Evans JJ; Curran WJ; Machtay M; Fragoso R; Eldredge H; Champ CE; Witek M; Mishra MV; Dicker AP; Werner-Wasik M

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA. xshen@kumc.edu.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Skull base meningiomas commonly present with cranial neuropathies. Fractionated stereotactic radiation therapy (FSRT) has been used to treat these tumors with excellent local control, but rates of improvement in cranial neuropathies have not been well defined. We review the experience at Thomas Jefferson University using FSRT in the management of these patients with a focus on symptom outcomes. METHODS: We identified 225 cases of skull base meningiomas treated with FSRT at Thomas Jefferson University from 1994 through 2009. The target volume was the enhancing tumor, treated to a standard prescription dose of 54 Gy. Symptoms at the time of RT were classified based on the cranial nerve affected. Logistic regression was performed to determine predictors of symptom improvement after FSRT. RESULTS: The median follow-up time  was 4.4 years. In 92% of cases, patients were symptomatic at the time of RT; the  most common were impaired visual field/acuity (58%) or extraocular movements (34%). After FSRT, durable improvement of at least one symptom occurred in 57% of cases, including 40% of visual acuity/visual field deficits, and 40% of diplopia/ptosis deficits. Of all symptomatic patients, 27% experienced improvement of at least one symptom within 2 months of the end of RT. CONCLUSIONS: FSRT is very effective in achieving improvement of cranial neuropathies from skull base meningiomas, particularly visual symptoms. Over half of treated patients experience a durable improvement of at least one symptom, frequently within 2 months from the end of RT.

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[541]

TÍTULO / TITLE:  - Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients.

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

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.PEDS12265

AUTORES / AUTHORS:  - Due-Tonnessen BJ; Lundar T; Egge A; Scheie D

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Object The objective of this study was to delineate the long-term results of surgical treatment of pediatric low-grade cerebellar astrocytoma. Methods One hundred consecutive children and adolescents (0-19 years old) who underwent primary tumor resection for a low-grade cerebellar astrocytoma during the years 1980-2011 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. Results Of the 100 patients, 61 children were in the 1st decade, and 39 were 10-19 years old. The male/female ratio was 1.13:1 (53 males, 47 females). No patients were lost to follow-up. There were no deaths in this series and all 100  patients are currently alive. In 29 patients, the follow-up duration was less than 10 years, in 37 it was between 10 and 19 years, and in 34 it was between 20  and 31 years. The Barthel Index was 100 (normal) in 97 patients, 90 in 2 patients, and 40 in the last patient. A total of 113 tumor resections were performed. Two patients underwent further tumor resection due to MRI-confirmed residual tumor demonstrated on the immediate postoperative MR image (obtained the day after the initial procedure). Furthermore, 9 children underwent repeat tumor  resection after MRI-confirmed progressive tumor recurrence up to 10 years after the initial operation. Two of these patients also underwent a third resection, without subsequent radiation therapy, and have experienced 8 and 12 years of tumor-free follow-up thereafter, respectively. A total of 15% of the patients required treatment for persistent hydrocephalus. Conclusions Low-grade cerebellar astrocytoma is a surgical disease, in need of long-term follow-up, but with excellent long-term results. Nine percent of the children in this study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus.

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[542]

TÍTULO / TITLE:  - Long-term health-related quality of life of surgically treated pituitary adenoma  patients: a descriptive study.

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

REVISTA / JOURNAL:  - ISRN Endocrinol. 2012;2012:675310. doi: 10.5402/2012/675310. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 5402/2012/675310

AUTORES / AUTHORS:  - Raappana A; Pirila T; Ebeling T; Salmela P; Sintonen H; Koivukangas J

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology-Head & Neck Surgery, Institute of Clinical Medicine, University of Oulu, Oulu, Finland.

RESUMEN / SUMMARY:  - Context. The literature concerning the health-related quality of life (HRQoL) of  patients with surgically treated PA is controversial. Objective. To describe the  long-term HRQoL of surgically treated patients in all PA classes. Design and subjects. The 15D, a generic HRQoL instrument producing a 15-dimensional profile  and a single 15D index score (a difference >/=0.03 on a 0-1 scale is considered clinically important), was used to assess the HRQoL of a 13-year surgical cohort  of PA patients in Northern Finland. Results and Conclusion. Nighty-eight eligible consecutive patients with surgically treated PA were studied at an average of 6.3 years after their latest pituitary operation. The average postoperative 15D profiles in patients with non-functioning PA and in acromegalics without GH-suppressive medical treatment were similar to those of the age-standardized general population. However, after this rather long followup, the mean 15D score  and the number of statistically significant 15D dimension impairments, compared with those of their reference population, were 0.11 and 9/15, 0.10 and 3/15, and  0.08 and 7/15 for Cushing’s disease, acromegalics needing somatostatin analog, and prolactinoma patients, respectively. Hypopituitarism with replacement medication was not associated with impaired HRQoL. The somatostatin-analog-associated HRQoL finding warrants further clinical research.

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[543]

TÍTULO / TITLE:  - Diffusion-weighted magnetic resonance imaging findings in a patient with trigeminal ganglioneuroma.

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

REVISTA / JOURNAL:  - Korean J Radiol. 2013 Jan;14(1):118-21. doi: 10.3348/kjr.2013.14.1.118. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 3348/kjr.2013.14.1.118

AUTORES / AUTHORS:  - Kim SK; Jeong MY; Kang HK; Yoon W

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju 501-757, Korea.

RESUMEN / SUMMARY:  - A case of intracranial ganglioneuroma arising from the trigeminal nerve in the pontine and cerebellopontine angle cistern, in a 44-year-old female, is presented with an emphasis on diffusion-weighted imaging findings. We will discuss on how the tumor in the very unusual location should be differentiated particularly focused on diffusion-weighted imaging findings.

 

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[544]

TÍTULO / TITLE:  - Intravitreal injection of anti-VEGF and diagnosis of primary intraocular central  nervous system lymphoma.

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

REVISTA / JOURNAL:  - J Fr Ophtalmol. 2013 Jan 7. pii: S0181-5512(12)00397-X. doi: 10.1016/j.jfo.2012.11.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jfo.2012.11.005

AUTORES / AUTHORS:  - Gambrelle J; Missotten G; Delhoum S; Desjardins L

INSTITUCIÓN / INSTITUTION:  - Service d’ophtalmologie, CHU de Brest, 2, avenue Foch, 29609 Brest, France. Electronic address: joel.gambrelle@hotmail.fr.

RESUMEN / SUMMARY:  - We report a case of primary intraocular central nervous system (CNS) lymphoma in  a patient previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD). An 88-year-old woman, with past medical history significant for bilateral age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections for 1year, was referred to our department for bilateral vitritis diagnosed 10days after the last anti-VEGF injection. A complete uveitis work-up including aqueous humour analysis, brain MRI and vitreous biopsy enabled us to confirm the diagnosis of primary intraocular CNS lymphoma. To the best of our knowledge, this is the first report of the diagnosis of primary intraocular CNS lymphoma in a patient treated with anti-VEGF for AMD. The differential diagnosis  of vitritis in elderly patients is relatively broad. Endophthalmitis and uveitis  have been described after anti-VEGF injections. In such a situation, there is actually a risk of missing the diagnosis of intraocular lymphoma in the mistaken  belief that the observed vitritis may be a reaction to administered anti-VEGFs. If no direct time-relationship with the anti-VEGF injections can be found, a classic vitritis work-up should be performed. Our observation suggests that ranibizumab, at the dosage used for AMD, does not impede the spread of CNS lymphoma in the eye nor interfere with cytological diagnosis.

 

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[545]

TÍTULO / TITLE:  - Targeting of TGFbeta signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma.

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

REVISTA / JOURNAL:  - RNA. 2013 Feb;19(2):177-90. doi: 10.1261/rna.036467.112. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1261/rna.036467.112

AUTORES / AUTHORS:  - Fox JL; Dews M; Minn AJ; Thomas-Tikhonenko A

RESUMEN / SUMMARY:  - The miR-17 approximately 92 cluster is thought to be an oncogene, yet its expression is low in glioblastoma multiforme (GBM) cell lines. This could allow unfettered expression of miR-17 approximately 92 target genes such as connective  tissue growth factor (CTGF; or CCN2), which is known to contribute to GBM pathogenesis. Indeed, microRNA-18a (but not other miR-17 approximately 92 members) has a functional site in the CTGF 3’ UTR, and its forced reexpression sharply reduces CTGF protein and mRNA levels. Interestingly, it also reduces the  levels of CTGF primary transcript. The unexpected effects of miR-18a on CTGF transcription are mediated in part by direct targeting of Smad3 and ensuing weakening of TGFbeta signaling. Having defined the TGFbeta signature in GBM cells, we demonstrate a significant anti-correlation between miR-18 and TGFbeta signaling in primary GBM samples from The Cancer Genome Atlas. Most importantly,  high levels of miR-18 combined with low levels of the TGFbeta metagene correlate  with prolonged patient survival. Thus, low expression of the miR-17 approximately 92 cluster, and specifically miR-18a, could significantly contribute to GBM pathogenesis.

 

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[546]

TÍTULO / TITLE:  - Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

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

REVISTA / JOURNAL:  - Int J Urol. 2013 Jan 17. doi: 10.1111/iju.12078.

            ●● Enlace al texto completo (gratuito o de pago) 1111/iju.12078

AUTORES / AUTHORS:  - May F; Buchner A; Schlenker B; Gratzke C; Arndt C; Stief C; Weidner N; Matiasek K

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Ludwigs-Maximilians-Universitat Munchen, Munich, Germany.

RESUMEN / SUMMARY:  - OBJECTIVES: To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. METHODS: Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection  without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. RESULTS: Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted  an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P < 0.001). Maximum intracavernous pressure on electrostimulation was significantly elevated using glial cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. CONCLUSIONS: Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a  viable approach for the treatment of erectile dysfunction after cavernous nerve injury.

 

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[547]

TÍTULO / TITLE:  - Multiple intracranial arachnoid cysts.

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

REVISTA / JOURNAL:  - JBR-BTR. 2012 Sep-Oct;95(5):339.

AUTORES / AUTHORS:  - Koc G; Altay C; Bozkurt T; Varer M; Oyar O

INSTITUCIÓN / INSTITUTION:  - Department of Diagnostic Radiology, Ataturk Research and Training Hospital, Izmir, Turkey.

 

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[548]

TÍTULO / TITLE:  - Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK.

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 http://stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Transl Med. 2012 Nov;1(11):811-24. doi: 10.5966/sctm.2012-0058. Epub 2012 Nov 15.

            ●● Enlace al texto completo (gratuito o de pago) 5966/sctm.2012-0058

AUTORES / AUTHORS:  - Sato A; Sunayama J; Okada M; Watanabe E; Seino S; Shibuya K; Suzuki K; Narita Y; Shibui S; Kayama T; Kitanaka C

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Cancer Science, Yamagata University, Yamagata, Japan. asato@med.id.yamagata-u.ac.jp

RESUMEN / SUMMARY:  - Control of the cancer stem/initiating cell population is considered key to realizing the long-term survival of glioblastoma patients. Recently, we demonstrated that FOXO3 activation is sufficient to induce differentiation of glioma-initiating cells having stem-like properties and inhibit their tumor-initiating potential. Here we identified metformin, an antidiabetic agent,  as a therapeutic activator of FOXO3. Metformin activated FOXO3 and promoted differentiation of such stem-like glioma-initiating cells into nontumorigenic cells. Furthermore, metformin promoted FOXO3 activation and differentiation via AMP-activated protein kinase (AMPK) activation, which was sensitive to extracellular glucose availability. Importantly, transient, systemic administration of metformin depleted the self-renewing and tumor-initiating cell  population within established tumors, inhibited tumor formation by stem-like glioma-initiating cells in the brain, and provided a substantial survival benefit. Our findings demonstrate that targeting glioma-initiating cells via the  AMPK-FOXO3 axis is a viable therapeutic strategy against glioblastoma, with metformin being the most clinically relevant drug ever reported for targeting of  glioma-initiating cells. Our results also establish a novel, direct link between  glucose metabolism and cancer stem/initiating cells.

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[549]

TÍTULO / TITLE:  - High-grade glioma: elderly patients, older treatments.

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

REVISTA / JOURNAL:  - Expert Rev Neurother. 2012 Nov;12(11):1293-6. doi: 10.1586/ern.12.118.

            ●● Enlace al texto completo (gratuito o de pago) 1586/ern.12.118

AUTORES / AUTHORS:  - De Bonis P; Mangiola A; Pompucci A; Porso M; Anile C

INSTITUCIÓN / INSTITUTION:  - Institute of Neurosurgery, Catholic University School of Medicine, Largo F. Vito, 1, 00168, Rome, Italy. debonisvox@gmail.com

RESUMEN / SUMMARY:  - Patients aged 65 years or older represent half of all patients with glioblastoma. Nonetheless, this older cohort is often excluded from trials. The NOA-08 Phase III trial compared radiotherapy (RT) (60 Gy) versus temozolomide (TMZ; 100 mg/m(2)) in the elderly patients (65 years and older) with high-grade glioma. Median overall survival was comparable between the two groups (8.6-RT- and 9.6-TMZ-months). Resection extent was the only independent prognostic factor for  overall survival. Several concerns arise: the inclusion of patients with a very low Karnofsky Performance Status (KPS; KPS = 20), the lack of an analysis of the  impact of KPS and comorbidities on outcome, the salvage therapy administered at tumor progression (RT in the TMZ group and TMZ in the RT group), which could have balanced the effects of primary treatments, the absence of information on spread  of disease/tumor site, the mixture of grade III and grade IV histologies. Ongoing trials evaluating RT plus TMZ, RT plus bevacizumab and other treatment modalities in the elderly population are going to change clinical practice in the near future.

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[550]

TÍTULO / TITLE:  - Predictive significance of mean apparent diffusion coefficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab: preliminary report.

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

REVISTA / JOURNAL:  - Int J Clin Oncol. 2013 Jan 26.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s10147-013-0517-x

AUTORES / AUTHORS:  - Nagane M; Kobayashi K; Tanaka M; Tsuchiya K; Shishido-Hara Y; Shimizu S; Shiokawa Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan, mnagane.g@gmail.com.

RESUMEN / SUMMARY:  - BACKGROUND: Recurrent glioblastoma after initial radiotherapy plus concomitant and adjuvant temozolomide is problematic. Here, patients with temozolomide-refractory high-grade gliomas were treated with bevacizumab (BV) and evaluated using apparent diffusion coefficient (ADC) for response. METHODS: Nine  post-temozolomide recurrent or progressive high-grade glioma patients (seven with glioblastoma and two with anaplastic astrocytoma) were treated with BV monotherapy. Average age was 57 years (range, 22-78), median Karnofsky Performance Scale (KPS) was 70 (30-80) and median BV line number was 2 (2-5). Two had additional stereotactic radiotherapy within 6 months prior to BV. Magnetic resonance (MR) imaging after BV therapy was performed within 2 weeks with calculation of mean ADC (mADC) values of enhancing tumor contours. RESULTS: Post-BV treatment MR imaging showed decreased tumor volumes in eight of nine cases (88.9 %). Partial response was obtained in four cases (44.4 %), four cases  had stable disease, and one had progressive disease. Of 15 evaluable enhancing lesions, 11 shrank and four did not. Pretreatment mADC values were above 1100 (10(-6) mm(2)/s) in all responding tumors, while all non-responding lesions scored below 1100 (p = 0.001). mADC decreased after the first BV treatment in all lesions except one. KPS improved in four cases (44.4 %). Median progression-free  survival and overall survival for those having all lesions with high mADC (>1100) were significantly longer than those with a low mADC (<1100) lesion (p = 0.018 and 0.046, respectively). CONCLUSIONS: Bevacizumab monotherapy is effective in patients with temozolomide-refractory recurrent gliomas and tumor mean ADC value  can be a useful marker for prediction of BV response and survival.

 

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[551]

TÍTULO / TITLE:  - The clinical results of pediatric brain tumors treated with Linac-based stereotactic radiosurgery and radiotherapy.

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

REVISTA / JOURNAL:  - J Med Assoc Thai. 2012 Nov;95(11):1466-71.

AUTORES / AUTHORS:  - Puataweepong P; Dhanachai M; Dangprasert S; Narkwong L; Sitathanee C; Junwityanujit T

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok Thailand. putipun.pua@mahidol.ac.th

RESUMEN / SUMMARY:  - OBJECTIVE: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for brain tumor is increasingly acceptable worldwide. In Thailand, the first Linac-based stereotactic radiation machine was implemented at the Radiosurgery Center, Ramathibodi Hospital since 1997. This is the first study in Thailand to report the results of pediatric brain tumor patients treated with  SRS and FSRT MATERIAL AND METHOD: The clinical outcome of 39 pediatric patients treated with SRS/FSRT between 1998 and 2010 was retrospectively reviewed. RESULTS: The median follow-up time was 26 months (range, 1 to 154 months). The local progression free survival (LPFS) at one and five years after SRS/FSRT for all patients was 87.5% and 54.2%, respectively. The 5-year LPFS by tumor histology was as follow, pituitary adenoma 100%, meningioma 100%, ependymoma, and low-grade astrocytoma 75%, and craniopharyngioma 68.6%. High-grade tumor had the  worst LPFS and the median LPFS of this group was only 12 months. On univariate analysis, low-grade tumor (pituitary adenoma and menigioma) and small tumor volume (< 10 ml) were the factors that correlated significantly with good local control. After multivariate analysis, small tumor volume was the only factor associated with good LPFS (HR = 2.35, p = 0.042). No other radiation complication except panhypopituitarism was reported. CONCLUSION: SRS/FSRT in pediatric brain tumor is technically feasible, with minimal acute side effects. SRS/FSRT plays an important role for the small low-grade tumor

 

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[552]

TÍTULO / TITLE:  - Fluorine-labeled Dasatinib Nanoformulations as Targeted Molecular Imaging Probes  in a PDGFB-driven Murine Glioblastoma Model.

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

REVISTA / JOURNAL:  - Neoplasia. 2012 Dec;14(12):1132-43.

AUTORES / AUTHORS:  - Benezra M; Hambardzumyan D; Penate-Medina O; Veach DR; Pillarsetty N; Smith-Jones P; Phillips E; Ozawa T; Zanzonico PB; Longo V; Holland EC; Larson SM; Bradbury MS

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, NY.

RESUMEN / SUMMARY:  - Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used a novel fluorinated dasatinib derivative (F-SKI249380), in combination with nanocarrier vehicles and  metabolic imaging tools (microPET) to evaluate drug delivery and uptake in a platelet-derived growth factor B (PDGFB)-driven genetically engineered mouse model (GEMM) of high-grade glioma. We assessed dasatinib survival benefit on the  basis of measured tumor volumes. Using brain tumor cells derived from PDGFB-driven gliomas, dose-dependent uptake and time-dependent inhibitory effects of F-SKI249380 on biologic activity were investigated and compared with the parent drug. PDGFR receptor status and tumor-specific targeting were non-invasively evaluated in vivo using (18)F-SKI249380 and (18)F-SKI249380-containing micellar and liposomal nanoformulations. A statistically significant survival benefit was found using dasatinib (95 mg/kg) versus saline vehicle (P < .001) in tumor volume-matched GEMM pairs. Competitive  binding and treatment assays revealed comparable biologic properties for F-SKI249380 and the parent drug. In vivo, Significantly higher tumor uptake was observed for (18)F-SKI249380-containing micelle formulations [4.9 percentage of the injected dose per gram tissue (%ID/g); P = .002] compared to control values (1.6%ID/g). Saturation studies using excess cold dasatinib showed marked reduction of tumor uptake values to levels in normal brain (1.5%ID/g), consistent with in vivo binding specificity. Using (18)F-SKI249380-containing micelles as radiotracers to estimate therapeutic dosing requirements, we calculated intratumoral drug concentrations (24-60 nM) that were comparable to in vitro 50%  inhibitory concentration values. (18)F-SKI249380 is a PDGFR-selective tracer, which demonstrates improved delivery to PDGFB-driven high-grade gliomas and facilitates treatment planning when coupled with nanoformulations and quantitative PET imaging approaches.

 

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[553]

TÍTULO / TITLE:  - A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease.

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

REVISTA / JOURNAL:  - BMC Genomics. 2012 Dec 7;13:686. doi: 10.1186/1471-2164-13-686.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2164-13-686

AUTORES / AUTHORS:  - Wagoner MP; Roopra A

INSTITUCIÓN / INSTITUTION:  - Department of Neuroscience, University of Wisconsin at Madison, Madison, USA. asroopra@wisc.edu.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Glioblastomas are the most common central nervous system neoplasia in adults, with 9,000 cases in the US annually. Glioblastoma multiformae, the most aggressive glioma subtype, has an 18% one-year survival rate, and 3% two year survival rate. Recent work has highlighted the role of the  transcription factor RE1 Silencing Transcription Factor, REST in glioblastoma but how REST function correlates with disease outcome has not been described. METHOD: Using a bioinformatic approach and mining of publicly available microarray datasets, we describe an aggressive subtype of gliomas defined by a gene signature derived from REST. Using this REST gene signature we predict that REST  function is enhanced in advanced glioblastoma. We compare disease outcomes between tumors based on REST status and treatment regimen, and describe downstream targets of REST that may contribute to the decreased benefits observed with high dose chemotherapy in REM tumors. RESULTS: We present human data showing that patients with “REST Enhanced Malignancies” (REM) tumors present with a shorter disease free survival compared to non-REM gliomas. Importantly, REM tumors are refractory to multiple rounds of chemotherapy and patients fail to respond to this line of treatment. CONCLUSIONS: This report is the first to describe a REST gene signature that predicts response to multiple rounds of chemotherapy, the mainline therapy for this disease. The REST gene signature may  have important clinical implications for the treatment of glioblastoma.

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[554]

TÍTULO / TITLE:  - Aryl hydrocarbon receptor interacting protein gene and familial isolated pituitary adenomas.

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

REVISTA / JOURNAL:  - Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2012 Dec 20;34(6):640-4. doi: 10.3881/j.issn.1000-503X.2012.06.021.

            ●● Enlace al texto completo (gratuito o de pago) 3881/j.issn.1000-503X.2012.06.021

AUTORES / AUTHORS:  - Feng C; Yi-Dan Z; Cong-Xin D; Xiao-Hai L; Ya-Kun Y; Yong Y; Ren-Zhi W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.

RESUMEN / SUMMARY:  - Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a  tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.

 

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[555]

TÍTULO / TITLE:  - A Radial Glia Gene Marker, Fatty Acid Binding Protein 7 (FABP7), Is Involved in Proliferation and Invasion of Glioblastoma Cells.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52113. doi: 10.1371/journal.pone.0052113. Epub 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052113

AUTORES / AUTHORS:  - De Rosa A; Pellegatta S; Rossi M; Tunici P; Magnoni L; Speranza MC; Malusa F; Miragliotta V; Mori E; Finocchiaro G; Bakker A

INSTITUCIÓN / INSTITUTION:  - Siena Biotech Spa, Siena, Italy.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC) might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS) in vitro, and seem to mirror the genetic features of the original tumor better than glioma  cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7) was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to  increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the  role of FABP7 expression in GBM migration and provide translational hints on the  timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.

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[556]

TÍTULO / TITLE:  - Comparison of intelligence quotient in children surviving leukemia who received different prophylactic central nervous system treatments.

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

REVISTA / JOURNAL:  - Adv Biomed Res. 2012;1:83. doi: 10.4103/2277-9175.103005. Epub 2012 Oct 31.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2277-9175.103005

AUTORES / AUTHORS:  - Nahid R; Leila K

INSTITUCIÓN / INSTITUTION:  - Pediatric Hematologist and Oncologist, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Neurocognitive deficits and decrease in intelligence quotient (IQ) is one of the complication of prophylactic central nervous system (CNS) treatment in acute lymphoblastic leukemia (ALL) patients. In this study, we compare the IQ in  survivors of ALL that were treated with different prophylactic CNS treatments. MATERIALS AND METHODS: We compared 43 long-term survivors of ALL: 21 survivors with intrathecal methotrexate (IT MTX) as CNS prophylaxis, 22 with IT MTX+1800-2400 rads cranial irradiation and 20 healthy controls. The IQ was measured using the Raven’s test in these patients. RESULTS: Raven’s test revealed significant differences in IQ between the survivors of ALL that were treated with IT MTX, IT MTX plus cranial irradiation and control group. There was no significant difference in the IQ with respect to sex, age and irradiation dose. CONCLUSION: We can that reveal that CNS prophylaxis treatment, especially the combined treatment, is associated with IQ score decline in ALL survivors. Therefore,a baseline and an annual assessment of their educational progress are suggested.

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[557]

TÍTULO / TITLE:  - Perioperative single photon emission computed tomography in predicting survival of malignant glioma patients.

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

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):739-744. Epub 2012 Jul 19.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.812

AUTORES / AUTHORS:  - Deltuva V; Bunevicius A; Jurkiene N; Kulakiene I; Tamasauskas A

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery and.

RESUMEN / SUMMARY:  - Single photon emission computed tomography (SPECT) is widely used in the evaluation of glioma patients and has been demonstrated to correlate with glioma  malignancy and proliferation indexes. The aim of this study was to evaluate the association between perioperative technetium-99m-methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake on SPECT scans and survival of malignant glioma patients. A total of 17 patients (11 males and 6 women; mean age, 62.2+/-8.4 years) with histologically confirmed malignant gliomas (16 glioblastoma multiforme and 1 gliosarcoma) underwent (99m)Tc-MIBI SPECT scans 2.8+/-1.9 days before surgery and 9.8+/-1.5 days after surgery. The total intensity index (TII) that corresponds to the area and intensity of tracer uptake was calculated before and after surgery.  In addition, the change of TII before versus after surgery (Delta TII) was calculated. The overall survival (OS) was defined as the period between the date  of surgery and the date of death. The median overall survival time was 12.4 months, ranging from 1.4 to 88 months; there were nine (45%) 12-month survivors.  In univariate analyses using a log-rank test, worse OS was significantly associated with higher preoperative TII (>/=12), higher postoperative TII (>/=6), lower Delta TII (<50%) and higher number of neurological symptoms prior to surgery (>/=4). In multivariate analyses, higher postoperative TII, a greater number of neurological symptoms and female gender were found to be factors with independent prognostic value of OS. Patients who survived more than 12 months following surgery had a significantly lower postoperative TII, higher Delta TII and greater rate of gross total resection compared to patients who survived less  than 12 months following surgery. Higher peri-operative tracer uptake and lower decrease of tracer uptake following surgery (suggesting less radical resection) were associated with worse OS of malignant glioma patients. Our results suggest that SPECT may be used to predict survival of malignant glioma patients; however, further studies using larger samples are required.

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[558]

TÍTULO / TITLE:  - Expression of glioma-associated oncogene 2 (Gli 2) is correlated with poor prognosis in patients with hepatocellular carcinoma undergoing hepatectomy.

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

REVISTA / JOURNAL:  - World J Surg Oncol. 2013 Jan 29;11(1):25.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-25

AUTORES / AUTHORS:  - Zhang D; Cao L; Li Y; Lu H; Yang X; Xue P

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Our previous studies showed that glioma-associated oncogene (Gli)2 plays an important role in the proliferation and apoptosis resistance of hepatocellular carcinoma (HCC) cells. The aim of this study was to explore the clinical significance of Gli2 expression in HCC. METHODS: Expression of Gli2 protein was detected in samples from 68 paired HCC samples, the corresponding paraneoplastic liver tissues, and 20 normal liver tissues using immunohistochemistry. Correlation of the immunohistochemistry results with clinicopathologic parameters, prognosis, and the expression of E-cadherin, N-cadherin, and vimentin were analyzed. RESULTS: Immunohistochemical staining showed high levels of Gli2 protein expression in HCC, compared with paraneoplastic and normal liver tissues (P < 0.05). This high expression level of Gli2 was significantly associated with tumor differentiation, encapsulation, vascular invasion, early recurrence, and intra-hepatic metastasis (P < 0.05). There was a significantly negative correlation between Gli2 and E-cadherin expression (r = -0.302, P < 0.05) and a significantly positive correlation between expression of Gli2 and expression of vimentin (r = -0.468, P < 0.05) and  N-cadherin (r = -0.505, P < 0.05). Kaplan-Meier analysis showed that patients with overexpressed Gli2 had significantly shorter overall survival and disease-free survival times (P < 0.05). Multivariate analysis suggested that the  level of Gli2 expression was an independent prognostic factor for HCC. CONCLUSIONS: Expression of Gli2 is high in HCC tissue, and is associated with poor prognosis in patients with HCC after hepatectomy.

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[559]

TÍTULO / TITLE:  - Achieving graft-versus-tumor effect in brain tumor patients: from autologous progenitor cell transplant to active immunotherapy.

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

REVISTA / JOURNAL:  - Immunotherapy. 2012 Nov;4(11):1139-51. doi: 10.2217/imt.12.96.

            ●● Enlace al texto completo (gratuito o de pago) 2217/imt.12.96

AUTORES / AUTHORS:  - Petrosiute A; Auletta JJ; Lazarus HM

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Hematology/Oncology, Rainbow Babies & Children’s Hospital, Case Western Reserve University, 11100 Euclid Avenue, Mailstop 6054, Cleveland, OH 44106, USA. agne.petrosiute2@uhhospitals.org

RESUMEN / SUMMARY:  - Success in treating aggressive brain tumors like glioblastoma multiforme and medulloblastoma remains challenging, in part because these malignancies overcome  CNS immune surveillance. New insights into brain tumor immunology have led to a rational development of immunotherapeutic strategies, including cytotoxic Tlymphocyte therapies and dendritic cell vaccines. However, these therapies are most effective when applied in a setting of minimal residual disease, so require  prior use of standard cytotoxic therapies or cytoreduction by surgery. Myeloablative chemotherapy with autologous hematopoietic cell transplantation (autoHCT) can offer a platform upon which different cellular therapies can be effectively instituted. Specifically, this approach provides an inherent ‘chemical debulking’ through high-dose chemotherapy and a graft-versus-tumor effect through an autologous T-cell replete graft. Furthermore, autoHCT may be beneficial in ‘resetting’ the body’s immune system, potentially ‘breaking’ tumor  tolerance, and in providing a ‘boost’ of immune effector cells (NK cells or cytotoxic T lymphocytes), which could augment desired anti-tumor effects. As literature on the use of autoHCT in brain tumors is scarce, aspects of immunotherapies applied in non-CNS malignancies are reviewed as potential therapies that could be used in conjunction with autoHCT to eradicate brain tumors.

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[560]

TÍTULO / TITLE:  - Preliminary results of randomized controlled study on decompressive craniectomy in treatment of malignant middle cerebral artery stroke.

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

REVISTA / JOURNAL:  - Medicina (Kaunas). 2012;48(10):521-4.

AUTORES / AUTHORS:  - Slezins J; Keris V; Bricis R; Millers A; Valeinis E; Stukens J; Minibajeva O

INSTITUCIÓN / INSTITUTION:  - Zentenes 5-58, 1069 Riga, Latvia. janis.slezins@inbox.lv.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE. Studies on decompressive craniectomy (DCE) after a malignant middle cerebral artery (MCA) stroke in selected population show an increased probability of survival without increasing the number of very severely  disabled. Cerebral infarct volume (CIV) as a triage criterion for performing surgery has not been discussed in literature. The aim of this study was to investigate the value of CIV and initial National Institutes of Health Stroke Scale (NIHHS) and Glasgow Coma Scale (GCS) scores as possible triage criteria in  the surgical treatment of patients with “malignant” MCA stroke. MATERIAL AND METHODS. According to the study protocol, 28 patients with a malignant MCA stroke were included and analyzed prospectively. The patients were randomly divided either into the DCE plus best medical treatment (BMT) group or BMT alone group. CIV and NIHHS and GCS scores were measured at time of enrollment in every case. Clinical outcome was evaluated 1 year after the treatment. RESULTS. Six patients  survived: 5 in the DCE group (none of them was older than 60 years) and 1 in the  BMT group (P=0.03/0.06). Among survivors, none had a cerebral infarct volume of more than 390 cm(3) (P=0.05). All survivors in the DCE group had favorable outcomes. There was no significant difference in the NIHSS and GCS scores between the groups and survivors/nonsurvivors (P>0.05). CONCLUSIONS. Decompressive surgery in the selected patients is likely to increase the probability of survival with a favorable outcome without increasing the number of severely disabled survivors. Patients with CIV of more than 390 cm(3) may be bad candidates for DCE, and the prognosis is likely to be bad regardless the treatment strategy. The initial NIHHS and GCS scores did not prove any prognostic value in outcome.

 

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[561]

TÍTULO / TITLE:  - Surgical extent impacts the value of the established prognosticators in glioblastoma patients: a prospective translational study in Asia.

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

REVISTA / JOURNAL:  - Head Neck Oncol. 2012 Nov 23;4(4):80.

AUTORES / AUTHORS:  - Wang Y; Li S; Zhang Z; Chen X; You G; Yang P; Yan W; Bao Z; Yao K; Wang L; Li M; Jiang T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. The Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, Houston, TX, USA.

RESUMEN / SUMMARY:  - BACKGROUND: While multimodal treatments have survival benefits in patients with glioblastoma, tumour volume resection still remains the most effective treatment. METHODS: In this prospective translational study, we analysed the clinical values of the established survival predictors in the context of extensive tumour resection (at least near-total resection) in 234 newly diagnosed glioblastoma patients. Common survival factors such as adjuvant therapy modality, O6-methylguanine DNA methyltransferase (MGMT) and isocitrate dehydrogenase 1 (IDH1) were analysed. RESULTS: The more extensive resection resulted in a favourable outcome, especially the median progression-free survival up to 11.1 months. Age at diagnosis, the initial alkylating radiochemotherapy and MGMT promoter status were correlated with survival in univariate analysis, but their independent predictive values were lost upon multivariate analysis. Multivariate  analysis identified the only independent prognosticators for a longer overall survival were gross total resection (relative risk [RR] = 0.36; P = 0.003) and higher Karnofsky Performance Status score (RR = 0.41; P = 0.008), and gross-total resection (RR = 0.56; P = 0.050), higher Karnofsky Performance Status score (RR = 0.52; P = 0.028) and IDH1 mutation (RR = 0.42; P = 0.011) for a favourable progression-free survival. Interestingly, in the subgroup of patients receiving gross-total resection, neither MGMT nor IDH1 effectively predicted overall survival or progression-free survival; and also radiotherapy alone did not significantly improve the outcome though alkylating radiochemotherapy showed a strong survival advantage. Further analysis showed an additive effect of surgical extent and molecular predictor IDH1 mutation. CONCLUSION: Surgical extent most significantly impacts the value of molecular and clinical predictors, and therefore should be taken into full account when assessing a new therapy or stratification variable in glioblastoma multiformes.

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[562]

TÍTULO / TITLE:  - Left atrial myxoma presenting with cerebral embolism.

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

REVISTA / JOURNAL:  - Med Health R I. 2012 Dec;95(12):397.

AUTORES / AUTHORS:  - Earl TJ; Poppas A

INSTITUCIÓN / INSTITUTION:  - Warren Alpert Medical School of Brown University, USA. tearl@lifespan.org

 

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[563]

TÍTULO / TITLE:  - Chronic Lymphocytic Leukemia With Central Nervous System Involvement: A High-Risk Disease?

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

REVISTA / JOURNAL:  - Clin Lymphoma Myeloma Leuk. 2013 Jan 16. pii: S2152-2650(12)00293-5. doi: 10.1016/j.clml.2012.12.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.clml.2012.12.007

AUTORES / AUTHORS:  - Benjamini O; Jain P; Schlette E; Sciffman JS; Estrov Z; Keating M

INSTITUCIÓN / INSTITUTION:  - Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

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[564]

TÍTULO / TITLE:  - UHRF2 mRNA expression is low in malignant glioma but silencing inhibits the growth of U251 glioma cells in vitro.

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

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5137-42.

AUTORES / AUTHORS:  - Wu TF; Zhang W; Su ZP; Chen SS; Chen GL; Wei YX; Sun T; Xie XS; Li B; Zhou YX; Du ZW

INSTITUCIÓN / INSTITUTION:  - Neurosurgery and Brain and Nerve Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, China.

RESUMEN / SUMMARY:  - UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative  PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay  was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down- regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

 

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[565]

TÍTULO / TITLE:  - Surgical resection of malignant gliomas-role in optimizing patient outcome.

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

REVISTA / JOURNAL:  - Nat Rev Neurol. 2013 Jan 29. doi: 10.1038/nrneurol.2012.279.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2012.279

AUTORES / AUTHORS:  - Eyupoglu IY; Buchfelder M; Savaskan NE

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6,  D-91054 Erlangen, Germany.

RESUMEN / SUMMARY:  - Malignant gliomas represent one of the most devastating human diseases. Primary treatment of these tumours involves surgery to achieve tumour debulking, followed by a multimodal regimen of radiotherapy and chemotherapy. Survival time in patients with malignant glioma has modestly increased in recent years owing to advances in surgical and intraoperative imaging techniques, as well as the systematic implementation of randomized trial-based protocols and biomarker-based stratification of patients. The role and importance of several clinical and molecular factors-such as age, Karnofsky score, and genetic and epigenetic status-that have predictive value with regard to postsurgical outcome has also been identified. By contrast, the effect of the extent of glioma resection on patient outcome has received little attention, with an ‘all or nothing’ approach  to tumour removal still taken in surgical practice. Recent studies, however, reveal that maximal possible cytoreduction without incurring neurological deficits has critical prognostic value for patient outcome and survival. Here, we evaluate state-of-the-art surgical procedures that are used in management of malignant glioma, with a focus on assessment criteria and value of tumour reduction. We highlight key surgical factors that enable optimization of adjuvant treatment to enhance patient quality of life and improve life expectancy.

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[566]

TÍTULO / TITLE:  - Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience.

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

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.PEDS12317

AUTORES / AUTHORS:  - Klimo P Jr; Pai Panandiker AS; Thompson CJ; Boop FA; Qaddoumi I; Gajjar A; Armstrong GT; Ellison DW; Kun LE; Ogg RJ; Sanford RA

INSTITUCIÓN / INSTITUTION:  - Semmes-Murphey Neurologic & Spine Institute;

RESUMEN / SUMMARY:  - Object Whereas diffuse intrinsic pontine gliomas generally have a short symptom duration and more cranial nerve involvement, focal brainstem gliomas are commonly low grade, with fewer cranial neuropathies. Although these phenotypic distinctions are not absolute predictors of outcome, they do demonstrate correlation in most cases. Because there is a limited literature on focal brainstem gliomas in pediatric patients, the objective of this paper was to report the management and outcome of these tumors. Methods The authors reviewed the records of all children diagnosed with radiographically confirmed low-grade focal brainstem gliomas from 1986 to 2010. Each patient underwent biopsy or resection for tissue diagnosis. Event-free survival (EFS) and overall survival were evaluated. Univariate analysis was conducted to identify demographic and treatment variables that may affect EFS. Results Fifty-two patients (20 girls, 32 boys) with follow-up data were identified. Median follow-up was 10.0 years, and the median age at diagnosis was 6.5 years (range 1-17 years). The tumor locations were midbrain (n = 22, 42%), pons (n = 15, 29%), and medulla (n = 15, 29%). Surgical extirpation was the primary treatment in 25 patients (48%). The 5- and 10-year EFS and overall survival were 59%/98% and 52%/90%, respectively. An event or treatment failure occurred in 24 patients (46%), including 5 deaths. Median time to treatment failure was 3.4 years. Disease progression in the other 19 patients transpired within 25.1 months of diagnosis. Thirteen of these patients received radiation, including 11 within 2 months of primary treatment failure. Although children with intrinsic tumors had slightly better EFS at 5 years compared with those with exophytic tumors (p = 0.054), this difference was not significant at 10 years (p = 0.147). No other variables were predictive of EFS. Conclusions Surgery suffices in many children with low-grade focal brainstem gliomas. Radiation treatment is often reserved for disease progression but offers comparable disease control following biopsy. In the authors’ experience, combining an assessment of clinical course, imaging, and tumor biopsy yields a reasonable model for managing children with focal brainstem tumors.

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[567]

TÍTULO / TITLE:  - Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by  suppression of anti-apoptotic signals and activation of cysteine proteases.

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

REVISTA / JOURNAL:  - Braz J Med Biol Res. 2013 Jan 11:1-8.

AUTORES / AUTHORS:  - Lizarte Neto FS; Tirapelli DP; Ambrosio SR; Tirapelli CR; Oliveira FM; Novais PC; Peria FM; Oliveira HF; Carlotti Junior CG; Tirapelli LF

RESUMEN / SUMMARY:  - Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to  their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 microM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 microM KA, and 31% for cells submitted to 48 h of treatment with 70 microM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

 

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[568]

TÍTULO / TITLE:  - Outcome following decompressive craniectomy for malignant middle cerebral artery  infarction in patients older than 70 years old.

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

REVISTA / JOURNAL:  - J Cerebrovasc Endovasc Neurosurg. 2012 Jun;14(2):65-74. doi: 10.7461/jcen.2012.14.2.65. Epub 2012 Jun 30.

            ●● Enlace al texto completo (gratuito o de pago) 7461/jcen.2012.14.2.65

AUTORES / AUTHORS:  - Yu JW; Choi JH; Kim DH; Cha JK; Huh JT

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Busan-Ulsan Regional Cardiocerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Korea.

RESUMEN / SUMMARY:  - OBJECTIVE: Malignant middle cerebral artery (MCA) infarction occurs in 10% of all ischemic strokes and these severe strokes are associated with high mortality rates. Recent clinical trials demonstrated that early decompressive craniectomy reduce mortality rates and improves functional outcomes in healthy young patients (less than 61 years of age) with a malignant infarction. The purpose of this study was to assess the efficacy of decompressive craniectomy in elderly patients (older than 70 years of age) with a malignant MCA infarction. METHODS: Between February 2008 and October 2011, 131 patients were diagnosed with malignant MCA infarctions. We divided these patients into two groups: patients who underwent decompressive craniectomy (n = 58) and those who underwent conservative care (n = 73). A cut-off point of 70 years of age was set, and the study population was segregated into those who fell above or below this point. Mortality rates and functional outcome scores were assessed, and a modified Rankin Scale (mRS) score  of > 3 was considered to represent a poor outcome. RESULTS: Mortality rates were  significantly lower at 29.3% (one-month mortality rate) and 48.3% (six-month mortality rate) in the craniectomy group as compared to 58.9% and 71.2%, respectively, in the conservative care group (p < 0.001, p = 0.007). Age (>/=70 years vs. < 70 years) did not statistically differ between groups for the six-month mortality rate (p = 0.137). However, the pre-operative National Institutes of Health Stroke Scale (NIHSS) score did contribute to the six-month mortality rate (p = 0.047). CONCLUSION: Decompressive craniectomy is effective for patients with a malignant MCA infarction regardless of their age. Therefore,  factors other than age should be considered and the treatment should be individualized in elderly patients with malignant infarctions.

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[569]

TÍTULO / TITLE:  - Complement activation in astrocytomas: deposition of C4d and patient outcome.

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

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 1;12:565. doi: 10.1186/1471-2407-12-565.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-565

AUTORES / AUTHORS:  - Makela K; Helen P; Haapasalo H; Paavonen T

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, University of Tampere Medical School, Tampere, Finland.  katri.s.makela@uta.fi

RESUMEN / SUMMARY:  - BACKGROUND: C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or  patient survival. METHODS: Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with  a point counting grid yielding a percent of C4d and CD34 positive area of the sample. RESULTS: The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann-Whitney  test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). CONCLUSION: The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement.

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[570]

TÍTULO / TITLE:  - Craniocervical arachnoid cyst in a patient with Klippel-Feil syndrome: a unique case.

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

REVISTA / JOURNAL:  - J Neurosurg Spine. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.SPINE12463

AUTORES / AUTHORS:  - Khan IS; Ahmed O; Thakur JD; Shorter CD; Guthikonda B

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee;

RESUMEN / SUMMARY:  - Klippel-Feil syndrome, or brevicollis, is a complex congenital disorder caused by the improper segmentation of the cervical vertebrae. The authors present the very rare case of a patient with Klippel-Feil syndrome who presented with an intradural arachnoid cyst at the craniocervical junction. They also examine possible factors contributing to this association. A 46-year-old woman presented  with complaints of progressively worsening headaches and dizziness of 18 months’  duration. She also demonstrated mild bilateral upper-extremity weakness. Magnetic resonance imaging revealed fused cervical vertebrae and a dorsal intradural arachnoid cyst at the craniocervical junction, extending down to the fourth cervical level. Because of worsening myelopathy and the presence of brainstem compression, the patient underwent surgical excision of the arachnoid cyst, which was approached via a midline posterior suboccipital/upper cervical route. An endoscope was introduced through a gap between the occiput and fused upper cervical vertebrae, and the arachnoid cyst was widely fenestrated. Postoperatively, the patient has remained symptom free for more than 2 years with evidence of good radiological decompression. The authors report a unique association between craniocervical arachnoid cyst and Klippel-Feil syndrome. To their knowledge, no other cases of this association have been reported in the literature. Arachnoid cysts should be part of the differential diagnosis in the presence of worsening myelopathic symptoms or pain in patients with Klippel-Feil  syndrome.

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[571]

TÍTULO / TITLE:  - Functional reorganization in the patient with progressing glioma of pure primary  motor cortex: A case report with special reference to the topographic central sulcus defined by SEP.

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

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 18. pii: S1878-8750(13)00145-9. doi: 10.1016/j.wneu.2013.01.084.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.084

AUTORES / AUTHORS:  - Hayashi Y; Nakada M; Kinoshita M; Hamada JI

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kanazawa University, Kanazawa, Japan. Electronic address: yuh@ns.m.kanazawa-u.ac.jp.

RESUMEN / SUMMARY:  - BACKGROUNDE: The concept of human brain reorganization due to slow-growing lesions, including low-grade glioma, has been gradually and generally accepted. However, few cases have been reported in which the reorganization, especially in  the topographic pure primary motor cortex, was observed during brain surgery. We  report a case of slow-growing oligodendroglioma located in the pure primary motor cortex, as detected by magnetic resonance imaging that could be resected in part  thanks to the brain plasticity. Moreover, we describe a pitfall of topographic guidance using somatosensory-evoked potential (SEP) monitoring. CASE DESCRIPTION: A 36-year-old right-handed patient underwent resection of a gradually growing oligodendroglioma located in the right primary motor cortex, with no other adjacent lesions, 8 years after the initial biopsy. The central sulcus was defined with intraoperative SEP monitoring in both operations. Based on the findings of the intraoperative direct electrical stimulation (DES) under awake craniotomy, we suspect that motor function shifted posteriorly and reorganized beyond the central sulcus. CONCLUSION: Pure primary motor cortex could be reorganized by its own lesion. In reorganized brain, topographic central sulcus defined based on SEP findings may be an inappropriate guidance to estimate true functional area. In such a condition, intraoperative DES under awake craniotomy makes it feasible to resect pure primary motor cortex invaded by tumors.

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[572]

TÍTULO / TITLE:  - Infiltrating medulloblastoma in a child mimicking Lhermitte-Duclos disease.

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

REVISTA / JOURNAL:  - J Pediatr Neurosci. 2012 May;7(2):159-60. doi: 10.4103/1817-1745.102595.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1817-1745.102595

AUTORES / AUTHORS:  - Kamble RB; Mathew S; Rao RM

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Neurosurgery, Vikram Hospital, Bangalore, Karnataka,  India.

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[573]

TÍTULO / TITLE:  - Combination Chemotherapy with Cyclophosphamide, Vincristine, and Dacarbazine in Patients with Malignant Pheochromocytoma and Paraganglioma.

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

REVISTA / JOURNAL:  - Horm Cancer. 2013 Jan 30.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12672-013-0133-2

AUTORES / AUTHORS:  - Tanabe A; Naruse M; Nomura K; Tsuiki M; Tsumagari A; Ichihara A

INSTITUCIÓN / INSTITUTION:  - Department of Medicine II, Tokyo Women’s Medical University, 8-1, Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan, akiyotana@endm.twmu.ac.jp.

RESUMEN / SUMMARY:  - Choosing effective therapy for patients with malignant pheochromocytoma or paraganglioma (PPGL) is problematic and none of the options are curative. Although combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) is an established treatment option, only a limited number of case series have been reported in the literature. To determine the efficacy of CVD in patients treated at Tokyo Women’s Medical University. Retrospective review of patients treated with CVD between 1989 and 2012 was conducted. Demographics, clinical presentation, imaging, and laboratory reports were reviewed and analyzed. Efficacy of CVD was ascertained from the biochemical and tumor responses. Twenty-three patients fulfilled study criteria and 6 of these were excluded due to inadequate follow-up or discontinuance by poor general condition  or adverse effects. Thus, 17 cases were included in the study. The age and duration of the disease before initiation of CVD were 54.7 +/- 12.0 years and 9.1 +/- 8.1 years, respectively. The follow-up period after initiation of CVD ranged  from 12 to 192 months (median, 60 months). Complete or partial biochemical and/or partial tumor response was achieved in 47.1 % (responders). No significant biochemical or tumor response was seen in 23.5 % and deterioration in biochemical and tumor outcomes was seen in 29.4 % (non-responders). No patient showed complete biochemical and tumor responses. In responders, these effects were documented within 4 months after initiation of CVD with a progression-free survival of 31 to 60 months (median, 40 months). Age at the first diagnosis with  PPGL was younger (P < 0.05) and the lag time to eventual diagnosis of malignant disease was longer (P < 0.05) in responders than those in non-responders. The responders had improvements in hypertension and impaired glucose tolerance. Although CVD chemotherapy is not curative for patients with malignant PPGL, it does provide approximately half of the patients with biochemical, tumor, and hypertension benefits.

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[574]

TÍTULO / TITLE:  - Mast cells evaluation in meningioma of various grades.

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

REVISTA / JOURNAL:  - Folia Histochem Cytobiol. 2012;50(4):542-6. doi: 10.5603/14744.

            ●● Enlace al texto completo (gratuito o de pago) 5603/14744

AUTORES / AUTHORS:  - Reszec J; Hermanowicz A; Kochanowicz J; Turek G; Mariak Z; Chyczewski L

INSTITUCIÓN / INSTITUTION:  - MD PhD Department of Medical Pathomorphology Medical University of Bialystok. joannareszec@gmail.com.

RESUMEN / SUMMARY:  - Introduction: Meningioma is a heterogenous group of primary brain tumors. The progression or recurrence is relatively very common; however there is lack of prognostic factors which may indicate those events. The aim of the study was to evaluate the presence of mast cells within the low grade and high grade meningiomas. Material and Methods: The immunohistochemical reaction was done. The tryptase expression was estimated in slides of meningiomas of various grades in 10 random fields under the light microscope. Results: The expression of tryptase  was observed in 31,8% low grade meningiomas and in 85,9% high grade meningiomas.  The immunostaining was observed next to the blood vessels. Conclusion: The presence of mast cells might be a significant prognostic factor for the recurrence or the worse prognosis of meningiomas.

 

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[575]

TÍTULO / TITLE:  - Targeting the Unfolded Protein Response in Glioblastoma Cells with the Fusion Protein EGF-SubA.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52265. doi: 10.1371/journal.pone.0052265. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052265

AUTORES / AUTHORS:  - Prabhu A; Sarcar B; Kahali S; Shan Y; Chinnaiyan P

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, United States of America ; Experimental Therapeutics, H. Lee Moffitt Cancer Center, Tampa, Florida, United States of America.

RESUMEN / SUMMARY:  - Rapidly growing tumors require efficient means to allow them to adapt to fluctuating microenvironments consisting of hypoxia, nutrient deprivation, and acidosis. The unfolded protein response (UPR) represents a defense mechanism allowing cells to respond to these adverse conditions. The chaperone protein GRP78 serves as a master UPR regulator that is aberrantly expressed in a variety  of cancers, including glioma. Therefore, cancer cells may be particularly reliant upon the adaptive mechanisms offered by the UPR and targeting GRP78 may represent a unique therapeutic strategy. Here we report that diffuse expression of GRP78 protein is present in Grade III-IV, but not Grade I-II glioma. To determine the role GRP78 plays in glioblastoma tumorigenesis, we explored the anti-tumor activity of the novel fusion protein EGF-SubA, which combines EGF with the cytotoxin SubA that has been recently shown to selectively cleave GRP78. EGF-SubA demonstrated potent tumor-specific proteolytic activity and cytotoxicity in glioblastoma lines and potentiated the anti-tumor activity of both temozolomide and ionizing radiation. To determine if the tumor microenvironment influences EGF-SubA activity, we maintained cells in acidic conditions that led to both UPR  activation and increased EGF-SubA induced cytotoxicity. EGF-SubA was well tolerated in mice and led to a significant tumor growth delay in a glioma xenograft mouse model. The UPR is emerging as an important adaptive pathway contributing to glioma tumorigenesis. Targeting its primary mediator, the chaperone protein GRP78, through specific, proteolytic cleavage with the immunotoxin EGF-SubA represents a novel and promising multi-targeted approach to  cancer therapy.

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[576]

TÍTULO / TITLE:  - Upregulation of microRNA-224 confers a poor prognosis in glioma patients.

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

REVISTA / JOURNAL:  - Clin Transl Oncol. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0972-2

AUTORES / AUTHORS:  - Lu S; Wang S; Geng S; Ma S; Liang Z; Jiao B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Shijiazhuang, 050000, Hebei, China.

RESUMEN / SUMMARY:  - OBJECTIVE: MicroRNA-224 (miR-224) has been consistently reported to be dysregulated in various human malignancies and can potentially affect many cancer-related cellular processes, including transcription, cell differentiation, cell death, growth, and cell proliferation. However, its roles in human glioma have not been reported. The aim of this study was to explore the expression pattern, clinical significance, and prognostic value of miR-224 in glioma patients using large cohorts. METHODS: Quantitative real-time polymerase chain reaction analysis was used to characterize the expression patterns of miR-224 in  108 glioma and 20 normal brain tissues. The associations of miR-224 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. RESULTS: miR-224 expression is significantly upregulated  in glioma tissues compared with normal brain tissues (P < 0.001). In addition, high expression of miR-224 was significantly associated with advanced pathological grade (P = 0.006) and low Karnofsky performance score (KPS, P = 0.01). Moreover, Kaplan-Meier survival analysis showed that high miR-224 expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates than low miR-224 expression group (both P < 0.001). Multivariate analysis with the Cox’s proportional hazards model revealed that high expression of miR-224 (P = 0.006 and P = 0.01, respectively) and advanced pathological grade (both P = 0.02) were independent factors for shorter DFS and OS. Furthermore, subgroup analyses showed that miR-224 expression was significantly associated with poor DFS and OS in glioma patients with high pathological grades (for grade III-IV: P < 0.001 and P = 0.005, respectively). CONCLUSIONS: MiR-224 is upregulated and confers a poor prognosis in glioma patients.

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[577]

TÍTULO / TITLE:  - Epidermal growth factor receptor is related to poor survival in glioblastomas: single-institution experience.

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

REVISTA / JOURNAL:  - Yonsei Med J. 2013 Jan 1;54(1):101-7. doi: /10.3349/ymj.2013.54.1.101.

AUTORES / AUTHORS:  - Choi Y; Song YJ; Lee HS; Hur WJ; Sung KH; Kim KU; Choi SS; Kim SJ; Kim DC

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Dong-A University School of Medicine, Seo-gu, Busan,  Korea.

RESUMEN / SUMMARY:  - PURPOSE: There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy. MATERIALS AND METHODS: Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. RESULTS: EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent. CONCLUSION: The expression of EGFR demonstrated a significantly  deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.

 

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[578]

TÍTULO / TITLE:  - An initial exploration of surgery following radiotherapy for the treatment of gliomatosis cerebri.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4526-7.

AUTORES / AUTHORS:  - Wang JF; Jiang T; Qiu XG; Jin Q; Chen BS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.

 

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[579]

TÍTULO / TITLE:  - Decision forests for tissue-specific segmentation of high-grade gliomas in multi-channel MR.

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

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 3):369-76.

AUTORES / AUTHORS:  - Zikic D; Glocker B; Konukoglu E; Criminisi A; Demiralp C; Shotton J; Thomas OM; Das T; Jena R; Price SJ

INSTITUCIÓN / INSTITUTION:  - Microsoft Research Cambridge, UK

RESUMEN / SUMMARY:  - We present a method for automatic segmentation of high-grade gliomas and their subregions from multi-channel MR images. Besides segmenting the gross tumor, we also differentiate between active cells, necrotic core, and edema. Our discriminative approach is based on decision forests using context-aware spatial  features, and integrates a generative model of tissue appearance, by using the probabilities obtained by tissue-specific Gaussian mixture models as additional input for the forest. Our method classifies the individual tissue types simultaneously, which has the potential to simplify the classification task. The  approach is computationally efficient and of low model complexity. The validation is performed on a labeled database of 40 multi-channel MR images, including DTI.  We assess the effects of using DTI, and varying the amount of training data. Our  segmentation results are highly accurate, and compare favorably to the state of the art.

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[580]

TÍTULO / TITLE:  - Thyroid-stimulating hormone-secreting pituitary adenoma presenting with recurrent hyperthyroidism in post-treated Graves’ disease: a case report.

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

REVISTA / JOURNAL:  - J Med Case Rep. 2013 Jan 21;7(1):27. doi: 10.1186/1752-1947-7-27.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-7-27

AUTORES / AUTHORS:  - Ogawa Y; 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:  - ABSTRACT: INTRODUCTION: The coexistence of autoimmune hyperthyroid disease and thyroid-stimulating hormone-secreting pituitary adenoma is rare. The simple presumption of coincidence of these two diseases has a calculated incidence of less than one/several hundred million, and only four cases with histological confirmation have been reported. A rapid decrease in thyroid-stimulating hormone  level after pituitary tumor removal may induce subsequent activation of autoimmune responses against the thyroid gland. We report the first case of a sequential and paradoxical occurrence of Graves’ disease and a thyroid-stimulating hormone-secreting pituitary adenoma. CASE PRESENTATION: A 32-year-old Japanese woman had recurrent hyperthyroidism. She had a history of Graves’ hyperthyroidism, which had been successfully treated with propylthiouracil. A head magnetic resonance imaging showed a less enhanced area in the left lateral wing of her sella turcica. Transsphenoidal surgery was performed, and the diagnosis was established as thyroid-stimulating hormone-secreting plurihormonal adenoma. A rapid reduction in thyroid hormone levels was achieved, and her blood pressure was normalized after the operation. CONCLUSION: Although incidental occurrence is the most probable etiology, long and repeated followup examinations of both thyroid and pituitary gland should be  performed in patients with an atypical clinical course.

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[581]

TÍTULO / TITLE:  - Transsphenoidal surgery for GH-secreting pituitary adenomas in 130 patients.

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

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 8. pii: S1878-8750(13)00070-3. doi: 10.1016/j.wneu.2013.01.021.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.021

AUTORES / AUTHORS:  - Shirvani M; Motiei-Langroudi R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shohada Tajrish Hospital, Shahid Beheshti University  of Medical Sciences, Tehran, Iran. Electronic address: dmshirvani@gmail.com.

RESUMEN / SUMMARY:  - OBJECTIVE: Transsphenoid surgery is the treatment of choice for GH-producing pituitary adenomas. The measures which may predict postoperative remission need to be elucidated. METHODS: Transsphenoid surgery was performed in 163 patients by a single neurosurgeon from 1992 till 2010. Thirty three patients were lost from follow-up and the results of the remaining 130 are presented here. RESULTS: 81.5% of patients obtained a 1st post-operative day GH less than 5 mug/l, while 60.5% achieved a value less than 2.5 mug/l. 56.9% had achieved both a GH less than 2.5  mug/l and normal IGF-I on delayed follow-up and could be regarded as in remission. Duration of symptoms before surgery, age, preoperative GH and IGF-I levels did not significantly influence remission. Analysis showed that cavernous  sinus extension and larger tumor size were associated with decreased remission rate, while sellar floor invasion or suprasellar extension did not significantly  influence remission. CONCLUSION: Results of our study show that TSS is an optimal treatment modality for GH-secreting pituitary adenoma. Suprasellar or sellar floor invasion, and preoperative GH or IGF-I do not necessarily predict poor outcome. Large tumor size and cavernous sinus extension are measures of higher recurrence rate.

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[582]

TÍTULO / TITLE:  - Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia.

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

REVISTA / JOURNAL:  - Rev Bras Hematol Hemoter. 2012;34(6):436-41. doi: 10.5581/1516-8484.20120109.

            ●● Enlace al texto completo (gratuito o de pago) 5581/1516-8484.20120109

AUTORES / AUTHORS:  - Cancela CS; Murao M; Viana MB; de Oliveira BM

INSTITUCIÓN / INSTITUTION:  - Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, MG, Brazil.

RESUMEN / SUMMARY:  - BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infancia - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (+/- 3.6%) and 58.8% (+/- 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis >/= 50 x 10(9)/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 10(9)/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. CONCLUSIONS: These results suggest that a leukocyte count > 50 x 10(9)/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

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[583]

TÍTULO / TITLE:  - Deltamethrin-Induced [Ca (2)(+) ]i Rise and Death in HGB Human Glioblastoma Cells.

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

REVISTA / JOURNAL:  - Chin J Physiol. 2012 Aug 31;55(4):294-304. doi: 10.4077/CJP.2012.BAB114.

            ●● Enlace al texto completo (gratuito o de pago) 4077/CJP.2012.BAB114

AUTORES / AUTHORS:  - Hsu SS; Chou CT

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.

RESUMEN / SUMMARY:  - The effect of the pesticide deltamethrin on cytosolic free Ca (2)(+) concentrations ([Ca(2)(+) ]i) and viability in human glioblastoma DBTRG-05MG cells is explored. [Ca(2)(+) ]i was measured in suspended cells using fura-2 as a Ca(2)(+) -sensitive fluorescent dye. Deltamethrin at concentrations of 5-60 muM increased [Ca(2)(+)]i in a concentration-dependent fashion. The Ca(2)(+) signal was reduced partly by removing extracellular Ca (2)(+) . Deltamethrin induced Mn  (2)(+) entry leading to quenching of fura-2 fluorescence. Deltamethrin-induced [Ca(2)(+) ]i rise was not inhibited by nifedipine, econazole, SKF96365, and phorbol 12-myristate 13 acetate, but was inhibited by the protein kinase C (PKC)  inhibitor GF109203X via blocking Ca(2)(+) release. In Ca(2)(+) -free medium, 50 muM deltamethrin pretreatment abolished the [Ca(2)(+)]i rise induced by the endoplasmic reticulum Ca(2)(+) pump inhibitor thapsigargin (TG) or 2,5-di-tertbutylhydroquinone (BHQ). Conversely, pretreatment with TG/BHQ abolished deltamethrin-induced [Ca(2)(+)]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 suppressed 50% of deltamethrin-induced  [Ca(2)(+)]i rise. At concentrations between 10 and 80 muM deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca(2)(+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA). Annexin V/ propidium iodide staining data suggest that deltamethrin (10-40 muM) induced apoptosis in a concentrationdependent manner. Deltamethrin also increased levels  of reactive oxygen species. Together, in human glioblastoma cells, deltamethrin induced a [Ca(2)(+)]i rise by inducing phospholipase C- and PKC-dependent Ca(2)(+) release from the endoplasmic reticulum and Ca(2)(+) entry via non-store-operated Ca(2)(+) channels. Deltamethrin induced cell death that might  involve apoptosis via mitochondrial pathways.

 

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[584]

TÍTULO / TITLE:  - Differential Inhibitory Effects of 2-Azafluorenones on PI-PLC Activation but not  on PC-PLC- or PC-PLD-Activation Induced by Histamine, PAF, PMA or A23187 in C6 Glioma Cells.

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

REVISTA / JOURNAL:  - Chin J Physiol. 2013 Feb 28;56(1):xxx. doi: 10.4077/CJP.2013.BAA073.

            ●● Enlace al texto completo (gratuito o de pago) 4077/CJP.2013.BAA073

AUTORES / AUTHORS:  - Wang HL; Wang LC; Wei JW

INSTITUCIÓN / INSTITUTION:  - Institute of Neuroscience, National Yang Ming University, Shih-Pai, Beitou Taipei 112, Taiwan, R.O.C.

RESUMEN / SUMMARY:  - In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [(3)H]-labeled inositol phosphate (IP1) formation by histamine (100 muM) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 muM of 2-azafluorenones. Histamine induced the increase of IP1  formation, but failed to cause an increase in extracellularly releasing of [3H]choline metabolites, or intracellular accumulation of [(3)H]phosphscholine. However, platelet activation factor (PAF) from 0.2 to 1 muM, and phorbol 12-myristate-13-acetate (PMA) at 1 muM caused an increase in extracellularly releasing of [(3)H]choline metabolites, and intracellular accumulation of [(3)H]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at high concentration (10(-)(4) M). A23187 induced  an increase of intracellular [(3)H]choline release via the activation of PCphospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at a high concentration of 10(-)(4) M. In summary, the inhibitory effect of 2-azafluorenone and its related  compound 4-methyl-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.

 

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[585]

TÍTULO / TITLE:  - CD133/CD15 defines distinct cell subpopulations with differential in vitro clonogenic activity and stem cell-related gene expression profile in in vitro propagated glioblastoma multiforme-derived cell line with a PNET-like component.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):357-68.

AUTORES / AUTHORS:  - Kahlert UD; Bender NO; Maciaczyk D; Bogiel T; Bar EE; Eberhart CG; Nikkhah G; Maciaczyk J

INSTITUCIÓN / INSTITUTION:  - Jaroslaw Maciaczyk, MD, Department of General Neurosurgery, University Freiburg Medical Center, Germany, e-mail: jaroslaw.maciaczyk@uniklinik-freiburg.de.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM), as many other solid tumours, contains a subpopulation of cells termed cancer stem-like cells responsible for the initiation and propagation of tumour growth. However, a unique immunophenotype/surface antigen composition for the clear identification of brain tumour stem cells (BTSC) has not yet been found. Here we report a novel code of cell surface markers for the identification of different cell subpopulations in neurospheres derived from a GBM with a primitive neuroectodermal tumour (PNET)-like component (GBM-PNET). These subgroups differ in their CD133/CD15 expression pattern and resemble cells with different stem-like genotype and developmental pathway activation levels. Strikingly, clonogenic analysis of cultures differentially expressing the investigated markers enabled the identification of distinct subpopulations of cells endowed with stem cell characteristics. High clonogenicity could be found in CD133-/CD15- and CD133+/CD15+ but not in CD133-/CD15+ cells. Moreover, cell subpopulations with pronounced clonogenic growth were characterized by high expression of stem cell-related genes. Interestingly, these observations were unique for GBM-PNET and differed from ordinary GBM cultures derived from tumours lacking a PNET component. This work elucidates the complex molecular heterogeneity of in vitro propagated glioblastoma-derived cells and potentially contributes to the development of novel diagnostic modalities aiming at the identification of the brain tumour stem-like cell population in a subgroup of GBMs.

 

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[586]

TÍTULO / TITLE:  - Glioma stem cell-targeted dendritic cells as a tumor vaccine against malignant glioma.

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

REVISTA / JOURNAL:  - Yonsei Med J. 2013 Jan 1;54(1):92-100. doi: 10.3349/ymj.2013.54.1.92.

            ●● Enlace al texto completo (gratuito o de pago) 3349/ymj.2013.54.1.92

AUTORES / AUTHORS:  - Ji B; Chen Q; Liu B; Wu L; Tian D; Guo Z; Yi W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, China.

RESUMEN / SUMMARY:  - PURPOSE: Cancer stem cells have recently been thought to be closely related to tumor development and reoccurrence. It may be a promising way to cure malignant glioma by using glioma stem cell-targeted dendritic cells as a tumor vaccine. In  this study, we explored whether pulsing dendritic cells with antigens of glioma stem cells was a potent way to induce specific cytotoxic T lymphocytes and anti-tumor immunity. MATERIALS AND METHODS: Cancer stem cells were cultured from  glioma cell line U251. Lysate of glioma stem cells was obtained by the repeated freezing and thawing method. Dendritic cells (DCs) were induced and cultured from the murine bone marrow cells, the biological characteristics were detected by electron microscope and flow cytometry. The DC vaccine was obtained by mixing DCs with lysate of glioma stem cells. The DC vaccine was charactirizated through the  mixed lymphocyte responses and cell killing experiment in vitro. Level of interferon-gamma (IFN-gamma) in the supernatant was checked by ELISA. RESULTS: After stimulation of lysate of glioma stem cell, expression of surface molecules  of DC was up-regulated, including CD80, CD86, CD11C and MHC-II. DCs pulsed with lysate of glioma stem cells were more effective than the control group in stimulating original glioma cells-specific cytotoxic T lymphocytes responses, killing glioma cells and boosting the secretion of IFN-gamma in vitro. CONCLUSION: The results demonstrated DCs loaded with antigens derived from glioma stem cells can effectively stimulate naive T cells to form specific cytotoxic T cells, kill glioma cells cultured in vitro.

 

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[587]

TÍTULO / TITLE:  - Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Jan 22;8(1):17.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-17

AUTORES / AUTHORS:  - Su SF; Huang SM; Han F; Huang Y; Chen CY; Xiao WW; Sun XM; Lu TX

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The radiation tolerance dose-volume in brain remains unclear for nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). We performed this study to investigate dosimetric  factors associated with temporal lobe necrosis (TLN) in NPC patients treated with IMRT. METHODS: From 2001 to 2008, 870 NPC patients were treated with IMRT. For the whole group, 40 patients have developed MRI-diagnosed TLN, and 219 patients were followed-up more than 60 months. Predictive dosimetric factors for TLN were  identified by using univariate and multivariate analysis in these 259 patients. RESULTS: By univariate analyses, rVX ( percent of temporal lobes receiving >= X Gy) and aVX ( absolute volumes of temporal lobes receiving >= X Gy, values of X considered were 10, 20, 30, 40, 50, 60, 66 and 70) were all significantly associated with TLN. Multivariate analysis by logistic regression showed that rV40 and aV40 were significant factors for TLN. All dosimetric factors in current serials were highly correlated one another (p < 0.001). The 5-year incidence of TLN for rV40 <10% or aV40 <5 cc is less than 5%. The incidence for rV40 >= 15% or aV40c >= 10c is increased significantly and more than 20%. CONCLUSIONS: In this study, all dosimetric factors were highly correlated, rV40 and aV40 were independent predictive factors for TLN, IMRT with rV40 <10% or aV40 <5 cc in temporal lobe is relatively safe.

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[588]

TÍTULO / TITLE:  - Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote glioblastoma multiforme proliferation.

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 http://stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Dev. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1089/scd.2012.0486

AUTORES / AUTHORS:  - Akimoto K; Kimura K; Nagano M; Takano S; Salazar G; Yamashita T; Ohneda O

INSTITUCIÓN / INSTITUTION:  - University of Tsukuba, Regenerative Medicine, Tsukuba, Japan; c0930378@md.tsukuba.ac.jp.

RESUMEN / SUMMARY:  - Mesenchymal stem cells (MSC) possess self-renewal and multipotential differentiation abilities, and are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSC has been studied as a novel therapeutic approach for cancers that show refractory progressive and poor prognosis. MSC from different tissues have different properties. However, the potential application of MSC anticancer properties has not been thoroughly investigated. In this study, to examine the anticancer therapeutic application of MSC from different sources, we established two different kinds of human MSC: umbilical cord blood-derived MSC (UCB-MSC) and adipose tissue-derived MSC (AT-MSC). We used these MSC in a co-culture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSC from different sources can inhibit GBM growth. We found UCB-MSC inhibited GBM growth and caused  apoptosis, but AT-MSC promoted GBM growth. TUNEL assay clearly demonstrated UCB-MSC promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that UCB-MSC expressed more highly than AT-MSC. AT-MSC showed higher expression of mRNA of angiogenic factors (VEGF, Ang-1, PDGF, and IGF) and stromal-derived factor-1 (SDF-1/CXCL12), and highly vascularized tumors were developed when AT-MSC and GBM were co-transplanted. Importantly, addition of CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting AT-MSC may support GBM development in vivo by at least two distinct mechanisms. The opposite effects of AT-MSC and UCB-MSC on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

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[589]

TÍTULO / TITLE:  - Quality of life in patients with primary and metastatic brain cancer as reported  in the literature using the EORTC QLQ-BN20 and QLQ-C30.

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

REVISTA / JOURNAL:  - Expert Rev Pharmacoecon Outcomes Res. 2012 Dec;12(6):831-7. doi: 10.1586/erp.12.70.

            ●● Enlace al texto completo (gratuito o de pago) 1586/erp.12.70

AUTORES / AUTHORS:  - Chiu L; Chiu N; Zeng L; Zhang L; Popovic M; Chow R; Lam H; Poon M; Chow E

INSTITUCIÓN / INSTITUTION:  - Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.

RESUMEN / SUMMARY:  - The objective of this study is to compare the differences in quality of life (QoL) as assessed by the QLQ-BN20 and QLQ-C30 in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted over the OvidSP platform in MEDLINE (1980-2012) and EMBASE (1980-2012). Studies in which the QLQ-BN20 was used as a QoL assessment for patients with malignant brain tumors (either metastatic or primary) were included in the study. Articles were included if they reported scores of at least one subscale of the QLQ-C30 or QLQ-BN20. The weighted means of the QLQ-BN20 and QLQ-C30 subscales were calculated based on sample size for included studies. Weighted analysis of variance was conducted to compare these scores in primary and metastatic brain patients. A p-value of < 0.05 was considered statistically significant. A total of 14 studies (16 arms: three brain metastases and 13 primary brain tumors) were  identified and included in the data analysis. Fifteen of the 16 arms included QLQ-C30 scores along with QLQ-BN20 scores. Performance status of patients in both cohorts was similar. Patients with primary brain tumors and brain metastases had  the following findings: physical functioning (weighted mean: 79.18 vs 74.93), global QoL (61.88 vs 59.44), role functioning (67.37 vs 75.00) and emotional functioning (70.44 vs 71.86); but none of them were statistically significantly different. Only cognitive functioning from the QLQ-C30 was significantly worse in patients with primary brain tumors (p-value = 0.0199). Despite cognitive function being significantly worse in patients with primary brain tumors, patients with metastatic brain tumors and patients with primary brain tumors have very similar  QoL profiles. The study is limited by the large discrepancy in cohort sizes (1260 patients with primary brain cancer vs 183 patients with brain metastases) and the lack of clinical data.

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[590]

TÍTULO / TITLE:  - Prediction of brain MR scans in longitudinal tumor follow-up studies.

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

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 2):179-87.

AUTORES / AUTHORS:  - Weizman L; Ben-Sira L; Joskowicz L; Aizenstein O; Shofty B; Constantini S; Ben-Bashat D

INSTITUCIÓN / INSTITUTION:  - School of Eng. and Computer Science, Hebrew University of Jerusalem, Israel. lweizm45@cs.huji.ac.il

RESUMEN / SUMMARY:  - We present a new method for the estimation of the next brain MR scan in a longitudinal tumor follow-up study. Our method effectively incorporates information of the past scans in the time series to predict the future scan of the patient. Its advantages are that it requires no user intervention and does not assume any particular tumor growth model. Instead, the patient-specific tumor growth parameters are estimated individually from the past patient scans. To validate our method, we conducted an experimental study on four patients with Optic Path Gliomas (OPGs) and four patients with glioblastomas multiforma (GBM),  each scanned at five time points. The tumor volumes in the predicted and actual future scans, both segmented by an expert radiologist, yield a mean volume overlap difference of 13.65% for the OPG patients, and 34.23% for the GBM patients.

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[591]

TÍTULO / TITLE:  - Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ.

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

REVISTA / JOURNAL:  - Cell Rep. 2013 Jan 16. pii: S2211-1247(12)00458-5. doi: 10.1016/j.celrep.2012.12.013.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.celrep.2012.12.013

AUTORES / AUTHORS:  - Joo KM; Kim J; Jin J; Kim M; Seol HJ; Muradov J; Yang H; Choi YL; Park WY; Kong DS; Lee JI; Ko YH; Woo HG; Lee J; Kim S; Nam DH

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy and Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea; Samsung Biomedical Research Institute, Seoul, 135-710, Korea.

RESUMEN / SUMMARY:  - Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have  established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs.

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[592]

TÍTULO / TITLE:  - Primary lymphoma of the pituitary gland: an unusual cause of hemianopia in an immunocompetent patient.

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

REVISTA / JOURNAL:  - JRSM Short Rep. 2012 Aug;3(8):55. doi: 10.1258/shorts.2012.012067. Epub 2012 Aug  17.

            ●● Enlace al texto completo (gratuito o de pago) 1258/shorts.2012.012067

AUTORES / AUTHORS:  - Rainsbury P; Mitchell-Innes A; Clifton Nj; Khalil H

INSTITUCIÓN / INSTITUTION:  - Salisbury District Hospital , Salisbury , Wiltshire SP2 8BJ , UK.

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[593]

TÍTULO / TITLE:  - Impact of temozolomide on gonadal function in patients with primary malignant brain tumors.

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

REVISTA / JOURNAL:  - J Oncol Pharm Pract. 2013 Jan 4.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1078155212469243

AUTORES / AUTHORS:  - Strowd R; Blackwood R; Brown M; Harmon M; Lovato J; Yalcinkaya T; Lesser G

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Wake Forest School of Medicine, NC, USA.

RESUMEN / SUMMARY:  - BackgroundCumulative exposure to alkylating agents may produce impaired reproductive function. Temozolomide is an alkylating agent approved for treating  malignant gliomas. OBJECTIVE: /st>A pilot study was undertaken to investigate the effects of temozolomide on semen integrity in men with newly diagnosed or recurrent malignant gliomas. METHODS: /st>Eligible patients had no known fertility problems or impotence. Comprehensive semen analysis and serum sex hormones were obtained at baseline and following 3 and at least 6 months of temozolomide. RESULTS: /st>Thirteen men were recruited. Mean age was 42 years (28-58). Three had recurrent and 10 newly diagnosed malignant glioma. Four were unable to ejaculate or were azoospermic at baseline. Four provided samples at baseline and after at least 6 months of temozolomide. Five were unable to complete the study. Two of four patients with paired baseline and 6-month samples received 6 months of standard monthly temozolomide. Two patients received standard radiation and concurrent temozolomide followed by adjuvant temozolomide. At 6 months, three of these four patients demonstrated low sperm motility (two low at baseline); three had abnormally low percent normal forms (one abnormal at  baseline); two developed abnormally low sperm density. Sex hormone values were normal in all four patients at all time points. CONCLUSION: /st>Changes in semen  analysis parameters following 6 months of temozolomide were observed. The small sample size precludes any firm conclusions regarding the importance and duration  of these findings and their relation to temozolomide exposure. With validation in a larger study, these results may have important implications for counseling prior to initiation of temozolomide therapy in these patients.

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[594]

TÍTULO / TITLE:  - Genetic oxidative stress variants and glioma risk in a Chinese population: a hospital-based case-control study.

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

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 22;12:617. doi: 10.1186/1471-2407-12-617.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-617

AUTORES / AUTHORS:  - Zhao P; Zhao L; Zou P; Lu A; Liu N; Yan W; Kang C; Fu Z; You Y; Jiang T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. zhaopeng@njmu.edu.cn.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: The oxidative stress mechanism is of particular interest in the pathogenesis of glioma, given the high rate of oxygen metabolism in the brain. Potential links between polymorphisms of antioxidant genes and glioma risk are currently unknown. We therefore investigated the association between polymorphisms in antioxidant genes and glioma risk. METHODS: We examined 16 single nucleotide polymorphisms (SNPs) of 9 antioxidant genes (GPX1, CAT, PON1, NQO1, SOD2/MnSOD, SOD3, and NOS1*2*3) in 384 glioma and 384 control cases in a Chinese hospital-based case-control study. Genotypes were determined using the OpenArray platform, which employs the chip-based Taq-Man genotyping technology. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression. RESULTS: Using single-locus analysis, we identified four SNPs (SOD2 V16A, SOD3 T58A, GPX1 -46 C/T, and NOS1 3’-UTR) that were significantly associated with the risk of glioma development. To assess the  cumulative effects, we performed a combined unfavourable genotype analysis. Compared with the reference group that exhibited no unfavourable genotypes, the medium- and high-risk groups exhibited a 1.86-fold (95% CI, 1.30-2.67) and a 4.86-fold (95% CI, 1.33-17.71) increased risk of glioma, respectively (P-value for the trend < 0.001). CONCLUSIONS: These data suggest that genetic variations in oxidative stress genes might contribute to the aetiology of glioma.

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[595]

TÍTULO / TITLE:  - Analysis of Gene Expression Profiling in Meningioma: Deregulated Signaling Pathways Associated with Meningioma and EGFL6 Overexpression in Benign Meningioma Tissue and Serum.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52707. doi: 10.1371/journal.pone.0052707. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052707

AUTORES / AUTHORS:  - Wang X; Gong Y; Wang D; Xie Q; Zheng M; Zhou Y; Li Q; Yang Z; Tang H; Li Y; Hu R; Chen X; Mao Y

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - Molecular mechanisms underlying the pathogenesis of meningioma are not fully elucidated. In this study, we established differential gene expression profiles between meningiomas and brain arachnoidal tissue by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis demonstrated that PI3K/Akt and TGFbeta signaling pathways were up-regulated in fibroblastic meningioma, and focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. EGFL6 was one of the most up-regulated genes in fibroblastic meningioma by microarray analysis. Quantitative real-time PCR demonstrated that benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissue and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene  was also highly expressed in ovarian cancer, but expressed lowly in other investigated tumors. ELISA analysis showed that patients with benign meningiomas  and ovarian cancers had the highest serum levels of EGFL6 (mean concentration: 672 pg/ml for benign meningiomas, and 616 pg/ml for ovarian cancers). Healthy people and patients with other tumors, however, had low levels of serum EGFL6. In conclusion, we proposed that activation of PI3K/Akt and integrin-mediated signaling pathways was involved in the pathogenesis of benign and anaplastic meningiomas, respectively. We also presented evidence that EGFL6 was overexpressed in benign meningioma tissues and serum.

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[596]

TÍTULO / TITLE:  - Survival time following hospital discharge in dogs with palliatively treated primary brain tumors.

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

REVISTA / JOURNAL:  - J Am Vet Med Assoc. 2013 Jan 15;242(2):193-8. doi: 10.2460/javma.242.2.193.

            ●● Enlace al texto completo (gratuito o de pago) 2460/javma.242.2.193

AUTORES / AUTHORS:  - Rossmeisl JH Jr; Jones JC; Zimmerman KL; Robertson JL

INSTITUCIÓN / INSTITUTION:  - Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College  of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

RESUMEN / SUMMARY:  - Objective-To analyze survival time and identify prognostic factors associated with outcome following discharge in dogs with primary brain tumors treated palliatively. Design-Prospective case series. Animals-51 dogs with 5 histopathologic types of brain tumors. Procedures-Owners with dogs examined from  2004 to 2008 were invited to participate if dogs had CT or MRI evidence of a brain mass that was histopathologically confirmed as a neoplasm upon death, dogs  survived for >/= 48 hours after hospital discharge, and treatments following discharge were limited to administration of prednisone or phenobarbital. Prognostic factors, including signalment, clinical signs (including duration), tumor type, tumor location, degree of peritumoral edema, lesion burden, and prescribed treatment, were evaluated. Survival time was estimated and animal- and tumor-specific variables evaluated as potential prognostic factors. Results-The median survival time in all dogs was 69 days (95% confidence interval [CI], 18 to 201 days). Multivariate analyses identified neuroanatomic location as the only significant prognostic variable, with the survival time of dogs with infratentorial tumors (n = 18) being significantly shorter (median, 28 days; 95%  CI, 19 to 68 days) than survival time of dogs with supratentorial (33) tumors (median, 178 days; 95% CI, 119 to 270 days). Seizures were the most common clinical sign associated with supratentorial tumors (24/33 [73%]) and central vestibular dysfunction with infratentorial tumors (12/18). Conclusions and Clinical Relevance-Dogs with palliatively treated primary brain tumors, particularly those with tumors in the cerebellum, pons, or medulla, had a poor prognosis. However, dogs with supratentorial tumors had survival times > 3 months.

 

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[597]

TÍTULO / TITLE:  - Critical multiple angiogenic factors secreted by glioblastoma stem-like cells underline the need for combinatorial anti-angiogenic therapeutic strategies.

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

REVISTA / JOURNAL:  - Proteomics Clin Appl. 2013 Jan;7(1-2):79-90. doi: 10.1002/prca.201200102.

            ●● Enlace al texto completo (gratuito o de pago) 1002/prca.201200102

AUTORES / AUTHORS:  - Thirant C; Gavard J; Junier MP; Chneiweiss H

INSTITUCIÓN / INSTITUTION:  - Leukemia and Stem Cell Biology Laboratory, Department of Hematological Medicine,  Rayne Institute, King’s College London, London, UK.

RESUMEN / SUMMARY:  - Glioblastomas are the most frequent adult primary brain tumors that still remain  fatal despite major clinical efforts. As in other solid tumors, populations of glioblastoma stem-like cells (GSCs) endowed with tumor initiating and therapeutic resistance properties have been identified. Glioblastomas are highly vascularized tumors resulting in a rich dialog between GSCs and endothelial cells. In one direction, endothelial cells and their secreted proteins are able to sustain GSC  properties while, in turn, GSCs can promote neoangiogenesis, modulate endothelial cell functions and may even transdifferentiate into endothelial cells. Accordingly, targeting tumor vasculature seems a promising issue despite incomplete and transient results obtained from anti-vascular endothelial growth factor therapeutic trials. Recent findings of novel GSC-secreted molecules with pro-angiogenic properties (Semaphorin 3A, hepatoma-derived growth factor) open the path to the design of a concerted attack of glioblastoma vasculature that could overcome the development of resistance to single-targeted therapies while keeping away the toxicity of the treatments.

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[598]

TÍTULO / TITLE:  - Joint tumor segmentation and dense deformable registration of brain MR images.

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

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 2):651-8.

AUTORES / AUTHORS:  - Parisot S; Duffau H; Chemouny S; Paragios N

INSTITUCIÓN / INSTITUTION:  - Center for Visual Computing, Ecole Centrale Paris, Chatenay Malabry, France.

RESUMEN / SUMMARY:  - In this paper we propose a novel graph-based concurrent registration and segmentation framework. Registration is modeled with a pairwise graphical model formulation that is modular with respect to the data and regularization term. Segmentation is addressed by adopting a similar graphical model, using image-based classification techniques while producing a smooth solution. The two  problems are coupled via a relaxation of the registration criterion in the presence of tumors as well as a segmentation through a registration term aiming the separation between healthy and diseased tissues. Efficient linear programming is used to solve both problems simultaneously. State of the art results demonstrate the potential of our method on a large and challenging low-grade glioma data set.

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[599]

TÍTULO / TITLE:  - Surgical treatment of pituitary adenomas using low-field intraoperative magnetic  resonance imaging.

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

REVISTA / JOURNAL:  - Adv Clin Exp Med. 2012 Jul-Aug;21(4):495-503.

AUTORES / AUTHORS:  - Tabakow P; Czyz M; Jarmundowicz W; Lechowicz-Glogowska E

INSTITUCIÓN / INSTITUTION:  - Department and Clinic of Neurosurgery, Wroclaw Medical University, Wroclaw, Poland. p.tabakov@wp.pl

RESUMEN / SUMMARY:  - BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a new technique for imaging of the brain and is used with increasing frequency during neurosurgical operations, enabling the surgeon to make decisions based on real-time images. OBJECTIVES: This paper presents the technique for the surgical  treatment of pituitary adenomas using low-field iMRI, evaluates the safety of iMRI usage in pituitary surgery and examines the influence of iMRI on the extent  of tumor removal. MATERIAL AND METHODS: From October 2008 to December 2010, 18 patients were treated for pituitary adenomas using the low-field iMRI system Polestar N20. The procedures were conducted via the transsphenoidal approach, using the microscopic technique in 15 cases and endoscopically in three cases. The patients’ mean age was 56 +/- 15 years; their mean American Society of Anesthesiologists (ASA) score was 2; 67% of them were male. Most of the patients  were operated on for macroadenomas, 83% of which were hormonally inactive. The analysis concerned the technical aspects of iMRI usage, such as preparation and surgery time and the quality of the iMRI-scans performed. The safety of iMRI and  its influence on decisions regarding further tumor resection. RESULTS: The operations on pituitary adenomas using iMRI were safe. Only two hemorrhagic complications were noted, and they were not related to iMRI usage. The mean preparation and surgery times were 109 +/- 37 minutes and 238 +/- 188 minutes, respectively. The iMRI images of sella turcica were of satisfactory quality in 16 patients. In 50% of the cases, iMRI conducted when the surgeon believed that the  desired extent of tumor resection had been attained showed that there were still  tumor remnants to be resected. In 67% of these cases, continued tumor removal lead to achievement of the desired degree of resection. CONCLUSIONS: Low-field iMRI-guided operations on pituitary tumors are safe and feasible, and they ensure an increased radicality of tumor resection.

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[600]

TÍTULO / TITLE:  - Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Jan 2;8:1. doi: 10.1186/1748-717X-8-1.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-1

AUTORES / AUTHORS:  - Ken S; Vieillevigne L; Franceries X; Simon L; Supper C; Lotterie JA; Filleron T; Lubrano V; Berry I; Cassol E; Delannes M; Celsis P; Cohen-Jonathan EM; Laprie A

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology and Medical Physics, Institut Claudius Regaud, Toulouse, 31052, France. Ken.Soleakhena@claudiusregaud.fr.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). METHODS: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy  SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). RESULTS: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and </=1.15 degrees for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). CONCLUSIONS: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps  integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

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[601]

TÍTULO / TITLE:  - Plexiform (multinodular) schwannoma of soft palate. Report of a case.

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

REVISTA / JOURNAL:  - Folia Med (Plovdiv). 2012 Jul-Sep;54(3):62-4.

AUTORES / AUTHORS:  - Kapetanakis S; Vasileiadis I; Petousis A; Fiska A; Stavrianaki A

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy, Medical school of Alexandroupolis, Democritus University of Thrace, Heraklion, Greece. kastegepe@yahoo.gr

RESUMEN / SUMMARY:  - Plexiform schwannoma is a rare benign neoplasm of the neural sheath characterized by a multinodular plexiform growth pattern. Only 5% of schwannomas have a plexiform or multinodular growth pattern. Schwannoma apparently derives from the  Schwann cells. Extracranially, 25% of all schwannomas are located in the head and neck region, but only 1% show an intraoral origin. The intraoral lesions show a predilection for the tongue, followed by the palate, buccal mucosa, lip and gingival. Microscopic examination is necessary to confirm the diagnosis. Characteristic histological signs are the palisading of the spindle-shaped Schwann cells around the central acellular area, so called Verocay bodies. We report a case of a 21-year-old woman with a smooth mass of the soft palate that was gradually increasing. Surgical excision of the mass was done and the histopathology and immunohistochemistry study of the excised lesion revealed a multinodular plexiform schwannoma of the soft palate. The patient is under regular clinical control, with no signs of recurrence after 17 months. Plexiform  schwannomas of the soft palate are mentioned very rarely in the English literature. This rare benign tumor is worthy of recognition because it can be misdiagnosed as plexiform neurofibroma.

 

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[602]

TÍTULO / TITLE:  - Biological and clinical implications of cancer stem cells in primary brain tumors.

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

REVISTA / JOURNAL:  - Front Oncol. 2013;3:6. doi: 10.3389/fonc.2013.00006. Epub 2013 Jan 25.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00006

AUTORES / AUTHORS:  - Maugeri-Sacca M; Martino Sd; Maria RD

INSTITUCIÓN / INSTITUTION:  - “Regina Elena” National Cancer Institute Rome, Italy.

RESUMEN / SUMMARY:  - Despite therapeutic advances, glioblastoma multiforme (GBM) remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs). The initial GBM-SC concept has been challenged, and refined according  to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.

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[603]

TÍTULO / TITLE:  - KDM1 is a novel therapeutic target for the treatment of gliomas.

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

REVISTA / JOURNAL:  - Oncotarget. 2012 Nov 17.

AUTORES / AUTHORS:  - Sareddy GR; Nair BC; Krishnan SK; Gonugunta VK; Zhang QG; Suzuki T; Miyata N; Brenner AJ; Brann DW; Vadlamudi RK

INSTITUCIÓN / INSTITUTION:  - The Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio TX.

RESUMEN / SUMMARY:  - Glioma development is a multistep process, involving alterations in genetic and epigenetic mechanisms. Understanding the mechanisms and enzymes that promote epigenetic changes in gliomas are urgently needed to identify novel therapeutic targets. We examined the role of histone demethylase KDM1 in glioma progression.  KDM1 was overexpressed in gliomas and its expression positively correlated with histological malignancy. Knockdown of KDM1 expression or its pharmacological inhibition using pargyline or NCL-1 significantly reduced the proliferation of glioma cells. Inhibition of KDM1 promoted up regulation of the p53 target genes p21 and PUMA. Patient-derived primary GBM cells expressed high levels of KDM1 and pharmacological inhibition of KDM1 decreased their proliferation. Further, KDM1 inhibition reduced the expression of stemness markers CD133 and nestin in GBM cells. Mouse xenograft assays revealed that inhibition of KDM1 significantly reduced glioma xenograft tumor growth. Inhibition of KDM1 increased levels of H3K4-me2 and H3K9-Ac histone modifications, reduced H3K9-me2 modification and promoted expression of p53 target genes (p21 and PUMA), leading to apoptosis of glioma xenograft tumors. Our results suggest that KDM1 is overexpressed in gliomas and could be a potential therapeutic target for the treatment of gliomas.

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[604]

TÍTULO / TITLE:  - Expression of the CXCL12/SDF-1 chemokine receptor CXCR7 in human brain tumours.

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

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5281-6.

AUTORES / AUTHORS:  - Tang T; Xia QJ; Chen JB; Xi MR; Lei D

INSTITUCIÓN / INSTITUTION:  - West China Medical School, Sichuan University, Chengdu, China.

RESUMEN / SUMMARY:  - PURPOSE: Receptor 7 (CXCR7) has recently been characterized as a novel receptor for CXCL12/SDF-1 (stromal cell derived factor-1). Given the demonstrated importance of CXCL12/SDF-1 in angiogenesis and tumour metastasis, we hypothesized that CXCR7 may also play a role in tumour pathogenesis. Located in the limited space of the intracranial cavity, any brain tumours can be inherently serious and life-threatening. However, the expression of CXCR7 in pituitary adenoma, neurilemmoma or hemangioblastoma remains to be elucidated. Therefore, we aimed to determine the potential contribution of CXCR7 in the development of brain tumours. METHODS: In this study we examined and quantified the mRNA expression of CXCR7 in four different human brain tumours - 27 patients with neurilemmoma (8 patients), pituitary adenoma (7 patients), hemangioblastoma (6 patients), or meningioma (6 patients) undergoing surgical resection in the West China Hospital  of Sichuan University. There were 15 females and 12 males aged from 28 to 70 years old. Total RNA was isolated and mRNA was measured by quantitative real-time RT-PCR. One-way analysis of variance (ANOVA) was performed using SPSS 11.0 statistical software to compare the mRNA levels of CXCR7 among four groups. RESULTS: We found that CXCR7 mRNA was detected in all tumour samples. Quantitative results showed that the levels of CXCR7 mRNA in brain tissues from patients with neurilemmoma or meningioma were significantly higher than those with pituitary adenoma or hemangioblastoma. CONCLUSIONS: The results suggest that the CXCR7 may play a role in progression, metastasis and angiogenesis of brain tumours.

 

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[605]

TÍTULO / TITLE:  - Vascular endothelial growth factor participates in modulating the C6 glioma-induced migration of rat bone marrow-derived mesenchymal stem cells and upregulates their vascular cell adhesion molecule-1 expression.

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

REVISTA / JOURNAL:  - Exp Ther Med. 2012 Dec;4(6):993-998. Epub 2012 Sep 14.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.707

AUTORES / AUTHORS:  - Gao Z; Cheng P; Xue Y; Liu Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004;

RESUMEN / SUMMARY:  - Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to be able to  migrate towards glioma, but the molecular mechanisms responsible for this migratory behavior still require further elucidation. This study aimed to test the role of vascular endothelial growth factor (VEGF) in the C6 glioma-induced migration of BMSCs, evaluate the effect of VEGF on the migratory capacity and vascular cell adhesion molecule-1 (VCAM-1) expression of BMSCs and explore the role of VCAM-1 in the VEGF-induced migration of BMSCs. The results showed that C6 glioma cells significantly increased the migration of BMSCs in vitro, which was partially blocked by a VEGF neutralizing antibody, and 20 ng/ml recombinant rat VEGF(164) incubation enhanced the migration of BMSCs. Moreover, 12 h of 20 ng/ml  VEGF(164) incubation upregulated the VCAM-1 expression of BMSCs and the blocking  of VCAM-1 reduced the VEGF(164)-induced migration of BMSCs. The data also revealed that LY294002, an inhibitor of phosphoinositide-3-kinase (PI3K), decreased the VEGF-induced migration and VCAM-1 expression of BMSCs. These findings indicate that VEGF participates in mediating the C6 glioma-induced migration of BMSCs by upregulating their VCAM-1 expression, and that PI3K is involved in the signal transduction of VEGF(164)-induced migration and VCAM-1 expression of BMSCs.

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[606]

TÍTULO / TITLE:  - Outcome following decompressive hemicraniectomy in malignant middle cerebral artery infarct: Does age matters?

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

REVISTA / JOURNAL:  - Neurol India. 2012 Nov-Dec;60(6):565-6. doi: 10.4103/0028-3886.105186.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.105186

AUTORES / AUTHORS:  - Murthy JM

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, The Institute of Neurological Sciences, CARE Hospital, Nampally, Hyderabad, India.

 

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[607]

TÍTULO / TITLE:  - An optimized method for manufacturing a clinical scale dendritic cell-based vaccine for the treatment of glioblastoma.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52301. doi: 10.1371/journal.pone.0052301. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052301

AUTORES / AUTHORS:  - Nava S; Dossena M; Pogliani S; Pellegatta S; Antozzi C; Baggi F; Gellera C; Pollo B; Parati EA; Finocchiaro G; Frigerio S

INSTITUCIÓN / INSTITUTION:  - Cell Therapy Production Unit - UPTC, Fondazione IRCCS Istituto Neurologico Carlo  Besta, Milan, Italy.

RESUMEN / SUMMARY:  - Immune-based treatments represent a promising new class of therapy designed to boost the immune system to specifically eradicate malignant cells. Immunotherapy  may generate specific anti-tumor immune responses, and dendritic cells (DC), professional antigen-presenting cells, are widely used in experimental cancer immunotherapy. Several reports describe methods for the generation of mature, antigen-pulsed DC for clinical use. Improved quality and standardization are desirable to obtain GMP-compliant protocols. In this study we describe the generation of DC from 31 Glioblastoma (GB) patients starting from their monocytes isolated by immunomagnetic CD14 selection using the CliniMACS® device. Upon differentiation of CD14+ with IL-4 and GM-CSF, DC were induced to maturation with TNF-alpha, PGE(2), IL-1beta, and IL-6. Whole tumor lysate was obtained, for the first time, in a closed system using the semi-automated dissociator GentleMACS®. The yield of proteins improved by 130% compared to the manual dissociation method. Interestingly the Mean Fluorescence Intensity for CD83 increased significantly in DC pulsed with “new method” lysate compared to DC pulsed with “classical method” lysate. Our results indicate that immunomagnetic isolation of CD14(+) monocytes using the CliniMACS® device and their pulsing with whole tumor lysate proteins is a suitable method for clinical-scale generation of high quality, functional DC under GMP-grade conditions.

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[608]

TÍTULO / TITLE:  - Intranasal delivery of neural stem/progenitor cells: a noninvasive passage to target intracerebral 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 http://stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Transl Med. 2012 Dec;1(12):866-73. doi: 10.5966/sctm.2012-0045. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 5966/sctm.2012-0045

AUTORES / AUTHORS:  - Reitz M; Demestre M; Sedlacik J; Meissner H; Fiehler J; Kim SU; Westphal M; Schmidt NO

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Medical Center, Eppendorf, Hamburg, Germany.

RESUMEN / SUMMARY:  - Stem cell-based therapies for neurological disorders, including brain tumors, advance continuously toward clinical trials. Optimized cell delivery to the central nervous system remains a challenge since direct intracerebral injection is an invasive method with low transplantation efficiency. We investigated the feasibility of intranasal administration of neural stem/progenitor cells (NSPCs)  as an alternative, noninvasive, and direct passage for the delivery of stem cells to target malignant gliomas. Tumor-targeting and migratory pathways of murine and human NSPCs were investigated by intravital magnetic resonance imaging and in histological time course analyses in the intracerebral U87, NCE-G55T2, and syngenic Gl261 glioblastoma models. Intranasally administered NSPCs displayed a rapid, targeted tumor tropism with significant numbers of NSPCs accumulating specifically at the intracerebral glioma site within 6 hours after intranasal delivery. Histological time series analysis revealed that NSPCs migrated within the first 24 hours mainly via olfactory pathways but also by systemic distribution via the microvasculature of the nasal mucosa. Intranasal application of NSPCs leads to a rapid, targeted migration of cells toward intracerebral gliomas. The directional distribution of cells accumulating intra- and peritumorally makes the intranasal delivery of NSPCs a promising noninvasive and  convenient alternative delivery method for the treatment of malignant gliomas with the possibility of multiple dosing regimens.

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[609]

TÍTULO / TITLE:  - Comprehensive study on associations between nine SNPs and glioma risk.

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

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):4905-8.

AUTORES / AUTHORS:  - Liu HB; Peng YP; Dou CW; Su XL; Gao NK; Tian FM; Bai J

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Affiliated Nanfang Hospital of Southern Medical University, Guangzhou, China.

RESUMEN / SUMMARY:  - AIM: Glioma cancer is the most common type of adult brain tumor. Recent genome-wide association studies (GWAS) have identified various new susceptibility regions and here we conducted an extensive analysis of associations between 12 single nucleotide polymorphisms (SNPs) and glioma risk. METHODS: A total of 197 glioma cases and 197 health controls were selected, and 9 SNPs in 8 genes were analyzed using the Sequenom MassARRAY platform and Sequenom Assay Design 3.1 software. RESULTS: We found the MAF among selected controls were consistent with  the MAF from the NCBI SNP database. Among 9 SNPs in 8 genes, we identified four significant SNP genotypes associated with the risk of glioma, C/C genotype at rs730437 and T/T genotype at rs1468727 in ERGF were protective against glioma, whereas the T/T genotype at rs1799782 in XRCC1 and C/C genotype at rs861539 in XRCC3 conferred elevated risk. CONCLUSION: Our comprehensive analysis of nine SNPs in eight genes suggests that the rs730437 and rs1468727 in ERGF, rs1799782 in XRCC1 gene, and rs861539 in XRCC3 gene are associated with glioma risk. These  findings indicate that genetic variants of various genes play a complex role in the development of glioma.

 

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[610]

TÍTULO / TITLE:  - SWI/SNF gene variants and glioma risk and outcome.

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

REVISTA / JOURNAL:  - Cancer Epidemiol. 2012 Dec 28. pii: S1877-7821(12)00159-2. doi: 10.1016/j.canep.2012.12.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.canep.2012.12.001

AUTORES / AUTHORS:  - Amankwah EK; Thompson RC; Nabors LB; Olson JJ; Browning JE; Madden MH; Egan KM

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Epidemiology & Genetics, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: ernest.amankwah@moffitt.org.

RESUMEN / SUMMARY:  - Background: The human SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays essential roles in a variety of cellular processes and has been implicated in human cancer. However, the role of germline genetic variants in this complex in relation to cancer risk is not well studied. Methods: We assessed the association of 16 variants in the catalytic subunits (SMARCA2 and SMARCA4) of the SWI/SNF complex with the risk of glioma subtypes (lower grade astrocytoma, oligodendroglioma and glioblastoma [GBM]) and with mortality from high-grade tumors (GBM) in a multicenter US case-control study that included 561  cases and 574 controls. Associations were estimated with odds ratios (OR, for risk) or hazards ratios (HR, for mortality) with 95% confidence intervals (CI). False discovery rate (FDR-q) was used to control for multiple testing in risk associations. Results: None of the investigated SNPs was associated with overall  glioma risk. However, analyses according to histological subtypes revealed a statistically significant increased risk of oligodendroglioma in association with SMARCA2 rs2296212 (OR=4.05, 95%CI=1.11-14.80, P=0.030, q=0.08) and rs4741651 (OR=4.68, 95%CI=1.43-15.30, P=0.011, q=0.08) and SMARCA4 rs11672232 (OR=1.90, 95%CI=1.01-3.58, P=0.048, q=0.08) and rs12232780 (OR=2.14, 95%CI=1.06-4.33, P=0.035, q=0.08). No significant risk associations were observed for GBM or lower grade astrocytoma. Suggestive associations with GBM mortality were not validated  in the Cancer Genome Atlas. Conclusion: Our findings suggest that genetic variants in SMARCA2 and SMARCA4 influence the risk of oligodendroglioma. Further  research is warranted on the SWI/SNF complex genes and epigenetic mechanisms more generally in the development of glioma in adults.

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[611]

TÍTULO / TITLE:  - Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2012 Dec 21;7:220. doi: 10.1186/1748-717X-7-220.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-7-220

AUTORES / AUTHORS:  - Champ CE; Siglin J; Mishra MV; Shen X; Werner-Wasik M; Andrews DW; Mayekar SU; Liu H; Shi W

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Kimmel Cancer Center and Jefferson Medical College of Thomas Jefferson University, 111 S, 11th Street, Philadelphia, PA, 19107, USA. Colin.Champ@jeffersonhospital.org.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Adjuvant radiation therapy (RT) with temozolomide (TMZ) is  standard of care for high grade gliomas (HGG) patients. RT is commonly started 3  to 5 weeks after surgery. The deformation of the tumor bed and brain from surgery to RT is poorly studied. This study examined the magnitude of volume change in the postoperative tumor bed and the potential impact of RT planning. METHOD AND MATERIALS: This study includes 24 patients with HGG who underwent craniotomy and  adjuvant RT with TMZ at our institution. All patients had immediate postoperative MRI and repeat MRI during the day of RT simulation. Gross tumor volumes (GTV), clinical target volumes (CTV) of initial 46 Gy (CTV1) and boost to 60 Gy (CTV2) were contoured on both sets of MRIs according to RTOG (Radiation Therapy Oncology Group) guidelines. For patients who recurred after RT, the recurrence pattern was evaluated. RESULTS: An average of 17 days elapsed between immediate and delayed MRIs. GTV1 (FLAIR abnormality and tumor bed) decreased significantly on the delayed MRI as compared to immediate post-operative MRI (mean = 30.96cc, p = 0.0005), while GTV2 (contrast-enhanced T1 abnormality and tumor bed) underwent a  non-significant increase (mean = 6.82cc, p = 0.07). Such changes lead to significant decrease of CTV1 (mean decrease is 113.9cc, p<0.01), and significant  increase of CTV2 (mean increase is 32.5cc, p=0.05). At a median follow-up of 13 months, 16 patients (67%) progressed, recurred, or died, with a progression-free  survival time of 13.7 months. Twelve patients failed within all CTVs based on immediate and delayed MRIs, while one patient recurred outside of CTV2 based on immediate post-operative MRI, but within the CTV2 defined on delayed MRI. CONCLUSION: The postoperative tumor bed of HGGs undergoes substantial volumetric  changes after surgery. Treatment planning based on delayed MRI significantly reduces the volume of treated brain tissue without local control detriment. The marked reduction of volume treated to 46 Gy based on delayed MRI scan, could result in increased sparing of organs at risk. There may be a small risk of inadequate radiation field design if radiation planning is based on immediate post-operative MRI.

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[612]

TÍTULO / TITLE:  - Intradural chordoma mimicking a lateral sphenoid wing meningioma: a case report.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):407-12.

AUTORES / AUTHORS:  - Kunert P; Dziedzic T; Matyja E; Marchel A

INSTITUCIÓN / INSTITUTION:  - Przemyslaw Kunert, MD, PhD, Department of Neurosurgery, Medical University ofWarsaw, Banacha street 1a, 02-097 Warsaw, Poland, phone: +48 22 599 25 75, fax: +48 22 658 36 53, e-mail: pkunert@wp.pl.

RESUMEN / SUMMARY:  - Chordomas are rare tumours arising from notochordal remnants. Classical chordomas are generally extradural and, despite benign histopathology, they typically destroy the clivus and surrounding bone structures. Intradural lesions are extremely rare and less than thirty cases of intracranial, exclusively intradural chordomas have been reported so far. The intracranial, intradural but extranotochordal location of chordoma is extremely unique. The authors present a  case of chordoma in intracranial location that clinically mimics lateral sphenoid wing meningioma. A previously healthy 39-year-old man was admitted to our Department because of optic disc oedema without neurological deficits. Neuroimaging studies showed a large, contrast-enhanced tumour in the right frontotemporal region that was thought to be a pterional meningioma. The patient  underwent successful removal of the tumour. Histopathological study revealed a typical pattern of chordoma, confirmed by immunohistochemical findings. Because of the tumour location the differentiation between chordoma and chordoid meningioma ought to be considered. Such cases, including the present one, may lead to the conclusion that embryonic notochordal remnants may be lost in different places, even away from the neuroaxis.

 

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[613]

TÍTULO / TITLE:  - Granulomatous inflammation of dura mater - a rare side effect after application of hemostatic and insulation materials in case of two-stage operation of huge meningioma.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):417-24.

AUTORES / AUTHORS:  - Andrychowski J; Czernicki Z; Taraszewska A; Frontczak-Baniewicz M; Przytula E; Zebala M

INSTITUCIÓN / INSTITUTION:  - Jaroslaw Andrychowski, Department of Neurosurgery, Medical University of Warsaw,  Bielanski Hospital, ul. Ceglowska 80, 01-809 Warsaw, phone/fax: +48 22 569 04 90/22 835 00 05, e-mail: j.andrychowski@wp.pl.

RESUMEN / SUMMARY:  - Haemostatic and isolating materials may cause local reactions as a foreign body.  The case presented here of intracranial granulomatous lesion pertains to a patient operated in two stages due to a huge meningioma. During the first operation the tumour was partially removed. Because of persistent intraoperative  haemorrhage haemostatic flakes of Oxycel and Spongostan were applied locally. In  order to cover the lack of the dura, an insulation material - Tachosil was used.  Histological examination of the tumour specimens confirmed the preoperative diagnosis of benign meningioma, mainly of the angiomatous subtype. The second stage of operation was performed after 3 months and the meningioma was completely removed, as well as dura mater and meningioma attachment with its oncological margin. The resected dura mater was thickened and histologically showed intensive granulomatous infiltrations and foreign body reactions most likely to Oxycel. Clinically no local and general infection and improper healing was observed after the first and the second treatment stage, but an allergic skin lesions and increased eosinophils in peripheral blood smear were noted. It was stated that systemic allergic reaction and granulomatous inflammation of dura mater were an uncommon response to the applied haemostatics and/or insulation material used during the first operation. This report show that haemostatic and isolating agents, generally used in neurosurgical procedure, may rarely cause local granulomatous processes considered as delayed hypersensitivity and the foreign body reactions. Therefore, they may hinder morphological assessment of the tissues during re-exploration and must be differentiate with the other infectious and non-infectious granulomatous processes.

 

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[614]

TÍTULO / TITLE:  - Pathologic features and clinical outcome of central neurocytoma: analysis of 15 cases.

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

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Dec;24(4):284-90. doi: 10.3978/j.issn.1000-9604.2012.08.02.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.08.02

AUTORES / AUTHORS:  - Li Y; Ye XF; Qian G; Yin Y; Pan QG

INSTITUCIÓN / INSTITUTION:  - Institute of Neuroscience, Department of Pathology, Chongqing Medical University, Chongqing 400016, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To get better recognition of central neurocytoma and diminish misdiagnosis. METHODS: A retrospective review identified 15 cases of central neurocytoma. All cases of central neurocytoma were analyzed for their clinical symptoms, pathologic changes, immunohistochemical staining, prognosis and differential diagnosis. Clinical follow up was performed. RESULTS: There were 8 males and 7 females aged 10-64 years (median 32.93 years). The most common presenting symptoms were those related to increased intracranial pressure (ICP),  including headache (100%), papilledema (93%) and vomiting (80%). All tumors were  located in the ventricular system. The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern, and in some areas, small cells with perinuclear halo could be seen. In particular, the anuclear areas may have a fine fibrillary matrix (neuropil). Nuclear atypia and vascular proliferation appeared  in two cases, respectively. Focal necrosis could be seen in one case. Immunohistochemical findings included expression of synaptophysin (15/15), neuron specific enolase (12/15) and glial fibrillary acidic protein (GFAP) (3/15). MIB-1 proliferation index ranged from 0.8-12.5%, and was more than 2% in 3 of 15 cases  assessed. Follow-up information of 11 patients was available. CONCLUSIONS: Central neurocytoma has a favorable prognosis in general, but in some cases, the  clinical course could be aggressive. Increase of GFAP positivity, proliferation index and vascular proliferation might suggest a more malignant process.

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[615]

TÍTULO / TITLE:  - Magnetic resonance study on fractional anisotropy and neuronal metabolite ratios  in peritumoral area of cerebral gliomas.

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

REVISTA / JOURNAL:  - Medicina (Kaunas). 2012;48(10):497-506.

AUTORES / AUTHORS:  - Bieza A; Krumina G

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Hospital Gailezers, Riga Eastern Clinical University Hospital, Hipokrata 2, 1038 Riga, Latvia. anvita@inbox.lv.

RESUMEN / SUMMARY:  - BACKGROUND AND OBJECTIVE. Cerebral gliomas have a tendency to infiltrate the surrounding brain tissue for several centimeters from the core of tumor. The usefulness of structural magnetic resonance (MR) sequences is limited because of  their insensitivity for the detection of tumor cells outside the visible tumor border. The aim of this study was to investigate the validity and the repeatability of 2 functional MR methods: fractional anisotropy (FA) and spectroscopy in the assessment of the peritumoral area of cerebral gliomas. MATERIAL AND METHODS. Forty-five patients with histologically verified brain gliomas underwent diffusion tensor imaging (DTI) and MR spectroscopy (MRS). Metabolic ratios were calculated from choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lactate/lipids (LL), myo-inositol (MI) spectroscopic values obtained within the tumor center, perifocal edema, and distant and contralateral normal-appearing white matter. DTI maps of FA were calculated at the same locations. RESULTS. A significant gradual increase of FA and a decrease  of LL/Cr ratios from the tumor center to the normal-appearing white matter were observed. The Cho/Cr ratio was significantly lower in the distant normal-appearing white matter than in the perifocal edema and the tumor center. The NAA/Cr ratio was significantly reduced in the tumor center, perifocal edema,  and distant normal-appearing white matter compared with the contralateral hemisphere. MRS and DTI measurements of glioma and peritumoral area had a high degree of repeatability. CONCLUSIONS. Our study shows that MRS and DTI measurements are reproducible. The combined use of Cho/Cr, LL/Cr, and FA measurements is a promising MR technique that provides valuable additional information about the location of glioma potential border.

 

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[616]

TÍTULO / TITLE:  - Multimodal magnetic resonance imaging in the diagnosis and therapeutical follow-up of brain tumors.

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

REVISTA / JOURNAL:  - Neurosciences (Riyadh). 2013 Jan;18(1):3-10.

AUTORES / AUTHORS:  - Housni A; Boujraf S

INSTITUCIÓN / INSTITUTION:  - Department of Radiology and Medical Imaging, University Hospital of Fez, Fez, Morocco.

RESUMEN / SUMMARY:  - Multimodal MRI has an important contribution to cancer research. This technique is completely non-invasive and non-ionizing, it provides major information for diagnosis, and answers the questions of therapists before, during, and after treatment. Hence, in this paper we review the interest of these MRI modalities and their impact on the diagnosis, during and after therapeutic care of brain tumors. The MRI modalities allow specifying the localization of the expanding pathological tumoral process, the differential diagnosis between brain tumors and confined lesions of different categories, the diagnosis of the tumoral type of the lesion, assessing the histological grade in cases of glial tumor, and its local extension as well as the therapeutic follow-up. The multimodal MRI approach has a major contribution to the advanced care of brain tumors.

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[617]

TÍTULO / TITLE:  - Rapid improvement in visual field with cabergoline in suprasellar tumor in a young adult: Clinical dilemma solved and surgery averted.

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

REVISTA / JOURNAL:  - Indian J Endocrinol Metab. 2012 Nov;16(6):1052-3. doi: 10.4103/2230-8210.103043.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2230-8210.103043

AUTORES / AUTHORS:  - Kharb S; Pandit A; Garg MK; Brar KS

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantonment, India.

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[618]

TÍTULO / TITLE:  - Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

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

REVISTA / JOURNAL:  - Sci China Life Sci. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11427-012-4433-5

AUTORES / AUTHORS:  - Dai C; Cai F; Hwang KC; Zhou Y; Zhang Z; Liu X; Ma S; Yang Y; Yao Y; Feng M; Bao X; Li G; Wei J; Jiao Y; Wei Z; Ma W; Wang R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

RESUMEN / SUMMARY:  - Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery  agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles  were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation  or received the same neutron irradiation alone did not show significant decrease  in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for  BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring  these new applications of BNCT for tumors, especially benign tumors.

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[619]

TÍTULO / TITLE:  - Proptosis as the presenting sign of giant prolactinoma in a prepubertal boy: successful resolution of hydrocephalus by use of medical therapy.

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

REVISTA / JOURNAL:  - Future Oncol. 2012 Dec;8(12):1621-6. doi: 10.2217/fon.12.149.

            ●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.149

AUTORES / AUTHORS:  - Cackett P; Eunson G; Bath L; Mulvihill A

INSTITUCIÓN / INSTITUTION:  - Department of Ophthalmology, Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, EH3 9HA, UK. peter.cackett@luht.scot.nhs.uk

RESUMEN / SUMMARY:  - We report the case of a 13-year-old prepubertal boy who presented with a left-sided proptosis, bilateral papilloedema and hydrocephalus who was subsequently diagnosed with a giant prolactinoma invading the left orbit. He was  commenced on dopamine receptor agonists in the form of quinagolide and cabergoline, and made an excellent response to medical therapy alone, with resolution of hydrocephalus, restoration of normal vision and a 98% reduction in  serum prolactin. The rapid improvement achieved negated the requirement for surgery and this highlights the efficacy of the dopamine agonists in the management of giant prolactinomas, even in the presence of neurological symptoms.

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[620]

TÍTULO / TITLE:  - Transsphenoidal surgery for pituitary adenoma: indications and outcomes.

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

REVISTA / JOURNAL:  - Croat Med J. 2012 Dec 15;53(6):639-41.

AUTORES / AUTHORS:  - Dusek T; Melada A; Paladino J; Kastelan D

INSTITUCIÓN / INSTITUTION:  - Tina Dusek, University of Zagreb School of Medicine, Zagreb, Croatia, tdusek@mef.hr.

 

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[621]

TÍTULO / TITLE:  - Toll-like receptors as an innate immunity bridge to neuroinflammation in medulloblastoma.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):375-81.

AUTORES / AUTHORS:  - Maslinska D; Laure-Kamionowska M; Maslinska S

INSTITUCIÓN / INSTITUTION:  - Danuta Maslinska, Department of Clinical and Experimental Neuropathology, Mossakowski Medical Research Centre, PASci, Pawinskiego 5, 02-106 Warszawa, e-mail: maslinskad@imdik.pan.pl.

RESUMEN / SUMMARY:  - The relationship between inflammation, immunity and cancer is widely accepted but mechanisms mediating this relationship remain unknown. Our present study was undertaken to examine the presence and distribution of Toll-like receptors (TLRs) in necrotic areas of medulloblastoma. These receptors fulfil the criteria postulated for the receptors of innate immunity and signalling from TLRs induces  synthesis of various pro-inflammatory cytokines, enzymes and mediators. The study was performed on human medulloblastoma samples containing areas of necrosis within the tumour and/or within the normal nerve tissue at the periphery of the tumour. Proteins of four TLRs: TLR 2, 3, 4 and 9 were detected in the tissue with the immunohistochemical method using the specific antibodies. Two types of necrotic areas were found. In the first type, the area of dead cells was surrounded by undifferentiated medulloblastoma cells. A lot of these cells expressed TLR 2 and TLR 3 antigens. TLR 2 was also expressed on the wall of de novo formed blood vessels that fill tumour regions already cleared from dead cells. The second type of necrotic areas were found at the periphery of the tumour and composed of normal nerve tissue cells. TLR 2, TLR 3 and TLR 9 were detected in hypertrophic glia cells. Our findings show a new function of TLRs as  sensors of pathogens released by medulloblastoma dead cells. This new function may provide a key link connecting innate immunity, neuroinflammation and angiogenesis in the tumour.

 

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[622]

TÍTULO / TITLE:  - Long term toxicity and prognostic factors of radiation therapy for secreting and  non-secreting pituitary adenomas.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2013 Jan 23;8(1):18.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-18

AUTORES / AUTHORS:  - Rieken S; Habermehl D; Welzel T; Mohr A; Lindel K; Debus J; Combs SE

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Radiotherapy is controversially discussed in the management of benign disorders for fear of late sequelae such as tumor induction. This study was initiated to investigate long-term toxicity, treatment outcome and prognostic factors after radiotherapy (RT) in patients with pituitary adenomas. METHODS: 92  patients with pituitary adenomas were included in this analysis. RT was conducted using either 3D conformal (16%) or fractionated stereotactic techniques (83%) in  a postoperative adjuvant setting (16%), as second-line treatment for recurring tumors (78%) or as primary treatment (6%). Postoperatively, RT was offered to patients with residual tumor tissue or in case of locally extensive adenomas, in  whom early recurrence was deemed likely. Patients were followed for a median time of 152.5 months, and analysed for overall and local progression-free survival (OS and LPFS). Multiple factors were analysed for prognostic impact. Patients were contacted with an institutional questionnaire about qualiy of life (QOL). Statistical analysis was performed using the log-rank test and the Kaplan-Meier method using a software tool (SPSS 19.0). RESULTS: Median follow-up was 152.5 months. Before treatment, 2% of all patients were diagnosed with adenoma-related  hypopituitarism. Following surgery, 68% suffered from new pituitary deficits. RT  was associated with mild toxicity, including visual deficits (5.4%) and hypopituitarism (10.9%). In particular, no radiation-induced brain necrosis or malignancy was observed. QOL was reported to be stable or improved in 92% of all  patients, and RT was perceived to not compromise but increase QOL in the vast majority of patients (95%). OS after RT was 93.3% and 61.0% at 120 and 240 months. LPFS following RT was 90.4 and 75.5% at 120 and 240 months. Early initiation of RT after surgery instead of reserving it for recurring adenomas predisposed for improved outcome. CONCLUSIONS: RT for pituitary adenomas is safe  and and self-reported QOL is stable or improved by almost all patients. Hypopituitarism rates are low. Local control appears improved in patients irradiated postoperatively over those undergoing RT for previously resected recurrent tumors.

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[623]

TÍTULO / TITLE:  - Changes in brain glioma incidence and laterality correlates with use of mobile phones - a nationwide population based study in Israel.

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

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(11):5857-63.

AUTORES / AUTHORS:  - Barchana M; Margaliot M; Liphshitz I

INSTITUCIÓN / INSTITUTION:  - School of Public Health, Haifa University, Haifa, Israel E-mail : micha.barchana@gmail.com.

RESUMEN / SUMMARY:  - Introduction: Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor’s laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. Materials and Methods: All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups - low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones  was assessed with a questionnaire in a sample of adult individuals. Results: A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the  period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor  location for all adult gliomas combined and separately for LGG and HGG was noted  from 1995 onward. The shift was more marked for those who were diagnosed in ages  20-49 (p=0.03). Conclusions: We found a statistically significant decrease in LGG’s over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

 

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[624]

TÍTULO / TITLE:  - State-of-the-art treatment alternatives for base of skull meningiomas: complementing and controversial indications for neurosurgery, stereotactic and robotic based radiosurgery or modern fractionated radiation techniques.

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

REVISTA / JOURNAL:  - Radiat Oncol. 2012 Dec 29;7:226. doi: 10.1186/1748-717X-7-226.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-7-226

AUTORES / AUTHORS:  - Combs SE; Ganswindt U; Foote RL; Kondziolka D; Tonn JC

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Stephanie.Combs@med.uni-heidelberg.de.

RESUMEN / SUMMARY:  - ABSTRACT: For skull base meningiomas, several treatment paradigms are available:  Observation with serial imaging, surgical resection, stereotactic radiosurgery, radiation therapy or some combination of both. The choice depends on several factors. In this review we evaluate different treatment options, the outcome of modern irradiation techniques as well as the clinical results available, and establish recommendations for the treatment of patients with skull-base meningiomas.

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[625]

TÍTULO / TITLE:  - Clinical target volume definition for glioblastoma radiotherapy planning: magnetic resonance imaging and computed tomography.

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

REVISTA / JOURNAL:  - Clin Transl Oncol. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0992-y

AUTORES / AUTHORS:  - Fiorentino A; Caivano R; Pedicini P; Fusco V

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, IRCCS/CROB, via San Pio 1, 85028, Rionero in Vulture, PZ, Italy, albafiorentino@hotmail.it.

RESUMEN / SUMMARY:  - PURPOSE: To assess the differences between the target delineation using computed  tomography (CT) and imaging fusion CT/magnetic resonance imaging (MRI) for the radiotherapy planning of glioblastoma. METHODS: One hundred-twenty gross tumor volume and clinical target volume on CT and MRI (GTV(CT)/CTV(CT), GTV(MRI)/CTV(MRI), respectively) were contoured and evaluated. The treatments planning (total dose 60 Gy) based on CTV(CT) were analysed in terms of percentage of CTV(CT) and CTV(MRI) receiving 95 % of the prescribed dose (V(95)-CTV(CT), V(95)-CTV(MRI)). RESULTS: GTVs and CTVs contoured on MRI were significantly larger than those delineated on CT (p = 0.0003, p = 0.0006, respectively). Nighty-two percent of CTV(CT) was coincident with the CTV(MRI) and 8 % was normal tissue; 20 % of CTV(MRI), considered as tumor volume, was not included on CTV(CT). The V(95)-CTV(MRI) was significantly lower than the V(95)-CTV(CT) (p = 0.0005). CONCLUSIONS: In the delineation of glioblastoma target volume, fusion CT/MRI was preferred. The CT only is insufficient for the CTV dose coverage.

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[626]

TÍTULO / TITLE:  - Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4334-7.

AUTORES / AUTHORS:  - Qu JR; Jiang T; Dai JP; Li HL; Luo JP; Li SW; Ai L; Jiang TZ

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Radiology, Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan 450008, China.

RESUMEN / SUMMARY:  - BACKGROUND: Reliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research. Proton magnetic resonance spectroscopy ((1)H-MRS) has been applied with variable success in clinical application, and we hypothesize that (1)H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery. METHODS: (1)H-MRS was performed before surgery on 25 patients who  had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (mI/Cr) were determined in the solid tumor. RT response was classified as follows: complete resolution (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression  by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, mI/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. RESULTS: Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO  histologic grade, extent of surgery, and Karnofsky score (KPS). The correlation between the ratios of lipid/Cr and TTP was significant (r = 0.894, P = 0.000), and between the ratios of mI/Cr and TTP was also significant (r = 0.891, P = 0.000). As predicted, RT response correlated significantly with TTP (r = 0.59, P  = 0.002): median TTP was 49.9 days for patients with PD compared with 202.7 days  for SD, 208.0 days for PR, and 234.5 days for CR. CONCLUSION: The ratios of Lip/Cr and mI/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

 

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[627]

TÍTULO / TITLE:  - ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers.

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

REVISTA / JOURNAL:  - Front Oncol. 2012;2:192. doi: 10.3389/fonc.2012.00192. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00192

AUTORES / AUTHORS:  - Wellstein A

INSTITUCIÓN / INSTITUTION:  - Lombardi Cancer Center, Georgetown University Washington, DC, USA.

RESUMEN / SUMMARY:  - The intracellular anaplastic lymphoma kinase (ALK) fragment shows striking homology with members of the insulin receptor family and was initially identified as an oncogenic fusion protein resulting from a translocation in lymphoma and more recently in a range of cancers. The full-length ALK transmembrane receptor of ~220 kDa was identified based on this initial work. This tyrosine kinase receptor and its ligands, the growth factors pleiotrophin (PTN) and midkine (MK)  are highly expressed during development of the nervous system and other organs. Each of these genes has been implicated in malignant progression of different tumor types and shown to alter phenotypes as well as signal transduction in cultured normal and tumor cells. Beyond its role in cancer, the ALK receptor pathway is thought to contribute to nervous system development, function, and repair, as well as metabolic homeostasis and the maintenance of tissue regeneration. ALK receptor activity in cancer can be up-regulated by amplification, overexpression, ligand binding, mutations in the intracellular domain of the receptor and by activity of the receptor tyrosine phosphatase PTPRz. Here we discuss the evidence for ligand control of ALK activity as well as the potential prognostic and therapeutic implications from gene expression and functional studies. An analysis of 18 published gene expression data sets from different cancers shows that overexpression of ALK, its smaller homolog LTK (leukocyte tyrosine kinase) and the ligands PTN and MK in cancer tissues from patients correlate significantly with worse course and outcome of the disease. This observation together with preclinical functional studies suggests that this  pathway could be a valid therapeutic target for which complementary targeting strategies with small molecule kinase inhibitors as well as antibodies to ligands or the receptors may be used.

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[628]

TÍTULO / TITLE:  - Deregulated expression of cry1 and cry2 in human gliomas.

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

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(11):5725-8.

AUTORES / AUTHORS:  - Luo Y; Wang F; Chen LA; Chen XW; Chen ZJ; Liu PF; Li FF; Li CY; Liang W

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First People’s Hospital of Jingmen, Jingmen, China E-mail : wangfan19840303@126.com.

RESUMEN / SUMMARY:  - Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important  clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and  cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.

 

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[629]

TÍTULO / TITLE:  - B7-H4 expression is high in human U251 glioma stem-like cells and is induced in monocytes cultured in U251 stem-like cell conditioned medium.

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

REVISTA / JOURNAL:  - Chin J Cancer. 2013 Jan 18. doi: 10.5732/cjc.012.10228.

            ●● Enlace al texto completo (gratuito o de pago) 5732/cjc.012.10228

AUTORES / AUTHORS:  - Mo LJ; Ye HX; Mao Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P. R. China zjm135@vip.sina.com.

RESUMEN / SUMMARY:  - Previous studies indicated that B7-H4, the youngest B7 family, negatively regulates T cell-mediated immunity and is significantly overexpressed in many human tumors. Tumor stem cells are purported to play a role in tumor renewal and  resistance to radiation and chemotherapy. However, the link between B7-H4 and tumor stem cells is unclear. In this study, we investigated B7-H4 expression in the medium of human glioma U251 cell cultures. Immunofluorescence results showed  that U251 cells cultured in serum-free medium (supplemented with 2% B27, 20 ng/mL EGF, 20 ng/mL bFGF) maintained stem-like cell characteristics, including expression of stem cell marker CD133 and the neural progenitor cell markers nestin and SOX2. In contrast, U251 cells cultured in serum-containing medium highly expressed differentiation marker GFAP. Flow cytometry analysis showed serum-free medium cultured U251 cells expressed higher intracellular B7-H4 than serum-containing medium cultured U251 cells (24%-35% vs. 8%-11%, P <0.001). Immunofluorescence in purified monocytes from normal human peripheral blood mononuclear cells revealed moderate expression of B7-H4 after stimulation with conditioned medium from U251 cells cultured in serum-containing medium. Moreover, conditioned medium from U251 stem-like cells had a significant stimulation effect on B7-H4 expression compared with serum-containing condition medium (P < 0.01). Negative costimulatory molecule B7-H4 was preferentially expressed in U251 stem-like cells, and conditioned medium from these cells more effectively induced monocytes to express B7-H4 than conditioned medium from U251 cells cultured in the presence of serum. Our results show that U251 stem-like cells may play a more crucial role in tumor immunoloregulation with high expression of B7-H4.

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[630]

TÍTULO / TITLE:  - Comparison of L1 expression and secretion in glioblastoma and neuroblastoma cells.

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

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):812-816. Epub 2012 Jul 5.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.787

AUTORES / AUTHORS:  - Zhao W

INSTITUCIÓN / INSTITUTION:  - Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.

RESUMEN / SUMMARY:  - The expression of cell adhesion molecule L1 has been identified in a vast spectrum of tumors; however, its expression pattern with regard to tumor type is  rarely discussed. In the present study, we studied L1 levels in human glioblastomas and neuroblastomas, and compared the expression and secretion of L1 in human glioblastoma U87-MG and neuroblastoma SK-N-SH cells. Immunofluorescence  staining revealed different grades of L1 staining in human glioblastoma and neuroblastoma samples. In U87-MG cells, full-length L1 was weakly detected in cell lysates (CLs), while greater levels of abundant soluble L1 were confined in  conditioned culture medium (CCM). In contrast, higher levels of full-length L1 were confined in SK-N-SH CLs, while almost no soluble forms of L1 were detected in CCM. Our data indicates various expression patterns of L1 in U87-MG and SK-N-SH cells, which may underlie the different malignancies of the two neural tumor types and further stress the importance of soluble L1-mediated signaling pathways in cell malignancy.

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[631]

TÍTULO / TITLE:  - uPAR and cathepsin B shRNA impedes TGF-beta1-driven proliferation and invasion of meningioma cells in a XIAP-dependent pathway.

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

REVISTA / JOURNAL:  - Cell Death Dis. 2012 Dec 6;3:e439. doi: 10.1038/cddis.2012.170.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.170

AUTORES / AUTHORS:  - Gogineni VR; Gupta R; Nalla AK; Velpula KK; Rao JS

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology & Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.

RESUMEN / SUMMARY:  - Overexpression of transforming growth factor beta1 (TGF-beta1) has been linked to immune suppression, tumor angiogenesis, tumor cell migration, tumor cell survival, and tumor cell invasion in many cancers. In the present study, we found abundant expression of TGF-beta1 in the microenvironment of four different pathological types of meningioma tumors. TGF-beta1 induced invasion in malignant  meningioma cells with an associated upregulation of urokinase-type plasminogen activator (uPA), uPAR, cathepsin B, and MMP-9, and this increase in proliferation was coupled with the expression of anti-apoptotic and pro-survival signaling molecules. In addition to the intense immunoreactivity of meningioma tumors to X-linked inhibitor to apoptosis (XIAP), its knockdown abolished the TGF-beta1-induced proliferation of these cells. The stimulation of XIAP expression and the activation of pSMAD-2 is mediated by phosphatidylinositol 3-kinase (PI3K)- and MEK-dependent pathways, and the addition of anti-TGF-beta1 antibodies prevented their expression with a consequent decrease in invasion. Bicistronic shRNA constructs targeting uPAR and cathepsin B (pUC) quenched TGF-beta1-driven invasion and survival of meningioma cells by downregulation of XIAP and pSMAD-2 expression. Animal models with intracranial tumors showed elevated levels of TGF-beta1, XIAP and pSMAD-2, and pUC treatment prevented this  increased expression. Thus, targeted silencing of TGF-beta1-induced signaling by  pUC in meningioma would provide new treatment approaches for management of meningioma.

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[632]

TÍTULO / TITLE:  - Registration and analysis of white matter group differences with a multi-fiber model.

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

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 3):313-20.

AUTORES / AUTHORS:  - Taquet M; Scherrer B; Commowick O; Peters J; Sahin M; Macq B; Warfield SK

INSTITUCIÓN / INSTITUTION:  - Computational Radiology Laboratory, Children’s Hospital Boston, Harvard, USA.

RESUMEN / SUMMARY:  - Diffusion magnetic resonance imaging has been used extensively to probe the white matter in vivo. Typically, the raw diffusion images are used to reconstruct a diffusion tensor image (DTI). The incapacity of DTI to represent crossing fibers  leaded to the development of more sophisticated diffusion models. Among them, multi-fiber models represent each fiber bundle independently, allowing the direct extraction of diffusion features for population analysis. However, no method exists to properly register multi-fiber models, seriously limiting their use in group comparisons. This paper presents a registration and atlas construction method for multi-fiber models. The validity of the registration is demonstrated on a dataset of 45 subjects, including both healthy and unhealthy subjects. Morphometry analysis and tract-based statistics are then carried out, proving that multi-fiber models registration is better at detecting white matter local differences than single tensor registration.

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[633]

TÍTULO / TITLE:  - Malignant behaviorial characteristics of CD133(+/-) glioblastoma cells from a Northern Chinese population.

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

REVISTA / JOURNAL:  - Exp Ther Med. 2013 Jan;5(1):65-72. Epub 2012 Oct 15.

            ●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.747

AUTORES / AUTHORS:  - Liu X; Chen L; Jiang Z; Wang J; Su Z; Li G; Yu S; Liu Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Binhai Neurological Institute;

RESUMEN / SUMMARY:  - Following emergence of the tumor stem cell theory, the increasing number of related studies demonstrates the theory’s growing importance in cancer research and its potential for clinical applications. Few studies have addressed the in vitro or in vivo properties of glioma stem cells from a Han Chinese population. In the present study, surgically obtained glioblastoma tissue was classified into two subtypes, CD133(+) and CD133(-). The hierarchy, invasiveness, growth tolerance under low nutrient conditions and colony forming abilities of the tissue samples were analyzed. Additionally, the characteristics of tumor cells transplanted subcutaneously or re-transplanted into nude mice were observed. The  results demonstrated that CD133(+) glioblastoma cells derived from Han Chinese glioma specimens were more prone to primitive cell differentiation and more invasive than CD133(-) glioblastoma cells, leading to increased tumor malignancy  compared with CD133(-) cells. The tumor formation rates of CD133(+) and CD133(-)  cells in mice were 26/30 and 2/30, respectively. A comparison of tumor subtypes demonstrated that CD133(+) glioblastoma cells had a lower incidence of cell apoptosis in the tumor tissue and higher protein expression levels of Oct4, Sox2, PCNA, EGFR, Ang2, MMP2 and MMP9 compared with CD133(-) cells. Flow cytometry revealed that in the CD133(+) and CD133(-) glioblastoma cell-induced tumors, the  percentage of CD133(+) cells was 2.47+/-0.67 and 0.44+/-0.14%, respectively. The  tumor formation rates following the re-transplantation of CD133(+) or CD133(-) tumors into nude mice were 10/10 and 4/10, respectively. These findings suggest that the CD133(+) glioblastoma cell subpopulation has a stronger malignant cell phenotype than the CD133(-) subpopulation and that its recurrence rate is increased compared with the primitive tumorigenic rate following in vivo transplantation.

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[634]

TÍTULO / TITLE:  - A case of central nervous system lymphoma manifesting as multiple patchy white matter lesions with a past history of tonsil lymphoma.

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

REVISTA / JOURNAL:  - Kurume Med J. 2012;59(1-2):33-8.

AUTORES / AUTHORS:  - Kobayashi S; Sakurai K; Tanikawa M; Nishikawa Y; Matsukawa N; Okita K; Fujiyoshi Y; Shibamoto Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Nagoya City University Graduate School of Medical Sciences.

RESUMEN / SUMMARY:  - Lymphoma of the central nervous system (CNS) parenchyma is known to present as a  well-demarcated mass with strong and homogenous gadolinium enhancement in the periventricular and/or superficial region. We report a case of central nervous system lymphoma (CNSL) manifesting as multiple white matter lesions with non-tumorous patchy or ring-like enhancement and partial spontaneous resolution on magnetic resonance imaging (MRI). Such findings are unusual and could lead to  misdiagnosis without pathological evaluation.

 

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[635]

TÍTULO / TITLE:  - Extracerebral metastases of glioblastoma have a different vasculature than primary tumour. A case report of glioblastoma extracranial metastases.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):413-6.

AUTORES / AUTHORS:  - Snopkowska-Wiaderna D; Zielinski KW; Radek M; Papierz W

INSTITUCIÓN / INSTITUTION:  - Dorota Snopkowska-Wiaderna, Department of Pathomorphology and Clinical Cytopathology, Medical University of Lodz, 113 Zeromskiego Str, 90-549 Lodz, Poland, phone: +48 42 639 37 05, fax: +48 42 639 36 60, e-mail: durota@wp.pl.

RESUMEN / SUMMARY:  - The paper presents a case report of a 38-year-old female suffering from metastatic glioblastoma in the jugular lymph node that developed 9 months after craniotomy and tumorectomy in the left temporal region of the brain. The histological evaluation of metastatic tumour reveals lower density of vasculature as well as less significant pathologic changes in blood vessels morphology in comparison to primary tumour. Moreover, in this report we present cytological characteristics of the material obtained by fine needle aspiration of the metastatic mass.

 

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[636]

TÍTULO / TITLE:  - Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4349-54.

AUTORES / AUTHORS:  - Dong J; Dai XL; Lu ZH; Fei XF; Chen H; Zhang QB; Zhao YD; Wang ZM; Wang AD; Lan Q; Huang Q

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215004, China; Chinese Glioma Collaboration Group.

RESUMEN / SUMMARY:  - BACKGROUND: The primary reasons for local recurrence and therapeutic failure in the treatment of malignant gliomas are the invasion and interactions of tumor cells with surrounding normal brain cells. However, these tumor cells are hard to be visualized directly in histopathological preparations, or in experimental glioma models. Therefore, we developed an experimental human dual-color in vivo glioma model, which made tracking solitary invasive glioma cells possible, for the purpose of visualizing the interactions between red fluorescence labeled human glioma cells and host brain cells. This may offer references for further studying the roles of tumor microenvironment during glioma tissue remodeling. METHODS: Transgenic female C57BL/6 mice expressing enhanced green fluorescent protein (EGFP) were crossed with male Balb/c nude mice. Then sib mating was allowed to occur continuously in order to establish an inbred nude mice strain with 50% of their offspring that are EGFP positive. Human glioma cell lines U87-MG and SU3 were transfected with red fluorescent protein (RFP) gene, and a rat C6 glioma cell line was stained directly with CM-DiI, to establish three glioma cell lines emitting red fluorescence (SU3-RFP, U87-RFP, and C6-CM-DiI). Red fluorescence tumor cells were inoculated via intra-cerebral injection into caudate nucleus of the EGFP nude mice. Tumor-bearing mice were sacrificed when their clinical symptoms appeared, and the whole brain was harvested and snap frozen for further analysis. Confocal laser scanning microscopy was performed to  monitor the mutual interactions between tumor cells and host brain cells. RESULTS: Almost all the essential tissues of the established EGFP athymic Balb/c  nude mice, except hair and erythrocytes, fluoresced green under excitation using  a blue light-emitting flashlight with a central peak of 470 nm, approximately 50% of the offsprings were nu/nu EGFP+. SU3-RFP, U87-RFP, and C6-CM-DiI almost 100% expressed red fluorescence under the fluorescence microscope. Under fluorescence  microscopic view, RFP+ cells were observed growing wherever they arrived at, locating in the brain parenchyma, ventricles, and para-vascular region. The interactions between the transplanted tumor cells and host adjacent cells could be classified into three types: (1) interweaving; (2) mergence; and (3) fusion. Interweaving was observed in the early stage of tumor remodeling, in which both transplantable tumor cells and host cells were observed scattered in the tumor invading and spreading area without organic connections. Mergence was defined as  mutual interactions between tumor cells and host stroma during tumorigenesis. Direct cell fusion between transplantable tumor cells and host cells could be observed occasionally. CONCLUSIONS: This study showed that self-established EGFP  athymic nude mice offered the possibility of visualizing tumorigenesis of human xenograft tumor, and the dual-color xenograft glioma model was of considerable utility in studying the process of tumor remodeling. Based on this platform, mutual interactions between glioma cells and host tissues could be observed directly to further elucidate the development of tumor microenvironment.

 

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[637]

TÍTULO / TITLE:  - Engineered Drug Resistant gammadelta T Cells Kill Glioblastoma Cell Lines during  a Chemotherapy Challenge: A Strategy for Combining Chemo- and Immunotherapy.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e51805. doi: 10.1371/journal.pone.0051805. Epub 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051805

AUTORES / AUTHORS:  - Lamb LS Jr; Bowersock J; Dasgupta A; Gillespie GY; Su Y; Johnson A; Spencer HT

INSTITUCIÓN / INSTITUTION:  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America ; Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

RESUMEN / SUMMARY:  - Classical approaches to immunotherapy that show promise in some malignancies have generally been disappointing when applied to high-grade brain tumors such as glioblastoma multiforme (GBM). We recently showed that ex vivo expanded/activated gammadelta T cells recognize NKG2D ligands expressed on malignant glioma and are  cytotoxic to glioma cell lines and primary GBM explants. In addition, gammadelta  T cells extend survival and slow tumor progression when administered to immunodeficient mice with intracranial human glioma xenografts. We now show that  temozolomide (TMZ), a principal chemotherapeutic agent used to treat GBM, increases the expression of stress-associated NKG2D ligands on TMZ-resistant glioma cells, potentially rendering them vulnerable to gammadelta T cell recognition and lysis. TMZ is also highly toxic to gammadelta T cells, however, and to overcome this cytotoxic effect gammadelta T cells were genetically modified using a lentiviral vector encoding the DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) from the O(6)-methylguanine methyltransferase (MGMT) cDNA, which confers resistance to TMZ. Genetic modification of gammadelta T cells did not alter their phenotype or their cytotoxicity against GBM target cells. Importantly, gene modified gammadelta T cells showed greater cytotoxicity to two TMZ resistant GBM cell lines, U373(TMZ-R) and SNB-19(TMZ-R) cells, in the presence of TMZ than unmodified cells, suggesting that TMZ exposed more receptors for gammadelta T cell-targeted  lysis. Therefore, TMZ resistant gammadelta T cells can be generated without impairing their anti-tumor functions in the presence of high concentrations of TMZ. These results provide a mechanistic basis for combining chemotherapy and gammadelta T cell-based drug resistant cellular immunotherapy to treat GBM.

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[638]

TÍTULO / TITLE:  - E series prostaglandins alter the proliferative, apoptotic and migratory properties of T98G human glioma cells in vitro.

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

REVISTA / JOURNAL:  - Lipids Health Dis. 2012 Dec 11;11:171. doi: 10.1186/1476-511X-11-171.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-511X-11-171

AUTORES / AUTHORS:  - Gomes RN; Colquhoun A

INSTITUCIÓN / INSTITUTION:  - Department of Cell and Developmental Biology, University of Sao Paulo, Sao Paulo, CEP 05508-900, SP, Brazil. alison@usp.br.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: In many types of cancer, prostaglandin E2 (PGE2) is associated with tumour related processes including proliferation, migration, angiogenesis and apoptosis. However in gliomas the role of this prostanoid is poorly understood. Here, we report on the proliferative, migratory, and apoptotic effects of PGE1, PGE2 and Ibuprofen (IBP) observed in the T98G human glioma cell  line in vitro. METHODS: T98G human glioma cells were treated with IBP, PGE1 or PGE2 at varying concentrations for 24-72 hours. Cell proliferation, mitotic index and apoptotic index were determined for each treatment. Caspase-9 and caspase-3 activity was measured using fluorescent probes in live cells (FITC-LEHD-FMK and FITC-DEVD-FMK respectively). The migratory capacity of the cells was quantified using a scratch migration assay and a transwell migration assay. RESULTS: A significant decrease was seen in cell number (54%) in the presence of 50 muM IBP. Mitotic index and bromodeoxyuridine (BrdU) incorporation were also decreased 57%  and 65%, respectively, by IBP. The apoptotic index was increased (167%) and the in situ activity of caspase-9 and caspase-3 was evident in IBP treated cells. The inhibition of COX activity by IBP also caused a significant inhibition of cell migration in the monolayer scratch assay (74%) and the transwell migration assay  (36%).In contrast, the presence of exogenous PGE1 or PGE2 caused significant increases in cell number (37% PGE1 and 45% PGE2). When mitotic index was measured no change was found for either PG treatment. However, the BrdU incorporation rate was significantly increased by PGE1 (62%) and to a greater extent by PGE2 (100%). The apoptotic index was unchanged by exogenous PGs. The addition of exogenous PGs caused an increase in cell migration in the monolayer scratch assay (43% PGE1 and 44% PGE2) and the transwell migration assay (28% PGE1 and 68% PGE2). CONCLUSIONS: The present study demonstrated that treatments which alter PGE1 and PGE2 metabolism influence the proliferative and apoptotic indices of T98G glioma cells. The migratory capacity of the cells was also significantly affected by the change in prostaglandin metabolism. Modifying PG metabolism remains an interesting target for future studies in gliomas.

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[639]

TÍTULO / TITLE:  - Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro.

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

REVISTA / JOURNAL:  - Mol Med Report. 2013 Feb;7(2):531-6. doi: 10.3892/mmr.2012.1218. Epub 2012 Dec 3.

            ●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2012.1218

AUTORES / AUTHORS:  - Zhou GS; Song LJ; Yang B

INSTITUCIÓN / INSTITUTION:  - Neurosurgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

RESUMEN / SUMMARY:  - Isoliquiritigenin (ISL), a member of the flavonoids, has been demonstrated to possess antitumor activity in various cancer cell lines in vitro and in vivo. In  this study, we investigated the antitumor effects of ISL on U87 glioma cells in vitro. As determined by MTT assay, ISL inhibited the proliferation of U87 cells in a time-dependent and dose-dependent manner. The results of fluorescence-activated cell sorting (FACS) analysis suggested that ISL induced the apoptosis of the U87 cells and blocked cell cycle progression at the S and G2/M phases. Moreover, it was identified that ISL induced the apoptosis of the U87 cells in a caspase-dependent manner. Although treatment with the pan-caspase  inhibitor Z-VAD-FMK efficiently blocked the ISL-induced caspase activation, it did not eliminate the ISL-induced cell death. Further examination using western blot analysis revealed that ISL upregulated p21/WAF1 and p27. These results indicate that cell cycle arrest and the caspase-mediated apoptosis pathway may participate in the antiproliferative activity of ISL in U87 cells by regulating the expression of specific molecules.

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[640]

TÍTULO / TITLE:  - Commentary on Vaienti et al. Perineural fat grafting in the treatment of painful  end-neuromas of the upper limb.

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

REVISTA / JOURNAL:  - J Hand Surg Eur Vol. 2013 Jan;38(1):43. doi: 10.1177/1753193412466203.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1753193412466203

AUTORES / AUTHORS:  - Elliot D

INSTITUCIÓN / INSTITUTION:  - Hand Surgery Department, Broomfield Hospital, Chelmsford, Essex, UK david@david-elliot.co.uk.

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[641]

TÍTULO / TITLE:  - Case report of interstitial nephritis induced by bevacizumab therapy for glioblastoma multiforme.

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

REVISTA / JOURNAL:  - J Oncol Pharm Pract. 2012 Dec 12.

            ●● Enlace al texto completo (gratuito o de pago) 1177/1078155212466421

AUTORES / AUTHORS:  - Lomax AJ; Hill PA; Ashley DM

INSTITUCIÓN / INSTITUTION:  - Royal Melbourne Hospital, Australia.

RESUMEN / SUMMARY:  - Glioblastoma multiforme is an aggressive malignant brain tumor. The monoclonal antibody, bevacizumab, is active in recurrent disease via inhibition of angiogenesis. Proteinuria and renal thrombotic microangiopathy are known complications. We report a case of a patient developing acute renal failure with  biopsy-proven interstitial nephritis while receiving bevacizumab for recurrent disease. The patient was otherwise well with a history of controlled hypertension. Renal function improved with discontinuation of bevacizumab and the administration of corticosteroid therapy.

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[642]

TÍTULO / TITLE:  - Specific inhibition of SRC kinase impairs malignant glioma growth in vitro and in vivo.

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

REVISTA / JOURNAL:  - Mol Ther Nucleic Acids. 2012 May 1;1:e19. doi: 10.1038/mtna.2012.13.

            ●● Enlace al texto completo (gratuito o de pago) 1038/mtna.2012.13

AUTORES / AUTHORS:  - Stedt H; Alasaarela L; Samaranayake H; Pikkarainen J; Maatta AM; Kholova I; Parker AS; Yla-Herttuala S

INSTITUCIÓN / INSTITUTION:  - Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for  Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

RESUMEN / SUMMARY:  - Malignant glioma is a severe cancer with a poor prognosis. Local occurrence and rare metastases of malignant glioma make it a suitable target for gene therapy. Several studies have demonstrated the importance of Src kinase in different cancers. However, these studies have focused mainly on Src-deficient mice or pharmacological inhibitors of Src. In this study we have used Src small hairpin RNAs (shRNAs) in a lentiviral backbone to mimic a long-term stable treatment and  determined the role of Src in tumor tissues. Efficacy of Src shRNAs was confirmed in vitro demonstrating up to 90% target gene inhibition. In a mouse malignant glioma model, Src shRNA tumors were almost 50-fold smaller in comparison to control tumors and had significantly reduced vascularity. In a syngenic rat intracranial glioma model, Src shRNA-transduced tumors were smaller and these rats had a survival benefit over the control rats. In vivo treatment was enhanced by chemotherapy and histone deacetylase inhibition. Our results emphasise the importance of Src in tumorigenesis and demonstrate that it can be efficiently inhibited in vitro and in vivo in two independent malignant glioma models. In conclusion, Src is a potential target for RNA interference-mediated treatment of  malignant glioma.

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[643]

TÍTULO / TITLE:  - MicroRNA-149 inhibits proliferation and invasion of glioma cells via blockade of  AKT1 signaling.

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

REVISTA / JOURNAL:  - Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):871-81.

AUTORES / AUTHORS:  - Pan SJ; Zhan SK; Pei BG; Sun QF; Bian LG; Sun BM

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai PRC.

RESUMEN / SUMMARY:  - MicroRNAs (miRNAs) play important roles in the regulation of gene expressions. Aberrant expression of miRNAs is implicated in a variety of biological and pathological processes, including the tumorigenesis of glioma (GM). Though the molecular mechanisms of protein kinase B (AKT) survival signal have been comprehensively explored, the role of miR-149 in glioblastoma (GBM) and its regulation on AKT signaling have not yet been ascertained. The present study aimed to elucidate the role and molecular mechanisms of miR-149 in U251 GM cells. Using a gain-of-function approach, we investigated the effects of lentivirus-mediated overexpression of miR-149 on the expression of phosphated-AKT1 (p-AKT1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and CyclinD1 in U251 cells and nude mice subcutaneous  xenograft tumors by Real-time PCR, Western blot and immunohistochemical assays. Proliferative activities indicated by MTT assay, invasive potential by Transwell  and cycle distribution by flow cytometry were carried out for functional analysis of U251 cells after infection with miR-149 mimic. As a consequence, miR-149 inhibited the expression of p-AKT1, PCNA, CyclinD1 and MMP-2, reduced the proliferative activities and invasive potential, and induced cycle arrest in G0/G1 phase in U251 cells. In conclusion, our findings show that miR-149 as tumor suppressor may be involved in the proliferation and invasion of GM cells via blockade of the AKT1 signaling, and be considered as a candidate target for the treatment of cancer.

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[644]

TÍTULO / TITLE:  - Nanoparticles for imaging and treating brain cancer.

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

REVISTA / JOURNAL:  - Nanomedicine (Lond). 2013 Jan;8(1):123-43. doi: 10.2217/nnm.12.185.

            ●● Enlace al texto completo (gratuito o de pago) 2217/nnm.12.185

AUTORES / AUTHORS:  - Meyers JD; Doane T; Burda C; Basilion JP

INSTITUCIÓN / INSTITUTION:  - Departments of Biomedical Engineering & Radiology, Case Western Reserve University, Cleveland, OH 44106, USA.

RESUMEN / SUMMARY:  - Brain cancer tumors cause disruption of the selective properties of vascular endothelia, even causing disruptions in the very selective blood-brain barrier, which are collectively referred to as the blood-brain-tumor barrier. Nanoparticles (NPs) have previously shown great promise in taking advantage of this increased vascular permeability in other cancers, which results in increased accumulation in these cancers over time due to the accompanying loss of an effective lymph system. NPs have therefore attracted increased attention for treating brain cancer. While this research is just beginning, there have been many successes demonstrated thus far in both the laboratory and clinical setting. This review serves to present the reader with an overview of NPs for treating brain cancer and to provide an outlook on what may come in the future. For NPs, just like the blood-brain-tumor barrier, the future is wide open.

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[645]

TÍTULO / TITLE:  - Imaging glioma initiation in vivo through a polished and reinforced thin-skull cranial window.

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

REVISTA / JOURNAL:  - J Vis Exp. 2012 Nov 20;(69). pii: 4201. doi: 10.3791/4201.

            ●● Enlace al texto completo (gratuito o de pago) 3791/4201

AUTORES / AUTHORS:  - Zhang L; Lapierre A; Roy B; Lim M; Zhu J; Wang W; Sampson SB; Yun K; Lyons B; Li Y; Lin DT

INSTITUCIÓN / INSTITUTION:  - The Jackson Laboratory.

RESUMEN / SUMMARY:  - Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers patients only modest benefits, as most patients do not survive more than five years following diagnosis due to glioma relapse (1,2). The discovery of cancer stem cells in human brain tumors holds promise for having an enormous impact on the development of novel therapeutic strategies for glioma (3). Cancer stem cells are defined by their ability both to self-renew and to differentiate, and are thought to be the only cells in a tumor that have the capacity to initiate new tumors (4). Glioma relapse following radiation therapy is thought to arise from resistance of glioma stem cells (GSCs) to therapy (5-10). In vivo, GSCs are shown to reside in a perivascular niche that is important for maintaining their stem cell-like characteristics (11-14). Central to the organization of the GSC niche are vascular endothelial cells (12). Existing evidence suggests that GSCs and their interaction with the vascular endothelial cells are important for tumor development, and identify GSCs and their interaction with endothelial cells as important therapeutic targets for glioma. The presence of GSCs is determined experimentally by their capability to initiate new tumors upon orthotopic transplantation (15). This is typically achieved by injecting a specific number of GBM cells isolated from human tumors into the brains of severely immuno-deficient mice, or of mouse GBM cells into the brains of congenic host mice. Assays for tumor growth are then performed following sufficient time to allow GSCs among the injected GBM cells to give rise to new tumors-typically several weeks or months. Hence, existing assays do not allow examination of the important pathological process of tumor initiation from single GSCs in vivo. Consequently, essential insights into the specific roles of GSCs and their interaction with the vascular endothelial cells in the early stages of tumor initiation are lacking. Such insights are critical for developing novel therapeutic strategies for glioma, and will have great implications for preventing glioma relapse in patients. Here we have adapted the PoRTS cranial window procedure (16)and in vivo two-photon microscopy to allow visualization of  tumor initiation from injected GBM cells in the brain of a live mouse. Our technique will pave the way for future efforts to elucidate the key signaling mechanisms between GSCs and vascular endothelial cells during glioma initiation.

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[646]

TÍTULO / TITLE:  - Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells.

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 http://stemcells.alphamedpress.org/ 

            ●● Cita: Stem Cells: <> Transl Med. 2012 Apr;1(4):322-32. doi: 10.5966/sctm.2011-0035. Epub 2012 Mar 21.

            ●● Enlace al texto completo (gratuito o de pago) 5966/sctm.2011-0035

AUTORES / AUTHORS:  - Sgubin D; Wakimoto H; Kanai R; Rabkin SD; Martuza RL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Brain Tumor Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

RESUMEN / SUMMARY:  - Glioblastoma (GBM), a fatal malignant brain tumor, contains abundant hypoxic regions that provide a “niche” to promote both the maintenance and enrichment of  glioblastoma stem-like cells (GSCs) and confer resistance to chemo- and radiotherapy. Since GSCs, with an ability to resist conventional therapies, may be responsible for tumor recurrence, targeting GSCs located in such a hypoxic environment may be critical to improving the therapeutic outcome for GBM patients. Oncolytic viral therapies have been tested in the clinic as a promising therapeutic approach for GBM. In this study, we analyzed and compared the therapeutic effects of oncolytic herpes simplex virus (oHSV) type 1 G47Delta (gamma34.5(-)ICP6(-)LacZ(+)alpha47(-)) in patient-derived GSCs under normoxia (21% oxygen) and hypoxia (1% oxygen). GSCs cultured in hypoxia showed an increased ability to form neurospheres and expressed higher levels of the putative stem cell marker CD133 compared with GSCs cultured in normoxia. G47Delta exhibited a comparable ability to infect, replicate, and kill GSCs in normoxia and hypoxia in vitro. Importantly, G47Delta could counteract hypoxia-mediated enhancement of the stem-like properties of GSCs, inhibiting their self-renewal and stem cell marker expression. Using orthotopic human GSC xenografts in mice, we demonstrated that intratumoral injection of G47DeltaUs11fluc, a newly developed G47Delta derivative that expresses firefly luciferase driven by a true  late viral promoter, led to an equivalent frequency of viral infection and replication in hypoxic and nonhypoxic tumor areas. These findings suggest that oHSV G47Delta represents a promising therapeutic strategy to target and kill GSCs, not only in normoxic areas of GBM but also within the hypoxic niche.

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[647]

TÍTULO / TITLE:  - Rosette-forming glioneuronal tumor in the pineal gland and the third ventricle: a case with radiological and clinical implications.

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

REVISTA / JOURNAL:  - Quant Imaging Med Surg. 2012 Sep;2(3):227-31. doi: 10.3978/j.issn.2223-4292.2012.09.03.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2223-4292.2012.09.03

AUTORES / AUTHORS:  - Xu J; Yang Y; Liu Y; Wei M; Ren J; Chang Y; Huan Y; Yin H; Xue Y

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China;

RESUMEN / SUMMARY:  - A 39-year-old man presented with more than 20 years history of episodic headache  and one year history of dizziness, impaired vision and memory disorders. Computed tomography and Magnetic resonance imaging revealed a cystic mass involving the pineal gland, tectum and the third ventricle and obstruction of the aqueduct. Interestingly, the fourth ventricle was not involved in this case. The pathological diagnosis was rosette forming glioneuronal tumor (RGNT). These lesions are considered low-grade tumors (WHO grade I). We describe here the fifth reported patient with a pineal gland RGNT and the eighth reported patient with a  RGNT outside the fourth ventricle.

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[648]

TÍTULO / TITLE:  - Combined temozolomide and radiation as an initial treatment for anaplastic glioma.

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

REVISTA / JOURNAL:  - Asia Pac J Clin Oncol. 2012 Dec 21. doi: 10.1111/ajco.12038.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ajco.12038

AUTORES / AUTHORS:  - Tham CK; See SJ; Tan SH; Lim KH; Ng WH; Thomas J; Chong DQ; Chua ET

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, National Cancer Centre, Singapore.

RESUMEN / SUMMARY:  - AIM: Combined temozolomide (TMZ) and radiation therapy (RT) is often used as initial treatment for anaplastic glioma. However, there is no prospective randomized data available that proves the efficacy of the combination for anaplastic glioma. In this retrospective study we aimed to compare the outcome of patients who had combined TMZ and RT with those who had RT alone for the initial  treatment of anaplastic glioma in our centers. METHODS: Patients with anaplastic  astrocytoma or oligoastrocytoma treated at our centers between 2000 and 2010 were reviewed. Only patients who received initial RT or concurrent TMZ and RT (TMZ-RT) were included. RESULTS: Of 62 patients, 55 were less than 66-years old; 36 (58.1%) had a tumor resection and 26 had a biopsy only. An oligodendroglial component in their tumor histology was present in 21 patients (33.9%). At a median follow up of 20.7 months for all patients, median progression-free survival was similar for the two treatment groups (RT alone: 16.7 months (95% CI  9.4, 34.8 months) versus TMZ-RT: 14.8 months (95% CI 8.6, 28.6 months, P = NS). Median overall survival was 27.4 months (95% CI 10.6, not estimable [NE] months)  for patients who had RT alone and 34.1 months (95% CI 19.8, 42.1 months) for those who had TMZ-RT. CONCLUSION: No significant benefit of combined TMZ with RT  compared to RT alone was observed as the initial treatment of anaplastic glioma.  Prospective randomized trials are needed to evaluate the optimal treatment for this disease.

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[649]

TÍTULO / TITLE:  - Established and emerging variants of glioblastoma multiforme: review of morphological and molecular features.

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

REVISTA / JOURNAL:  - Folia Neuropathol. 2012;50(4):301-21.

AUTORES / AUTHORS:  - Karsy M; Gelbman M; Shah P; Balumbu O; Moy F; Arslan E

INSTITUCIÓN / INSTITUTION:  - Michael Karsy, Department of Pathology, Department of Neurosurgery, New York Medical College, Basic Sciences Building, Room 413, Valhalla,NY 10595, USA, phone: 914-594-4146, fax: 914-594-4163, e-mail: Michael_Karsy@nymc.edu.

RESUMEN / SUMMARY:  - Since the recent publication of the World Health Organization brain tumour classification guidelines in 2007, a significant expansion in the molecular understanding of glioblastoma multiforme (GBM) and its pathological as well as genomic variants has been evident. The purpose of this review article is to evaluate the histopathological, molecular and clinical features surrounding emerging and currently established GBM variants. The tumours discussed include classic glioblastoma multiforme and its four genomic variants, proneural, neural, mesenchymal, classical, as well as gliosarcoma (GS), and giant cell GBM (gcGBM).  Furthermore, the emerging variants include fibrillary/epithelial GBM, small cell  astrocytoma (SCA), GBM with oligodendroglial component (GBMO), GBM with primitive neuroectodermal features (GBM-PNET), gemistocytic astrocytoma (GA), granular cell astrocytoma (GCA), and paediatric high-grade glioma (HGG) as well as diffuse intrinsic pontine glioma (DIPG). Better understanding of the heterogeneous nature of GBM may provide improved treatment paradigms, prognostic classification, and approaches towards molecularly targeted treatments.

 

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[650]

TÍTULO / TITLE:  - Signal transduction alterations in glioma: implications for diagnosis and therapy.

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

REVISTA / JOURNAL:  - J Signal Transduct. 2012;2012:704247. doi: 10.1155/2012/704247. Epub 2012 Dec 9.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/704247

AUTORES / AUTHORS:  - Cerchia L; Martinez Montero JC; Monfared P

INSTITUCIÓN / INSTITUTION:  - Istituto per l’Endocrinologia e l’Oncologia Sperimentale “G. Salvatore” (IEOS), CNR, 80131 Naples, Italy.

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[651]

TÍTULO / TITLE:  - Fine mapping of a region of chromosome 11q23.3 reveals independent locus associated with risk of glioma.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52864. doi: 10.1371/journal.pone.0052864. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052864

AUTORES / AUTHORS:  - Chen H; Sun B; Zhao Y; Song X; Fan W; Zhou K; Zhou L; Mao Y; Lu D

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Genetic Engineering, Fudan-VARI Genetic Epidemiology Center and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.

RESUMEN / SUMMARY:  - BACKGROUND: A single nucleotide polymorphism (SNP) at locus 11q23.3 (rs498872) in the near 5’-UTR of the PHLDB1 gene was recently implicated as a risk factor for gliomas in a genome-wide association study, and this involvement was confirmed in three additional studies. METHODOLOGY/PRINCIPAL FINDINGS: To identify possible causal variants in the region, the authors genotyped 15 tagging SNPs in the 200 kb genomic region at 11q23.3 locus in a Chinese Han population-based case-control study with 983 cases and 1024 controls. We found evidence for an association between two independent loci (both the PHLDB1 and the ACRN1 genes) and a predisposition for gliomas. Among the multiple significant SNPs in the PHLDB1 gene region, the rs17749 SNP was the most significant [P = 1.31x10(-6) in a recessive genetic model]. Additionally, two novel SNPs (rs2236661 and rs494560) that were independent of rs17749 were significantly associated with glioma risk in a recessive genetic model [P = 1.31x10(-5) and P = 3.32x10(-5), respectively]. The second novel locus was within the ARCN1 gene, and it was associated with a significantly reduced risk for glioma. CONCLUSIONS/SIGNIFICANCE: Our data strongly support PHLDB1 as a susceptibility gene for glioma, also shedding light  on a new potentially candidate gene, ARCN1.

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[652]

TÍTULO / TITLE:  - Enhancing the Efficacy of Drug-loaded Nanocarriers against Brain Tumors by Targeted Radiation Therapy.

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

REVISTA / JOURNAL:  - Oncotarget. 2012 Dec 23.

AUTORES / AUTHORS:  - Baumann BC; Kao GD; Mahmud A; Harada T; Swift J; Chapman C; Xu X; Discher DE; Dorsey JF

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is a common, usually lethal disease with a median survival of only ~15 months. It has proven resistant in clinical trials to chemotherapeutic agents such as paclitaxel that are highly effective in vitro, presumably because of impaired drug delivery across the tumor’s blood-brain barrier (BBB). In an effort to increase paclitaxel delivery across the tumor BBB, we linked the drug to a novel filomicelle nanocarrier made with biodegradable poly(ethylene-glycol)-block-poly(epsilon-caprolactone-r-D,L-lactide) and used precisely collimated radiation therapy (RT) to disrupt the tumor BBB’s permeability in an orthotopic mouse model of GBM. Using a non-invasive bioluminescent imaging technique to assess tumor burden and response to therapy in our model, we demonstrated that the drug-loaded nanocarrier (DLN) alone was ineffective against stereotactically implanted intracranial tumors yet was highly effective against GBM cells in culture and in tumors implanted into the flanks of mice. When targeted cranial RT was used to modulate the tumor BBB, the paclitaxel-loaded nanocarriers became effective against the intracranial tumors.  Focused cranial RT improved DLN delivery into the intracranial tumors, significantly improving therapeutic outcomes. Tumor growth was delayed or halted, and survival was extended by >50% (p less than 0.05) compared to the results obtained with either RT or the DLN alone. Combinations of RT and chemotherapeutic agents linked to nanocarriers would appear to be an area for future investigations that could enhance outcomes in the treatment of human GBM.

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[653]

TÍTULO / TITLE:  - Microglia-derived proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta induce Purkinje neuronal apoptosis via their receptors in hypoxic neonatal rat brain.

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

REVISTA / JOURNAL:  - Brain Struct Funct. 2012 Dec 22.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00429-012-0491-5

AUTORES / AUTHORS:  - Kaur C; Sivakumar V; Zou Z; Ling EA

INSTITUCIÓN / INSTITUTION:  - Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore, 117597, Singapore, antkaurc@nus.edu.sg.

RESUMEN / SUMMARY:  - The developing cerebellum is extremely vulnerable to hypoxia which can damage the Purkinje neurons. We hypothesized that this might be mediated by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) derived from activated  microglia as in other brain areas. One-day-old rats were subjected to hypoxia following, which the expression changes of various proteins in the cerebellum including hypoxia inducible factor-1alpha, TNF-alpha, IL-1beta, TNF-R(1) and IL-1R(1) were analyzed. Following hypoxic exposure, TNF-alpha and IL-1beta immunoexpression in microglia was enhanced coupled by that of TNF-R(1) and IL-1R(1) in the Purkinje neurons. Along with this, hypoxic microglia in vitro showed enhanced release of TNF-alpha and IL-1beta whose receptor expression was concomitantly increased in the Purkinje neurons. In addition, nitric oxide (NO) level was significantly increased in the cerebellum and cultured microglia subjected to hypoxic exposure. Moreover, cultured Purkinje neurons treated with conditioned medium derived from hypoxic microglia underwent apoptosis but the incidence was significantly reduced when the cells were treated with the same medium that was neutralized with TNF-alpha/IL-1beta antibody. We conclude that hypoxic microglia in the neonatal cerebellum produce increased amounts of NO, TNF-alpha and IL-1beta which when acting via their respective receptors could induce Purkinje neuron death.

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[654]

TÍTULO / TITLE:  - Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4338-43.

AUTORES / AUTHORS:  - Shao CJ; Wu MW; Chen FR; Li C; Xia YF; Chen ZP

INSTITUCIÓN / INSTITUTION:  - State Key Laboratory of Oncology in South China, Cancer Center of Sun Yat-sen University, Guangzhou, Guangdong 510060, China; Department of Neurosurgery/Neuro-oncology, Cancer Center of Sun Yat-sen University, Guangzhou,  Guangdong 510060, China.

RESUMEN / SUMMARY:  - BACKGROUND: Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to  investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines. METHODS: Human glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups. RESULTS: Mild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 +/- 0.58) mmol/L and (2.15 +/- 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 +/- 0.09) mmol/L for T98-G and (0.08 +/- 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G  and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01). CONCLUSION: VPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.

 

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[655]

TÍTULO / TITLE:  - Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma.

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

REVISTA / JOURNAL:  - Front Oncol. 2012;2:186. doi: 10.3389/fonc.2012.00186. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00186

AUTORES / AUTHORS:  - Yoshimoto K; Mizoguchi M; Hata N; Murata H; Hatae R; Amano T; Nakamizo A; Sasaki T

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.

RESUMEN / SUMMARY:  - Many conventional chemotherapeutic drugs exert their cytotoxic function by inducing DNA damage in the tumor cell. Therefore, a cell-inherent DNA repair pathway, which reverses the DNA-damaging effect of the cytotoxic drugs, can mediate therapeutic resistance to chemotherapy. The monofunctional DNA-alkylating agent temozolomide (TMZ) is a commonly used chemotherapeutic drug and the gold standard treatment for glioblastoma (GBM). Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been described as the main modulator to determine the sensitivity of GBM to TMZ, a subset of GBM does not respond despite MGMT inactivation, suggesting that another DNA repair mechanism may also modulate the tolerance to TMZ. Considerable interest has focused on MGMT, mismatch repair (MMR), and the base excision repair (BER) pathway in the mechanism of mediating TMZ resistance, but emerging roles for the  DNA strand-break repair pathway have been demonstrated. In the first part of this review article, we briefly review the significant role of MGMT, MMR, and the BER  pathway in the tolerance to TMZ; in the last part, we review the recent publications that demonstrate possible roles of DNA strand-break repair pathways, such as single-strand break repair and double-strand break repair, as well as the Fanconi anemia pathway in the repair process after alkylating agent-based therapy. It is possible that all of these repair pathways have a potential to modulate the sensitivity to TMZ and aid in overcoming the therapeutic resistance  in the clinic.

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[656]

TÍTULO / TITLE:  - Glioma-related edema: new insight into molecular mechanisms and their clinical implications.

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

REVISTA / JOURNAL:  - Chin J Cancer. 2013 Jan;32(1):49-52. doi: 10.5732/cjc.012.10242. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 5732/cjc.012.10242

AUTORES / AUTHORS:  - Lin ZX

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P. R. China. lzx1967@sina.com.

RESUMEN / SUMMARY:  - Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral  brain edema via an active process that supplies a suitable niche for peritumoral  invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.

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[657]

TÍTULO / TITLE:  - Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo.

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

REVISTA / JOURNAL:  - Neurosci Bull. 2013 Feb;29(1):83-93. doi: 10.1007/s12264-012-1296-5. Epub 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s12264-012-1296-5

AUTORES / AUTHORS:  - Sun C; Wang Q; Zhou H; Yu S; Simard AR; Kang C; Li Y; Kong Y; An T; Wen Y; Shi F; Hao J

INSTITUCIÓN / INSTITUTION:  - Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital; Key Laboratory of Post-trauma Neuro-repair and Regeneration in the Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, 300052, China.

RESUMEN / SUMMARY:  - The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the  present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-ASMMP9), which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4- to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group), subcutaneous injection of endostatin (endostatin-treated group), or both (combined therapy group). Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of  tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower  than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the  malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.

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[658]

TÍTULO / TITLE:  - Contact and encirclement of glioma cells in vitro is an intrinsic behavior of a clonal human neural stem cell line.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51859. doi: 10.1371/journal.pone.0051859. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051859

AUTORES / AUTHORS:  - Khosh N; Brown CE; Aboody KS; Barish ME

INSTITUCIÓN / INSTITUTION:  - Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.

RESUMEN / SUMMARY:  - Pathotropic neural stem and/or progenitor cells (NSCs) can potentially deliver therapeutic agents to otherwise inaccessible cancers. In glioma, NSCs are found in close contact with tumor cells, raising the possibility that specificity of NSC contact with glioma targets originates in the tumor cells themselves. Alternatively, target preferences may originate, at least in part, in the tumor microenvironment. To better understand mechanisms underlying NSC interactions with glioma cells, we examined NSC-target cell contacts in a highly simplified 3-dimensional peptide hydrogel (Puramatrix) in which cell behaviors can be studied in the relative absence of external cues. HB1.F3 is an immortalized clonal human NSC line extensively characterized in preclinical investigations. To study contact formation between HB1.F3 NSCs and glioma cells, we first examined co-cultures of eGFP-expressing HB1.F3 (HB1.F3.eGFP) NSCs and dsRed-expressing U251 glioma (U251.dsRed) cells. Using confocal microscopy, HB1.F3.eGFP cells were observed contacting or encircling U251.dsRed glioma cells, but never the reverse. Next, examining specificity of these contacts, no significant quantitative differences in either percentages of HB1.F3 NSCs contacting targets, or in the extent of target cell encirclement, were observed when HB1.F3.eGFP cells were presented with various potential target cells (human glioma and breast cancer cell lines, patient-derived brain tumor lines, non-tumor fibroblasts, primary mouse and human astroglial cells, and primary adult and newborn human dermal fibroblasts) except that interactions between HB1.F3 cells did not progress beyond establishing contacts. Finally cytoskeletal mechanisms employed by HB1.F3.eGFP cells varied with the substrate. When migrating in Puramatrix, HB1.F3 NSCs exhibited intermittent process extension followed by soma translocation, while during encirclement their movements were more amoeboid. We conclude that formation of contacts and subsequent encirclement of target cells by HB1.F3 NSCs  is an intrinsic property of these NSCs, and that preferential contact formation with tumor cells in vivo must therefore be highly dependent on microenvironmental cues.

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[659]

TÍTULO / TITLE:  - In Vitro Comparison of Hypericin and 5-Aminolevulinic Acid-Derived Protoporphyrin IX for Photodynamic Inactivation of Medulloblastoma Cells.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51974. doi: 10.1371/journal.pone.0051974. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051974

AUTORES / AUTHORS:  - Ritz R; Scheidle C; Noell S; Roser F; Schenk M; Dietz K; Strauss WS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Eberhard Karls University Tubingen, Tubingen, Germany.

RESUMEN / SUMMARY:  - BACKGROUND: Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX). METHODS: In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX  was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells. RESULTS: All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation  with HYP up to 10 microM resulted in a rapid increase in fluorescence intensity,  which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in  D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The [Formula: see text] [lethal dose (light dose that  is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm(2) in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 microM after an  incubation time of 2 h and an illumination wavelength of 595 nm. The [Formula: see text] value was 0.47 J/cm(2). CONCLUSION: By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor  visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower [Formula: see text]. Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas.

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[660]

TÍTULO / TITLE:  - Recurrent low-grade astroblastoma with signet ring-like cells and high proliferative index.

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

REVISTA / JOURNAL:  - Fetal Pediatr Pathol. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 3109/15513815.2012.754525

AUTORES / AUTHORS:  - Nasit JG; Trivedi P

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, P.D.U. Government Medical College and Hospital , Rajkot, Gujrat , India.

RESUMEN / SUMMARY:  - Astroblastoma is a rare primary glial tumor of children and young adults. Radiologically astroblastoma presents as a large well-circumscribed supratentorial, solid-cystic heterogeneous mass. Histology shows perivascular pseudorosettes with hyalinization. Only a single case has been reported with signet-ring-like cell morphology. Signet-ring morphology in primary central nervous system tumors is exceedingly rare. Complete surgical resection is the recommended treatment. Prognosis of astroblastoma depends on the extent of resection and histology. The proliferative index may be a useful tool to define prognosis. We present a case of 10-year-old girl having recurrent low-grade astroblastoma with signet ring-like cells and high proliferative index.

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[661]

TÍTULO / TITLE:  - Cytokines associated with toxicity in the treatment of recurrent glioblastoma with aflibercept.

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

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0254-0

AUTORES / AUTHORS:  - Shonka N; Piao Y; Gilbert M; Yung A; Chang S; Deangelis LM; Lassman AB; Liu J; Cloughesy T; Robins HI; Lloyd R; Chen A; Prados M; Wen PY; Heymach J; de Groot J

INSTITUCIÓN / INSTITUTION:  - Division of Oncology and Hematology, University of Nebraska Medical Center, 987680, Omaha, NE, 68198-7680, USA, nshonka@unmc.edu.

RESUMEN / SUMMARY:  - Plasma profiling of patients treated with antiangiogenic agents may identify markers that correlate with toxicity. Objectives were to correlate changes in cytokine and angiogenic factors as potential markers of toxicity to aflibercept.  Circulating cytokine and angiogenic factors were measured in 28 patients with recurrent glioblastoma in a single-arm phase II study of aflibercept. Plasma samples were analyzed at baseline, 24 h, and 28 days using multiplex assays or ELISA. We evaluated log-transformed baseline biomarker expressions with Cox proportional hazard regression models to assess the effect of markers on any grade II-IV (Gr II-IV) toxicity, on-target toxicity (hypertension, proteinuria, thromboembolism), and fatigue. All tests were two sided with a statistical significance level of p = 0.05. Among 28 pts, there were 116 Gr II-IV events. Changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases  in IL-1b, IL-6, and IL-10 at 24 h were significantly associated with fatigue. Progression-free survival was 14.9 months for patients in the all-toxicity group  and 9.0 months for patients in the on-target toxicity group compared to 4.3 months for those who did not develop any Gr II-IV toxicity (p = 0.002 and p = 0.045, respectively). Toxicity from antiangiogenic therapy remains an important cause of antiangiogenic treatment discontinuation and patient morbidity. Changes  in IL6, IL10, and IL13 were repeatedly correlated with toxicity. Profiling of IL-13 as a surrogate for endothelial dysfunction could individualize patients at  risk during antiangiogenic therapy, as could identifying those at higher risk for fatigue using IL-6 and IL-10.

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[662]

TÍTULO / TITLE:  - Genetics of adult glioma.

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

REVISTA / JOURNAL:  - Cancer Genet. 2012 Dec;205(12):613-21. doi: 10.1016/j.cancergen.2012.10.009. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.cancergen.2012.10.009

AUTORES / AUTHORS:  - Goodenberger ML; Jenkins RB

INSTITUCIÓN / INSTITUTION:  - Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.

RESUMEN / SUMMARY:  - Gliomas make up approximately 30% of all brain and central nervous system tumors  and 80% of all malignant brain tumors. Despite the frequency of gliomas, the etiology of these tumors remains largely unknown. Diffuse gliomas, including astrocytomas and oligodendrogliomas, belong to a single pathologic class but have very different histologies and molecular etiologies. Recent genomic studies have  identified separate molecular subtypes within the glioma classification that appear to correlate with biological etiology, prognosis, and response to therapy. The discovery of these subtypes suggests that molecular genetic tests are and will be useful, beyond classical histology, for the clinical classification of gliomas. While a familial susceptibility to glioma has been identified, only a small percentage of gliomas are thought to be due to single-gene hereditary cancer syndromes. Through the use of linkage studies and genome-wide association  studies, multiple germline variants have been identified that are beginning to define the genetic susceptibility to glioma.

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[663]

TÍTULO / TITLE:  - Rapid local recurrence of an extraventricular neurocytoma that had disappeared after gamma knife radiosurgery.

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2013 Jan;126(2):393-4.

AUTORES / AUTHORS:  - Zhu JM; Zhao YY; Feng F; Fu WM; Zhang JM; Ma J; Zhao ZS; Lu G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medcine, Hangzhou, Zhejiang 310009, China.

 

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[664]

TÍTULO / TITLE:  - Is cerebral cavernous malformation a pre-glioma lesion?

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

REVISTA / JOURNAL:  - Chin Med J (Engl). 2012 Dec;125(24):4511-3.

AUTORES / AUTHORS:  - Zhang JY; Ming ZY; Wu AH

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China; Department of Neurosurgery, 463 Hospital, Shenyang, Liaoning 110042, China.

RESUMEN / SUMMARY:  - Glioma is the most malignant tumor in the brain, the origin of glioma is still unknown. Recently some papers indicated that glioma may be developed from cerebral cavernous malformation (CCM). We describe a man with a right temporal lobe CCM, after gamma-knife radiotherapy, the patient developed a low-grade astrocytoma in the area of the preexistent CCM. This case, together with other reports, may indicated an oncogenetic properties of CCM, and we proposed that CCM may be a pre-glioma lesion.

 

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[665]

TÍTULO / TITLE:  - Aberrant activation of Hedgehog/Gli1 pathway on angiogenesis in gliomas.

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

REVISTA / JOURNAL:  - Neurol India. 2012 Nov-Dec;60(6):589-96. doi: 10.4103/0028-3886.105192.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.105192

AUTORES / AUTHORS:  - Cui D; Chen X; Yin J; Wang W; Lou M; Gu S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - Background: Hedgehog/Gli1 (HH/Gli1) pathway plays an important role in the patterning and development of the central nervous system during embryogenesis. Recent data have shown its potential involvement in a subset of human gliomas and inhibition of the pathway resulted in tumor suppression in both in vitro and in vivo studies. The underlying mechanisms of tumor suppression, however, remain to  be fully elucidated. Materials and Methods: Gli1 expression was investigated in 60 surgically resected glioma tissues (World Health Organization (WHO) III-IV). Results: Gli1 was expressed in 43 gliomas with high Gli1 expression in nine cases, moderate expression in 21 cases, and low expression in 13 cases. Additionally, microvessel counts were higher in Gli1 positive gliomas than those  in Gli1 negative gliomas. Gli1 expression in gliomas was positively correlated with microvessel density (MVD). To explore the molecular mechanisms of the phenotypic changes, we performed quantitative real-time polymerase chain reaction (PCR) and Western blot analysis to monitor the changes of a series of genes, which play critical roles in the regulation of glioma angiogenesis. In conclusion, HH/Gli1 pathway inhibition resulted in down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) expressions, whereas this pathway activation led to up-regulation of VEGF, MMP2, and MMP9 expressions. These molecular changes of the HH/Gli1 pathway inhibited by indirect drug approach were consistent with Gli1 RNA-interference (RNAi) in glioma cell lines. Conclusion: Our findings demonstrated that the aberrantly active HH/Gli1 pathway contributed to angiogenesis in part through induction of VEGF, MMP2, and MMP9.

 

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[666]

TÍTULO / TITLE:  - Mirror image subependymoma.

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

REVISTA / JOURNAL:  - Neurol India. 2012 Nov-Dec;60(6):684-5. doi: 10.4103/0028-3886.105228.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0028-3886.105228

AUTORES / AUTHORS:  - Kumar R; Sarkari A; Kakkar A

INSTITUCIÓN / INSTITUTION:  - All India Institute of Medical Sciences, New Delhi, India.

 

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[667]

TÍTULO / TITLE:  - Contribution of (18)F-Fluoro-ethyl-tyrosine Positron Emission Tomography to Target Volume Delineation in Stereotactic Radiotherapy of Malignant Cranial Base  Tumours: First Clinical Experience.

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

REVISTA / JOURNAL:  - Int J Mol Imaging. 2012;2012:412585. doi: 10.1155/2012/412585. Epub 2012 Oct 8.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/412585

AUTORES / AUTHORS:  - Graf R; Plotkin M; Nyuyki F; Wust P; Wurm R; Budach V; Brenner W; Fahdt D

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Charite Universitatsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

RESUMEN / SUMMARY:  - Increased amino acid uptake has been demonstrated in intracerebral tumours and head and neck carcinomas of squamous cell origin. We investigated the potential impact of using (18)F-fluoro-ethyl-tyrosine ((18)F-FET)-PET/CT in addition to conventional imaging for gross tumour volume (GTV) delineation in stereotactic radiotherapy of skull base tumours. The study population consisted of 14 consecutive patients with cranial base tumours (10 with squamous cell histology,  4 others). All patients underwent a FET-PET/CT examination in addition to contrast-enhanced CT and 11 patients underwent MRI. All tumours and histologic types showed increased FET uptake. The GTV was defined by all voxels showing hyperintensity in MRI or CT (GTV(MRI/CT)) or enhancement in PET (GTV(PET)), forming a GTV(composite) that was used for the initial treatment fields. An additional volume of infiltrative growth outside the GTV(MRI/CT) of about 1.0 +/- 2 cm(3) (5% of the conventional volume) was demonstrated by FET-PET only (GTV(PETplus)) with significant enlargement (>10% of GTV(MRI/CT)) in three patients. From existing data, we found correlation between cellular density and the standardized uptake value (SUV) of FET. We were able to substantially reduce  the volume of escalated radiation dose (GTV(boost)) by 11 +/- 2 cm(3) (24%) of the conventional volume.

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[668]

TÍTULO / TITLE:  - Management of intracranial germ cell tumors at the King Chulalongkorn Memorial Hospital.

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

REVISTA / JOURNAL:  - J Med Assoc Thai. 2012 Oct;95(10):1327-34.

AUTORES / AUTHORS:  - Raiyawa T; Khorprasert C; Lertbutsayanukul C; Seksarn P; Sosothikul D; Amornfa J; Shotelersuk K

INSTITUCIÓN / INSTITUTION:  - Division of Therapeutic Radiology and Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.

RESUMEN / SUMMARY:  - OBJECTIVE: To study the outcome of less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication in the treatment of intracranial germ cell tumor (ICGCT) at the King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: A descriptive study was established by reviewing patients’ records from the Division of Therapeutic Radiology and Oncology admitted between  2001 and 2008. Median follow-up time was 65 months. Patient characteristics, investigations, and treatment modalities were presented in proportion. Survival analysis was evaluated by Kaplan-Meier method. The results were compared with the previous study in done in 1990 to 2000. RESULTS: Forty-two records were reviewed  and 71% were male. The median age was 16 years. Pineal region was the most common site in 55%. Interestingly, 12% had synchronous lesions at both pineal and suprasellar regions. Out of 41 patients who had histopathological confirmation, 71% were germinoma. Out of 37 patients who had MRI spine or CSF cytology, 43% had CNS dissemination. Less aggressive radiotherapy combined with surgery and chemotherapy was increasingly utilized; however five-year overall survival rate in all patients was 83%, comparable to 82% from the previous study. Survival rates of patients without CNS dissemination were 88% in the present study and 83% in the previous study. Survival rates adjusted for histopathology were 86% for germinoma and 76% for non-germinoma. CONCLUSION: Less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication is an effective treatment for ICGCT.

 

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[669]

TÍTULO / TITLE:  - Monocyte-Derived Cells of the Brain in Malignant Gliomas.

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

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 17. pii: S1878-8750(13)00135-6. doi: 10.1016/j.wneu.2013.01.074.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.074

AUTORES / AUTHORS:  - Grossman R; Ram Z

INSTITUCIÓN / INSTITUTION:  - Tel Aviv Sourasky Medical Center Department of Neurosurgery 6 Weizman Street 64239 Tel-Aviv, Israel.

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[670]

TÍTULO / TITLE:  - Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures.

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

REVISTA / JOURNAL:  - Cell Cycle. 2013 Jan 16;12(3).

AUTORES / AUTHORS:  - Carra E; Barbieri F; Marubbi D; Pattarozzi A; Favoni RE; Florio T; Daga A

INSTITUCIÓN / INSTITUTION:  - Department of Experimental Medicine (DIMES); University of Genova; Genova, Italy; Gene Transfer Lab; IRCSS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro; Genova, Italy.

RESUMEN / SUMMARY:  - Glioblastomas are grade IV brain tumors characterized by high aggressiveness and  invasiveness, giving patients a poor prognosis. We investigated the effects of the multi-kinase inhibitor sorafenib on six cultures isolated from human glioblastomas and maintained in tumor initiating cells-enriching conditions. These cell subpopulations are thought to be responsible for tumor recurrence and  radio- and chemo-resistance, representing the perfect target for glioblastoma therapy. Sorafenib reduces proliferation of glioblastoma cultures, and this effect depends, at least in part, on the inhibition of PI3K/Akt and MAPK pathways, both involved in gliomagenesis. Sorafenib significantly induces apoptosis/cell death via downregulation of the survival factor Mcl-1. We provide  evidence that sorafenib has a selective action on glioblastoma stem cells, causing enrichment of cultures in differentiated cells, downregulation of the expression of stemness markers required to maintain malignancy (nestin, Olig2 and Sox2) and reducing cell clonogenic ability in vitro and tumorigenic potential in  vivo. The selectivity of sorafenib effects on glioblastoma stem cells is confirmed by the lower sensitivity of glioblastoma cultures after differentiation as compared with the undifferentiated counterpart. Since current GBM therapy enriches the tumor in cancer stem cells, the evidence of a selective action of sorafenib on these cells is therapeutically relevant, even if, so far, results from first phase II clinical trials did not demonstrate its efficacy.

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[671]

TÍTULO / TITLE:  - Medulloblastoma or not? Crucial role in tumorigenesis of the timing of migration  of cerebellar granule precursor cells, regulated by Nos2 and Tis21.

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

REVISTA / JOURNAL:  - Front Neurosci. 2012;6:198. doi: 10.3389/fnins.2012.00198. Epub 2013 Jan 24.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fnins.2012.00198

AUTORES / AUTHORS:  - Farioli-Vecchioli S; Micheli L; Leonardi L; Ceccarelli M; Cavallaro S; Tirone F

INSTITUCIÓN / INSTITUTION:  - Institute of Cell Biology and Neurobiology, National Research Council, Fondazione Santa Lucia Rome, Italy.

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[672]

TÍTULO / TITLE:  - Deconstructing mTOR complexes in regulation of Glioblastoma Multiforme and its stem cells.

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

REVISTA / JOURNAL:  - Adv Biol Regul. 2012 Oct 26. pii: S2212-4926(12)00096-6. doi: 10.1016/j.jbior.2012.10.001.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.jbior.2012.10.001

AUTORES / AUTHORS:  - Jhanwar-Uniyal M; Jeevan D; Neil J; Shannon C; Albert L; Murali R

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, New York Medical College, Valhalla, NY 10595, USA. Electronic address: meena_jhanwar@nymc.edu.

RESUMEN / SUMMARY:  - Atypical serine-threonine kinase, mTOR (mechanistic target of Rapamycin; originally coined “mammalian TOR”), exists in two distinct multi-protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), that senses and integrates a variety of environmental signals to control organism growth and homeostasis via non-overlapping signaling pathways. mTOR belongs to the phosphoinositide 3-kinase (PI3-K)-related kinase family, and an aberrant activation of mTORC1 is a potential contributing factor in uncontrolled cell growth, proliferation, and survival of tumor cells via specific effects on cap-dependent translation initiation, as well as in a more sustained manner via advancing ribosome biogenesis. It is thereby shown to be deregulated in numerous  pathological conditions including cancer, obesity, type 2 diabetes, and neurodegeneration. Notably, mTOR itself, or through its substrates, regulates stem cell differentiation and maintenance of plueropotency. mTORC2 has been linked to cytoskeletal reorganization and cell survival through Akt, and is crucial to many divergent physiological functions, which may include stem cell regulation.

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[673]

TÍTULO / TITLE:  - Astrocytes enhance the invasion potential of glioblastoma stem-like cells.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54752. doi: 10.1371/journal.pone.0054752. Epub 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054752

AUTORES / AUTHORS:  - Rath BH; Fair JM; Jamal M; Camphausen K; Tofilon PJ

INSTITUCIÓN / INSTITUTION:  - Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, United  States of America.

RESUMEN / SUMMARY:  - Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown under standard in  vitro conditions and in co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media in the bottom chamber significantly increased the invasion of GSCs yet had no effect on CD133- cells. In addition, a  monolayer invasion assay showed that the GSCs invaded farther into an astrocyte monolayer than their differentiated progeny. Gene expression profiles were generated from two GSC lines grown in trans-well culture with astrocytes in the bottom chamber or directly in contact with astrocyte monolayers. In each co-culture model, genes whose expression was commonly increased in both GSC lines involved cell movement and included a number of genes that have been previously associated with tumor cell invasion. Similar gene expression modifications were not detected in CD133- cells co-cultured under the same conditions with astrocytes. Finally, evaluation of the secretome of astrocytes grown in monolayer identified a number of chemokines and cytokines associated with tumor cell invasion. These data suggest that astrocytes enhance the invasion of CD133+ GSCs  and provide additional support for a critical role of brain microenvironment in the regulation of GBM biology.

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[674]

TÍTULO / TITLE:  - CXCR4-Expressing Glial Precursor Cells Demonstrate Enhanced Migratory Tropism for Glioma.

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

REVISTA / JOURNAL:  - J Cancer Ther. 2012 Dec 1;3(6):1086-1091. Epub 2012 Aug 17.

            ●● Enlace al texto completo (gratuito o de pago) 4236/jct.2012.36142

AUTORES / AUTHORS:  - Ehtesham M; Thompson RC

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, USA.

RESUMEN / SUMMARY:  - Malignant glioma remains one of the most intractable of human cancers principally due to the highly infiltrative nature of these neoplasms. The use of neural precursor cells (NPC) has received considerable attention based on their ability  to selectively migrate towards disseminated areas of tumor in vivo and their described ability to deliver tumor-directed therapies specifically to infiltrating tumor cells. Fundamental to optimizing the use of these cells for potential clinical translation is the development of an understanding regarding the biologic cues that govern their ability to migrate towards infiltrative glioma foci. To this end, in this paper we detail that NPC selected for double-expression of the glial-precursor marker A2B5 and the cell-surface chemokine receptor, CXCR4, demonstrate enhanced in vitro glioma-directed tropism. These findings demonstrate the relevance of these markers for the phenotypic segregation of an optimally tumor-tropic NPC sub-population as a means of enhancing NPC-based therapeutic strategies for the treatment of glioma.

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[675]

TÍTULO / TITLE:  - Nano Size Effects of TiO2 Nanotube Array on the Glioma Cells Behavior.

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

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Dec 21;14(1):244-54. doi: 10.3390/ijms14010244.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms14010244

AUTORES / AUTHORS:  - Yang H; Qin X; Tian A; Zhang D; Xue X; Wu A

INSTITUCIÓN / INSTITUTION:  - Liaoning Provincial Universities Key Laboratory of Boron Resource Ecological Utilization Technology and Boron Materials, Northeastern University, No.11, Lane  3, Wenhua Road, Heping District, Shenyang 110819, China. Tiana@smm.neu.edu.cn.

RESUMEN / SUMMARY:  - In order to investigate the interplay between the cells and TiO(2) nanotube array, and to explore the ability of cells to sense the size change in nano-environment, we reported on the behavior of glioma C6 cells on nanotube array coatings in terms of proliferation and apoptosis. The behavior of glioma C6 cells was obviously size-dependent on the coatings; the caliber with 15 nm diameter provided effective spacing to improve the cells proliferation and enhanced the cellular activities. C6 cells’ biological behaviors showed many similar tendencies to many phorocytes; the matching degree of geometry between nanotube and integrin defined that a spacing of 15 nm was optimal for inducing signals to nucleus, which results in achieving maximum activity of glioma cells.  In addition, the immune behavior of cells was studied, a variety of inflammatory  mediator’s gene expression levels were controlled by the nanoscale dimension, the expressions of IL-6 and IL-10 were higher on 30 nm than on 15 nm nanotube.

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[676]

TÍTULO / TITLE:  - Correction: Gene expression and network-based analysis reveals a novel role for hsa-miR-9 and drug control over the p38 network in glioblastoma multiforme progression.

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

REVISTA / JOURNAL:  - Genome Med. 2012 Nov 29;4(11):87.

            ●● Enlace al texto completo (gratuito o de pago) 1186/gm388

AUTORES / AUTHORS:  - Ben-Hamo R; Efroni S

INSTITUCIÓN / INSTITUTION:  - The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, 1 Keren-Hayesod St, Ramat-Gan, 52900, Israel. sol.efroni@biu.ac.il.

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[677]

TÍTULO / TITLE:  - Prolactin gene expression in primary central nervous system tumors.

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

REVISTA / JOURNAL:  - J Negat Results Biomed. 2013 Jan 14;12(1):4. doi: 10.1186/1477-5751-12-4.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1477-5751-12-4

AUTORES / AUTHORS:  - Mendes GA; Pereira-Lima JF; Kohek MB; Trott G; Di Domenico M; Ferreira NP; Oliveira Mda C

INSTITUCIÓN / INSTITUTION:  - Postgraduate Program in Pathology, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), Porto Alegre, Brazil. grazi_mendes@hotmail.com.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Prolactin (PRL) is a hormone synthesized in both the pituitary gland and extrapituitary sites. It has been associated with the occurrence of neoplasms and, more recently, with central nervous system (CNS) neoplasms. The aim of this study was to evaluate prolactin expression in primary  central nervous system tumors through quantitative real-time PCR and immunohistochemistry (IH). RESULTS: Patient mean age was 49.1 years (SD 15.43), and females accounted for 70% of the sample. The most frequent subtype of histological tumor was meningioma (61.5%), followed by glioblastoma (22.9%). Twenty cases (28.6%) showed prolactin expression by immunohistochemistry, most of them females (18 cases, 90%). Quantitative real-time PCR did not show any prolactin expression. CONCLUSIONS: Despite the presence of prolactin expression by IH, the lack of its expression by quantitative real-time PCR indicates that its presence in primary tumors in CNS is not a reflex of local production.

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[678]

TÍTULO / TITLE:  - Long-term follow-up result of hydroxyurea chemotherapy for recurrent meningiomas.

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

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2012 Dec;52(6):517-22. doi: 10.3340/jkns.2012.52.6.517. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2012.52.6.517

AUTORES / AUTHORS:  - Kim MS; Yu DW; Jung YJ; Kim SW; Chang CH; Kim OL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, College of Medicine, Yeungnam University, Daegu, Korea.

RESUMEN / SUMMARY:  - OBJECTIVE: Meningiomas represent 18-20% of all intracranial tumors and have a 20-50% 10-year recurrence rate, despite aggressive surgery and irradiation. Hydroxyurea, an inhibitor of ribonucleotide reductase, is known to inhibit meningioma cells by induction of apoptosis. We report the long-term follow-up result of hydroxyurea therapy in the patients with recurrent meningiomas. METHODS: Thirteen patients with recurrent WHO grade I or II meningioma were treated with hydroxyurea (1000 mg/m(2)/day orally divided twice per day) from June 1998 to February 2012. Nine female and 4 male, ranging in age from 32 to 83  years (median age 61.7 years), were included. Follow-up assessment included physical examination, computed tomography, and magnetic resonance imaging (MRI).  Standard neuro-oncological response criteria (Macdonald criteria) were used to evaluate the follow-up MRI scans. The treatment was continued until there was objective disease progression or onset of unmanageable toxicity. RESULTS: Ten of  the 13 patients (76.9%) showed stable disease after treatment, with time to progression ranging from 8 to 128 months (median 72.4 months; 6 patients still accruing time). However, there was no complete response or partial response in any patients. Three patients had progressive disease after 88, 89, 36 months, respectively. There was no severe (Grade III-IV) blood systemic disorders and no  episodes of non-hematological side effects. CONCLUSION: This study showed that hydroxyurea is a modestly active agent against recurrent meningiomas and can induce long-term stabilization of disease in some patients. We think that hydroxyurea treatment is well tolerated and convenient, and could be considered as an alternative treatment option in patients with recurrent meningiomas prior to reoperation or radiotherapy.

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[679]

TÍTULO / TITLE:  - Pseudotumor cerebri presenting with visual failure in promyelocytic leukemia: a case report.

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

REVISTA / JOURNAL:  - J Med Case Rep. 2012 Nov 29;6(1):408. doi: 10.1186/1752-1947-6-408.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-6-408

AUTORES / AUTHORS:  - Rasul FT; Toma AK; Khan AA; Plant GT; Watkins LD

INSTITUCIÓN / INSTITUTION:  - Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK. fahidrasul@doctors.org.uk.

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Pseudotumor cerebri secondary to all-trans retinoic acid  in acute promyelocytic leukemia is a reported but rare complication of the therapy. Most cases improve following the discontinuation of all-trans retinoic acid. There is no published literature on how to manage such patients if severe symptoms of increased intracranial pressure continue after discontinuation of the drug. CASE PRESENTATION: We report the case of a 16-year-old Afro-Caribbean woman with aggressive secondary pseudotumor cerebri who presented to our facility with  visual failure that persisted despite discontinuation of all-trans retinoic acid. A lumbar drain was inserted for 11 days resulting in symptomatic relief of headaches and objective improvement of visual failure. Pressure settings were titrated regularly to ensure optimal symptomatic relief. CONCLUSIONS: The use of  a lumbar drain for continuous drainage of cerebrospinal fluid in patients with all-trans retinoic acid-induced pseudotumor cerebri resistant to all-trans retinoic acid discontinuation is a feasible management option. This method can be used when other less invasive measures have failed to improve signs and symptoms. Permanent drainage of cerebrospinal fluid with a shunt may also provide a long-term viable management strategy but the use of a lumbar drain may be preferable if the cause of pseudotumor cerebri is known to be self-limiting.

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[680]

TÍTULO / TITLE:  - The role of brevican in glioma: promoting tumor cell motility in vitro and in vivo.

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

REVISTA / JOURNAL:  - BMC Cancer. 2012 Dec 19;12(1):607.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-12-607

AUTORES / AUTHORS:  - Lu R; Wu C; Guo L; Liu Y; Mo W; Wang H; Ding J; Wong ET; Yu M

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this  study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility. METHODS: In this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies. RESULTS: Our results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies. CONCLUSIONS: This study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of glioma.

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[681]

TÍTULO / TITLE:  - Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings.

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

REVISTA / JOURNAL:  - Int J Nanomedicine. 2012;7:6105-14. doi: 10.2147/IJN.S38927. Epub 2012 Dec 17.

            ●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S38927

AUTORES / AUTHORS:  - Li D; Yang K; Li JS; Ke XY; Duan Y; Du R; Song P; Yu KF; Ren W; Huang D; Li XH; Hu X; Zhang X; Zhang Q

INSTITUCIÓN / INSTITUTION:  - Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.

RESUMEN / SUMMARY:  - BACKGROUND: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. METHODS: The in vitro cytotoxicity of  a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. RESULTS: The average droplet size of the CLA-PTX microemulsion was approximately 176.3 +/- 0.8 nm and the polydispersity index was 0.294 +/- 0.024. In vitro cytotoxicity results showed that the IC(50) of the CLA-PTX microemulsion was 1.61 +/- 0.83 muM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion  against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol(®) had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD(50) of  CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. CONCLUSION: CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

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[682]

TÍTULO / TITLE:  - Neuro-oncology: Glioblastoma detection and therapy monitoring by microvesicle release.

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

REVISTA / JOURNAL:  - Nat Rev Neurol. 2012 Dec 11;9(1):4. doi: 10.1038/nrneurol.2012.247. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2012.247

AUTORES / AUTHORS:  - Bible E

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[683]

TÍTULO / TITLE:  - Quadrigeminal Cistern Arachnoid Cyst Treated by Endoscopic Ventriculocystostomy through the Trigonal Region.

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

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Jan 10.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1331384

AUTORES / AUTHORS:  - Sharifi G; Jahanbakhshi A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.

RESUMEN / SUMMARY:  - Background When symptomatic, quadrigeminal cistern arachnoid cysts (QCACs), comprising 5 to 10% of all intracranial arachnoid cysts, are treated by open fenestration or shunt placement and in recent decades by endoscopic techniques. We introduce a novel endoscopic technique that may be used for surgery of QCACs.Patient A 52-year-old woman with a known history of QCAC (treated twice previously by open procedures) presented with symptoms, signs, and radiologic indicators of shunt malfunction and cyst recollection. Because of high-riding pineal gland and distortion of anatomy that resulted from the last surgeries, and loss of a suitable visual angle, a satisfactory ventriculocystostomy was not possible through the third ventricle. Therefore, the cyst was approached by entering the trigonal region of the lateral ventricle, allowing to perform ventriculocystostomy.Results and Conclusion Postoperative imaging and follow-up visits proved this approach to be efficacious. This report, for the first time, introduces the so-called transtrigone lateral ventricle cystostomy as an alternative for cases of QCAC for which the ventriculocystostomy via the third ventricle is not suitable.

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[684]

TÍTULO / TITLE:  - Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e53339. doi: 10.1371/journal.pone.0053339. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053339

AUTORES / AUTHORS:  - Morgan RM; Hernandez-Ramirez LC; Trivellin G; Zhou L; Roe SM; Korbonits M; Prodromou C

INSTITUCIÓN / INSTITUTION:  - Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.

RESUMEN / SUMMARY:  - Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset  acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal alpha-7 helix (Calpha-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with  the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Calpha-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Calpha-7h is sufficient to predispose to pituitary adenoma.  We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20.

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[685]

TÍTULO / TITLE:  - Durable complete remission of a brainstem glioma treated with a combination of bevacizumab and cetuximab.

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

REVISTA / JOURNAL:  - Case Rep Oncol. 2012 Sep;5(3):676-81. doi: 10.1159/000341852. Epub 2012 Dec 20.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000341852

AUTORES / AUTHORS:  - Blesa JM; Molla SB; Esparcia MF; Ortells JM; Godoy MP; Das AM; Magan BM; Pulla MP; Sanchez JL; Canales JB; Candel VA

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Hospital de Denia, Marina Salud, Denia, España.

RESUMEN / SUMMARY:  - Treatment of a relapsed glioma is a clinical challenge nowadays. New active treatments are required to treat these difficult diseases. Here we present a durable complete remission of a relapsed glioblastoma that has achieved a complete radiologic response with the combination of cetuximab and bevacizumab, in a third-line setting, that has offered a progression-free survival of 20 months. We consider here both potential mechanisms for the explanation of this result. First, the potential target of the cancer stem cells (CSCs) with these two antibodies, and second, the potential recruitment of the immune system to directly pursue the CSCs.

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[686]

TÍTULO / TITLE:  - Frequency Of Pituitary Tumor Apoplexy During Treatment Of Prolactinomas With Dopamine Agonists: A Systematic Review.

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

REVISTA / JOURNAL:  - CNS Neurol Disord Drug Targets. 2012 Dec 12.

AUTORES / AUTHORS:  - Carija R; Vucina D

INSTITUCIÓN / INSTITUTION:  - Clinical Department of Neurosurgery, Clinical Hospital Center, Spinciceva 1, 21 000 Split, Croatia. robertcarija@yahoo.com.

RESUMEN / SUMMARY:  - Many researches that discourse the treatment of prolactinomas with dopamine agonists (DA) provide data about pituitary tumor apoplexy of some prolactinomas.  Therefore, DA are listed as risk factors for apoplexy of prolactinomas. The authors wish to explore the percentage (frequency) of pituitary tumor apoplexy during the treatment of prolactinomas with DA. From June 2011 to February 2012, we sought electronic databases and found 2169 articles and 71 book chapters relevant to DA. Only seven articles have been included into systematic review and from 4 articles we extracted numerical data that showed percentage of pituitary tumor apoplexy. One hundred and fifty-seven patients treated with DA were included in four studies. Results showed the following percentage of apoplexy during the treatment of prolactinomas with DA (apoplexy/therapy ratio): 1/84(1,19%), 13/29(44,83%), 1/15(6,67%) and 1/29(3,45%). One result stands out from the other (13/29-44,83%) because of retrospective search for pituitary hemorrhage by MRI imaging of sellar region and some of the patients were without  clinical signs of apoplexy. Median and mean age of included patients was usually  over 30 years. Pituitary tumor apoplexy appeared more frequently in macroprolactinomas than in microprolactinomas and also within a year and a half since the beginning of treatment with DA. Conclusively, clinically manifested pituitary tumor apoplexy appears in relatively small percentage of prolactinomas  treated with DA. We were also concluded that apoplexy appears asymptomatic and because of that and because of more frequently appearing in macroprolactinomas, there are recommendations for performing MRI imaging of sellar region more often  in patients with macroprolactinomas than in patients with microprolactinomas who  are treated with DA.

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[687]

TÍTULO / TITLE:  - Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma.

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

REVISTA / JOURNAL:  - Case Report Rheumatol. 2012;2012:208606. doi: 10.1155/2012/208606. Epub 2012 Nov  29.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/208606

AUTORES / AUTHORS:  - Graceffa D; Maiani E; Pace A; Solivetti FM; Elia F; De Mutiis C; Bonifati C

INSTITUCIÓN / INSTITUTION:  - Centre for the Study and Treatment of Psoriasis, Department of Clinical Dermatology, San Gallicano Dermatological Institute IRCCS, 00144 Rome, Italy.

RESUMEN / SUMMARY:  - Bevacizumab is a recombinant humanised monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The drug, alone or in combination with other anticancer agents, has been shown to be effective against several types of  neoplasms. We report a case of a woman with a history of severe psoriasis who developed psoriatic arthritis during a course of bevacizumab, which was administered for a malignant glioma.

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[688]

TÍTULO / TITLE:  - 1H-MR spectroscopy guided gamma knife radiosurgery for treatment of glioma.

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

REVISTA / JOURNAL:  - Turk Neurosurg. 2012;22(6):690-4. doi: 10.5137/1019-5149.JTN.5676-12.1.

            ●● Enlace al texto completo (gratuito o de pago) 5137/1019-5149.JTN.5676-12.1

AUTORES / AUTHORS:  - Shen G; Xu L; Xu M; Geng M; Tan Y; Li F

INSTITUCIÓN / INSTITUTION:  - Research Institute of Surgery & Daping Hospital, Third Military Medical University, Department of Neurosurgery, Chongqing, Chongqing, China.

RESUMEN / SUMMARY:  - AIM: To observe the outcomes of 1H- MR-spectroscopy (MRS) guided gamma knife surgery for treatment of glioma. MATERIAL AND METHODS: Twenty patients with glioma diagnosed pathologically were randomly divided into MRI group and MRI plus MRS group. The target volume was defined as the tumor enhanced area plus the surrounding area with a short T1 and a long T2 in the MRI group, while the tumor  enhanced area plus the surrounding area with a short T1 and a long T2 and choline: N-acetyl aspartate index (CNI) >/= 1.6 in the MRI plus MRS group.12 months after surgery were set as the endpoint. RESULTS: Thirteen (65%) patients were successfully treated, of whom 6 were in the MRI group and 7 in the MRI plus  MRS group. Ten patients suffered from cerebral edema during treatment, including  8 in the MRI group and 2 in the other group. The cases of cerebral edema were significantly fewer in the MRI plus MRS group than the MRI group. The average maximum diameter of the target volume was smaller in the MRI plus MRS group. CONCLUSION: The MRS-guided gamma knife radiosurgery helps to identify and remove  the lesion of glioma and reduce complications due to extended surgical scope.

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[689]

TÍTULO / TITLE:  - An unresolved relationship - Treated Arachnoid Cysts and Idiopathic Intracranial  Hypertension.

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

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 16. pii: S1878-8750(13)00123-X. doi: 10.1016/j.wneu.2013.01.062.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.062

AUTORES / AUTHORS:  - Quintana LM

INSTITUCIÓN / INSTITUTION:  - Valparaiso University, Neurosurgery, Av.Libertad 1405-Office 301, Vina del Mar, 254-1194, CHILE. Electronic address: leonquin@gmail.com.

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[690]

TÍTULO / TITLE:  - Everolimus (RAD001): first systemic treatment for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

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

REVISTA / JOURNAL:  - Future Oncol. 2012 Dec;8(12):1515-23. doi: 10.2217/fon.12.146.

            ●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.146

AUTORES / AUTHORS:  - Jozwiak S; Stein K; Kotulska K

INSTITUCIÓN / INSTITUTION:  - Department of Neurology & Epileptology, The Children’s Memorial Health Institute, 04-730, Warsaw, Poland. sergiusz.jozwiak@gmail.com

RESUMEN / SUMMARY:  - Everolimus (RAD001), a mTOR inhibitor, was initially used as an immunosuppressant in organ transplant patients; however, it also has significant antineoplastic properties. In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability. In the Phase III, randomized, placebo-controlled trial, everolimus was associated with a SEGA response rate of 35% compared with 0% in the placebo group. The most common adverse events in clinical trials were stomatitis/mouth ulceration and upper respiratory tract infections, and most adverse events were grade 1 or 2; grade 4 events were rare.

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[691]

TÍTULO / TITLE:  - Editorial: emerging treatment strategies for malignant gliomas.

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

REVISTA / JOURNAL:  - Curr Drug Discov Technol. 2012 Dec 1;9(4):235-6.

AUTORES / AUTHORS:  - Adamson DC

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, Duke University Medical Center, 463 Medical Sciences Research Building-1, Box 3807 Med. Ctr., Durham, NC 27710, USA. cory.adamson@duke.edu.

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[692]

TÍTULO / TITLE:  - Preventing lower cranial nerve injuries during fourth ventricle tumor resection by utilizing intraoperative neurophysiological monitoring.

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

REVISTA / JOURNAL:  - Neurodiagn J. 2012 Dec;52(4):320-32.

AUTORES / AUTHORS:  - Jahangiri FR; Minhas M; Jane J Jr

INSTITUCIÓN / INSTITUTION:  - Division of Neurology, Department of Medicine, King Abdulaziz Medical City, King  Fahad National Guard Hospital, Riyadh, Saudi Arabia. faisal.jahangiri@gmail.com

RESUMEN / SUMMARY:  - We present two cases illustrating the benefit of utilizing intraoperative neurophysiological monitoring (IONM) for prevention of injuries to the lower cranial nerves during fourth ventricle tumor resection surgeries. Multiple cranial nerve nuclei are located on the floor of the fourth ventricle with a high risk of permanent damage. Two male patients (ages 8 and 10 years) presented to the emergency department and had brain magnetic resonance imaging (MRI) scans showing brainstem/fourth ventricle tumors. During surgery, bilateral posterior tibial and median nerve somatosensory evoked potentials (SSEPs); four-limb and cranial nerves transcranial electrical motor evoked potentials (TCeMEPs); brainstem auditory evoked responses (BAERs); and spontaneous electromyography (s-EMG) were recorded. Electromyography (EMG) was monitored bilaterally from cranial nerves V VII, IX, X, XI, and XII. Total intravenous anesthesia was used.  Neuromuscular blockade was used only for initial intubation. Pre-incision baselines were obtained with good morphology of waveforms. After exposure the floor of the fourth ventricle was mapped by triggered-EMG (t-EMG) using 0.4 to 1.0 mA. In both patients the tumor was entangled with cranial nerves VII to XII on the floor of the fourth ventricle. The surgeon made the decision not to resect the tumor in one case and limited the resection to 70% of the tumor in the second case on the basis of neurophysiological monitoring. This decision was made to minimize any post-operative neurological deficits due to surgical manipulation of the tumor involving the lower cranial nerves. Intraoperative spontaneous and triggered EMG was effectively utilized in preventing injuries to cranial nerves during surgical procedures. All signals remained stable during the surgical procedure. Postoperatively both patients were well with no additional cranial nerve weakness. At three months follow-up, the patients continued to have no deficits.

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[693]

TÍTULO / TITLE:  - Intravascular CNS lymphoma: Successful therapy using high-dose methotrexate-based polychemotherapy.

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

REVISTA / JOURNAL:  - Exp Hematol. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://www.medicinedirect.com/journal 

            ●● Cita: Experimental Hematology: <> Oncol. 2012 Dec 5;1(1):37. doi: 10.1186/2162-3619-1-37.

            ●● Enlace al texto completo (gratuito o de pago) 1186/2162-3619-1-37

AUTORES / AUTHORS:  - Kebir S; Kuchelmeister K; Niehusmann P; Nelles M; Kim Y; Thanendrarajan S; Schafer N; Stuplich M; Mack F; Scheffler B; Urbach H; Glas M; Herrlinger U

INSTITUCIÓN / INSTITUTION:  - Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Ulrich.Herrlinger@ukb.uni-bonn.de.

RESUMEN / SUMMARY:  - ABSTRACT: Intravascular diffuse large B-cell lymphoma limited to the CNS (cIVL) is a very rare malignant disorder characterized by a selective accumulation of neoplastic lymphocytes (usually B cells) within the lumen of CNS blood vessels but not in the brain parenchyma. In the past, treatment of cIVL with anthracycline-based regimens was unsatisfactory with very short survival times. In the case of cIVL presented here, high-dose methotrexate-based polychemotherapy according to the Bonn protocol plus rituximab therapy was successful and led to a complete clinical and MRI remission which is ongoing 29 months after diagnosis.

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[694]

TÍTULO / TITLE:  - Effects of combined sonodynamic and photodynamic therapies with photolon on a glioma C6 tumor model.

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

REVISTA / JOURNAL:  - Exp Oncol. 2012 Dec;34(4):332-5.

AUTORES / AUTHORS:  - Tserkovsky DA; Alexandrova EN; Chalau VN; Istomin YP

INSTITUCIÓN / INSTITUTION:  - N.N. Alexandrov National Cancer Center of Belarus, Minsk 223040, Belarus.

RESUMEN / SUMMARY:  - The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats. Methods: The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2.5 mg/kg b.w). Sonication was performed with 0.4; 0.7 and 1.0 W/cm(2)  power density at 1 MHz frequency for 10 min, 2.0 h after Photolon administration  using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out  2.5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm(2) with 0,17 W/cm(2) fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination. Results: The maximal tumor necrosis area that underwent sonication (1 MHz; 0.7 W/cm(2); 10 min.) followed by PDT at a dose of 100 J/cm(2) was 100%. Conclusion: This is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models.

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[695]

TÍTULO / TITLE:  - Expression of beta-adrenergic receptors in pediatric malignant brain tumors.

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

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):221-225. Epub 2012 Oct 23.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.989

AUTORES / AUTHORS:  - Sardi I; Giunti L; Bresci C; Buccoliero AM; Degl’innocenti D; Cardellicchio S; Baroni G; Castiglione F; Ros MD; Fiorini P; Giglio S; Genitori L; Arico M; Filippi L

INSTITUCIÓN / INSTITUTION:  - Department of Pediatric Hematology-Oncology;

RESUMEN / SUMMARY:  - beta-adrenergic receptors (beta-ARs) are G protein-coupled receptors that activate signal transduction pathways involved in angiogenesis, resulting in enhanced tumor vascularization and more aggressive growth. In this study, we evaluated the expression of beta-ARs in a population of 12 children affected by malignant primary brain tumors. We found a significant expression of beta1- and beta2-ARs in all 12 samples as well as the 3 cell lines tested (U87MG, T98G and DAOY). The mean absolute beta1-AR mRNA level standardized to GAPDH was 5.81 (range, -7.91 to 11.29) for brain tumors and 8.59 (range, 6.046 to 12.59) for cell lines (U87MG, DAOY and T98G), respectively. The mean absolute beta2-AR mRNA  level was 4.74 (range, -9.30 to 8.45) for tumor specimens and 7.64 (range, 5.85 to 8.88) for cell lines. These real-time quantitative (qRT)-PCR expression data were confirmed by immunohistochemical analysis. Our study evaluated the presence  of beta1- and beta2-ARs in malignant pediatric brain tumors and brain tumor cell  lines.

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[696]

TÍTULO / TITLE:  - Role of Biomarkers in the Clinical Management of Glioblastomas: What are the Barriers and How Can We Overcome Them?

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

REVISTA / JOURNAL:  - Front Neurol. 2012;3:188. doi: 10.3389/fneur.2012.00188. Epub 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fneur.2012.00188

AUTORES / AUTHORS:  - McDonald KL; Aw G; Kleihues P

INSTITUCIÓN / INSTITUTION:  - Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales Kensington, Australia.

RESUMEN / SUMMARY:  - Thousands of articles describing biomarkers predictive of treatment and prognostic of survival in cancer have been published, yet only a handful of biomarkers are currently used routinely in the clinic. Biomarkers need to be analytically standardized, validated, and clinically useful. This review will address the challenges and ways in which we can improve our discovery and translation of prospective biomarkers from the lab into validated diagnostic tests with a specific focus on patients diagnosed with glioblastoma and MGMT promoter methylation status. There has been long-held enthusiasm to use MGMT promoter methylation as a predictive biomarker for patients treated with the alkylating agent, temozolomide; however in the majority of centers around the world, this has not yet transpired.

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[697]

TÍTULO / TITLE:  - Clinicopathoradiological findings in SEGA: A rare astroglial tumor.

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

REVISTA / JOURNAL:  - Indian J Med Paediatr Oncol. 2012 Jul;33(3):192-3. doi: 10.4103/0971-5851.103158.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0971-5851.103158

AUTORES / AUTHORS:  - Verma N; Babu S; Singhai A; Gupta C

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, C.S.M. Medical University, (Formerly King George Medical University), Lucknow, Uttar Pradesh, India. E-mail: rubyruby2k4@yahoo.com.

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[698]

TÍTULO / TITLE:  - Giant cell glioblastoma in a child: A rare case report.

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

REVISTA / JOURNAL:  - Asian J Neurosurg. 2012 Jul;7(3):144-6. doi: 10.4103/1793-5482.103723.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1793-5482.103723

AUTORES / AUTHORS:  - Jain SK; Sundar IV; Sinha VD; Sharma V; Bhasme V; Goel RS

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, SMS Medical College, Jaipur, Rajasthan, India.

RESUMEN / SUMMARY:  - Giant cell glioblastoma (GCG) is a subtype of Glioblastoma multiforme that is rare in incidence and distinct in features and histopathological examination. It  is reported to have better prognosis than common glioblastomas. The incidence of  GCG in children is even more rare. We report a case of GCG in a 10-year-old boy along with a review of the relevant literature focusing on the differentiating points from common glioblastoma.

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[699]

TÍTULO / TITLE:  - New Zealand adolescents’ cellphone and cordless phone user-habits: are they at increased risk of brain tumours already?: a cross-sectional study.

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

REVISTA / JOURNAL:  - Environ Health. 2013 Jan 10;12(1):5.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1476-069X-12-5

AUTORES / AUTHORS:  - Redmayne M

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current  research findings. METHODS: This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.7-13.3 years) from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson’s correlation coefficient ®. Analyses were undertaken using SPSS version 19.0. RESULTS: Both  cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for >= 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (>= 1640 hours), at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. CONCLUSIONS: While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.

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[700]

TÍTULO / TITLE:  - Giant velum interpositum meningioma in a child.

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

REVISTA / JOURNAL:  - Indian J Med Paediatr Oncol. 2012 Jul;33(3):173-5. doi: 10.4103/0971-5851.103147.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0971-5851.103147

AUTORES / AUTHORS:  - Moiyadi AV; Shetty P

INSTITUCIÓN / INSTITUTION:  - Department of Surgical Oncology, Neurosurgical Services, Tata Memorial Centre, Mumbai, India.

RESUMEN / SUMMARY:  - Intraventricular meningiomas are rare, but are relatively more often seen in children. Large size at presentation often obscures anatomical details. A particular subset of such tumors arising from the velum interpositum pose a significant surgical challenge. Thorough preoperative imaging, especially with respect to the course of the deep venous structures, provides useful evidence as  to the origin. Preservation of venous anatomy at surgery is vital. We describe a  3-year-old girl with a giant velum interpositum meningioma that was completely excised with excellent outcome. This is probably the youngest such case reported.

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[701]

TÍTULO / TITLE:  - DNA methylation profiles of long- and short-term glioblastoma survivors.

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

REVISTA / JOURNAL:  - Epigenetics. 2013 Jan 4;8(2).

AUTORES / AUTHORS:  - Shinawi T; Hill VK; Krex D; Schackert G; Gentle D; Morris MR; Wei W; Cruickshank G; Maher ER; Latif F

INSTITUCIÓN / INSTITUTION:  - Centre for Rare Diseases and Personalized Medicine; Department of Medical & Molecular Genetics; School of Clinical and Experimental Medicine; University of Birmingham College of Medical and Dental Sciences; Birmingham, UK.

RESUMEN / SUMMARY:  - Glioblastoma (GBM) is the most common and malignant type of primary brain tumor in adults and prognosis of most GBM patients is poor. However, a small percentage of patients show a term survival of 36 mo or longer after diagnosis. Epigenetic profiles can provide molecular markers for patient prognosis: recently, a G-CIMP  positive phenotype associated with IDH1 mutations has been described for GBMs with good prognosis. In the present analysis we performed genome-wide DNA methylation profiling of short-term survivors (STS; overall survival < 1 y) and long-term survivors (LTS; overall survival > 3 y) by utilizing the HumanMethylation450K BeadChips to assess quantitative methylation at > 480,000 CpG sites. Cluster analysis has shown that a subset of LTS showed a G-CIMP positive phenotype that was tightly associated with IDH1 mutation status and was  confirmed by analysis of the G-CIMP signature genes. Using high stringency criteria for differential hypermethylation between brain non-cancer and tumor samples, we identified 2,638 hypermethylated CpG loci (890 genes) in STS GBMs, 3,101 hypermethylated CpG loci (1,062 genes) in LTS (wild type IDH1) and 11,293 hypermethylated CpG loci in LTS (mutated for IDH1), reflecting the CIMP positive  phenotype. The location of differentially hypermethylated CpG loci with respect to CpG content, neighborhood context and functional genomic distribution was similar in our sample set, with the majority of CpG loci residing in CpG islands  and in gene promoters. Our preliminary study also identified a set of CpG loci differentially hypermethylated between STS and LTS cases, including members of the homeobox gene family (HOXD8, HOXD13 and HOXC4), the transcription factors NR2F2 and TFAP2A, and Dickkopf 2, a negative regulator of the wnt/beta-catenin signaling pathway.

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[702]

TÍTULO / TITLE:  - Endoscopy-verified occult subependymal dissemination of glioblastoma and brain metastasis undetected by MRI: prognostic significance.

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

REVISTA / JOURNAL:  - Onco Targets Ther. 2012;5:449-56. doi: 10.2147/OTT.S39429. Epub 2012 Dec 13.

            ●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S39429

AUTORES / AUTHORS:  - Iacoangeli M; Di Rienzo A; Colasanti R; Zizzi A; Gladi M; Alvaro L; Nocchi N; Di Somma LG; Scarpelli M; Scerrati M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Universita Politecnica delle Marche, Umberto I General Hospital, Ancona, Italy.

RESUMEN / SUMMARY:  - Although various prognostic indices exist for patients with malignant brain tumors, the prognostic significance of the subependymal spread of intracranial tumors is still a matter of debate. In this paper, we report the cases of two intraventricular lesions, a recurrent glioblastoma multiforme (GBM) and a brain metastasis, each successfully treated with a neuroendoscopic approach. Thanks to  this minimally invasive approach, we achieved good therapeutic results: we obtained a histological diagnosis; we controlled intracranial hypertension by treating the associated hydrocephalus and, above all, compared with a microsurgical approach, we reduced the risks related to dissection and brain retraction. Moreover, in both cases, neuroendoscopy enabled us to identify an initial, precocious subependymal tumor spreading below the threshold of magnetic  resonance imaging (MRI) detection. This finding, undetected in pre-operative MRI  scans, was then evident during follow-up neuroimaging studies. In light of these  data, a neuroendoscopic approach might play a leading role in better defining the prognosis and optimally tailored management protocols for GBM and brain metastasis.

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[703]

TÍTULO / TITLE:  - OASIS/CREB3L1 Is Induced by Endoplasmic Reticulum Stress in Human Glioma Cell Lines and Contributes to the Unfolded Protein Response, Extracellular Matrix Production and Cell Migration.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54060. doi: 10.1371/journal.pone.0054060. Epub 2013 Jan 15.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054060

AUTORES / AUTHORS:  - Vellanki RN; Zhang L; Volchuk A

INSTITUCIÓN / INSTITUTION:  - Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.

RESUMEN / SUMMARY:  - OASIS is a transcription factor similar to ATF6 that is activated by endoplasmic  reticulum stress. In this study we investigated the expression of OASIS in human  glioma cell lines and the effect of OASIS knock-down on the ER stress response and cell migration. OASIS mRNA was detected in three distinct glioma cell lines (U373, A172 and U87) and expression levels were increased upon treatment with ER  stress-inducing compounds in the U373 and U87 lines. OASIS protein, which is glycosylated on Asn-513, was detected in the U373 and U87 glioma lines at low levels in control cells and protein expression was induced by ER stress. Knock-down of OASIS in human glioma cell lines resulted in an attenuated unfolded protein response to ER stress (reduced GRP78/BiP and GRP94 induction) and decreased expression of chondroitin sulfate proteoglycan extracellular matrix proteins, but induction of the collagen gene Col1a1 was unaffected. Cells in which OASIS was knocked-down exhibited altered cell morphology and reduced cell migration. These results suggest that OASIS is important for the ER stress response and maintenance of some extracellular matrix proteins in human glioma cells.

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[704]

TÍTULO / TITLE:  - Posterior fossa arachnoid cyst masking a delayed diagnosis of hyperparathyroidism in a child.

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

REVISTA / JOURNAL:  - Case Report Endocrinol. 2012;2012:931371. doi: 10.1155/2012/931371. Epub 2012 Nov 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/931371

AUTORES / AUTHORS:  - Dhamija B; Kombogiorgas D; Hussain I; Solanki GA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Birmingham Children’s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK.

RESUMEN / SUMMARY:  - Background. Primary hyperparathyroidism in childhood is a very rare entity, often being diagnosed late after the onset of its presenting symptoms. It most commonly affects patients in their fourth decade of life and beyond. The inclusion of primary hyperparathyroidism in the differential diagnosis is necessary when evaluating patients presenting with nonspecific symptoms such as polyuria, fatigue, weight loss, abdominal pain, nausea, and vomiting. Methods. We report the case of an eleven-year-old girl presenting with three years history of headaches, visual disturbance, along with episodes of emotional lability. Neuroimaging confirmed a large posterior fossa arachnoid cyst. It was decided to  manage this lesion conservatively with surveillance. Only after further hospital  admissions with recurrent loss of consciousness, dizziness, and nausea to add to  her already existing symptoms, a full biochemical and endocrine assessment was performed to look for more specific causes for her presentation. These pointed to a diagnosis of primary hyperparathyroidism. Conclusions. The inclusion of primary hyperparathyroidism in the differential diagnosis should be considered when evaluating paediatric patients presenting with nonspecific (neurological, gastrointestinal, and renal) symptoms in order to establish a prompt diagnosis of the disorder and to avoid severe complications of prolonged hypercalcaemia and end-organ damage.

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[705]

TÍTULO / TITLE:  - Promoter Methylation Analysis of IDH Genes in Human Gliomas.

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

REVISTA / JOURNAL:  - Front Oncol. 2012;2:193. doi: 10.3389/fonc.2012.00193. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00193

AUTORES / AUTHORS:  - Flanagan S; Lee M; Li CC; Suter CM; Buckland ME

INSTITUCIÓN / INSTITUTION:  - Discipline of Pathology, University of Sydney Sydney, NSW, Australia ; Department of Neuropathology, Royal Prince Alfred Hospital Sydney, NSW, Australia.

RESUMEN / SUMMARY:  - Mutations in isocitrate dehydrogenase (IDH)-1 or -2 are found in the majority of  WHO grade II and III astrocytomas and oligodendrogliomas, and secondary glioblastomas. Almost all described mutations are heterozygous missense mutations affecting a conserved arginine residue in the substrate binding site of IDH1 (R132) or IDH2 (R172). But the exact mechanism of IDH mutations in neoplasia is not understood. It has been proposed that IDH mutations impart a “toxic gain-of-function” to the mutant protein, however a dominant-negative effect of mutant IDH has also been described, implying that IDH may function as a tumor suppressor gene. As most, if not all, tumor suppressor genes are inactivated by epigenetic silencing, in a wide variety of tumors, we asked if IDH1 or IDH2 carry the epigenetic signature of a tumor suppressor by assessing cytosine methylation  at their promoters. Methylation was quantified in 68 human brain tumors, including both IDH-mutant and IDH wildtype, by bisulfite pyrosequencing. In all tumors examined, CpG methylation levels were less than 8%. Our data demonstrate that inactivation of IDH function through promoter hypermethylation is not common in human gliomas and other brain tumors. These findings do not support a tumor suppressor role for IDH genes in human gliomas.

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[706]

TÍTULO / TITLE:  - Low grade gliomas in eloquent locations - implications for surgical strategy, survival and long term quality of life.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51450. doi: 10.1371/journal.pone.0051450. Epub 2012 Dec 10.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051450

AUTORES / AUTHORS:  - Jakola AS; Unsgard G; Myrmel KS; Kloster R; Torp SH; Lindal S; Solheim O

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, St.Olavs University Hospital, Trondheim, Norway ; MI  Lab, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.

RESUMEN / SUMMARY:  - BACKGROUND: Surgical management of suspected LGG remains controversial. A key factor when deciding a surgical strategy is often the tumors’ perceived relationship to eloquent brain regions OBJECTIVE: To study the association between tumor location, survival and long-term health related quality of life (HRQL) in patients with supratentorial low-grade gliomas (LGG). METHODS: Adults (>/=18 years) operated due to newly diagnosed LGG from 1998 through 2009 included from two Norwegian university hospitals. After review of initial histopathology,  153 adults with supratentorial WHO grade II LGG were included in the study. Tumors’ anatomical location and the relationship to eloquent regions were graded. Survival analysis was adjusted for known prognostic factors and the initial surgical procedure (biopsy or resection). In long-term survivors, HRQL was assessed with disease specific questionnaires (EORTC QLQ-C30 and BN20) as well as a generic questionnaire (EuroQol 5D). RESULTS: There was a significant association between eloquence and survival (log-rank, p<0.001). The estimated 5-year survival was 77% in non-eloquent tumors, 71% in intermediate located tumors and 54% in eloquent tumors. In the adjusted analysis the hazard ratio of increasing eloquence was 1.5 (95% CI 1.1-2.0, p = 0.022). There were no differences in HRQL between patients with eloquent and non-eloquent tumors. The most frequent self-reported symptoms were related to fatigue, cognition, and future uncertainty. CONCLUSION: Eloquently located LGGs are associated with impaired survival compared to non-eloquently located LGG, but in long-term survivors HRQL is similar. Although causal inference from observational data should be done with caution, the findings illuminate the delicate balance in surgical decision making in LGGs, and add support to the probable survival benefits of aggressive surgical strategies, perhaps also in eloquent locations.

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[707]

TÍTULO / TITLE:  - Neurofibromatosis Type 2 Tumor Suppressor Protein, NF2, Induces Proteasome-Mediated Degradation of JC Virus T-Antigen in Human Glioblastoma.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53447. doi: 10.1371/journal.pone.0053447. Epub 2013 Jan 7.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053447

AUTORES / AUTHORS:  - Beltrami S; Branchetti E; Sariyer IK; Otte J; Weaver M; Gordon J

INSTITUCIÓN / INSTITUTION:  - Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America ; Biomedical Neuroscience Graduate Program, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.

RESUMEN / SUMMARY:  - Neurofibromatosis type 2 protein (NF2) has been shown to act as tumor suppressor  primarily through its functions as a cytoskeletal scaffold. However, NF2 can also be found in the nucleus, where its role is less clear. Previously, our group has  identified JC virus (JCV) tumor antigen (T-antigen) as a nuclear binding partner  for NF2 in tumors derived from JCV T-antigen transgenic mice. The association of  NF2 with T-antigen in neuronal origin tumors suggests a potential role for NF2 in regulating the expression of the JCV T-antigen. Here, we report that NF2 suppresses T-antigen protein expression in U-87 MG human glioblastoma cells, which subsequently reduces T-antigen-mediated regulation of the JCV promoter. When T-antigen mRNA was quantified, it was determined that increasing expression  of NF2 correlated with an accumulation of T-antigen mRNA; however, a decrease in  T-antigen at the protein level was observed. NF2 was found to promote degradation of ubiquitin bound T-antigen protein via a proteasome dependent pathway concomitant with the accumulation of the JCV early mRNA encoding T-antigen. The interaction between T-antigen and NF2 maps to the FERM domain of NF2, which has been shown previously to be responsible for its tumor suppressor activity. Co-immunoprecipitation assays revealed a ternary complex among NF2, T-antigen, and the tumor suppressor protein, p53 within a glioblastoma cell line. Further, these proteins were detected in various degrees in patient tumor tissue, suggesting that these associations may occur in vivo. Collectively, these results demonstrate that NF2 negatively regulates JCV T-antigen expression by proteasome-mediated degradation, and suggest a novel role for NF2 as a suppressor of JCV T-antigen-induced cell cycle regulation.

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[708]

TÍTULO / TITLE:  - Early Surgical Resection of Low-grade Glioma Increases Survival.

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

REVISTA / JOURNAL:  - Cancer Discov. 2013 Jan;3(1):OF20. doi: 10.1158/2159-8290.CD-RW2012-214. Epub 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2012-214

RESUMEN / SUMMARY:  - Survival of patients with LGG was improved by early resection compared with watchful waiting.

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[709]

TÍTULO / TITLE:  - Glioma pathogenesis-related protein 1 induces prostate cancer cell death through  Hsc70-mediated suppression of AURKA and TPX2.

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

REVISTA / JOURNAL:  - Mol Oncol. 2012 Dec 31. pii: S1574-7891(12)00131-7. doi: 10.1016/j.molonc.2012.12.005.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2012.12.005

AUTORES / AUTHORS:  - Li L; Yang G; Ren C; Tanimoto R; Hirayama T; Wang J; Hawke D; Kim SM; Lee JS; Goltsov AA; Park S; Ittmann MM; Troncoso P; Thompson TC

INSTITUCIÓN / INSTITUTION:  - Department of Genitourinary Medical Oncology, Unit 18-3, The University of Texas  MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA.

RESUMEN / SUMMARY:  - In this study we report that expression of glioma pathogenesis-related protein 1  (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically,  GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is  associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-DeltaTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or  mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.

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[710]

TÍTULO / TITLE:  - Prognosis by tumor location in adults with spinal ependymomas.

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

REVISTA / JOURNAL:  - J Neurosurg Spine. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.12.SPINE12591

AUTORES / AUTHORS:  - Oh MC; Kim JM; Kaur G; Safaee M; Sun MZ; Singh A; Aranda D; Molinaro AM; Parsa AT

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery and.

RESUMEN / SUMMARY:  - Object Ependymomas are primary central nervous system tumors that occur more frequently in the spines of adults than they do there in children. Previous studies consist mainly of retrospective single-institutional experiences or case  studies. In this study, a comprehensive literature review was performed on reported cases of spinal ependymoma treated with resection to determine whether tumor location along the spinal axis conveys important prognostic information. Methods A PubMed search was performed to identify all papers that included data on patients with spinal ependymoma. Only cases involving adult patients who underwent ependymoma resection with a clearly reported tumor location were included for analysis. Tumor locations were separated into 6 groups: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar, and conus + cauda equina. Kaplan-Meier survival and Cox regression analyses were performed to determine the effect of tumor location on progression-free survival (PFS) and overall survival (OS). Results A total of 447 patients who underwent resection of spinal ependymomas with clearly indicated location of tumor were identified. The  most common locations of spinal ependymomas were the cervical (32.0%) and conus + cauda equina (26.8%) regions. The thoracolumbar and cervicomedullary regions had  the fewest tumors (accounting for, respectively, 5.1% and 3.4% of the total number of cases). The conus + cauda equina and thoracolumbar regions had the highest percentage of WHO Grade I tumors, while tumors located above these regions consisted of mostly WHO Grade II tumors. Despite the tendency for benign  grades in the lower spinal regions, PFS for patients with spinal ependymomas in the lower 3 regions (thoracic, thoracolumbar, conus + cauda equina) was significantly shorter (p < 0.001) than for those with tumors in the upper regions (cervicomedullary, cervical, cervicothoracic), but the difference in OS did not achieve statistical significance (p = 0.131). Conclusions Spinal ependymomas along different regions of spinal axis have different characteristics and clinical behaviors. Tumor grade, extent of resection, and PFS varied by tumor location (upper vs lower spinal regions), while OS did not. Recurrence rates were higher for the lower spinal cord tumors, despite a greater prevalence of lower WHO grade lesions, compared with upper spinal cord tumors, suggesting that tumor  location along the spinal axis is an important prognostic factor.

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[711]

TÍTULO / TITLE:  - EGFR gene variants are associated with specific somatic aberrations in glioma.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e47929. doi: 10.1371/journal.pone.0047929. Epub 2012 Dec 7.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0047929

AUTORES / AUTHORS:  - Wibom C; Ghasimi S; Van Loo P; Brannstrom T; Trygg J; Lau C; Henriksson R; Bergenheim T; Andersson U; Ryden P; Melin B

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Sciences, Oncology, Computational Life Science Cluster (CLiC), Umea University, Umea, Sweden. carl.wibom@onkologi.umu.se

RESUMEN / SUMMARY:  - A number of gene variants have been associated with an increased risk of developing glioma. We hypothesized that the reported risk variants may be associated with tumor genomic instability. To explore potential correlations between germline risk variants and somatic genetic events, we analyzed matched tumor and blood samples from 95 glioma patients by means of SNP genotyping. The generated genotype data was used to calculate genome-wide allele-specific copy number profiles of the tumor samples. We compared the copy number profiles across samples and found two EGFR gene variants (rs17172430 and rs11979158) that were associated with homozygous deletion at the CDKN2A/B locus. One of the EGFR variants (rs17172430) was also associated with loss of heterozygosity at the EGFR locus. Our findings were confirmed in a separate dataset consisting of matched blood and tumor samples from 300 glioblastoma patients, compiled from publically  available TCGA data. These results imply there is a functional effect of germline EGFR variants on tumor progression.

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[712]

TÍTULO / TITLE:  - Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

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

REVISTA / JOURNAL:  - Mol Biosyst. 2013 Jan 23.

            ●● Enlace al texto completo (gratuito o de pago) 1039/c2mb25528f

AUTORES / AUTHORS:  - Gu Y; Wang H; Qin Y; Zhang Y; Zhao W; Qi L; Zhang Y; Wang C; Guo Z

INSTITUCIÓN / INSTITUTION:  - College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China. guoz@ems.hrbmu.edu.cn guyunyan@ems.hrbmu.edu.cn.

RESUMEN / SUMMARY:  - The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the  individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma  (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

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[713]

TÍTULO / TITLE:  - Automated differentiation of glioblastomas from intracranial metastases using 3T  MR spectroscopic and perfusion data.

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

REVISTA / JOURNAL:  - Int J Comput Assist Radiol Surg. 2013 Jan 19.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11548-012-0808-0

AUTORES / AUTHORS:  - Tsolaki E; Svolos P; Kousi E; Kapsalaki E; Fountas K; Theodorou K; Tsougos I

INSTITUCIÓN / INSTITUTION:  - Medical Physics Department, Medical School, University of Thessaly, 41110 , Biopolis, Larissa, Greece, etsolaki@med.uth.gr.

RESUMEN / SUMMARY:  - Purpose Differentiation of glioblastomas from metastases is clinical important, but may be difficult even for expert observers. To investigate the contribution of machine learning algorithms in the differentiation of glioblastomas multiforme (GB) from metastases, we developed and tested a pattern recognition system based  on 3T magnetic resonance (MR) data. Materials and Methods Single and multi-voxel  proton magnetic resonance spectroscopy (1H-MRS) and dynamic susceptibility contrast (DSC) MRI scans were performed on 49 patients with solitary brain tumors (35 glioblastoma multiforme and 14 metastases). Metabolic (NAA/Cr, Cho/Cr, (Lip [Formula: see text] Lac)/Cr) and perfusion (rCBV) parameters were measured in both intratumoral and peritumoral regions. The statistical significance of these  parameters was evaluated. For the classification procedure, three datasets were created to find the optimum combination of parameters that provides maximum differentiation. Three machine learning methods were utilized: Naive-Bayes, Support Vector Machine (SVM) and [Formula: see text]-nearest neighbor (KNN). The  discrimination ability of each classifier was evaluated with quantitative performance metrics. Results Glioblastoma and metastases were differentiable only in the peritumoral region of these lesions ([Formula: see text]). SVM achieved the highest overall performance (accuracy 98 %) for both the intratumoral and peritumoral areas. Naive-Bayes and KNN presented greater variations in performance. The proper selection of datasets plays a very significant role as they are closely correlated to the underlying pathophysiology. Conclusion The application of pattern recognition techniques using 3T MR-based perfusion and metabolic features may provide incremental diagnostic value in the differentiation of common intraaxial brain tumors, such as glioblastoma versus metastasis.

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[714]

TÍTULO / TITLE:  - Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children.

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

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.10.PEDS12142

AUTORES / AUTHORS:  - Anderson RC; Kennedy B; Yanes CL; Garvin J; Needle M; Canoll P; Feldstein NA; Bruce JN

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery.

RESUMEN / SUMMARY:  - Convection-enhanced delivery (CED) for the treatment of malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine gliomas (DIPGs) are universally fatal childhood tumors  for which there is currently no effective treatment. In this report the authors describe CED of the topoisomerase inhibitor topotecan for the treatment of DIPG in 2 children. As part of a pilot feasibility study, the authors treated 2 pediatric patients with DIPG. Stereotactic biopsy with frozen section confirmation of glial tumor was followed by placement of bilateral catheters for  CED of topotecan during the same procedure. The first patient underwent CED 210 days after initial diagnosis, after radiation therapy and at the time of tumor recurrence, with a total dose of 0.403 mg in 6.04 ml over 100 hours. Her Karnofsky Performance Status (KPS) score was 60 before CED and 50 posttreatment.  Serial MRI initially demonstrated a modest reduction in tumor size and edema, but the tumor progressed and the patient died 49 days after treatment. The second patient was treated 24 days after the initial diagnosis prior to radiation with a total dose of 0.284 mg in 5.30 ml over 100 hours. Her KPS score was 70 before CED and 50 posttreatment. Serial MRI similarly demonstrated an initial modest reduction in tumor size. The patient subsequently underwent fractionated radiation therapy, but the tumor progressed and she died 120 days after treatment. Topotecan delivered by prolonged CED into the brainstem in children with DIPG is technically feasible. In both patients, high infusion rates (> 0.12  ml/hr) and high infusion volumes (> 2.8 ml) resulted in new neurological deficits and reduction in the KPS score, but lower infusion rates (< 0.04 ml/hr) were well tolerated. While serial MRI showed moderate treatment effect, CED did not prolong survival in these 2 patients. More studies are needed to improve patient selection and determine the optimal flow rates for CED of chemotherapeutic agents into DIPG to maximize safety and efficacy. Clinical trial registration no.: NCT00324844.

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[715]

TÍTULO / TITLE:  - Posterior fossa meningioma “our experience” in 64 cases.

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

REVISTA / JOURNAL:  - Asian J Neurosurg. 2012 Jul;7(3):116-24. doi: 10.4103/1793-5482.103710.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1793-5482.103710

AUTORES / AUTHORS:  - Velho V; Agarwal V; Mally R; Palande DA

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Grant Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India.

RESUMEN / SUMMARY:  - BACKGROUND: Posterior fossa meningiomas are 20% of all intracranial meningiomas.  These are slow-growing tumors thus become large before presentation. Microsurgical resection is the treatment of choice for the majority of these lesions, but variable locations, large size at diagnosis, frequent encroachment of neural and vascular structures, and their potentially invasive behavior are some of the features of these tumors that make their resection challenging. MATERIALS AND METHODS: We studied 64 cases of posterior fossa meningioma operated in last 6 years, and analysed the technical difficulties encountered during excision of these tumors. Postoperative complications and outcomes of these patients were also analysed. RESULTS: Gross total excision was achieved in 72% cases. Partial excision or subtotal excision was more in petroclival, jugular foramen with extra cranial extension, tentorial with intrasinus extension and ventral foramen magnum. Postoperative complication in form of new or aggravation  of existing neurological deficit was found in 33% cases and CSF leak in 12.5% cases. We encountered the recurrence of total 10 cases (16%) over mean follow-up  of 4 years. Most of the recurrent cases were seen in petroclival and tentorial subgroups with partial or subtotal excision. CONCLUSION: Posterior fossa meningiomas are difficult to excise due to close relation to cranial nerves and vessels. Use of microscope, CUSA, intraoperative nerve monitor help in removal and preserving surrounding important anatomical structures. Although neurological deterioration is common postoperatively, recovery does occur completely after total removal thus increasing the recurrence free period and improving the outcome.

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[716]

TÍTULO / TITLE:  - Increased expression of microRNA-17 predicts poor prognosis in human glioma.

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

REVISTA / JOURNAL:  - J Biomed Biotechnol. 2012;2012:970761. doi: 10.1155/2012/970761. Epub 2012 Nov 19.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/970761

AUTORES / AUTHORS:  - Lu S; Wang S; Geng S; Ma S; Liang Z; Jiao B

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Second Hospital of Hebei Medical University, No. 215  Hepingxi Road, Hebei Province, Shijiazhuang City 050000, China.

RESUMEN / SUMMARY:  - AIM: To investigate the clinical significance of microRNA-17 (miR-17) expression  in human gliomas. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-17 in  108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. RESULTS: Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P < 0.001). In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P = 0.006) and low Karnofsky performance score (KPS, P = 0.01). Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P = 0.008) and advanced pathological grade (P = 0.02) were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P < 0.001). CONCLUSIONS: Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

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[717]

TÍTULO / TITLE:  - Identification and characterization of alternative exon usage linked glioblastoma multiforme survival.

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

REVISTA / JOURNAL:  - BMC Med Genomics. 2012 Dec 4;5:59. doi: 10.1186/1755-8794-5-59.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1755-8794-5-59

AUTORES / AUTHORS:  - Sadeque A; Serao NV; Southey BR; Delfino KR; Rodriguez-Zas SL

INSTITUCIÓN / INSTITUTION:  - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA. rodrgzzs@illinois.edu.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Alternative exon usage (AEU) is an important component of gene regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival. METHODS: The expression of exons  corresponding to 25,403 genes was related to the survival of 250 individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training data set were confirmed in an independent validation data set of 78 patients. A hierarchical mixed model that allows the consideration of covariation between exons within a gene and of the effect of the epidemiological characteristics of the patients was developed to identify associations between exon expression and patient survival. This general model describes all three possible scenarios: multi-exon genes with and without AEU, and single-exon genes. RESULTS: AEU associated with GBM survival was identified on 2477 genes (P-value < 5.0E-04 or FDR-adjusted P-value < 0.05). G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, respectively. Pathways enriched among the AEU genes included focal adhesion, ECM-receptor interaction, ABC transporters and pathways  in cancer. In addition, 24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM survival (FDR-adjusted P-value < 0.05). CONCLUSIONS: The inferred patterns of AEU were consistent with in silico AS models. The hierarchical model used offered a flexible and simple way to interpret and identify associations between survival that accommodates multi-exon genes with or without AEU and single exon genes. Our results indicate that differential expression of AEU could be used as biomarker for GBM and potentially other cancers.

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[718]

TÍTULO / TITLE:  - Gold nanoparticle imaging and radiotherapy of brain tumors in mice.

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

REVISTA / JOURNAL:  - Nanomedicine (Lond). 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 2217/nnm.12.165

AUTORES / AUTHORS:  - Hainfeld JF; Smilowitz HM; O’Connor MJ; Dilmanian FA; Slatkin DN

INSTITUCIÓN / INSTITUTION:  - Nanoprobes, Inc., 95 Horseblock Road, Unit 1 Yaphank, NY 11980, USA.

RESUMEN / SUMMARY:  - Aim: To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods: Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total  of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results: Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion: Intravenously injected gold nanoparticles cross the blood-tumor barrier, but are largely blocked by the normal blood-brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy  of human brain tumors and other cancers. Original submitted 14 February 2012; Revised submitted 16 September 2012.

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[719]

TÍTULO / TITLE:  - The role of intraoperative magnetic resonance imaging in glioma surgery.

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

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3(Suppl 4):S320-7. doi: 10.4103/2152-7806.103029. Epub 2012 Oct 31.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.103029

AUTORES / AUTHORS:  - Liang D; Schulder M

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, USA.

RESUMEN / SUMMARY:  - For patients with gliomas, the goal of surgery is to maximize the extent of tumor resection while avoiding injury to functional tissue. The hope is to improve patients’ survival and maintain the highest quality of life as possible. However, because of the infiltrative nature of gliomas these two goals often oppose each other so a compromise must be met. Many tools have been developed to help with this challenge of glioma surgery. Over the past two decades, intraoperative-magnetic resonance imaging (iMRI) has emerged as an increasingly important modality to enhance surgical safety while providing the surgeon with updated information to guide their resection. Here the authors review the studies that demonstrate a positive correlation between extent of resection (EOR) and overall survival (OS), although the data is clearer in patients with low-grade gliomas (LGG) and still somewhat controversial in those with higher-grade tumors. We will then review some of the studies that support the role of iMRI and how it  has impacted glioma surgery by increasing the EOR. The value of iMRI usage in regards to overall patient outcome can be extrapolated through its effect on EOR. Overall, available data support the safe use of iMRI and as an effective adjunct  in glioma surgery.

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[720]

TÍTULO / TITLE:  - A population-based study of high-grade gliomas and mutated isocitrate dehydrogenase 1.

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

REVISTA / JOURNAL:  - Int J Clin Exp Pathol. 2013;6(1):31-40. Epub 2012 Nov 20.

AUTORES / AUTHORS:  - Dahlrot RH; Kristensen BW; Hjelmborg J; Herrstedt J; Hansen S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Odense University Hospital Odense, Denmark. Rikke.dahlrot@ouh.regionsyddanmark.dk

RESUMEN / SUMMARY:  - High-grade gliomas have a dismal prognosis, and prognostic factors are needed to  optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically. Mutated IDH1 was predominantly observed in oligodendroglial tumors (WHO grade III). Patients with mutated IDH1 had a significantly better outcome than patients with wildtype IDH1: 2-year OS 59% and 18%, respectively (HR 0.38, 95% CI 0.21-0.68). However, when adjusting for other prognostic factors, IDH1 status was not a significant independent prognostic factor (HR=0.58, 95% CI  0.32-1.07). Young age, absence of neurological deficit, performance status 0-1, tumor not crossing the midline, and receiving post-surgical treatment were significant independent indicators of a good prognosis in multivariate analysis.  In conclusion: This population-based study could not demonstrate IDH1 status to be an independent prognostic factor in high-grade gliomas when adjusting for the  effect of classic prognostic factors.

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[721]

TÍTULO / TITLE:  - Intraoperative diagnosis of functional retroperitoneal multiple paraganglioma: A  case report.

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

REVISTA / JOURNAL:  - Oncol Lett. 2012 Oct;4(4):829-831. Epub 2012 Jul 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.795

AUTORES / AUTHORS:  - Guo Q; Li B; Guan J; Yang H; Wu Y

INSTITUCIÓN / INSTITUTION:  - Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang 310009;

RESUMEN / SUMMARY:  - Paragangliomas are extra-adrenal chromaffin tumors that arise from neuroectodermal cells of the autonomous nervous system. It is difficult to make an accurate preoperative clinical diagnosis of silent paraganglioma. The best choice of treatment is complete surgical resection. However, it is important to note that in patients with functional paragangliomas, the tumor’s ability to produce catecholamines may cause abrupt changes in blood pressure. Thus, surgery  may induce life-threatening complications. In the present study, we present a case of functional retroperitoneal multiple paraganglioma in a 39-year-old male patient who was diagnosed during surgery. Four years after the operation, the patient remains asymptomatic and free of disease.

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[722]

TÍTULO / TITLE:  - Thalamic astrocytic hamartoma and associated meningoangiomatosis in a German shepherd dog.

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

REVISTA / JOURNAL:  - Res Vet Sci. 2012 Dec 19. pii: S0034-5288(12)00337-2. doi: 10.1016/j.rvsc.2012.11.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.rvsc.2012.11.004

AUTORES / AUTHORS:  - Sebastianelli M; Mandara MT; Pavone S; Canal S; Bernardini M

INSTITUCIÓN / INSTITUTION:  - Department of Biopathological Science and Hygiene of Animal and Food Productions, Faculty of Veterinary Medicine, University of Perugia, Italy.

RESUMEN / SUMMARY:  - The present paper describes an astrocytic thalamic hamartoma associated with tectal meningoangiomatosis in a 3-month-old female German shepherd dog showing strabismus, opistotonus, circling, and fore limb hypermetria. MR images of the brain showed a well-defined intra-axial mass in the tectal region. The mass was hypointense to gray matter on T2-weighted images and hyperintense to gray matter  on precontrast T1-weighted images. Histologically, glial cells arranged in a multinodular pattern characterized the mass. More caudally the lesion merged with subpial abnormal newly formed plaque-like shaped tissue characterized by thick branching bundles of spindle-shaped cells surrounding a central vessel. In the nodules, GFAP and vimentin were diffusely expressed. In the vascular proliferation Factor VIII-positive reaction was limited to endothelial cells while the remaining spindle-shaped cells were diffusely SMA-positive. The glial nodules did not express lysozyme and MAC387, nor neurofilaments and nestin.

 

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[723]

TÍTULO / TITLE:  - Retrieval of brain tumors with region-specific bag-of-visual-words representations in contrast-enhanced MRI images.

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

REVISTA / JOURNAL:  - Comput Math Methods Med. 2012;2012:280538. doi: 10.1155/2012/280538. Epub 2012 Nov 25.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/280538

AUTORES / AUTHORS:  - Huang M; Yang W; Yu M; Lu Z; Feng Q; Chen W

INSTITUCIÓN / INSTITUTION:  - School of Biomedical Engineering, Southern Medical University, Guangzhou 510515,  China.

RESUMEN / SUMMARY:  - A content-based image retrieval (CBIR) system is proposed for the retrieval of T1-weighted contrast-enhanced MRI (CE-MRI) images of brain tumors. In this CBIR system, spatial information in the bag-of-visual-words model and domain knowledge on the brain tumor images are considered for the representation of brain tumor images. A similarity metric is learned through a distance metric learning algorithm to reduce the gap between the visual features and the semantic concepts in an image. The learned similarity metric is then used to measure the similarity between two images and then retrieve the most similar images in the dataset when  a query image is submitted to the CBIR system. The retrieval performance of the proposed method is evaluated on a brain CE-MRI dataset with three types of brain  tumors (i.e., meningioma, glioma, and pituitary tumor). The experimental results  demonstrate that the mean average precision values of the proposed method range from 90.4% to 91.5% for different views (transverse, coronal, and sagittal) with  an average value of 91.0%.

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[724]

TÍTULO / TITLE:  - Delayed contrast extravasation MRI for depicting tumor and non-tumoral tissues in primary and metastatic brain tumors.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52008. doi: 10.1371/journal.pone.0052008. Epub 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052008

AUTORES / AUTHORS:  - Zach L; Guez D; Last D; Daniels D; Grober Y; Nissim O; Hoffmann C; Nass D; Talianski A; Spiegelmann R; Cohen ZR; Mardor Y

INSTITUCIÓN / INSTITUTION:  - Oncology Institute, Sheba Medical Center, Ramat-Gan, Israel ; Sackler Faculty of  Medicine, Tel-Aviv University, Tel-Aviv, Israel.

RESUMEN / SUMMARY:  - The current standard of care for newly diagnosed glioblastoma multiforme (GBM) is resection followed by radiotherapy with concomitant and adjuvant temozolomide. Recent studies suggest that nearly half of the patients with early radiological deterioration post treatment do not suffer from tumor recurrence but from pseudoprogression. Similarly, a significant number of patients with brain metastases suffer from radiation necrosis following radiation treatments. Conventional MRI is currently unable to differentiate tumor progression from treatment-induced effects. The ability to clearly differentiate tumor from non-tumoral tissues is crucial for appropriate patient management. Ten patients with primary brain tumors and 10 patients with brain metastases were scanned by delayed contrast extravasation MRI prior to surgery. Enhancement subtraction maps calculated from high resolution MR images acquired up to 75 min after contrast administration were used for obtaining stereotactic biopsies. Histological assessment was then compared with the pre-surgical calculated maps. In addition,  the application of our maps for prediction of progression was studied in a small  cohort of 13 newly diagnosed GBM patients undergoing standard chemoradiation and  followed up to 19.7 months post therapy. The maps showed two primary enhancement  populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation. Comparison with histology confirmed the fast population to consist of morphologically active tumor and the slow population to consist of  non-tumoral tissues. Our maps demonstrated significant correlation with perfusion-weighted MR data acquired simultaneously, although contradicting examples were shown. Preliminary results suggest that early changes in the fast volumes may serve as a predictor for time to progression. These preliminary results suggest that our high resolution MRI-based delayed enhancement subtraction maps may be applied for clear depiction of tumor and non-tumoral tissues in patients with primary brain tumors and patients with brain metastases.

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[725]

TÍTULO / TITLE:  - Intramedullary spinal cord ganglioglioma presenting as hyperhidrosis: unique symptoms and magnetic resonance imaging findings.

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

REVISTA / JOURNAL:  - J Neurosurg Spine. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.SPINE12530

AUTORES / AUTHORS:  - Murakami T; Koyanagi I; Kaneko T; Yoneta A; Keira Y; Wanibuchi M; Hasegawa T; Mikuni N

INSTITUCIÓN / INSTITUTION:  - Departments of Neurosurgery.

RESUMEN / SUMMARY:  - Hyperhidrosis is caused by a sympathetic dysfunction of the central or peripheral nervous system. Intramedullary spinal cord lesions can be a cause of hyperhidrosis. The authors report a rare case of intramedullary thoracic spinal cord ganglioglioma presenting as hyperhidrosis. This 16-year-old boy presented with abnormal sweating on the right side of the neck, chest, and the right arm that had been occurring for 6 years. Neurological examination revealed mild motor weakness of the right lower extremity and slightly decreased sensation in the left lower extremity. Hyperhidrosis was observed in the right C3-T8 dermatomes. Magnetic resonance imaging showed an intramedullary tumor at the right side of the spinal cord at the T2-3 level. The tumor showed partial enhancement after Gd  administration. The patient underwent removal of the tumor via hemilaminectomy of T2-3. Only subtotal resection was achieved because the margins of the tumor were  unclear. Histopathological examination revealed ganglioglioma. Hyperhidrosis gradually improved after surgery. Hyperhidrosis is a rare clinical manifestation  of intramedullary spinal cord tumors, and only a few cases have been reported in  the literature. The location of the tumor origin, around the right gray matter of the lateral spinal cord, may account for the hyperhidrosis as the initial symptom in this patient. Physicians should examine the spinal cord using MRI studies when a patient has hyperhidrosis with some motor or sensory symptoms of the extremities.

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[726]

TÍTULO / TITLE:  - A tale of two tumors: pediatric and adult medulloblastoma.

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

REVISTA / JOURNAL:  - Oncology (Williston Park). 2012 Nov;26(11):1095-7.

AUTORES / AUTHORS:  - Aizer AA; Chan AW

INSTITUCIÓN / INSTITUTION:  - Dept of Radiation Oncology, Massachusetts General Hospital (MGH), Harvard Medical School, Boston, Massachusetts, USA.

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[727]

TÍTULO / TITLE:  - DNA methylation in the malignant transformation of meningiomas.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54114. doi: 10.1371/journal.pone.0054114. Epub 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054114

AUTORES / AUTHORS:  - Gao F; Shi L; Russin J; Zeng L; Chang X; He S; Chen TC; Giannotta SL; Weisenberger DJ; Zada G; Mack WJ; Wang K

INSTITUCIÓN / INSTITUTION:  - Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States of America.

RESUMEN / SUMMARY:  - Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3-5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands  at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as  diagnostic biomarkers or candidate causal genes for malignant transformation.

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[728]

TÍTULO / TITLE:  - Cerebral multicystic lesions in a child with neurofibromatosis.

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 http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 25;2013. pii: bcr-2012-007639. doi: 10.1136/bcr-2012-007639.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007639

AUTORES / AUTHORS:  - Isikay S; Yilmaz K

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics, Gaziantep University, Gaziantep, Turkey.

RESUMEN / SUMMARY:  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous syndrome, with frequent involvement of the central nervous system (CNS). As well as abnormal cellular differentiation, disordered cell migration during development is the most common cause of the various brain lesions. Cystic lesions are rarely  observed in neurocutaneous diseases, and the origin of the cysts is not known. This paper presents a rare case, a child at the age of 3, who was diagnosed as NF-1 and was observed to have asymptomatic cystic lesions in right temporal lobe  in radiological examination of CNS. This study draws attention to the relationship between these rare cystic lesions of unknown origin and neurocutaneous diseases.

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[729]

TÍTULO / TITLE:  - Secondary glioblastoma multiforme in a child with disseminated juvenile pilocytic astrocytoma.

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

REVISTA / JOURNAL:  - Case Rep Oncol Med. 2012;2012:290905. doi: 10.1155/2012/290905. Epub 2012 Nov 19.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/290905

AUTORES / AUTHORS:  - Amene CS; Yeh-Nayre LA; Crawford JR

INSTITUCIÓN / INSTITUTION:  - The Departments of Neurosurgery, San Diego and Rady Children’s Hospital, University of California, 3020 Children’s Way San Diego, San Diego, CA 92123, USA.

RESUMEN / SUMMARY:  - Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis. Outcomes of radiation-induced sGBM remain poor in both children and adults. We report a case  of a 16-year-old girl with a history of disseminated juvenile pilocytic astrocytoma treated with chemotherapy and craniospinal radiation 9 years prior who developed sGBM in the absence of a tumor predisposition syndrome. She presented with a several-week history of headaches and no acute findings on computed tomography compared to baseline neuroimaging 3 months prior. Repeat computed tomography performed just 3 weeks later for worsening headaches revealed a new large posterior fossa tumor where pathology confirmed the diagnosis of sGBM. In spite of maximal surgical resection, reirradiation, and adjuvant chemotherapy, she died 1 year postdiagnosis. Our case highlights the potential late effects of high-dose cranial radiation, how symptomatology may precede neuroimaging findings, and the rapid formation of sGBM that mirrors that of de novo Glioblastoma Multiforme.

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[730]

TÍTULO / TITLE:  - Vascular endothelial growth factor and KIT expression in relation with microvascular density and tumor grade in supratentorial astrocytic tumors.

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

REVISTA / JOURNAL:  - Acta Cir Bras. 2013 Jan;28(1):48-54.

AUTORES / AUTHORS:  - Heinke T; Espirito Santo KS; Longatto Filho A; Stavale JN

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Investigative Pathology Division, EPM, UNIFESP, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY:  - PURPOSE: To evaluate the relationship between microvascular density and the expression of vascular endothelial growth factor (VEGF) and KIT as possible markers of angiogenic stimulus in astrocytic tumors and correlate it with histopathological grading. METHODS: We enrolled 99 surgical specimens of supratentorial astrocytic tumors for analysis of VEGF and KIT and subsequent correlation with MVD and grading. RESULTS: KIT and VEGF expression correlated with microvascular density (p<0.005) and both VEGF and microvascular density correlated with grading (p<0.005). KIT had no significant relationship with grading (p=0.657). CONCLUSION: KIT and VEGF constitute important pathways in the  angiogenesis of astrocytomas and therefore are promising prognostic tools and options for therapeutic intervention.

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[731]

TÍTULO / TITLE:  - Hypothalamic cavernous angioma associated with memory and behavior disturbance attacks: role of imaging in diagnosis.

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

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Mar;9(1):42-4. doi: 10.5812/iranjradiol.6737. Epub 2012 Mar 25.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.6737

AUTORES / AUTHORS:  - Patil PB; Kamalapur MG; Sindhur JC; Joshi SK

INSTITUCIÓN / INSTITUTION:  - Department of Radiodiagnosis and Imaging, S.D.M College of Medical Sciences and Hospital Dharwad, Dharwad, India.

RESUMEN / SUMMARY:  - Deep seated cavernous angioma (CA) is a very rare entity, those occurring in the  hypothalamus are still less common. We present a case of a 52-year-old man who presented with behavior and memory disturbance attacks. He had a CA of the hypothalamus as revealed by magnetic resonance imaging (MRI). We will discuss the role and importance of imaging in such scenario and also the differential diagnoses of this rare entity.

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[732]

TÍTULO / TITLE:  - Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis.

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

REVISTA / JOURNAL:  - J Drug Deliv. 2012;2012:975763. doi: 10.1155/2012/975763. Epub 2012 Dec 5.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/975763

AUTORES / AUTHORS:  - Kasai T; Nakamura K; Vaidyanath A; Chen L; Sekhar S; El-Ghlban S; Okada M; Mizutani A; Kudoh T; Murakami H; Seno M

INSTITUCIÓN / INSTITUTION:  - Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.

RESUMEN / SUMMARY:  - Chlorotoxin is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which has been shown to inhibit low-conductance chloride channels in colonic epithelial cells. Chlorotoxin also binds to matrix metalloproteinase-2 and other proteins on glioma cell surfaces. Glioma cells are  considered to require the activation of matrix metalloproteinase-2 during invasion and migration. In this study, for targeting glioma, we designed two types of recombinant chlorotoxin fused to human IgG-Fcs with/without a hinge region. Chlorotoxin fused to IgG-Fcs was designed as a dimer of 60 kDa with a hinge region and a monomer of 30 kDa without a hinge region. The monomeric and dimeric forms of chlorotoxin inhibited cell proliferation at 300 nM and induced internalization in human glioma A172 cells. The monomer had a greater inhibitory  effect than the dimer; therefore, monomeric chlorotoxin fused to IgG-Fc was multivalently displayed on the surface of bionanocapsules to develop a drug delivery system that targeted matrix metalloproteinase-2. The target-dependent internalization of bionanocapsules in A172 cells was observed when chlorotoxin was displayed on the bionanocapsules. This study indicates that chlorotoxin fused to IgG-Fcs could be useful for the active targeting of glioblastoma cells.

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[733]

TÍTULO / TITLE:  - 5-Aminolevulinic Acid Fluorescence-guided Surgery for Spinal Meningioma.

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

REVISTA / JOURNAL:  - World Neurosurg. 2012 Dec 13. pii: S1878-8750(12)01450-7. doi: 10.1016/j.wneu.2012.12.017.

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

AUTORES / AUTHORS:  - Muroi C; Fandino J; Coluccia D; Berkmann S; Fathi AR; Landolt H

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland. Electronic address: carl.muroi@ksa.ch.

RESUMEN / SUMMARY:  - OBJECTIVE: Fluorescence-guided surgery for cranial meningioma has been reported to be useful. There are no reports about spinal cases using this technique. We report on a meningioma of the cervical spine for which fluorescence-guided surgery was applied. CASE ILLUSTRATION AND SURGICAL TECHNIQUE: A 78-year-old female patient with a meningioma located in the cervical spine underwent surgery  using fluorescence guidance. After complete removal of the meningioma and removal and coagulation of the dural attachment (equal to Simpson grade II resection), a  fluorescence-positive remnant could be identified and successfully removed. The remnant was found to harbor meningioma tissue on histological examination. CONCLUSION: Fluorescence-guided microsurgery is helpful in achieving a total resection of spinal meningiomas and might therefore reduce the risk of recurrence.

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[734]

TÍTULO / TITLE:  - Correlation of expression pattern of aquaporin-1 in primary central nervous system tumors with tumor type, grade, proliferation, microvessel density, contrast-enhancement and perilesional edema.

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

REVISTA / JOURNAL:  - J Cancer Res Ther. 2012 Oct;8(4):571-7. doi: 10.4103/0973-1482.106542.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0973-1482.106542

AUTORES / AUTHORS:  - Deb P; Pal S; Dutta V; Boruah D; Chandran VM; Bhatoe HS

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Armed Forces Medical College, Pune, India.

RESUMEN / SUMMARY:  - Objectives: Brain edema, a hallmark of malignant brain tumors, continues to be a  major cause of mortality. The underlying molecular mechanisms are poorly understood and thought to be mediated through membrane water-channels: aquaporins (AQP1,4,9). The abnormal upregulation of AQP1 in certain glial neoplasms has suggested a potential role in tumor pathogenesis, apart from being a novel target for newer therapeutic regimen. This study was undertaken to evaluate the expression of AQP1 in primary CNS tumors of various histologic types and grades,  and its correlation with contrast-enhancement, perilesional edema, histomorphology, proliferation index and microvessel density. Materials and Methods: Biopsy tissues from 30 patients (10 each from gliomas, meningiomas and other primary CNS tumors) were studied. Autopsy brain sections served as control. AQP1-immunoreactivity was correlated with histomorphology, radiology, proliferation index and microvessel density (MVD). Results: AQP1 expression was increased in gliomas and ependymal tumors as compared to meningiomas. Intratumoral expression was homogenous in high-grade and membranous in low-grade  neoplasms, while peritumoral areas showed expression around vessels and reactive  astrocytes. High-grade tumors showed peritumoral upregulation, while low-grade had intense intratumoral expression. A trend of positive correlation was observed between AQP1-immunopositivity and increasing grade, higher MIB-1LI, increasing contrast-enhancement and more perilesional edema, and elevated MVD with raised AQP1:MVD ratio. Conclusions: AQP1-immunoexpression had a good correlation with high-grade tumors. AQP-upregulation in perilesional areas of high-grade tumors suggests its role in vasogenic edema. Further studies involving other AQP molecules, vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1alpha) should be undertaken to evaluate its possible role as a potential surrogate marker of high-grade tumors heralding poor outcome, inhibition of which may serve as the basis for future targeted therapy.

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[735]

TÍTULO / TITLE:  - Evaluation of matrix metalloproteinase-2 and -9 in the cerebrospinal fluid of dogs with intracranial tumors.

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

REVISTA / JOURNAL:  - Am J Vet Res. 2013 Jan;74(1):122-9. doi: 10.2460/ajvr.74.1.122.

            ●● Enlace al texto completo (gratuito o de pago) 2460/ajvr.74.1.122

AUTORES / AUTHORS:  - Mariani CL; Boozer LB; Braxton AM; Platt SR; Vernau KM; McDonnell JJ; Guevar J

INSTITUCIÓN / INSTITUTION:  - Comparative Neuroimmunology and Neurooncology Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607., Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

RESUMEN / SUMMARY:  - Objective-To identify matrix metalloproteinase (MMP)-2 and -9 in CSF from dogs with intracranial tumors. Sample-CSF from 55 dogs with intracranial tumors and 37 control dogs. Procedures-Latent and active MMP-2 and -9 were identified by use of gelatin zymography. The presence of MMPs in the CSF of dogs with intracranial tumors was compared with control dogs that were clinically normal and with dogs that had idiopathic or cryptogenic epilepsy or peripheral vestibular disease. Relationships between MMP-9 and CSF cell counts and protein were also investigated. Results-Latent MMP-2 was found in CSF samples from all dogs, although active MMP-2 was not detected in any sample. Latent MMP-9 was detected in a subset of dogs with histologically documented intracranial tumors, including meningiomas (2/10), gliomas (3/10), pituitary tumors (1/2), choroid plexus tumors (5/6), and lymphoma (4/4), but was not detected in any control samples. Dogs with tumors were significantly more likely than those without to have detectable MMP-9 in the CSF, and the presence of MMP-9 was associated with higher CSF nucleated cell counts and protein concentration. Conclusions and Clinical Relevance-Latent  MMP-9 was detected in most dogs with choroid plexus tumors or lymphoma but in a smaller percentage of dogs with meningiomas, gliomas, or pituitary tumors. Detection of MMP in CSF may prove useful as a marker of intracranial neoplasia or possibly to monitor response of tumors to therapeutic intervention.

 

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[736]

TÍTULO / TITLE:  - DNA methylation at the Igf2/H19 imprinting control region is associated with cerebellum mass in outbred mice.

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

REVISTA / JOURNAL:  - Mol Brain. 2012 Dec 6;5:42. doi: 10.1186/1756-6606-5-42.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1756-6606-5-42

AUTORES / AUTHORS:  - Pidsley R; Fernandes C; Viana J; Paya-Cano JL; Liu L; Smith RG; Schalkwyk LC; Mill J

INSTITUCIÓN / INSTITUTION:  - Institute of Psychiatry, King’s College London, De Crespigny Park, Denmark Hill,  London, SE5 8AF, UK. j.mill@exeter.ac.uk.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Insulin-like growth factor 2 (Igf2) is a paternally expressed imprinted gene regulating fetal growth, playing an integral role in the development of many tissues including the brain. The parent-of-origin specific expression of Igf2 is largely controlled by allele-specific DNA methylation at CTCF-binding sites in the imprinting control region (ICR), located immediately upstream of the neighboring H19 gene. Previously we reported evidence of a negative correlation between DNA methylation in this region and cerebellum weight in humans. RESULTS: We quantified cerebellar DNA methylation across all four CTCF binding sites spanning the murine Igf2/H19 ICR in an outbred population of Heterogeneous Stock (HS) mice (n = 48). We observe that DNA methylation at the second and third CTCF binding sites in the Igf2/H19 ICR shows a negative relationship with cerebellar mass, reflecting the association observed in human post-mortem cerebellum tissue. CONCLUSIONS: Given the important role of the cerebellum in motor control and cognition, and the link between structural cerebellar abnormalities and neuropsychiatric phenotypes, the identification of epigenetic factors associated with cerebellum growth and development may provide  important insights about the etiology of psychiatric disorders.

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[737]

TÍTULO / TITLE:  - Conservative management of presumed low-grade gliomas in the asymptomatic pediatric population.

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

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 12. pii: S1878-8750(13)00099-5. doi: 10.1016/j.wneu.2013.01.038.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.038

AUTORES / AUTHORS:  - Ali ZS; Lang SS; Sutton LN

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Neurosurgery, The Children’s Hospital of Philadelphia,  Philadelphia, Pennsylvania. Electronic address: zarina.ali@uphs.upenn.edu.

RESUMEN / SUMMARY:  - OBJECTIVES: Optimal management of asymptomatic children with small, nonenhancing  intracranial lesions, presumed to be low-grade gliomas (LGG) is not entirely clear in the literature. However, surgical intervention via resection or biopsy is not without risk and is of questionable long-term benefit in children with stable lesions. We present a series of twelve patients with incidentally detected, small, nonenhancing, intracranial lesions that were managed with watchful waiting and serial MRIs. METHODS: We retrospectively reviewed a series of twelve cases (8 male, 4 female) of children with T1 hypointense and T2 hyperintense intracranial lesions less than 2 cm without enhancement or surrounding edema. RESULTS: Most patients (n=5, 41.7%) received MRI studies after suffering a traumatic injury with evidence of an abnormality seen on computed tomography (CT) scan. Others received MRI scan as part of headache work-up (n=4,  33.3%). The majority of lesions were located infratentorially (n=8, 66.7%), while other locations included the frontal lobe and thalamus. The median age of the patients upon identification of the intracranial abnormality was 10 years (range  1-19 years of age). Patients were followed for a median of 16.7 months (range 2.7-59.5 months). The most common diagnosis based on clinical and radiographic features of these lesions consisted of LGG. No patient underwent surgery, radiation therapy or chemotherapy except one patient, in whom the lesion grew in  size. Surgical pathologic diagnosis in this case confirmed WHO grade II astrocytoma. CONCLUSIONS: Our case series suggests that conservative management and close follow-up of incidental radiographic lesions consistent with LGGs is a  safe and effective initial strategy in the pediatric population. In cases where lesion size or quality changes, surgical resection may be necessary to confirm diagnosis. Further studies that include a larger number of patients and longer follow-up period are required to compare outcomes between this approach and initial surgical, radiation, or chemotherapy management strategies.

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[738]

TÍTULO / TITLE:  - Mixed germ cell tumor with extensive yolk sac tumor elements in the frontal lobe  of an adult.

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

REVISTA / JOURNAL:  - Case Rep Surg. 2012;2012:473790. doi: 10.1155/2012/473790. Epub 2012 Dec 24.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/473790

AUTORES / AUTHORS:  - Takahashi T; Ishikawa E; Masuda Y; Yamamoto T; Sato T; Shibuya M; Matsumura A

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba,  Ibaraki, 305-8575, Japan.

RESUMEN / SUMMARY:  - Intracranial nongerminomatous germ cell tumors (NGGCTs) in unusual locations are  extremely rare. Here, we report a case of a yolk sac tumor in the frontal lobe in a middle-aged patient. A 42-year-old man was admitted to our hospital for headache and nausea. Magnetic resonance imaging (MRI) showed an enhanced mass lesion with a marked cyst component. The serum alpha-fetoprotein (alphaFP) level  was extremely high. Histological examination of specimens after subtotal removal  revealed a primary mixed germ cell tumor with extensive yolk sac tumor elements,  often referred to as an intracranial “yolk sac tumor.” The preoperative diagnosis of NGGCTs in unusual age and locations is extremely difficult. Clinicians should  consider the possibility of NGGCTs, including yolk sac tumors, when intracranial  tumors with unusual MRI findings are encountered.

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[739]

TÍTULO / TITLE:  - Extended adjuvant temozolomide with cis-retinoic acid for adult glioblastoma.

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

REVISTA / JOURNAL:  - Curr Oncol. 2012 Dec;19(6):308-14. doi: 10.3747/co.19.1151.

            ●● Enlace al texto completo (gratuito o de pago) 3747/co.19.1151

AUTORES / AUTHORS:  - Pitz MW; Lipson M; Hosseini B; Lambert P; Guilbert K; Lister D; Schroeder G; Jones K; Mihalicioiu C; Eisenstat DD

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine, University of Manitoba, Winnipeg, MB. ; Department of Haematology/Medical Oncology, CancerCare Manitoba, Winnipeg, MB.

RESUMEN / SUMMARY:  - OBJECTIVE: To determine the toxicity and effectiveness of 24 months of adjuvant temozolomide (tmz) with cis-retinoic acid (cra) for patients with glioblastoma. METHODS: This retrospective population-based review considered the charts of all  patients diagnosed with glioblastoma in Manitoba and referred to a provincial cancer centre during 2002-2008. Consecutive patients came from a population-based referral centre and provincial cancer registry. All patients were treated according to the local standard of care with surgical resection followed by concurrent radiotherapy and tmz 75 mg/m(2) daily, followed by tmz 150-200 mg/m(2) for days 1-5, repeated every 28 days for up to 24 cycles, and cra 50 mg/m(2) twice daily for days 1-21, repeated every 28 days. The main outcome measures were safety, tolerability, and effectiveness of long-term tmz and cra. RESULTS: Of 247 patients diagnosed with glioblastoma in Manitoba during the study period, 116 started concurrent chemoradiotherapy, and 80 received adjuvant tmz. Of the patients who started concurrent chemoradiotherapy, 80 began adjuvant chemotherapy. Patients completed a median of 5.5 cycles of tmz and 3 cycles of cra. Grade 3 or 4 hematologic toxicity was noted in 16% of patients. Median overall survival was 15.1 months, and 26.7% of patients remained alive at 2 years. CONCLUSIONS: Extended adjuvant tmz and cra is well tolerated. However, the population-based effectiveness of this regimen is similar to the clinical trial efficacy of 6 months of adjuvant tmz. Future studies in glioblastoma should incorporate duration of adjuvant chemotherapy into the study design.

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[740]

TÍTULO / TITLE:  - Unusual magnetic resonance imaging appearance of multiple cystic lesions in glioblastoma multiforme.

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

REVISTA / JOURNAL:  - Turk Neurosurg. 2013;23(1):95-7. doi: 10.5137/1019-5149.JTN.4109-11.1.

            ●● Enlace al texto completo (gratuito o de pago) 5137/1019-5149.JTN.4109-11.1

AUTORES / AUTHORS:  - Lyons M

INSTITUCIÓN / INSTITUTION:  - Mayo Clinic Arizona, Department of Neurological Surgery, Phoenix/AZ, USA.

RESUMEN / SUMMARY:  - The differential diagnosis of multiple ring-enhancing intraaxial lesions includes neoplastic, infectious, inflammatory, demyelinating and vascular lesions. We report a case of a 41-year-old man who presented with a brief history of left lower extremity weakness and sensory loss. Magnetic resonance imaging demonstrated multiple ring-enhancing lesions in the right frontal and parietal lobes. Neuroradiology interpretation was felt to be unlikely for a neoplastic process. The patient underwent stereotactic brain biopsy, which was diagnostic for glioblastoma multiforme. This case demonstrates the importance of histological confirmation of intraaxial brain lesions whenever feasible. The course of his disease and treatment are discussed and the literature reviewed.

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[741]

TÍTULO / TITLE:  - Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 beta.

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

REVISTA / JOURNAL:  - J Neuroinflammation. 2012 Dec 28;9:280. doi: 10.1186/1742-2094-9-280.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1742-2094-9-280

AUTORES / AUTHORS:  - Zurolo E; de Groot M; Iyer A; Anink J; van Vliet EA; Heimans JJ; Reijneveld JC; Gorter JA; Aronica E

INSTITUCIÓN / INSTITUTION:  - Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, AZ 1105, The Netherlands. e.aronica@amc.uva.nl.

RESUMEN / SUMMARY:  - ABSTRACT: OBJECTIVE: Decreased expression of inwardly rectifying potassium (Kir)  channels in astrocytes and glioma cells may contribute to impaired K+ buffering and increased propensity for seizures. Here, we evaluated the potential effect of inflammatory molecules, such as interleukin-1beta (IL-1beta) on Kir4.1 mRNA and protein expression. METHODS: We investigated Kir4.1 (Kcnj10) and IL-1beta mRNA expression in the temporal cortex in a rat model of temporal lobe epilepsy 24 h and 1 week after induction of status epilepticus (SE), using real-time PCR and western blot analysis. The U373 glioblastoma cell line and human fetal astrocytes were used to study the regulation of Kir4.1 expression in response to pro-inflammatory cytokines. Expression of Kir4.1 protein was also evaluated by means of immunohistochemistry in surgical specimens of patients with astrocytic tumors (n = 64), comparing the expression in tumor patients with (n = 38) and without epilepsy (n = 26). RESULTS: Twenty-four hours after onset of SE, Kir4.1 mRNA and protein were significantly down-regulated in temporal cortex of epileptic rats. This decrease in expression was followed by a return to control level at 1 week after SE. The transient downregulation of Kir4.1 corresponded to  the time of prominent upregulation of IL-1beta mRNA. Expression of Kir4.1 mRNA and protein in glial cells in culture was downregulated after exposure to IL-1beta. Evaluation of Kir4.1 in tumor specimens showed a significantly lower Kir4.1 expression in the specimens of patients with epilepsy compared to patients without epilepsy. This paralleled the increased presence of activated microglial  cells, as well as the increased expression of IL-1beta and the cytoplasmic translocation of high mobility group box 1 (HMGB1). CONCLUSIONS: Taken together,  these findings indicate that alterations in expression of Kir4.1 occurring in epilepsy-associated lesions are possibly influenced by the local inflammatory environment and in particular by the inflammatory cytokine IL-1beta.

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[742]

TÍTULO / TITLE:  - Infratentorial medulloepithelioma with divergent differentiation: Possibly a predictor of poor outcome.

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

REVISTA / JOURNAL:  - J Pediatr Neurosci. 2012 May;7(2):142-5. doi: 10.4103/1817-1745.102581.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1817-1745.102581

AUTORES / AUTHORS:  - Chakrabarti I; Majumdar K; Giri A

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, North Bengal Medical College, West Bengal, India.

RESUMEN / SUMMARY:  - Medulloepitheliomas (WHO grade IV) are rare, malignant embryonal tumors of pediatric population, classified under the central nervous system (CNS) primitive neuroectodermal tumors (PNET). Histologically, these tumors are characterized by  neoplastic neuroepithelium recapitulating the embryonic neural tube. We describe  a rare case of infratentorial medulloepithelioma with divergent differentiation in a 1-year-old male child who presented with headache, vomiting, and seizures. Histopathologic examination of the excised tumor revealed the characteristic neuroepithelium, along with other areas showing primitive neuroectodermal (blastemal) cells in sheets, ependymoblastic rosettes, and nodular areas of neuronal differentiation. Possibly, this proliferating immature neuroepithelium is the cause of poor outcome in medulloepitheliomas. Due to the rarity of these tumors, it remains to be established whether infratentorial location or tumors with divergent differentiation are also predictors of adverse prognosis.

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[743]

TÍTULO / TITLE:  - Safety and efficacy of concomitant chemotherapeutic wafers and iodine-125 seeds for recurrent glioblastoma.

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

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3:137. doi: 10.4103/2152-7806.103644. Epub 2012 Nov 20.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.103644

AUTORES / AUTHORS:  - Ko AL; Fink KR; Stelzer KM; Silbergeld DL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University of Washington, Seattle, WA 98195.

RESUMEN / SUMMARY:  - BACKGROUND: Patients with recurrent malignant gliomas have a uniformly poor prognosis. However, further treatment is often warranted at the time of recurrence. Low-activity implanted brachytherapeutic devices, such as iodine-125  seeds, and implantable chemotherapeutic devices such as 1, 3-bis (2-chloroethyl)-nitrosourea (BCNU) impregnated polymer wafers (Gliadel(®)) have been shown to be safe and modestly effective, but a comparison of combination therapy versus Gliadel(®) implantation alone has not been performed. METHODS: We retrospectively examined 24 patients following re-resection of recurrent glioblastoma, with 17 patients undergoing implantation of both Gliadel(®) and iodine-125 seeds, and 7 patients undergoing implantation of Gliadel(®) only. Outcomes examined included adverse events, survival after re-resection (SAR), and time to tumor progression after re-resection (PAR). RESULTS: Implantation of both Gliadel(®) and low activity iodine-125 seeds is safe with only two wound infections noted, a complication rate comparable to previous reports. The combination appears to confer a median SAR benefit if the activity per tumor resection volume exceeds 0.8 mCi/mL (60 versus 31 weeks, P = 0.02), and this benefit remained significant on multivariate analysis (HR =0.26 [CI:0.07-0.93], P = 0.03). Gross total resection of tumor was also significantly associated with longer time to PAR (HR =5.4 [CI: 1.13-26.0], P = 0.03). CONCLUSIONS: The concomitant use of Gliadel(®) and low activity iodine-125 seeds following re-resection of recurrent glioblastoma is safe. Our study demonstrated a significant benefit in SAR if the iodine-125 activity per tumor volume is greater than 0.8 mCi/mL. While our sample size is small, our results are in agreement with previous studies demonstrating the efficacy of combination treatment.

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[744]

TÍTULO / TITLE:  - Medulloblastoma: molecular classifications and prognostic associations.

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

REVISTA / JOURNAL:  - Oncology (Williston Park). 2012 Nov;26(11):1097, 1102.

AUTORES / AUTHORS:  - Shrieve DC; Colman H

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, The Huntsman Cancer Hospital, USA.

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[745]

TÍTULO / TITLE:  - Spheno-orbital meningioma resection and reconstruction: the role of piezosurgery  and premolded titanium mesh.

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

REVISTA / JOURNAL:  - Craniomaxillofac Trauma Reconstr. 2011 Dec;4(4):193-200. doi: 10.1055/s-0031-1286113.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0031-1286113

AUTORES / AUTHORS:  - Jung SH; Ferrer AD; Vela JS; Granados FA

INSTITUCIÓN / INSTITUTION:  - Department of Oral and Maxillofacial Surgery, Reina Sofia University Hospital, Cordoba, España.

RESUMEN / SUMMARY:  - We present the clinical case of a patient with a spheno-orbital meningioma. Literature review of the treatment options, including the application of piezoelectric or ultrasound surgery and orbital reconstruction after meningioma resection, is also presented. Complete resection was performed by means of a frontotemporal craniotomy and an orbitozygomatic approach. Piezoelectric osteotomy was used around the optic nerve canal and the superior orbital fissure  to minimize the damage to soft tissues. Orbital wall reconstruction was done using a titanium mesh previously premolded using a skull model. The superior orbital rim was reconstructed with calvarial bone grafts, and the sphenotemporal  bone defect was covered with a titanium mesh cranioplasty. Ultrasonic vibrations  to perform osteotomies in craniofacial surgery provide an interesting tool to reduce damage to surrounding soft tissues. Reconstruction of the roof and lateral orbital wall with premolded titanium meshes with a skull model is a safe and easy method to achieve a good orbital reconstruction and to avoid secondary sequelae.

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[746]

TÍTULO / TITLE:  - Immunohistochemical expression of IDH1 in gliomas: A tissue microarray-based approach.

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

REVISTA / JOURNAL:  - J Cancer Res Ther. 2012 Oct;8(4):598-601. doi: 10.4103/0973-1482.106567.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0973-1482.106567

AUTORES / AUTHORS:  - Sipayya V; Sharma I; Sharma KC; Singh A

INSTITUCIÓN / INSTITUTION:  - National Institute of Pathology, ICMR, New Delhi, India.

RESUMEN / SUMMARY:  - Background: Mutations in the gene encoding isocitrate dehydrogenase (IDH1) have been reported in gliomas. This study analyses a series of 184 glioma cases in a tissue microarray (TMA)-based approach to assess the frequency of R132H point mutations in formalin-fixed, paraffin-embedded tissue samples. Materials and Methods : A total of 195 gliomas (30 pilocytic astrocytoma (PA), 45 diffuse astrocytoma [DA], 75 glioblastoma multiforme [GBM], 25 oligodendroglioma [OLIG] and 20 ependymoma [EPEN]). A TMA of core size 1.0 mm was constructed using a semi-automatic tissue arrayer. Immunohistochemical staining for IDH1, p53 and EGFR proteins was performed by the labeled sterptavidin avidin biotin LSAB method. Results : The frequency of mutant IDH1 detection by immunohistochemistry  on formalin-fixed, paraffin-embedded tissue was 15.8% in 29/184 tumors found suitable for evaluation. DA, OLIG and GBM showed IDH1 expression in 17/40 (42.5%), 5/22 (22.7%) and 7/72 (9.7%) cases, respectively. Of all the GBMs, prim-GBM showed immunoexpression in 1/7 (1.5%) while sec-GBM showed IDH1 expression in 6/7 (85.7%). PA and EPEN did not react with anti-IDH1 antibody. DA  and GBM showed positive correlation with p53, but IDH1 and EGFR coexpression was  rare. Conclusion : Monoclonal antibody to IDH1 (R132) is a useful and less-labor-intensive method to detect mutations in gliomas. IDH1 is a useful immunohistochemical marker to differentiate reactive gliosis from low-grade astrocytoma, has potential as an independent prognostic marker and also helps in  distinguishing primary from secondary GBM. Its sensitivity and specificity need to be assessed by simultaneous sequencing and its validation on clinically annotated samples.

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[747]

TÍTULO / TITLE:  - The study of CD117 expression in glial tumors and its relationship with the tumor-type and grade.

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

REVISTA / JOURNAL:  - J Res Med Sci. 2012 Feb;17(2):159-63.

AUTORES / AUTHORS:  - Mahzouni P; Jafari M

INSTITUCIÓN / INSTITUTION:  - Associate Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: CD117 is a thyrosin kinase receptor encoded by c-kit proto-oncogene.  It is expressed during normal development in some tissues and also in a subset of neoplasia especially gastrointestinal stromal tumors (GISTs). Treatment with thyrosin kinase inhibitors (e.g., Imatinib) is useful in CD117- positive GISTs. The goal of this study is to investigate the expression of CD117 in glial tumors  as a potential diagnostic marker and target for therapy. MATERIALS AND METHODS: in this descriptive-analytical study, paraffin- embedded tissue blocks from 50 cases of glial tumors (various histological types and grades) were selected in a  convenience sampling for the CD117 immunhistochemical study including expression  of the marker, staining intensity, and percentage of the stained cells. The results were analyzed by Chi-square and Mann-Whitney tests. RESULTS: CD117 expression was detected in about 76% of glial tumors but the frequency of the expression showed no statistically significant relationship with the tumor type (P = 0.829). Although CD117 immunoreactivity was more frequent in high-grade tumors (84%) compared to the low-grade ones (68%), no statistically significant relationship was found between the CD117 expression and grade of the tumor (P = 0.09). Staining intensity and percentage of stained cells in high-grade tumors were significantly more than in low-grade tumors (P values of 0.046 and 0.023, respectively). CONCLUSION: according to the statistically significant difference  in the staining intensity and percentage of the stained cells between the low-grade and high-grade glial tumors, these two parameters may be useful for making distinction between various grades of these tumors. Moreover, according to the prominent expression of CD117 in high-grade gliomas, these tumors may be potential candidates for treatment with thyrosin kinase inhibitors.

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[748]

TÍTULO / TITLE:  - Subtyping glioblastoma by combining miRNA and mRNA expression data using compressed sensing-based approach.

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

REVISTA / JOURNAL:  - EURASIP J Bioinform Syst Biol. 2013 Jan 14;2013(1):2.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1687-4153-2013-2

AUTORES / AUTHORS:  - Tang W; Duan J; Zhang JG; Wang YP

RESUMEN / SUMMARY:  - ABSTRACT: In the clinical practice, many diseases such as glioblastoma, leukemia, diabetes, and prostates have multiple subtypes. Classifying subtypes accurately using genomic data will provide individualized treatments to target-specific disease subtypes. However, it is often difficult to obtain satisfactory classification accuracy using only one type of data, because the subtypes of a disease can exhibit similar patterns in one data type. Fortunately, multiple types of genomic data are often available due to the rapid development of genomic techniques. This raises the question on whether the classification performance can significantly be improved by combining multiple types of genomic data. In this article, we classified four subtypes of glioblastoma multiforme (GBM) with multiple types of genome-wide data (e.g., mRNA and miRNA expression) from The Cancer Genome Atlas (TCGA) project. We proposed a multi-class compressed sensing-based detector (MCSD) for this study. The MCSD was trained with data from TCGA and then applied to subtype GBM patients using an independent testing data.  We performed the classification on the same patient subjects with three data types, i.e., miRNA expression data, mRNA (or gene expression) data, and their combinations. The classification accuracy is 69.1% with the miRNA expression data, 52.7% with mRNA expression data, and 90.9% with the combination of both mRNA and miRNA expression data. In addition, some biomarkers identified by the integrated approaches have been confirmed with results from the published literatures. These results indicate that the combined analysis can significantly  improve the accuracy of classifying GBM subtypes and identify potential biomarkers for disease diagnosis.

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[749]

TÍTULO / TITLE:  - CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration.

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

REVISTA / JOURNAL:  - Mol Cancer Res. 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0498

AUTORES / AUTHORS:  - Kochanek DM; Wells DG

INSTITUCIÓN / INSTITUTION:  - Cellular & Developmental Biology, Yale University, New Haven, Connecticut.

RESUMEN / SUMMARY:  - Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an mRNA-binding  protein present in both neurons and glia. CPEB1 is capable of both repressing mRNA translation and activating it depending upon its phosphorylation state. CPEB1-bound mRNAs are held in translational dormancy until CPEB1 is phosphorylated, leading to the cytoplasmic polyadenylation of the bound mRNA that triggers translation. Here, we show that CPEB1 can bind to and regulate translation of the mRNA-encoding metadherin (MTDH, also known as AEG-1 and Lyric) in the rat glioblastoma cell line CNS1. MTDH/AEG-1 is being revealed as a critical signaling molecule in tumor progression, playing roles in invasion, metastasis, and chemoresistance. By using a mutant of CPEB1 that cannot be phosphorylated (thereby holding target mRNAs in translational arrest), we show that inhibiting CPEB1-mediated translation blocks MTDH/AEG-1 expression in vitro  and inhibits glioblastomas tumor growth in vivo. CPEB1-mediated translation is likely to impact several signaling pathways that may promote tumor progression, but we present evidence suggesting a role in directed cell migration in glioblastoma cells. In addition, reporter mRNA containing CPEB1-binding sites is  transported to the leading edge of migrating cells and translated, whereas the same mRNA with point mutations in the binding sites is synthesized perinuclearly. Our findings show that CPEB1 is hyperactive in rat glioblastoma cells and is regulating an important cohort of mRNAs whose increased translation is fueling the progression of tumor proliferation and dispersal in the brain. Thus, targeting CPEB1-mediated mRNA translation might be a sound therapeutic approach.  Mol Cancer Res; 1-12. ©2012 AACR.

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[750]

TÍTULO / TITLE:  - Immunohistochemical Expression of ErbB2 in Adamantinomatous Craniopharyngiomas: A Possible Target for Immunotherapy.

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

REVISTA / JOURNAL:  - Turk Neurosurg. 2013;23(1):55-60. doi: 10.5137/1019-5149.JTN.6706-12.1.

            ●● Enlace al texto completo (gratuito o de pago) 5137/1019-5149.JTN.6706-12.1

AUTORES / AUTHORS:  - Zuhur SS; Tanik C; Erol RS; Musluman AM; Kabukcuoglu F; Altuntas Y

INSTITUCIÓN / INSTITUTION:  - Sisli Etfal Training and Research Hospital, Department of Endocrinology and Metabolism, Istanbul, Turkey.

RESUMEN / SUMMARY:  - AIM: To determine the immunohistochemical expression of ErbB2 in adamantinomatous craniopharyngiomas (ACP) and to assess its relationship with nuclear expression of beta-catenin in surgically resected human ACP tissue sections and to estimate  whether these tumors could be candidates for anti-ErbB2 therapy. MATERIAL and METHODS: The ErbB2 and beta-catenin immunostaining was performed on paraffin embedded tissue sections of 20 ACP using avidin-biotin-peroxidase complex method. ErbB2 immunoreactivity was interpreted according to the American Society of Clinical Oncology/ College of American Pathologists criterions for breast carcinoma. RESULTS: Foci of nuclear reactivity for beta-catenin was observed in all ACP tissue specimens mainly concentrated in whorl like arrays of the epithelial cells. Two (10%) of the cases were score 3+ for ErbB2 as demonstrated  by strong complete membrane staining. However, the localization of 3+ ErbB2 cells was different from those with nuclear beta-catenin immunoreactivity. CONCLUSION:  Our preliminary data demonstrate score 3+ staining for ErbB2 in 10% of ACP and different localization of 3+ ErbB2 cells and cells with nuclear beta-catenin immunoreactivity. However, because of the small number of cases, further studies  with larger samples should be conducted to verify and validate our preliminary data and to determine the effect of ErbB2 protein in ACP cell growth, survival and differentiation.

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[751]

TÍTULO / TITLE:  - Expression and Distribution Characteristics of Human Ortholog of Mammalian Enabled (hMena) in Glioma.

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

REVISTA / JOURNAL:  - Chin J Cancer Res. 2011 Dec;23(4):312-6. doi: 10.1007/s11670-011-0312-z.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11670-011-0312-z

AUTORES / AUTHORS:  - Dong XT; Yang XJ; Wang HM; Wang W; Yu L; Zhang B; Yu SP; Ming HL

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin  Neurological Institute, Tianjin 300052, China.

RESUMEN / SUMMARY:  - OBJECTIVE: To investigate the utility of hMena, a family of enabled/vasodilator-stimulated phosphoprotein (Ena/VASP), we sought to characterize the expression profile and distribution characteristics of hMena in  a large panel of glioma samples and determine whether hMena expression levels might correlate with the pathological grade of glioma. METHODS: Sixty-five specimens of glioma with different pathological grades and five control brain tissues were collected. In 6 of the 21 glioblastoma patients, multi-specimens were obtained respectively from the main tumor mass, the junction zone between the tumor and the normal tissue, and adjacent brain tissue 1.5 cm away from the tumor boundary under assistance of neuronavigation system during the operation. Immunohistochemistry was used to detect the expression and distribution characteristics of hMena. hMena expression was analyzed by Western blot in 20 specimens. RESULTS: The hMena expression was negative in control brain tissue but positive in different grades of glioma. The expression rate of hMena was positively correlated with the increasing grade of the World Health Orgnization (WHO) classification (r(s)=0.682, P=0.000). hMena was located in cytoplasm. Positive cells only distributed around the vessels within the tumor mass in low grade glioma, while in high grade glioma, these cells were able to be detected not only in the tumor but also in the boundary zone and adjacent brain parenchyma. In the tumor mass, hMena expressed highly and diffusedly. In the junction zone, hMena positive cells formed radiolitic pattern around the vessels. In adjacent brain parenchyma, single positive cell was scattered. hMena expression was markedly elevated in Grade III and IV glioma compared with Grade II and I. CONCLUSION: Our data suggested that the expression of hMena is closely  related to malignant grade of glioma. hMena can label the migrating cells, and indicate the migrating path of glioma cells from the tumor to adjacent tissue along with the vascular basement membranes and tracts of white matter.

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[752]

TÍTULO / TITLE:  - Extrapontine myelinolysis of osmotic demyelination syndrome in a case of postoperative suprasellar arachnoid cyst.

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

REVISTA / JOURNAL:  - Case Report Med. 2012;2012:679257. doi: 10.1155/2012/679257. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/679257

AUTORES / AUTHORS:  - Zhao P; Zong X; Wang X; Zhang Y

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.

RESUMEN / SUMMARY:  - The extrapontine myelinolysis of osmotic demyelination syndrome (ODS) is a well-known but uncommon disorder of the central nervous system. Although the mechanism is not fully understood and the treatment is controversial, hyponatremia is probably considered to be the main pathophysiological basis. There are few reports of ODS caused by a sellar lesion. Here we present a case of suprasellar arachnoid cyst that developed extrapontine myelinolysis of ODS after  a neuroendoscopic treatment procedure. It is suggested that patients with suprasellar lesions are at risk of developing extrapontine myelinolysis of ODS and correction of hyponatremia in these cases should be closely monitored.

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[753]

TÍTULO / TITLE:  - Experience with 5-aminolevulinic Acid in fluorescence-guided resection of a deep  sylvian meningioma.

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

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2012 Dec;52(6):558-60. doi: 10.3340/jkns.2012.52.6.558. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2012.52.6.558

AUTORES / AUTHORS:  - Chae MP; Song SW; Park SH; Park CK

INSTITUCIÓN / INSTITUTION:  - University of Melbourne, Melbourne, Victoria, Australia.

RESUMEN / SUMMARY:  - The 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a useful intraoperative marker for the diagnosis and the detection of various malignancies, but its use in meningioma is only reported infrequently. In meningioma, a complete resection of the tumor mass is crucial for the prevention  of recurrence and postoperative morbidities. Deep sylvian meningioma is a rare type of meningioma where complete tumor removal is complicated by its deep anatomical location and close involvement with the middle cerebral artery. From our experience, 5-ALA-mediated fluorescence facilitated a safe excision whilst preserving critical neurovascular structures. To our best knowledge, this is first report from use of 5-ALA in a deep sylvian meningioma.

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[754]

TÍTULO / TITLE:  - Prognosis by tumor location for pediatric spinal cord ependymomas.

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

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2012 Dec 21.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.PEDS12292

AUTORES / AUTHORS:  - Oh MC; Sayegh ET; Safaee M; Sun MZ; Kaur G; Kim JM; Aranda D; Molinaro AM; Gupta N; Parsa AT

INSTITUCIÓN / INSTITUTION:  - Departments of Neurological Surgery.

RESUMEN / SUMMARY:  - Object Ependymoma is a common CNS tumor in children, with spinal cord ependymomas making up 13.1% of all ependymomas in this age group. The clinical features that  affect prognosis in pediatric spinal cord ependymomas are not well understood. A  comprehensive literature review was performed to determine whether a tumor location along the spinal cord is prognostically significant in children undergoing surgery for spinal cord ependymomas. Methods A PubMed search was performed to identify all papers that contained data on patients with spinal cord ependymomas. Only pediatric patients (age < 18 years) who underwent resection with a clearly reported tumor location were included in the analysis. Myxopapillary tumors were excluded from study. Tumor location was subdivided into 6 regions: cervicomedullary, cervical, cervicothoracic, thoracic, thoracolumbar,  and conus medullaris. Kaplan-Meier survival and Cox regression analyses were performed to determine the effects of tumor location on progression-free survival (PFS) and overall survival (OS). Results Fifty-eight patients who underwent resection of spinal cord ependymomas were identified. Ependymomas were located all along the spinal cord but occurred with the highest frequency in the cervical region (29.3%). Progression-free survival was significantly better in patients with tumors arising in the upper portion of the spinal cord (p = 0.031), which remained significant in the multivariate Cox regression analysis (p < 0.05). Moreover, OS was significantly better in patients with upper spinal cord ependymomas than in those harboring ependymomas in the lower spinal cord (p = 0.048). Conclusions Although more common in adults, spinal ependymomas can occur  anywhere along the spinal cord in the pediatric population; however, tumors occurring in the lower half of the spinal cord carry a worse prognosis with shorter PFS and OS. By comparison, ependymomas in the upper spinal cord recur later and less frequently, with little or no mortality in this patient group.

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[755]

TÍTULO / TITLE:  - Mucoepidermoid carcinoma in the external auditory canal: a case report.

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

REVISTA / JOURNAL:  - Cancer Res. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.

            ●● Enlace a la Editora de la Revista http://cancerres.aacrjournals.org/ 

            ●● Cita: Cancer Research: <> Treat. 2012 Dec;44(4):275-8. doi: 10.4143/crt.2012.44.4.275. Epub 2012 Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 4143/crt.2012.44.4.275

AUTORES / AUTHORS:  - Chung JH; Lee SH; Park CW; Tae K

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology-Head and Neck Surgery, Hanyang University School of  Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - Mucoepidermoid carcinoma in the external auditory canal is extremely rare. Strategies used for treatment of mucoepidermoid carcinoma remain controversial. We present a case of mucoepidermoid carcinoma of the external auditory canal. The patient underwent lateral temporal bone resection and the surgical defect was obliterated with temporal muscle. He is currently disease-free, four years after  surgery. Proper diagnostic measures and strategy for treatment of mucoepidermoid  carcinoma are discussed.

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[756]

TÍTULO / TITLE:  - Freiburg Neuropathology Case Conference: A Partially Calcified, Dura-based Tumour of the Frontal Lobe.

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

REVISTA / JOURNAL:  - Clin Neuroradiol. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-013-0199-9

AUTORES / AUTHORS:  - Taschner CA; Staszewski O; Jabbarli R; Keuler A; Prinz M

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany, Christian.taschner@uniklinik-freiburg.de.

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[757]

TÍTULO / TITLE:  - Intracranial cystic chondroma: a case report.

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

REVISTA / JOURNAL:  - J Med Case Rep. 2012 Dec 28;6(1):432. doi: 10.1186/1752-1947-6-432.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-6-432

AUTORES / AUTHORS:  - Uddin MM; Ashraf J; Memon AA; Ali J

INSTITUCIÓN / INSTITUTION:  - Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. akhtar.amin@live.com.

RESUMEN / SUMMARY:  - ABSTRACT: INTRODUCTION: Intracranial chondromas are rare benign tumors with an incidence of 0.2% to 0.3% of all intracranial tumors. This is the first case of an intracranial chondroma reported from Pakistan. CASE PRESENTATION: We report a  case of a 23-year-old Asian man presenting with intracerebral chondroma of the left frontal lobe, which was eroding the dura matter. The intracranial chondroma  was completely removed by surgery. CONCLUSION: Intracranial chondromas are rare benign cartilaginous tumors. Through this case presentation we have discussed the diagnostic procedures, radiological and pathological findings. The purpose of presenting such a rare case is to develop awareness among clinicians and medical  students and to highlight the requirement of immediate actions to ensure proper management of such cases.

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[758]

TÍTULO / TITLE:  - A Neuro-Behcet’s Case Operated with the Intracranial Mass Misdiagnosis.

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

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2012 Nov;52(5):488-90. doi: 10.3340/jkns.2012.52.5.488. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2012.52.5.488

AUTORES / AUTHORS:  - Tokgoz OS; Akpinar Z; Guney F; Seyithanoglu A

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Meram Medical Faculty, Konya University, Konya, Turkey.

RESUMEN / SUMMARY:  - Behcet’s disease (BD) is an inflammatory systemic disorder with oral and genital  ulcers, as well as ophthalmologic and cutaneous symptoms. Neurological manifestations in BD represent between 2.2% to 50% of the cases. The 25-year-old  male patient, diagnosed with BD three years earlier, was admitted to our clinic with complaints of recurrent headaches. Tumor-like-parenchimal involvement was detected on a cranial magnetic resonance imaging. The lesion was removed surgically and then he suffered from right hemiparesis and epilepsy. Pathological examination of the lesion noted a demyelinating non-tumoural etiology. A neuro-Behget’s case with parenchymal involvement has been examined in light of the literature, in terms of a tumor and a demyelinating disease differential diagnosis.

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[759]

TÍTULO / TITLE:  - Repair of Cerebrospinal Fluid Fistula from an Invasive Skull Base Prolactinoma Using a Septal Mucosal Vascularized Flap: Technical Case Report.

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

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Jan 11.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1331386

AUTORES / AUTHORS:  - Little AS

INSTITUCIÓN / INSTITUTION:  - Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, United States.

RESUMEN / SUMMARY:  - Repair of spontaneous cerebrospinal fluid (CSF) fistulas in patients with invasive skull base prolactinomas represents a surgical challenge because of the  many sites of potential leak around the tumor and the possibility of developing additional sites of leak as the tumor regresses on dopamine agonist therapy. Little has been published on effective methods for treating this problem. In this case, a vascularized nasoseptal flap was used to repair a spontaneous CSF leak in a 31-year-old male with an invasive prolactinoma who was commenced on dopamine agonist therapy. The patient underwent successful multilayer repair of the fistula with a nasoseptal vascularized flap and abdominal rectus fascia. After 3  months of follow-up, he has had no CSF leak. CSF fistulas caused by skull base prolactinomas can be repaired successfully using a vascularized nasoseptal flap.  Long-term follow-up will determine the durability of this repair technique.

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[760]

TÍTULO / TITLE:  - Tumor or Hematoma? : An Unusual Case of an Extradural Lesion of the Lumbar Spine.

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

REVISTA / JOURNAL:  - Clin Neuroradiol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-012-0187-5

AUTORES / AUTHORS:  - Neidert MC; Prommel P; Schuknecht B; Surucu O

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland, marian.neidert@usz.ch.

RESUMEN / SUMMARY:  - PURPOSE: Spinal epidural hematoma is a rare clinical entity. We present a case of atypical contrast enhancement pattern in a chronic epidural hematoma of the lumbar spine mimicking an extradural tumor. CASE REPORT: A 76-year-old man on treatment with oral anticoagulants presented with a 1-month history of lower back pain radiating into his right upper thigh accompanied by spinal claudication. Preoperative MRI showed a posterior epidural lesion compressing the cauda equina  with almost homogeneous contrast enhancement. Surgery was performed under the presumptive diagnosis of spinal extradural neoplasm. Intraoperative and histological findings were consistent with a chronic spinal epidural hematoma. Postoperatively, the patient had instant relief of his symptoms. CONCLUSION: Chronic spinal epidural hematoma may resemble an extradural tumor, requiring surgery for histological confirmation and decompression.

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[761]

TÍTULO / TITLE:  - Supratentorial Hemangioblastomas: Three Case Reports and Review of the Literature.

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

REVISTA / JOURNAL:  - Clin Neuroradiol. 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-012-0183-9

AUTORES / AUTHORS:  - She DJ; Xing Z; Liu Y; Cao DR

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, First Affiliated Hospital of Fujian Medical University,  20 Cha-Zhong Road, 350005, Fuzhou, Fujian, P.R. China, fyyingxiang@yahoo.com.cn.

RESUMEN / SUMMARY:  - Hemangioblastoma (HBL) within the central nervous system is a benign vascular neoplasm that usually occurs in the cerebellum. Supratentorial occurrence of HBL  is an extremely rare event. Till date, approximately 129 cases of supratentorial  HBL have been reported in the literature. Here, we present three new cases of supratentorial hemangioblatomas, one of which was found to have the lesions in a  unique location of the choroidal fissure. The clinical, histopathological, and neuroradiological characteristics, as well as management of this rare disease are discussed with a review of the pertinent literature.

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[762]

TÍTULO / TITLE:  - Glioblastoma multiforme with subcutaneous metastases, case report and literature  review.

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

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2012 Nov;52(5):484-7. doi: 10.3340/jkns.2012.52.5.484. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2012.52.5.484

AUTORES / AUTHORS:  - Guo L; Qiu Y; Ge J; Zhou D

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School  of Medicine, Shanghai, China.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is the most common primary brain tumor and the most malignant astrocytoma in adults, with rare extra-cranial metastases, especially for subcutaneous metastases. It could be easily misdiagnosed as primary subcutaneous tumor. In this report, we describe a patient with pontine GBM who developed a subcutaneous swelling at the ipsilateral posterior cervical region 8  months after operation, and the pathological and immunocytochemical examination carry the same characteristics as the primary intracranial GBM cells, which defined it as subcutaneous metastasis. GBM with subcutaneous metastasis is extremely rare, and knowledge of a prior intracranial GBM, pathological examinations and immunocytochemical tests with markers typically expressed by GBM are of vital importance for the diagnosis of GBM metastasis. Surgical resection of subcutaneous swelling, followed by chemotherapy and radiotherapy, could be the best strategy of treatment for the patients with GBM subcutaneous metastasis.

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[763]

TÍTULO / TITLE:  - A posterior petrous meningioma with recurrent vertigo.

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

REVISTA / JOURNAL:  - Clin Exp Otorhinolaryngol. 2012 Dec;5(4):234-6. doi: 10.3342/ceo.2012.5.4.234. Epub 2011 Sep 15.

            ●● Enlace al texto completo (gratuito o de pago) 3342/ceo.2012.5.4.234

AUTORES / AUTHORS:  - Choi SJ; Lee JB; Bae JH; Yoon JH; Lee HJ; Kim CH; Park K; Choung YH

INSTITUCIÓN / INSTITUTION:  - Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University College of Medicine, Daejeon, Korea.

RESUMEN / SUMMARY:  - Meningioma’s account for around 15% of all primary brain tumors with some 10% of  meningiomas arising in the posterior fossa. In rare cases, a meningioma can form  around the endolymphatic sac. When formed in the posterior fossa, meningioma tumors can produce vague, non-specific vertiginous symptoms. Research has observed that a subset of these lesions could produce symptoms indistinguishable  from those of Meniere’s disease. Therefore, we described the clinical features of a case of posterior petrous meningioma with recurrent vertigo as well as the substantial resolution of symptoms after tumor removal via transmastoid approach.

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[764]

TÍTULO / TITLE:  - Cranial aspergilloma masquerading as meningioma.

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 http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 9;2013. pii: bcr2012008118. doi: 10.1136/bcr-2012-008118.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008118

AUTORES / AUTHORS:  - Verma R; Singh P; Kumar A; Paliwal VK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

RESUMEN / SUMMARY:  - Cranial aspergillosis may present as meningitis, cerebral abscess, cerebral infarcts/haemorrhages or extra-axial mass. Extra-axial cranial aspergilloma may mimic meningioma owing to mass-like characteristics and intense contrast enhancement on MRI there by delaying the diagnosis and further worsening the already bad prognosis in these patients. We present a 45-year-old gentleman who presented with signs of raised intracranial hypertension, secondary optic atrophy and a contrast-enhancing mass arising from the planum sphenoidale. Postoperatively, mass was diagnosed as aspergilloma on histopathology and culture. Despite antifungal treatment, patient could not be saved due to large artery infarcts in the immediate postoperative period. We discuss the clinical and MRI features that could help to have sufficient and early suspicion of fungal aetiology in these patients.

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[765]

TÍTULO / TITLE:  - Neurocysticercosis, meningioma, and silent corticotroph pituitary adenoma in a 61-year-old woman.

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

REVISTA / JOURNAL:  - Case Report Pathol. 2012;2012:340840. doi: 10.1155/2012/340840. Epub 2012 Dec 30.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/340840

AUTORES / AUTHORS:  - Ramirez Mdel P; Restrepo JE; Syro LV; Rotondo F; Londono FJ; Penagos LC; Uribe H; Horvath E; Kovacs K

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia.

RESUMEN / SUMMARY:  - We report here the case of a 61-year-old woman who presented with hydrocephalus and cystic and solid lesions in sella turcica, suprasellar areas, and third ventricle. After ventriculoperitoneal shunt she developed cognitive changes and the cystic lesions enlarged. Magnetic resonance imaging (MRI) demonstrated multiple cysts and a solid lesion in the sella and around the anterior clinoid process. With diagnosis of neurocysticercosis she underwent craniotomy. Pathologic examination documented two different lesions: viable and dead cysticerci with inflaming infiltration and a left anterior clinoidal meningioma.  At the second surgery, six weeks later via transnasal transsphenoidal approach a  silent corticotroph pituitary adenoma was removed which was studied by histology, immunohistochemistry, and electron microscopy. To our knowledge, the occurrence of these three different lesions in the sellar area was not described before.

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[766]

TÍTULO / TITLE:  - Neuro-oncology: Anaplastic oligodendrogliomas-value of early chemotherapy.

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

REVISTA / JOURNAL:  - Nat Rev Neurol. 2012 Dec 11;9(1):7-8. doi: 10.1038/nrneurol.2012.248. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2012.248

AUTORES / AUTHORS:  - Ducray F; Idbaih A

INSTITUCIÓN / INSTITUTION:  - Service de Neuro-oncologie, Hospices Civils de Lyon, Hopital Neurologique, F-69677 Bron, France.

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[767]

TÍTULO / TITLE:  - CD5-Positive Diffuse Large B Cell Lymphoma Infiltrating the Central Nervous System Presenting Guillain-Barre-Like Syndrome after Chemotherapy.

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

REVISTA / JOURNAL:  - J Clin Exp Hematop. 2012;52(3):199-204.

AUTORES / AUTHORS:  - Machida H; Shinohara T; Hatakeyama N; Okano Y; Nakano M; Tobiume M; Naruse K; Iwahara Y; Ogushi F

INSTITUCIÓN / INSTITUTION:  - Division of Pulmonary Medicine National Hospital Organization National Kochi Hospital.

RESUMEN / SUMMARY:  - An 83-year-old woman was admitted to our hospital with abdominal pain. Examination revealed mediastinal lymphoadenopathy, hepatosplenomegaly, and infiltration of abnormal cells into the bone marrow with hemophagocytosis, and CD5-positive diffuse large B cell lymphoma was diagnosed. Chemotherapy was administered and progressive weakness of the limbs, resembling a Guillain-Barre-like syndrome, subsequently appeared. Cerebrospinal fluid examination indicated lymphoma cell infiltration. Although immune globulin and steroid therapies were not effective, intrathecal injection of methotrexate, predonisolone, and cytarabine improved these symptoms. Subsequent to chemotherapy, cell surface antigen changes were observed in the cerebrospinal fluid relative to those in bone marrow. [J Clin Exp Hematopathol 52(3) : 199-204, 2012].

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[768]

TÍTULO / TITLE:  - Rapid reduction with cystic transformation of invasive giant prolactinoma following short term low dose cabergoline.

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

REVISTA / JOURNAL:  - Indian J Endocrinol Metab. 2012 Nov;16(6):1048-51. doi: 10.4103/2230-8210.103041.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2230-8210.103041

AUTORES / AUTHORS:  - Dutta D; Ghosh S; Mukhopadhyay S; Chowdhury S

INSTITUCIÓN / INSTITUTION:  - Department of Endocrinology and Metabolism, IPGMER and SSKM Hospital, 244 AJC Bose Road, Kolkata, India.

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[769]

TÍTULO / TITLE:  - Diagnostic Value of Brain Tumor Neuroendoscopic Biopsy and Correlation with Open  Tumor Resection.

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

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1320032

AUTORES / AUTHORS:  - Chrastina J; Novak Z; Riha I; Hermanova M; Feitova V

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery MF MU, Faculty Hospital St. Ann Brno, Czech Republic.

RESUMEN / SUMMARY:  - Background The risks of stereotactic biopsy are increased not only in tumors located in the vicinity of vascular structures, but also in cystic, intraventricular, and periventricular lesions. The use of neuroendoscopy for cystic, intraventricular, or periventricular brain tumors is particularly advantageous because of the possibility of biopsy and immediate hemostasis under  direct vision. Neuroendoscopy provides the possibility of controlling tumor-associated obstructive hydrocephalus by means of endoscopic third ventriculostomy or septostomy. The literature gives good evidence for the diagnostic benefits of neuroendoscopic biopsy. The correlation of the histology obtained by neuroendoscopic biopsy and subsequent surgical resection may allow the evaluation of the validity of diagnostic neuroendoscopic biopsy.Materials and Methods Between 2003 and 2010, 23 patients with suspected cystic brain tumor (12  males; age range, 21-75 years; mean age, 49.7 years; and 11 females; age range, 22-76 years; mean age, 59.1 years) and 35 patients with intraventricular or periventricular brain tumors (19 males; age range, 6-80 years; mean age, 43.9 years; and 16 females; age range, 11-78 years; mean age, 46.2 years) underwent navigated neuroendoscopic biopsy.Results Diagnostic samples were obtained in all  cystic tumors and in 94.7% of intraventricular or periventricular tumors. Tumor resection after neuroendoscopic biopsy was performed in seven patients with cystic tumors. The results of the histological analysis of samples taken during endoscopic biopsy and surgical resection were identical in five of these patients (70.1%). Four patients with intraventricular or periventricular tumors underwent  tumor resection after neuroendoscopic biopsy. The histological results of neuroendoscopic biopsy and tumor resection were identical in three patients (75%). Neuroendoscopic biopsy was performed in six patients with expansive pseudocyst after tumor resection and oncological therapy. The results of the neuroendoscopic biopsy matched the results of open surgery in four patients (66%). In the two remaining patients, there was a difference in tumor grading.Conclusion The diagnostic accuracy of neuroendoscopic biopsy samples can  be compared with the results of stereotactic biopsy. The histological results of  endoscopically taken biopsy samples and the final histological results obtained during open surgery correlate in the majority of patients, and underlines the high diagnostic validity of neuroendoscopic biopsy.

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[770]

TÍTULO / TITLE:  - Hemodynamic response imaging: a potential tool for the assessment of angiogenesis in brain tumors.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(11):e49416. doi: 10.1371/journal.pone.0049416. Epub 2012 Nov 27.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0049416

AUTORES / AUTHORS:  - Ben Bashat D; Artzi M; Ben Ami H; Aizenstein O; Blumenthal DT; Bokstein F; Corn BW; Ram Z; Kanner AA; Lifschitz-Mercer B; Solar I; Kolatt T; Palmon M; Edrei Y; Abramovitch R

INSTITUCIÓN / INSTITUTION:  - Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. dafnab@tlvmc.gov.il

RESUMEN / SUMMARY:  - Blood oxygenation level dependence (BOLD) imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI)). Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors) and one with atypical-meningioma. Maps of percent signal intensity changes (DeltaS) during hyperoxia (carbogen; 95%O2+5%CO2) and hypercapnia (95%air+5%CO2) challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2) were calculated. VRM values were measured in white matter (WM) and gray matter (GM) areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3), increased response to carbogen was detected with substantially increased VRM response (compared to threshold values) within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors.

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[771]

TÍTULO / TITLE:  - Correlation of microrna-372 upregulation with poor prognosis in human glioma.

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

REVISTA / JOURNAL:  - Diagn Pathol. 2013 Jan 8;8:1. doi: 10.1186/1746-1596-8-1.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-1

AUTORES / AUTHORS:  - Li G; Zhang Z; Tu Y; Jin T; Liang H; Cui G; He S; Gao G

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tangdu hospital, the Fourth Military Medical University, No, 569, Xinsi Road, Xi’an, 710038, China. heshimingbrain@yahoo.com.cn.

RESUMEN / SUMMARY:  - ABSTRACT: MicroRNA-372 (miR-372) acts as either an oncogenic miRNA or an anti-oncomiR in various human malignancies. However, its roles in gliomas have not been elucidated. To address this problem, we here detected miR-372 expression in human gliomas and non-neoplastic brain tissues by real-time quantitative RT-PCR assay. The association of miR-372 expression with clinicopathological factors or prognosis of glioma patients was also statistically analyzed. As the results, miR-372 expression levels were significantly upregulated in glioma tissues compared to the corresponding non-neoplastic brain tissues (P<0.001). In  addition, the high miR-372 expression was significantly associated with the advanced pathological grade (P=0.008) and the low Karnofsky performance score (KPS) of glioma patients (P=0.01). Moreover, the overall survival of patients with high miR-372 expression was dramatically shorter than those with low miR-372 expression (P<0.001). Furthermore, multivariate Cox regression analysis indicated that miR-372 expression was an independent prognostic factor for glioma patients  (P=0.008). More importantly, subgroup analyses according to tumor pathological grade revealed that the cumulative overall survival of glioma patients with advanced pathological grades was significantly worse for high miR-372 expression  group than for low miR-372 expression group (P<0.001), but no significant difference was found for patients with low pathological grades (P=0.08). Taken together, these data offer the convincing evidence for the first time that miR-372 may act as an oncogenic miRNA in gliomas and represent a potential regulator of aggressive development and a candidate prognostic marker for this malignancy, especially for advanced tumors with high pathological grades. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707761328850011.

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[772]

TÍTULO / TITLE:  - A visual latent semantic approach for automatic analysis and interpretation of anaplastic medulloblastoma virtual slides.

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

REVISTA / JOURNAL:  - Med Image Comput Comput Assist Interv. 2012;15(Pt 1):157-64.

AUTORES / AUTHORS:  - Cruz-Roa A; Gonzalez F; Galaro J; Judkins AR; Ellison D; Baccon J; Madabhushi A; Romero E

INSTITUCIÓN / INSTITUTION:  - BioIngenium Research Group, Universidad Nacional de Colombia, Bogota, Colombia.

RESUMEN / SUMMARY:  - A method for automatic analysis and interpretation of histopathology images is presented. The method uses a representation of the image data set based on bag of features histograms built from visual dictionary of Haar-based patches and a novel visual latent semantic strategy for characterizing the visual content of a  set of images. One important contribution of the method is the provision of an interpretability layer, which is able to explain a particular classification by visually mapping the most important visual patterns associated with such classification. The method was evaluated on a challenging problem involving automated discrimination of medulloblastoma tumors based on image derived attributes from whole slide images as anaplastic or non-anaplastic. The data set  comprised 10 labeled histopathological patient studies, 5 for anaplastic and 5 for non-anaplastic, where 750 square images cropped randomly from cancerous region from whole slide per study. The experimental results show that the new method is competitive in terms of classification accuracy achieving 0.87 in average.

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[773]

TÍTULO / TITLE:  - Glioblastoma Multiforme versus Solitary Supratentorial Brain Metastasis: Differentiation Based on Morphology and Magnetic Resonance Signal Characteristics.

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

REVISTA / JOURNAL:  - Rofo. 2012 Nov 29.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330318

AUTORES / AUTHORS:  - Maurer MH; Synowitz M; Badakshi H; Lohkamp LN; Wustefeld J; Schafer ML; Wiener E

INSTITUCIÓN / INSTITUTION:  - Klinik fur diagnostische und interventionelle Radiologie, Charite - Universitatsmedizin Berlin.

RESUMEN / SUMMARY:  - Purpose: To evaluate the diagnostic potential of a multi-factor analysis of morphometric parameters and magnetic resonance (MR) signal characteristics of a mass and peritumoral area to distinguish solitary supratentorial metastasis from  glioblastoma multiforme (GBM). Materials and Methods: MR examinations of 51 patients with histologically proven GBM and 44 with a single supratentorial metastasis were evaluated. A large variety of morphologic criteria and MR signal  characteristics in different sequences were analyzed. The data were subjected to  logistic regression to investigate their ability to discriminate between GBM and  cerebral metastasis. Receiver-operating characteristic (ROC) analysis was used to select an optimal cut-off point for prediction and to assess the predictive value in terms of sensitivity, specificity, and accuracy of the final model. Results: The logistic regression analysis revealed that the ratio of the maximum diameter  of the peritumoral area measured on T2-weighted images (d T2) to the maximum diameter of the enhancing mass area (d T1, post-contrast) is the only useful criterion to distinguish single supratentorial brain metastasis from GBM with a lower ratio favoring GBM (accuracy 68 %, sensitivity 84 % and specificity 45 %).  The cut-off point for the ratio d T2/d T1 post-contrast was calculated as 2.35. Conclusion: Measurement of maximum diameters of the peritumoral area in relation  to the enhancing mass can be evaluated easily in the clinical routine to discriminate GBM from solitary supratentorial metastasis with an accuracy comparable to that of advanced MRI techniques.

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[774]

TÍTULO / TITLE:  - A Systematic Approach to the Diagnosis of Suspected Central Nervous System Lymphoma.

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

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Neurol. 2013 Jan 14:1-9. doi: 10.1001/jamaneurol.2013.606.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamaneurol.2013.606

AUTORES / AUTHORS:  - Scott BJ; Douglas VC; Tihan T; Rubenstein JL; Josephson SA

RESUMEN / SUMMARY:  - Central nervous system (CNS) lymphoma can present a diagnostic challenge. Currently, there is no consensus regarding what presurgical evaluation is warranted or how to proceed when lesions are not surgically accessible. We conducted a review of the literature on CNS lymphoma diagnosis (1966 to October 2011) to determine whether a common diagnostic algorithm can be generated. We extracted data regarding the usefulness of brain and body imaging, serum and cerebrospinal fluid (CSF) studies, ophthalmologic examination, and tissue biopsy  in the diagnosis of CNS lymphoma. Contrast enhancement on imaging is highly sensitive at the time of diagnosis: 98.9% in immunocompetent lymphoma and 96.1% in human immunodeficiency virus-related CNS lymphoma. The sensitivity of CSF cytology is low (2%-32%) but increases when combined with flow cytometry. Cerebrospinal fluid lactate dehydrogenase isozyme 5, beta2-microglobulin, and immunoglobulin heavy chain rearrangement studies have improved sensitivity over CSF cytology (58%-85%) but have only moderate specificity (85%). New techniques of proteomics and microRNA analysis have more than 95% specificity in the diagnosis of CNS lymphoma. Positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy remain the current standard for diagnosis. A combined stepwise systematic approach outlined here may facilitate an expeditious, comprehensive presurgical evaluation for cases of suspected CNS lymphoma.

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[775]

TÍTULO / TITLE:  - Paraganglioma with unusual presentation in parotid gland: A diagnostic dilemma in fine needle aspiration.

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

REVISTA / JOURNAL:  - Cytojournal. 2012;9:26. doi: 10.4103/1742-6413.105119. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1742-6413.105119

AUTORES / AUTHORS:  - Vora AA; Lai CK; Rao JY; Apple SK; Moatamed NA

INSTITUCIÓN / INSTITUTION:  - Address: Department of Pathology and Laboratory Medicine, David Geffen School of  Medicine at UCLA, Los Angeles, California, USA.

RESUMEN / SUMMARY:  - Paragangliomas (PGLs) are uncommon tumors. Although PGLs are known to occur in the head and neck region, especially the carotid body, middle ear, and larynx, involvement of the parotid glands has not been reported. In this article, we report the fine needle aspiration features of tumor in an unusual location, presenting as a parotid gland mass, submitted to pathology for initial diagnosis. The clinical presentation, cytomorphology, and the immunohistochemical features for the diagnosis are described. To our knowledge, this is the first case of paraganglioma of the parotid gland reported in the literature.

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[776]

TÍTULO / TITLE:  - Analysis of the BRAF(V600E) Mutation in Central Nervous System Tumors.

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

REVISTA / JOURNAL:  - Transl Oncol. 2012 Dec;5(6):430-6. Epub 2012 Dec 1.

AUTORES / AUTHORS:  - Myung JK; Cho H; Park CK; Kim SK; Lee SH; Park SH

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.

RESUMEN / SUMMARY:  - BRAF(V600E) mutations are involved in the development of melanoma, colon cancer,  and papillary thyroid carcinoma. These mutations are also found in primary brain  tumors at low to moderate frequencies. In this study, we investigated a series of brain tumors to determine the prevalence and associated clinicopathologic features of BRAF(V600E) mutations. By direct sequencing, we analyzed 223 brain tumors, including 51 gangliogliomas (GGs), 45 pilocytic astrocytomas (PAs), 12 pleomorphic xanthoastrocytomas (PXAs), 35 glioblastomas (GBs), 28 anaplastic astrocytomas (AAs), 44 oligodendroglial tumors (ODGs), 3 anaplastic oligoastrocytomas, and 5 diffuse astrocytomas. Thirty-six cases (16.1%) exhibited the BRAF(V600E) mutation, including 66.7% of PXAs, 23.5% of GGs, 15.6% of PAs, and 9.7% of the malignant gliomas; the latter included 14.3% of AAs, 8.6% of GBs, and 4.5% of ODGs. Copy number aberration at the 7q34 (BRAF) locus was found in 73.1% of PAs and 50% of PXAs. 9p Homozygous deletion was found in 66.7% of PXAs,  but it was not correlated with the BRAF(V600E) mutation. Patients’ age, sex, histologic grade, and progression-free survival were also not correlated with the BRAF(V600E) mutation. The BRAF(V600E) mutation in brain tumors did not have prognostic value but is certainly a diagnostic marker and therapeutic target, not only for pediatric low-grade gliomas but also for malignant gliomas, even though  the rate of mutation was not high. These results should be verified in a larger study with more cases and a longer follow-up period to overcome the limitation of small sample size.

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[777]

TÍTULO / TITLE:  - Microscopic endonasal access in pituitary surgery for tumour removal: eight-year  review of nasal complications.

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

REVISTA / JOURNAL:  - Head Neck Oncol. 2012 Nov 23;4(4):76.

AUTORES / AUTHORS:  - Raja H; Upile T; Jerjes W; Charakias N; Dewan V; Redfern RM

INSTITUCIÓN / INSTITUTION:  - Department of ENT, University Hospital Birmingham, UK. hemalraja@yahoo.co.uk.

RESUMEN / SUMMARY:  - INTRODUCTION: Trans-sphenoidal pituitary resection is possible via the traditional microscopic trans-septal approach or newer endoscopic transnasal approach. There is little in the literature to describe the nasal complications of the endonasal microscopic resection of pituitary lesions. We describe our experience of a single surgeon series and specifically the nasal complications from this method. METHOD: We preformed an 8-year retrospective case notes review  of transnasal endoscopic resections of 70 pituitary tumours. The data were collected on a proforma developed after consultation with a multidisciplinary team and validated independently by random interval analysis. RESULTS: Gross tumour removal rate was achieved in 77.1% (n = 54/70) cases by 24 months follow-up. One patient experienced a purulent nasal discharge, which required antibiotic intervention, whilst another had persistent maxillary nerve damage with paraesthesia. No patient experienced persistent epistaxis, septal perforation, anosmia, cerebrospinal fluid leaks or meningitis. Unfortunately, one patient succumbed from the consequences of internal carotid artery damage. CONCLUSION: Nasal complication rates from this method were low. A microscope can  be successfully used in an endonasal approach to the sella on its own. It can also be a useful adjunct to the endoscope and this skill should not be forgotten  by ear, nose and throat surgeons and neurosurgeons. It appears that the method of approaching the sella (transnasal vs trans-septal) rather than the instrument used helps to determine the rate of nasal complications.

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[778]

TÍTULO / TITLE:  - IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING FEATURES OF A CEREBRAL HEMANGIOBLASTOMA IN A DOG.

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

REVISTA / JOURNAL:  - Vet Radiol Ultrasound. 2012 Dec 12. doi: 10.1111/vru.12000.

            ●● Enlace al texto completo (gratuito o de pago) 1111/vru.12000

AUTORES / AUTHORS:  - Liebel FX; Summers BA; Lowrie M; Smith P; Garosi L

INSTITUCIÓN / INSTITUTION:  - Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, UK.

RESUMEN / SUMMARY:  - The magnetic resonance (MR) imaging features of a cerebral hemangioblastoma in a  9-year-old dog are described. Imaging revealed a well-defined contrast-enhancing  lesion of the rostral forebrain that appeared extraparenchymal. Histopathology of the excised mass showed clusters of small blood vessels interspersed with interstitial cells staining positive for neuronal specific enolase, features consistent with a cerebral hemangioblastoma; the mass also appeared intraparenchymal after further immunohistochemistry study. This neoplasm should be considered a rare differential diagnosis for intracranial masses in dogs.

 

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[779]

TÍTULO / TITLE:  - Injury-induced accumulation of glial cell line-derived neurotrophic factor in the rostral part of the injured rat spinal cord.

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

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Oct 19;13(10):13484-500. doi: 10.3390/ijms131013484.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms131013484

AUTORES / AUTHORS:  - Hara T; Fukumitsu H; Soumiya H; Furukawa Y; Furukawa S

INSTITUCIÓN / INSTITUTION:  - Laboratory of Molecular Biology, Gifu Pharmaceutical University, Daigaku-nishi 1-25-4, Gifu 501-1196, Japan. furukawa@gifu-pu.ac.jp.

RESUMEN / SUMMARY:  - The spinal cord of a 7-week-old female Wistar rat was hemi-transected at thoracic position 10 with a razor blade, and changes in glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expression levels in the spinal cord  were examined. GDNF protein and mRNA expression levels were evaluated by enzyme immunoassay and reverse transcription polymerase chain reaction, respectively. Although GDNF is distributed in the healthy spinal cord from 150 to 400 pg/g tissue in a regionally dependent manner, hemi-transection (left side) of the spinal cord caused a rapid increase in GDNF content in the ipsilateral rostral but not in the caudal part of the spinal cord. On the other hand, injury-induced  GDNF mRNA was distributed limitedly in both rostral and caudal stumps. These observations suggest the possibility that increased GDNF in the rostral part is responsible for the accumulation of GDNF that may be constitutively transported from the rostral to caudal side within the spinal cord. Although such local increase of endogenous GDNF protein may not be sufficient for nerve regeneration  and locomotor improvement, it may play a physiological role in supporting spinal  neurons including motoneurons.

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[780]

TÍTULO / TITLE:  - Network Pharmacology of Glioblastoma.

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

REVISTA / JOURNAL:  - Curr Drug Discov Technol. 2012 Dec 10.

AUTORES / AUTHORS:  - Aguda BD

INSTITUCIÓN / INSTITUTION:  - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

RESUMEN / SUMMARY:  - With increasing knowledge of cellular networks of gene and molecular interactions, and their alterations in GBM (glioblastoma multiforme), it is now possible to apply methods of Network Pharmacology (NP) to predict candidate drug  targets for this malignant brain tumor. NP requires the development of mathematical methods for network stability and perturbation analysis to identify  sensitive and druggable network components, as well as computational platforms to carry out in silico simulations of therapeutic interventions. This review focuses on the three most frequently deregulated GBM pathways involving membrane receptor tyrosine kinases, p53, and Rb. Structural features of these networks that may confound targeted therapies are discussed.

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[781]

TÍTULO / TITLE:  - The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction.

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

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):242-248. Epub 2012 Oct 22.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.982

AUTORES / AUTHORS:  - Yan YY; Bai JP; Xie Y; Yu JZ; Ma CG

INSTITUCIÓN / INSTITUTION:  - Institute of Brain Science, Shanxi Datong University, Datong, Shanxi 037009, P.R. China.

RESUMEN / SUMMARY:  - It has become evident that some of the natural or synthetic triterpenoids are natural proteasome inhibitors that have great potential for use in cancer prevention and treatment. However, the mechanisms for the antitumor activity of triterpenoids remain to be elucidated. In the present study, we investigated the  anticancer activities of a natural triterpenoid, pristimerin, and the signaling pathways affected. Pristimerin was found to possess potent cytotoxic effects, inducing apoptosis and inhibiting proliferation in U87 human glioma cells. Hoechst 33258 staining and Annexin V/PI double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, western blotting assay revealed that this apoptotic induction was associated with activated caspase-9, caspase-3, PARP cleavage and downregulation of Bcl-xl/Bax in a concentration-dependent manner. Pristimerin also increased the generation of reactive oxygen species and induced the subsequent release of cytochrome c from the mitochondria into the cytosol. Additionally, pristimerin downregulated EGFR protein expression and inhibited downstream signaling pathways in U87 cells. Our  results suggest that pristimerin may have potential as a new targeting therapeutic strategy in the treatment of EGFR-overexpressing gliomas.

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[782]

TÍTULO / TITLE:  - Microscopic Delineation of Medulloblastoma Margins in a Transgenic Mouse Model Using a Topically Applied VEGFR-1 Probe.

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

REVISTA / JOURNAL:  - Transl Oncol. 2012 Dec;5(6):408-14. Epub 2012 Dec 1.

AUTORES / AUTHORS:  - Wang D; Chen Y; Leigh SY; Haeberle H; Contag CH; Liu JT

INSTITUCIÓN / INSTITUTION:  - Department of Biomedical Engineering, State University of New York (SUNY) at Stony Brook, Stony Brook, NY.

RESUMEN / SUMMARY:  - The unambiguous demarcation of tumor margins is critical at the final stages in the surgical treatment of brain tumors because patient outcomes have been shown to correlate with the extent of resection. Real-time high-resolution imaging with the aid of a tumor-targeting fluorescent contrast agent has the potential to enable intraoperative differentiation of tumor versus normal tissues with accuracy approaching the current gold standard of histopathology. In this study,  a monoclonal antibody targeting the vascular endothelial growth factor receptor 1 (VEGFR-1) was conjugated to fluorophores and evaluated as a tumor contrast agent  in a transgenic mouse model of medulloblastoma. The probe was administered topically, and its efficacy as an imaging agent was evaluated in vitro using flow cytometry, as well as ex vivo on fixed and fresh tissues through immunohistochemistry and dual-axis confocal microscopy, respectively. Results show a preferential binding to tumor versus normal tissue, suggesting that a topically applied VEGFR-1 probe can potentially be used with real-time intraoperative optical sectioning microscopy to guide brain tumor resections.

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[783]

TÍTULO / TITLE:  - Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.

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

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54795. doi: 10.1371/journal.pone.0054795. Epub 2013 Jan 22.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054795

AUTORES / AUTHORS:  - Hernan Perez de la Ossa D; Lorente M; Gil-Alegre ME; Torres S; Garcia-Taboada E; Aberturas Mdel R; Molpeceres J; Velasco G; Torres-Suarez AI

INSTITUCIÓN / INSTITUTION:  - Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, España.

RESUMEN / SUMMARY:  - Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Delta(9)-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis  extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-epsilon-caprolactone microparticles as  an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1ratio1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

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[784]

TÍTULO / TITLE:  - Recapitulation of Tumor Heterogeneity and Molecular Signatures in a 3D Brain Cancer Model with Decreased Sensitivity to Histone Deacetylase Inhibition.

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

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e52335. doi: 10.1371/journal.pone.0052335. Epub 2012 Dec 18.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052335

AUTORES / AUTHORS:  - Smith SJ; Wilson M; Ward JH; Rahman CV; Peet AC; Macarthur DC; Rose FR; Grundy RG; Rahman R

INSTITUCIÓN / INSTITUTION:  - Children’s Brain Tumour Research Centre, School of Clinical Sciences, University  of Nottingham, Nottingham, United Kingdom.

RESUMEN / SUMMARY:  - INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor  aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS:  Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

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[785]

TÍTULO / TITLE:  - Brain cancer in 2012: Molecular characterization leads the way.

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

REVISTA / JOURNAL:  - Nat Rev Clin Oncol. 2013 Feb;10(2):69-70. doi: 10.1038/nrclinonc.2012.240. Epub 2013 Jan 8.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2012.240

AUTORES / AUTHORS:  - Stupp R; Hegi ME

INSTITUCIÓN / INSTITUTION:  - Division of Neurosurgery, Department of Clinical Neurosciences, University of Lausanne Hospital (CHUV), 46 Rue du Bugnon, Lausanne 1011, Switzerland.

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[786]

TÍTULO / TITLE:  - Medium-grade astrocytoma in a cougar (Puma concolor).

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

REVISTA / JOURNAL:  - J Zoo Wildl Med. 2012 Dec;43(4):956-60.

AUTORES / AUTHORS:  - Kondo H; Leone AM; Erlacher-Reid C; Gary J; Kiupel M; Farina LL; Abbott JR

INSTITUCIÓN / INSTITUTION:  - Department of Infectious Diseases and Pathology, College of Veterinary Medicine,  University of Florida, Gainesville, 32608, USA. kondoh@ufl.edu

RESUMEN / SUMMARY:  - A 17-year-old, male castrated cougar (Puma concolor) was presented minimally responsive and severely depressed, with bilateral mydriasis and absent pupillary  light response. On gross examination of the brain, there was a tan-to-gray, invasive mass with a central cavitation on the ventral aspect in the left cerebral hemisphere, rostral to the caudate nucleus. On histopathologic examination, the mass was composed of sheets of medium-sized, round-to-polygonal  cells that were multifocally separated by islands of neuropil. Approximately 80%  of the neoplastic cells showed strong cytoplasmic labeling for glial fibrillary acidic protein. These findings were consistent with a medium-grade astrocytoma. To the authors’ knowledge, neoplastic disease of the central nervous system has not been previously reported in cougars.

 

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[787]

TÍTULO / TITLE:  - Surgical excision with left atrial reconstruction of a primary functioning retrocardiac paraganglioma.

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

REVISTA / JOURNAL:  - J Cardiothorac Surg. 2013 Jan 29;8(1):22.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1749-8090-8-22

AUTORES / AUTHORS:  - Lopez MT; Gonzalez SG; Garcia ES; Romero SG; de Loma JG

RESUMEN / SUMMARY:  - ABSTRACT: About 2% of all paragangliomas are located in the chest, and a few have been described to be found in the heart. Primary cardiac paragangliomas are extremely uncommon tumors and surgical experience with this neoplasm is limited.  Treatment strategies described in the literature have included simple excision, excision with reconstruction, autotransplantation after excision of the tumor and even orthotopic cardiac transplantation, depending on the extent of disease. A primary retrocardiac paraganglioma catecholamine-productive was identified in an  asymptomatic 49-year old female associated to familial pheochromocytoma-paraganglioma syndrome caused by germline mutation of the gen which codifies for the subunit B of succinate dehydrogenase enzyme (SDHB). The neoplasm was surgically excised from the posterior surface of the left atrium via median sternotomy using cardiopulmonary bypass. Direct ligation of feeding vessels of the tumor along with left atrial reinforcement using a pericardial patch was performed. The post-operative course was uneventful, with normalization of catecholamine secretion and no recurrence at three-month follow-up. We review  the current literature about this exceptional cardiac tumor, pathophysiological conditions and options for surgical management.

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[788]

TÍTULO / TITLE:  - Postoperative radiotherapy for ependymoma.

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

REVISTA / JOURNAL:  - Radiat Oncol J. 2012 Dec;30(4):158-64. doi: 10.3857/roj.2012.30.4.158. Epub 2012  Dec 31.

            ●● Enlace al texto completo (gratuito o de pago) 3857/roj.2012.30.4.158

AUTORES / AUTHORS:  - Jung J; Choi W; Ahn SD; Park JH; Kim SS; Kim YS; Yoon SM; Song SY; Lee SW; Kim JH; Choi EK

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - PURPOSE: To evaluated the patterns of failure, survival rate, treatment-related toxicity and prognostic factors in postoperative radiotherapy of patients with ependymoma. MATERIALS AND METHODS: Thirty patients who underwent surgery and postoperative radiotherapy for ependymoma between the period of June 1994 and June 2008 were reviewed retrospectively. The age of patients ranged from 21 months to 66 years (median, 19 years). Seventeen patients had grade II ependymoma, and 13 had grade III anaplastic ependymoma according to the World Health Organization grading system. The postoperative irradiation was performed with 4 or 6 MV photon beam with median dose of 52.8 Gy (range, 45 to 63 Gy), and  radiation field including 2 cm beyond the preoperative tumor volume. Median follow-up period was 51 months (range, 12 to 172 months). RESULTS: Fourteen out of 30 (46.7%) patients experienced recurrence, and 12 of those died. Among those  14 patients who experienced recurrence, 11 were in-field and 3 were out-of-field  recurrence. The 5-year overall survival (OS) and progression-free survival (PFS)  rates were 66.7% and 56.1%, respectively. On univariate analysis, tumor grade was a statistically significant prognostic factor for OS and PFS. There were two complications after surgery and postoperative radiotherapy, including short stature and facial palsy on the left side. CONCLUSION: We observed good survival  rates, and histologic grade was a prognostic factor affecting the OS and PFS. Almost all recurrence occurred in primary tumor site, thus we suggest further evaluation on intensity-modulated radiotherapy or stereotatic radiosurgery for high-risk patients such as who have anaplastic ependymoma.

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[789]

TÍTULO / TITLE:  - Advances in the management of glioblastoma: the role of temozolomide and MGMT testing.

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

REVISTA / JOURNAL:  - Clin Pharmacol. 2013;5:1-9. doi: 10.2147/CPAA.S26586. Epub 2012 Dec 27.

            ●● Enlace al texto completo (gratuito o de pago) 2147/CPAA.S26586

AUTORES / AUTHORS:  - Thomas RP; Recht L; Nagpal S

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Sciences, Stanford University Hospital, Stanford, CA,  USA.

RESUMEN / SUMMARY:  - Glioblastoma (GB) is one of the most lethal forms of cancer, with an invasive growth pattern that requires the use of adjuvant therapies, including chemotherapy and radiation, to prolong survival. Temozolomide (TMZ) is an oral chemotherapy with a limited side effect profile that has become the standard of care in GB treatment. While TMZ has made an impact on survival, tumor recurrence  and TMZ resistance remain major challenges. Molecular markers, such as O6-methylguanine-DNA methyltransferase methylation status, can be helpful in predicting tumor response to TMZ, and therefore guides clinical decision making.  This review will discuss the epidemiology and possible genetic underpinnings of GB, how TMZ became the standard of care for GB patients, the pharmacology of TMZ, the practical aspects of using TMZ in clinic, and how molecular diagnostics - particularly the use of O6-methylguanine-DNA methyltransferase status - affect clinical management.

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[790]

TÍTULO / TITLE:  - Surgical procedures for external auditory canal carcinoma and the preservation of postoperative hearing.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Surg. 2012;2012:841372. doi: 10.1155/2012/841372. Epub 2012 Dec 1.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/841372

AUTORES / AUTHORS:  - Hoshikawa H; Miyashita T; Mori N

INSTITUCIÓN / INSTITUTION:  - Head and Neck Surgery, Department of Otolaryngology, Faculty of Medicine, Kagawa  University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

RESUMEN / SUMMARY:  - Carcinoma of the external auditory canal (EAC) is an unusual head and neck malignancy. The pathophysiology of these tumors is different from other skin lesions because of their anatomical and functional characteristics. Early-stage carcinoma of the EAC can be generally cured by surgical treatment, and reconstruction of the EAC with a tympanoplasty can help to retain hearing, thus improving the patients’ quality of life. In this study, we present two cases of early-stage carcinoma of the EAC treated by canal reconstruction using skin grafts after lateral temporal bone resection. A rolled-up skin graft with a temporal muscle flap was useful for keeping the form and maintaining the postoperative hearing. An adequate size of the skin graft and blood supply to the graft bed are important for achieving a successful operation.

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[791]

TÍTULO / TITLE:  - Pediatric glioblastoma multiforme: A single-institution experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Indian J Med Paediatr Oncol. 2012 Jul;33(3):155-60. doi: 10.4103/0971-5851.103142.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0971-5851.103142

AUTORES / AUTHORS:  - Ansari M; Nasrolahi H; Kani AA; Mohammadianpanah M; Ahmadloo N; Omidvari S; Mosalaei A

INSTITUCIÓN / INSTITUTION:  - Department of Radiation Oncology, Student Research Committee, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

RESUMEN / SUMMARY:  - BACKGROUND: Glioblastoma multiforme (GBM) is the most common astrocytoma in adults and has a poor prognosis, with a median survival of about 12 months. But,  it is rare in children. We report our experience on the pediatric population (20  years or younger) with GBM. PATIENTS AND METHODS: Twenty-three patients with GBM  who were treated at our hospital during 1990-2008 were evaluated. RESULTS: The mean age was 15.2 years, and the majority of them (14/23) were male. All had received radiotherapy and some had also received chemotherapy. The mean survival  was 16.0 months. Two cases survived more than 5 years. Age, radiation dose and performance status were significantly related to survival. CONCLUSION: GBM in pediatric patients were not very common in our center, and prognosis was unfavorable.

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[792]

TÍTULO / TITLE:  - Rapamycin inhibits human glioma cell proliferation through down-regulating mammalian target of rapamycin pathway and up-regulating microRNA-143.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Head Neck Oncol. 2012 Oct 14;4(3):66.

AUTORES / AUTHORS:  - Li C; Liu Y; Liu J; Chen Y; Li Z; Chen X; Yang K; Li M; Liu Z

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China Min.Li@uth.tmc.edu.

RESUMEN / SUMMARY:  - The objective of this study was to test the hypothesis that rapamycin regulates cell proliferation, apoptosis and glycolysis in human glioma cells and to investigate the underlying mechanism. Human malignant glioma cell line U251 cells were treated with 100 mM rapamycin for 6, 12 and 24 h. Cell proliferation and apoptosis were assayed by methylthiazol tetrazolium assay and flow cytometric analyses. RNA and protein expression levels were then measured by real-time polymerase chain reaction and Western blotting, respectively. The administration  of rapamycin inhibited the proliferation and induced the apoptosis of U251 cells. Prolonged treatment with rapamycin gradually decreased the mammalian target of rapamycin signalling in U251 cells. Moreover, our data showed rapamycin up-regulated miR-143 and down-regulated hexokinase 2-a key enzyme in glycolysis-in the glioma U251 cells. Collectively, our data suggests a new anti-tumour role of rapamycin in gliomas and indicates that rapamycin-mediated glioma cell proliferation might be through inhibiting the mammalian target of the rapamycin pathway and up-regulating tumour suppressing miR-143. These data suggest a promising, novel rapamycin- and miR-143-based therapy to treat malignant glioma.

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[793]

TÍTULO / TITLE:  - Targeted cell uptake of a non-internalizing antibody through conjugation to iron  oxide nanoparticles in primary central nervous system lymphoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 5. pii: S1878-8750(13)00018-1. doi: 10.1016/j.wneu.2013.01.011.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2013.01.011

AUTORES / AUTHORS:  - Wang T; Kievit FM; Veiseh O; Arami H; Stephen ZR; Fang C; Liu Y; Ellenbogen RG; Zhang M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.

RESUMEN / SUMMARY:  - Currently there is no standard of care for patients with primary central nervous  system lymphoma (PCNSL) primarily due to the difficulty in delivering therapeutically effective doses of drugs to the intracellular site of the target  PCNSL. Here we report the use of an iron oxide nanoparticle to promote the internalization of a PCNSL targeting antibody by target cells. Iron oxide nanoparticles coated with a copolymer of chitosan-grafted PEG (NPs) were conjugated with an anti-CD20 single-chain variable fragment-streptavidin fusion protein (FP), and optically activated with Oregon Green 488. The ability of NP-FP to target PCNSL cells was assessed using flow cytometry and the ferrozine assay.  Cell internalization of NP-FP was examined by confocal fluorescence microscopy. The antibody conjugated NPs had a near-neutral zeta potential and remained stable in biological media for over a week, which may minimizes non-specific cell uptake. The diameter of the NPs was around 70 nm, which is in an optimal range for maximizing cell uptake. The selective binding of these NPs was demonstrated with binding to PCNSL cells 3-4 fold higher than binding to control cells. Z-stack imaging by confocal microscopy revealed the NPs were internalized by PCNSL cells. The high-degree specific binding and cell uptake of NP-FP in PCNSL suggests this NP formulation can be further developed to improve therapy of PCNSL.

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[794]

TÍTULO / TITLE:  - Monitoring Glioma Growth and Tumor Necrosis with the U-SPECT-II/CT Scanner by Targeting Integrin alphavbeta3.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Mol Imaging. 2013 Feb 1;12(1):39-48.

AUTORES / AUTHORS:  - Shao G; Zhou Y; Wang F; Liu S

RESUMEN / SUMMARY:  - AbstractThe purpose of this study was to validate 99mTc-3P-RGD2 single-photon emission computed tomography/computed tomography (SPECT/CT) as an imaging tool to monitor alphavbeta3 expression and tumor necrosis. The animal model was established by subcutaneous injection of 5 x 106 U87MG cells into the shoulder flank of each mouse. Imaging was performed using the U-SPECT-II/CT scanner (Milabs, Utrecht, the Netherlands). Tumor volumes were determined, and the tumor  uptake of 99mTc-3P-RGD2 was calculated on the basis of SPECT/CT and compared to that from biodistribution. Immunohistochemistry was performed to determine CD31 and alphavbeta3 expression levels. We found that the tumor detection limit was approximately 0.5 mm3 by 99mTc-3P-RGD2 SPECT/CT. The tumor uptake of 99mTc-3P-RGD2 from SPECT/CT was almost identical to that from biodistribution. The alphavbeta3 was expressed mainly on blood vessels for the tumors of 0.2 to 0.5 cm3. In larger tumors, tumor alphavbeta3 expression increased due to more contribution from glioma cells. When tumors were > 0.5 cm3, the %ID/cm3 uptake of 99mTc-3P-RGD2 decreased because of necrosis. The overall relationship between the tumor size and %ID of 99mTc-3P-RGD2 was modeled as a quadratic polynomial fitting curve, with R2 being > .95. 99mTc-3P-RGD2 SPECT/CT is excellent for monitoring alphavbeta3 expression and tumor necrosis during tumor growth and may become a screening tool for patient selection before anti-alphavbeta3 therapy.

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[795]

TÍTULO / TITLE:  - Dendritic cell vaccination in glioblastoma after fluorescence-guided resection.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Clin Oncol. 2012 Nov 10;3(11):142-9. doi: 10.5306/wjco.v3.i11.142.

            ●● Enlace al texto completo (gratuito o de pago) 5306/wjco.v3.i11.142

AUTORES / AUTHORS:  - Valle RD; de Cerio AL; Inoges S; Tejada S; Pastor F; Villanueva H; Gallego J; Espinos J; Aristu J; Idoate MA; Andreu E; Bendandi M

INSTITUCIÓN / INSTITUTION:  - Ricardo Diez Valle, Sonia Tejada, Department of Neurosurgery, University of Navarra Hospital, 31008 Pamplona, Navarra, España.

RESUMEN / SUMMARY:  - AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-II clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patients were class V and one was class IV. In all five cases, fluorescence-guided surgery was  employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations. RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years. CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is  ongoing to possibly improve further on our very encouraging clinical results.

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[796]

TÍTULO / TITLE:  - High (18)F-FDG uptake in sporadic paraganglioma of the retroperitoneum may be related to intra-tumor haemorrhage and macrophages.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Hell J Nucl Med. 2012 Sep-Dec;15(3):261.

AUTORES / AUTHORS:  - Kaida H; Kurata S; Kawahara A; Hiromatsu Y; Kage M; Ishibashi M

INSTITUCIÓN / INSTITUTION:  - Division of Nuclear Medicine, PET Center, Kurume University, School of Medicine,  Fukuoka, Japan. hayato@med.kurume-u.ac.jp

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[797]

TÍTULO / TITLE:  - Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2012;2:176. doi: 10.3389/fonc.2012.00176. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00176

AUTORES / AUTHORS:  - Bobola MS; Kolstoe DD; Blank A; Chamberlain MC; Silber JR

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, University of Washington Medical Center Seattle, WA, USA.

RESUMEN / SUMMARY:  - Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O(6)-methylguanine (O(6)-meG) mediates GBM cell killing. Moreover, low or absent expression of O(6)-methylguanine-DNA methyltransferase (MGMT), the sole human repair protein that removes O(6)-meG from DNA, is frequently associated with longer survival in GBMs treated with TMZ, promoting interest in developing inhibitors of MGMT to counter resistance. However, the clinical efficacy of TMZ is unlikely to be due solely to O(6)-meG, as the agent produces approximately a dozen additional DNA adducts, including cytotoxic N3-methyladenine (3-meA) and abasic sites. Repair of 3-meA and abasic sites, both of which are produced in greater abundance than O(6)-meG, is mediated by the base excision repair (BER) pathway, and occurs independently of removal of O(6)-meG. These observations indicate that BER activities are also potential targets for strategies to potentiate TMZ cytotoxicity. Here we review the evidence that 3-meA and abasic sites mediate killing of GBM cells. We also present in vitro and in vivo evidence that alkyladenine-DNA glycosylase, the sole repair activity that excises 3-meA from DNA, and Ape1, the major human abasic site endonuclease, mediate TMZ resistance in GBMs and represent potential anti-resistance targets.

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[798]

TÍTULO / TITLE:  - MEF promotes stemness in the pathogenesis of gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Stem Cell. 2012 Dec 7;11(6):836-44. doi: 10.1016/j.stem.2012.09.012.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.stem.2012.09.012

AUTORES / AUTHORS:  - Bazzoli E; Pulvirenti T; Oberstadt MC; Perna F; Wee B; Schultz N; Huse JT; Fomchenko EI; Voza F; Tabar V; Brennan CW; DeAngelis LM; Nimer SD; Holland EC; Squatrito M

INSTITUCIÓN / INSTITUTION:  - Cancer Biology and Genetics Program, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.

RESUMEN / SUMMARY:  - High-grade gliomas are aggressive and uniformly fatal tumors, composed of a heterogeneous population of cells that include many with stem-cell-like properties. The acquisition of stem-like traits might contribute to glioma initiation, growth, and recurrence. Here we investigated the role of the transcription factor myeloid Elf-1 like factor (MEF, also known as ELF4) in gliomas. We found that MEF is highly expressed in both human and mouse glioblastomas and its absence impairs gliomagenesis in a PDGF-driven glioma mouse model. We show that modulation of MEF levels in both mouse neural stem cells and  human glioblastoma cells has a significant impact on neurosphere formation. Moreover, we identify Sox2 as a direct downstream target of MEF. Taken together,  our studies implicate MEF as a previously unrecognized gatekeeper gene in gliomagenesis that promotes stem cell characteristics through Sox2 activation.

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[799]

TÍTULO / TITLE:  - Visual function and optic pathway glioma: a critical response-reply.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - JAMA. Acceso gratuito al texto completo.

            ●● Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Ophthalmol. 2013 Jan 1;131(1):120-4. doi: 10.1001/2013.jamaophthalmol.519.

            ●● Enlace al texto completo (gratuito o de pago) 1001/2013.jamaophthalmol.519

AUTORES / AUTHORS:  - Parsa CF

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[800]

TÍTULO / TITLE:  - Medulloblastoma biology in the post-genomic era.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Future Oncol. 2012 Dec;8(12):1597-604. doi: 10.2217/fon.12.151.

            ●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.151

AUTORES / AUTHORS:  - Archer TC; Pomeroy SL

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Children’s Hospital Boston, Harvard Medical School, 300  Longwood Avenue, Fegan 1103, Boston, MA 02115, USA.

RESUMEN / SUMMARY:  - Medulloblastomas, the most common malignant pediatric brain tumors, are comprised of four molecularly distinct subtypes. However, treatment has yet to exploit these molecular vulnerabilities. Three recent studies sequenced a total of 310 primary tumors and identified that two of the four medulloblastoma subtypes are concomitantly associated with subtype-specific mutations as previously characterized. In contrast, the overwhelming majority of mutations occurred only  once in the entire cohort and just 12 genes were recurrently mutated with statistical significance. Perturbations in epigenetic regulation are emerging as  a unifying theme in cancer and similarly recurring mutations in epigenetic mechanisms were distributed across all subtypes in medulloblastoma. Designing targeted therapies to such a molecularly diverse disease in the post-genomic era  presents new challenges. This will require novel methods to link these nonrecurrent mutations into pathways, and preclinical models that faithfully recapitulate patient driver events. Presently, medulloblastoma reinforces epigenetic mechanisms as a tantalizing therapeutic target in cancers.

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[801]

TÍTULO / TITLE:  - Reversible parkinsonism due to a large intracranial tumour.

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 http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2012 Dec 23;2012. pii: bcr2012007823. doi: 10.1136/bcr-2012-007823.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007823

AUTORES / AUTHORS:  - Rocha H; Cerejo A; Garrett MC; Massano J

INSTITUCIÓN / INSTITUTION:  - Department of Neurology, Centro Hospitalar de Sao Joao, Oporto, Portugal.

RESUMEN / SUMMARY:  - A 77-year-old woman presented with progressively worsening apathy, depression, urinary incontinence and slowness of movement for the past 1 year. Asymmetric akinetic-rigid parkinsonism and mild left-sided hyper-reflexia were seen on examination. No ocular movement impairment, cerebellar or sensory signs were noticed. Routine laboratory testing was normal. Brain imaging revealed a large frontal tumour which was subsequently excised and pathologically confirmed as a meningioma. Marked clinical improvement was documented 3 months after surgery, and persistent clinical and imaging remission have been confirmed annually for the following 3 years. There have been some reports of parkinsonism associated with intracranial tumours. Although this is probably an uncommon situation, it is potentially treatable, and symptoms might even remit completely following successful management. Parkinson’s disease is a common cause of parkinsonism, but alternative aetiologies should be suspected whenever atypical findings are demonstrated by clinical history or examination.

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[802]

TÍTULO / TITLE:  - Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Cycle. 2013 Jan 1;12(1):145-56. doi: 10.4161/cc.23050. Epub 2012 Dec 19.

            ●● Enlace al texto completo (gratuito o de pago) 4161/cc.23050

AUTORES / AUTHORS:  - Wurth R; Pattarozzi A; Gatti M; Bajetto A; Corsaro A; Parodi A; Sirito R; Massollo M; Marini C; Zona G; Fenoglio D; Sambuceti G; Filaci G; Daga A; Barbieri F; Florio T

INSTITUCIÓN / INSTITUTION:  - Department of Internal Medicine; University of Genova; Genova, Italy.

RESUMEN / SUMMARY:  - Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate  of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction  of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts  antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.

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[803]

TÍTULO / TITLE:  - Brain tumor-related epilepsy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Curr Neuropharmacol. 2012 Jun;10(2):124-33. doi: 10.2174/157015912800604470.

            ●● Enlace al texto completo (gratuito o de pago) 2174/157015912800604470

AUTORES / AUTHORS:  - Maschio M

INSTITUCIÓN / INSTITUTION:  - Center for Tumor-Related Epilepsy, Neurology Unit, Department of Neuroscience and Cervical-Facial Pathology, National Institute for Cancer “Regina Elena” Via Elio  Chianesi, 53 00144 Roma, Italy.

RESUMEN / SUMMARY:  - In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course  of the disease. These patients present a complex therapeutic profile and require  a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures.In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient’s psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are  preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results  and should be considered a possible treatment option. Therefore, it is necessary  to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness.

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[804]

TÍTULO / TITLE:  - Proteoglycans and their roles in brain cancer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - FEBS J. 2013 Jan 2. doi: 10.1111/febs.12109.

            ●● Enlace al texto completo (gratuito o de pago) 1111/febs.12109

AUTORES / AUTHORS:  - Wade A; Robinson AE; Engler JR; Petritsch C; David James C; Phillips JJ

INSTITUCIÓN / INSTITUTION:  - Department of Neurological Surgery, UCSF; Brain Tumor Research Center, UCSF.

RESUMEN / SUMMARY:  - Glioblastoma (GBM), a malignant brain cancer, is characterized by abnormal activation of receptor tyrosine kinase (RTK) signaling pathways and poor prognosis. Extracellular proteoglycans, including heparan sulfate and chondroitin sulfate, play critical roles in the regulation of cell signaling and migration via interactions with extracellular ligands, growth factor receptors, extracellular matrix components, and intracellular enzymes and structural proteins. In cancer, proteoglycans help drive multiple oncogenic pathways in tumor cells and promote critical tumor-microenvironment interactions. In this review, we summarize the evidence for proteoglycan function in gliomagenesis and  we examine the expression of proteoglycans and their modifying enzymes in human GBM using data from The Cancer Genome Atlas (TCGA). Furthermore, we demonstrate an association between specific proteoglycan alterations and changes in RTKs. Based on these data we propose a model in which proteoglycans and their modifying enzymes promote RTK signaling and progression in GBM, and we suggest cancer associated proteoglycans are promising biomarkers for disease and therapeutic targets. © 2013 The Authors Journal compilation © 2013 FEBS.

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[805]

TÍTULO / TITLE:  - 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 http://jama.ama-assn.org/search.dtl 

            ●● Cita: JAMA: <> Ophthalmol. 2013 Jan 1;131(1):120-4. doi: 10.1001/jamaophthalmol.2013.571.

            ●● Enlace al texto completo (gratuito o de pago) 1001/jamaophthalmol.2013.571

AUTORES / AUTHORS:  - Gutmann DH; Avery R; Ferner RE; Listernick R

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[806]

TÍTULO / TITLE:  - Aspirin-/TMZ-coloaded Microspheres Exert Synergistic Antiglioma Efficacy via Inhibition of beta-catenin Transactivation.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - CNS Neurosci Ther. 2013 Feb;19(2):98-108. doi: 10.1111/cns.12041. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1111/cns.12041

AUTORES / AUTHORS:  - Shi ZD; Qian XM; Liu CY; Han L; Zhang KL; Chen LY; Zhang JX; Pu PY; Yuan XB; Kang CS

INSTITUCIÓN / INSTITUTION:  - Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and  Tianjin Municipal Government, Tianjin, China.

RESUMEN / SUMMARY:  - BACKGROUND AND AIMS: Currently temozolomide (TMZ) as a potent agent is widely used to treat the glioblastoma multiforme (GBM), whereas recurrence due to intrinsic or acquired therapeutic resistance often occurs. Combination chemotherapy with TMZ may be a promising therapeutic strategy to improve treatment efficacy. METHODS: Aspirin, TMZ, and aspirin-/TMZ-coloaded poly (L-lactide-co-glycolide) (PLGA) microspheres were prepared by spray drying, and cytotoxicities of glioblastoma cells were measured. RESULTS: Aspirin microsphere  treatment induced slight apoptosis and modestly inhibited proliferation of LN229  and U87 cells in vitro and in vivo through inhibition of beta-catenin transactivation. However, aspirin-/TMZ-coloaded microspheres presented synergistic antitumor efficacy compared with single TMZ-loaded microspheres. Aspirin/TMZ microspheres induced more apoptosis and repressed proliferation of LN229 and U87 cells. Corresponding to inhibition of beta-catenin signaling, beta-catenin/TCF4 transcriptional activity and STAT3 luciferase activity were strongly suppressed, and downstream targets expression was decreased. Furthermore, aspirin/TMZ microsphere intratumoral injection downregulated the expression of beta-catenin, TCF4, pAKT, pSTAT3, and PCNA and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts. CONCLUSIONS: Aspirin sensitized TMZ chemotherapy efficacy through inhibition of beta-catenin transactivation; furthermore, the coloaded microspheres achieved a sustained release action to reduce the TMZ dosage, offering the potential for improved treatment of glioblastomas.

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[807]

TÍTULO / TITLE:  - Paraganglioma of the bladder.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Adv Hematol Oncol. 2012 Dec;10(12):839-41.

AUTORES / AUTHORS:  - Jansen R; Zaslau S

INSTITUCIÓN / INSTITUTION:  - West Virginia University, Division of Urology, Morgantown, West Virginia.

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[808]

TÍTULO / TITLE:  - Malignant paraganglioma of the urinary bladder in a 45-year-old woman.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Adv Hematol Oncol. 2012 Dec;10(12):836-9.

AUTORES / AUTHORS:  - Palla AR; Hogan T; Singh S

INSTITUCIÓN / INSTITUTION:  - Danbury Hospital, Danbury, CT.

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[809]

TÍTULO / TITLE:  - Cerebellar metastasis from serous adenocarcinoma of the ovary mimicking pilocytic astrocytoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian J Neurosurg. 2012 Jul;7(3):141-3. doi: 10.4103/1793-5482.103720.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1793-5482.103720

AUTORES / AUTHORS:  - Tandon V; Garg K; Mahapatra AK

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.

RESUMEN / SUMMARY:  - Serous adenocarcinoma of the ovary rarely can present with solitary solid -cystic cerebellar metastasis, mimicking pilocytic astrocytoma. A middle aged women, who  underwent total abdominal hysterectomy with bilateral salpingoopherectomy and adjuvant chemotherapy for ovarian adenocarcinoma, presented to us with the history of headache, vomiting, and imbalance. Contrast enhanced magnetic resonance imaging (MRI) showed solitary cerebellar, solid cystic lesion with cyst lining and solid portion enhancing on contrast which was mimicking pilocytic astrocytoma and there was no perilesional edema. Gross total excision of the cerebellar lesion was done followed by resolution of her symptoms. Histopathology showed metastatic adenocarcinoma consistent with the primary ovarian carcinoma. In patients of ovarian carcinoma, presenting with features of raised intracranial pressureICP] thorough investigations must be done to rule out metastasis. Solitary metastasis of the cerebellum because of ovarian carcinoma may mimic pilocytic astrocytoma.

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[810]

TÍTULO / TITLE:  - Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2012 Dec 20;3:e445. doi: 10.1038/cddis.2012.182.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.182

AUTORES / AUTHORS:  - Kesanakurti D; Chetty C; Rajasekhar Maddirela D; Gujrati M; Rao JS

INSTITUCIÓN / INSTITUTION:  - Department of Cancer Biology and Pharmacology, University of Illinois College of  Medicine, Peoria, IL, USA.

RESUMEN / SUMMARY:  - Gliomas display anoikis resistance, enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies. Our studies on increased anoikis sensitization in matrix metalloproteinase-2 (MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 (PAK4) inhibition, prompting us to further investigate the role of PAK4 in glioma. Here, we report the PAK4 upregulation in  positive correlation with increasing glioma pathological grades. The siRNA-mediated PAK4 knockdown elevated anoikis, and inhibited invasion and migration by downregulating MMP-2, alphavbeta3-integrin and phospho-epidermal growth factor receptor (phospho-EGFR). The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation  and adhesion in PAK4-knockdown cells. Most importantly, glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain. Individual EGFR/ErbB2 inhibitor and alphavbeta3 antibody treatments in PAK4si-treated cells indicated the regulation of alphavbeta3/EGFR survival signaling by PAK4. Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines. Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death, and severely inhibited  invasive and migratory properties in these cells. PAK4si inhibited in vivo tumor  growth in nude mice by inhibiting MMP-2, beta3-integrin and phospho-EGFR levels in tumors. Our findings indicate a physical association between PAK4 and MMP-2, and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment.

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[811]

TÍTULO / TITLE:  - Role of Btg2 in the Progression of a PDGF-Induced Oligodendroglioma Model.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Mol Sci. 2012 Nov 12;13(11):14667-78. doi: 10.3390/ijms131114667.

            ●● Enlace al texto completo (gratuito o de pago) 3390/ijms131114667

AUTORES / AUTHORS:  - Appolloni I; Curreli S; Caviglia S; Barilari M; Gambini E; Pagano A; Malatesta P

INSTITUCIÓN / INSTITUTION:  - San Martino-IST, Largo Rosanna Benzi 10, 16132 Genoa, Italy. paolo.malatesta@unige.it.

RESUMEN / SUMMARY:  - Tumor progression is a key aspect in oncology. Not even the overexpression of a powerful oncogenic stimulus such as platelet derived growth factor-B (PDGF-B) is  sufficient per se to confer full malignancy to cells. In previous studies we showed that neural progenitors overexpressing PDGF-B need to undergo progression  to acquire the capability to give rise to secondary tumor following transplant. By comparing the expression profile of PDGF-expressing cells before and after progression, we found that progressed tumors consistently downregulate the expression of the antiproliferative gene Btg2. We therefore tested whether the downregulation of Btg2 is sufficient and necessary for glioma progression with loss and gain of function experiments. Our results show that downregulation of Btg2 is not sufficient but is necessary for tumor progression since the re-introduction of Btg2 in fully progressed tumors dramatically impairs their gliomagenic potential. These results suggest an important role of Btg2 in glioma  progression. Accordingly with this view, the analysis of public datasets of human gliomas showed that reduced level of Btg2 expression correlates with a significantly worse prognosis.

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[812]

TÍTULO / TITLE:  - Comparing predictive models of glioblastoma multiforme built using multi-institutional and local data sources.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - AMIA Annu Symp Proc. 2012;2012:1385-92. Epub 2012 Nov 3.

AUTORES / AUTHORS:  - Singleton KW; Hsu W; Bui AA

INSTITUCIÓN / INSTITUTION:  - Medical Imaging Informatics Group, Dept of Radiological Sciences University of California, Los Angeles, CA.

RESUMEN / SUMMARY:  - The growing amount of electronic data collected from patient care and clinical trials is motivating the creation of national repositories where multiple institutions share data about their patient cohorts. Such efforts aim to provide  sufficient sample sizes for data mining and predictive modeling, ultimately improving treatment recommendations and patient outcome prediction. While these repositories offer the potential to improve our understanding of a disease, potential issues need to be addressed to ensure that multi-site data and resultant predictive models are useful to non-contributing institutions. In this  paper we examine the challenges of utilizing National Cancer Institute datasets for modeling glioblastoma multiforme. We created several types of prognostic models and compared their results against models generated using data solely from our institution. While overall model performance between the data sources was similar, different variables were selected during model generation, suggesting that mapping data resources between models is not a straightforward issue.

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[813]

TÍTULO / TITLE:  - The different role of notch1 and notch2 in astrocytic gliomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e53654. doi: 10.1371/journal.pone.0053654. Epub 2013 Jan 21.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053654

AUTORES / AUTHORS:  - Xu P; Zhang A; Jiang R; Qiu M; Kang C; Jia Z; Wang G; Han L; Fan X; Pu P

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China ; Tianjin Neurological Institute, Tianjin, People’s Republic of China ; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, People’s Republic of China ; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, People’s Republic of China.

RESUMEN / SUMMARY:  - It is well known that Notch signaling plays either oncogenic or tumor suppressive role in a variety of tumors, depending on the cellular context. However, in our previous study, we found that Notch1 was overexpressed while Notch2 downregulated in the majority of astrocytic gliomas with different grades as well as in glioblastoma cell lines U251 and A172. We had knocked down Notch1 by siRNA in glioblastoma cells, and identified that the cell growth and invasion were inhibited, whereas cell apoptosis was induced either in vitro or in vivo. For further clarification of the role of Notch2 in pathogenesis of gliomas, enforced  overexpression of Notch2 was carried out with transfection of Notch2 expression plasmid in glioma cells and the cell growth, invasion and apoptosis were examined in vitro and in vivo in the present study, and siRNA targeting Notch1 was used as a positive control in vivo. The results showed that upregulating Notch2 had the effect of suppressing cell growth and invasion as well as inducing apoptosis, just the same as the results of knocking down Notch1. Meanwhile, the activity of  core signaling pathway-EGFR/PI3K/AKT in astrocytic glioma cells was repressed. Thus, the present study reveals, for the first time, that Notch1 and Notch2 play  different roles in the biological processes of astrocytic gliomas. Knocking down  the Notch1 or enforced overexpression of Notch2 both modulate the astrocytic glioma phenotype, and the mechanism by which Notch1 and 2 play different roles in the glioma growth should be further investigated.

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[814]

TÍTULO / TITLE:  - Rapid brain shift, remote site hemorrhage, and a spinal hematoma after craniotomy for a large arachnoid cyst.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Neurosci. 2012 May;7(2):106-8. doi: 10.4103/1817-1745.102568.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1817-1745.102568

AUTORES / AUTHORS:  - Bahl A; Connolly DJ; Sinha S; Zaki H; McMullan J

INSTITUCIÓN / INSTITUTION:  - Department of Paediatric Neurosurgery, Sheffield Children’s Hospital, Sheffield,  United Kingdom.

RESUMEN / SUMMARY:  - Arachnoid cysts are prevalent among the general population. The management options of symptomatic arachnoid cysts each have their own merits and disadvantages. We report a case where a large arachnoid cyst was treated by open  fenestration and marsupialization that was complicated by remote intraparenchymal and spinal subdural hemorrhage. The potential physiological changes underlying these complications as well as the related literature are reviewed.

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[815]

TÍTULO / TITLE:  - Cystic with mural nodule: Unusual radiological presentation of supratentorial anaplastic ependymoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Pediatr Neurosci. 2012 May;7(2):101-2. doi: 10.4103/1817-1745.102565.

            ●● Enlace al texto completo (gratuito o de pago) 4103/1817-1745.102565

AUTORES / AUTHORS:  - Borkar SA; Subbarao KC; Sharma MC; Mahapatra AK

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, AIIMS, New Delhi, India.

RESUMEN / SUMMARY:  - Supratentorial anaplastic ependymoma is an uncommon tumor which can rarely present as a cyst with mural nodule on imaging. Authors present this unusual radiological appearance of supratentorial extraventricular anaplastic ependymoma  in a 9-year-old boy.

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[816]

TÍTULO / TITLE:  - Global Tracking in Human Gliomas: A Comparison with Established Tracking Methods.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuroradiol. 2013 Jan 18.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-013-0198-x

AUTORES / AUTHORS:  - Nguyen-Thanh T; Reisert M; Anastasopoulos C; Hamzei F; Reithmeier T; Vry MS; Kiselev VG; Weyerbrock A; Mader I

INSTITUCIÓN / INSTITUTION:  - Department of Neuroradiology, University Medical Centre Freiburg, Breisacher St.  64, 79106, Freiburg, Germany, nguyen.thanh.thao@hue-radiology.com.

RESUMEN / SUMMARY:  - PURPOSE: Global tracking (GT) is a recently published fibre tractography (FT) method that takes simultaneously all fibres into account during their reconstruction. The purpose of this study was to compare this new method with fibre assignment by continuous tracking (FACT) and probabilistic tractography (PT) for the detection of the corticospinal tract (CST) in patients with gliomas. METHODS: Tractography of the CST was performed in 17 patients with eight low grade and nine anaplastic astrocytomas located in the motor cortex or the corticospinal tract. Diffusions metrics as fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD) were obtained. The methods were additionally applied on a physical phantom to assess their accuracy. RESULTS: PT  was successful in all (100 %), GT in 16 (94 %) and FACT in 15 patients (88 %). The case where GT and FACT, both, missed the CST showed the highest AD and RD, whereas the one where FACT algorithm, alone, was not successfully showed the lowest AD and RD of the group. FA was reduced on the pathologic side (FA(path) 0.35 +/- 0.16 (mean +/- SD) versus FA(contralateral) 0.51 +/- 0.15, p (corr) < 0.03). RD was increased on the pathologic side (RD(path) 0.67 +/- 0.29 x 10(-) (3) mm(2)/s versus RD(contralateral) 0.46 +/- 0.08 x 10(-) (3) mm(2)/s, p (corr)  < 0.03). In the phantom measurement, only GT did not detect false positive fibres at fibre crossings. CONCLUSION: PT performed well even in areas of increased diffusivities indicating a severe oedema or disintegration of tissue. FACT was also susceptible to a decrease of diffusivities and to a susceptibility artefact, where GT was robust.

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[817]

TÍTULO / TITLE:  - Emerging evidence of anti-tumor immune control in the central nervous system.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncoimmunology. 2012 Dec 1;1(9):1648-1649.

            ●● Enlace al texto completo (gratuito o de pago) 4161/onci.21747

AUTORES / AUTHORS:  - Donson AM; Foreman NK

INSTITUCIÓN / INSTITUTION:  - Department of Pediatrics; University of Colorado Anschutz Medical Campus and Children’s Hospital; Colorado Center for Cancer and Blood Disorders; Aurora, CO USA.

RESUMEN / SUMMARY:  - Microarray-based studies by our laboratory confirm that the immune control of tumor progression extends to the “immunoprivileged” central nervous system, identifying prognostic immune gene signatures in primary tumor specimens. Our results provide rationale and mechanistic insights for the development of immunotherapeutic strategies against brain tumors.

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[818]

TÍTULO / TITLE:  - Collaborative Labeling of Malignant Glioma with WebMILL: A First Look.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Proc Soc Photo Opt Instrum Eng. 2012 Apr 5;8318. pii: 831813.

            ●● Enlace al texto completo (gratuito o de pago) 1117/12.910802

AUTORES / AUTHORS:  - Singh E; Asman AJ; Xu Z; Chambless L; Thompson R; Landman BA

INSTITUCIÓN / INSTITUTION:  - Computer Engineering, Vanderbilt University, Nashville, TN, USA 37235.

RESUMEN / SUMMARY:  - Malignant gliomas are the most common form of primary neoplasm in the central nervous system, and one of the most rapidly fatal of all human malignancies. They are treated by maximal surgical resection followed by radiation and chemotherapy. Herein, we seek to improve the methods available to quantify the extent of tumors using newly presented, collaborative labeling techniques on magnetic resonance imaging. Traditionally, labeling medical images has entailed that expert raters operate on one image at a time, which is resource intensive and not practical for very large datasets. Using many, minimally trained raters to label images has the possibility of minimizing laboratory requirements and allowing high degrees of parallelism. A successful effort also has the possibility of reducing overall cost. This potentially transformative technology presents a new set of problems,  because one must pose the labeling challenge in a manner accessible to people with little or no background in labeling medical images and raters cannot be expected to read detailed instructions. Hence, a different training method has to be employed. The training must appeal to all types of learners and have the same  concepts presented in multiple ways to ensure that all the subjects understand the basics of labeling. Our overall objective is to demonstrate the feasibility of studying malignant glioma morphometry through statistical analysis of the collaborative efforts of many, minimally-trained raters. This study presents preliminary results on optimization of the WebMILL framework for neoplasm labeling and investigates the initial contributions of 78 raters labeling 98 whole-brain datasets.

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[819]

TÍTULO / TITLE:  - Subependymal giant cell astrocytoma: Cytological findings.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cytol. 2012 Oct;29(4):276-7. doi: 10.4103/0970-9371.103953.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0970-9371.103953

AUTORES / AUTHORS:  - Azarpira N; Pakbaz S; Rakei M

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Shiraz Medical School, Shiraz, Iran.

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[820]

TÍTULO / TITLE:  - Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cell Death Dis. 2013 Jan 17;4:e458. doi: 10.1038/cddis.2012.197.

            ●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.197

AUTORES / AUTHORS:  - Syed N; Langer J; Janczar K; Singh P; Lo Nigro C; Lattanzio L; Coley HM; Hatzimichael E; Bomalaski J; Szlosarek P; Awad M; O’Neil K; Roncaroli F; Crook T

INSTITUCIÓN / INSTITUTION:  - John Fulcher Neuro-oncology laboratory, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London W6 8RP, UK.

RESUMEN / SUMMARY:  - Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20,  induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation  status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.

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[821]

TÍTULO / TITLE:  - Low-Grade Esthesioneuroblastoma Presenting as SIADH: A Review of Atypical Manifestations.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Report Otolaryngol. 2012;2012:582180. doi: 10.1155/2012/582180. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/582180

AUTORES / AUTHORS:  - Senchak A; Freeman J; Ruhl D; Senchak J; Klem C

INSTITUCIÓN / INSTITUTION:  - Department of Otolaryngology, Walter Reed National Military Medical Center, 8901  Wisconsin Avenue Bethesda, MD 20889-5600, USA.

RESUMEN / SUMMARY:  - Esthesioneuroblastoma (ENB) is a neuroendocrine tumor that typically manifests as advanced stage malignancy in the superior nasal cavity. The hallmark symptoms include nasal obstruction and epistaxis, which result from local tissue invasion. Atypical clinical features can also arise and must be considered when diagnosing  and treating ENB. These can include origin in an ectopic location, unusual presenting symptoms, and associated paraneoplastic syndromes. The case described  here reports a nasal cavity ENB with atypical clinical features that occurred in  a young female. Her tumor was low grade, appeared to arise primarily from the middle nasal cavity, and presented as syndrome of inappropriate antidiuretic hormone (SIADH). She also became pregnant shortly after diagnosis, which had implications on her surgical management. We review the atypical features that uncommonly occur with ENB and the clinical considerations that arise from these unusual characteristics.

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[822]

TÍTULO / TITLE:  - Temozolomide suppresses MYC via activation of TAp63 to inhibit progression of human glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Sci Rep. 2013;3:1160. doi: 10.1038/srep01160. Epub 2013 Jan 29.

            ●● Enlace al texto completo (gratuito o de pago) 1038/srep01160

AUTORES / AUTHORS:  - Yamaki T; Suenaga Y; Iuchi T; Alagu J; Takatori A; Itami M; Araki A; Ohira M; Inoue M; Kageyama H; Yokoi S; Saeki N; Nakagawara A

INSTITUCIÓN / INSTITUTION:  - Division of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center  Research Institute , 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan ; Department of Neurological Surgery, School of Medicine, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan ; These authors contributed equally to this work.

RESUMEN / SUMMARY:  - Glioblastoma multiforme (GBM) is a highly invasive and chemoradioresistant brain  malignancy. Temozolomide (TMZ), a DNA-alkylating agent, is effective against GBM  and has become the standard first-line drug. However, the mechanism by which TMZ  regulates the progression of GBM remains elusive. Here, we demonstrate that TMZ targets TAp63, a p53 family member, inducing its expression to suppress the progression of human GBM. High levels of TAp63 expression in GBM tissues after TMZ treatment was an indicator of favourable prognosis. In human GBM cells, TMZ-induced TAp63 directly repressed MYC transcription. Activation of this TAp63-MYC pathway by TMZ inhibited human GBM progression both in vitro and in vivo. Furthermore, downregulation of MYC mRNA levels in recurrent GBMs after TMZ  treatment correlated with better patient survival. Therefore, our results suggest that the TAp63-mediated transcriptional repression of MYC is a novel pathway regulating TMZ efficacy in GBM.

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[823]

TÍTULO / TITLE:  - Letter to the Editor: Gliomatosis cerebri.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2010.11.PEDS10421

AUTORES / AUTHORS:  - Nejat F; Khashab ME

INSTITUCIÓN / INSTITUTION:  - Children’s Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran; and

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[824]

TÍTULO / TITLE:  - miRNAs as important drivers of glioblastomas: a no-brainer?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Biomark. 2012;11(6):245-52. doi: 10.3233/CBM-2012-0271.

            ●● Enlace al texto completo (gratuito o de pago) 3233/CBM-2012-0271

AUTORES / AUTHORS:  - Odjele A; Charest D; Morin P Jr

INSTITUCIÓN / INSTITUTION:  - Department of Chemistry and Biochemistry, Universite de Moncton, Moncton, NB, Canada.

RESUMEN / SUMMARY:  - There is no debate on the relevance of miRNAs in the pathogenesis of cancer. Numerous miRNAs with oncogenic and tumor-suppressive properties have been identified in glioblastoma multiforme (GBM), an aggressive type of brain tumor with dismal prognosis. Differential expression of these biomolecules in several cancer models makes them attractive therapeutic targets for the development of miRNA-based cancer treatments despite the hurdles associated with such an approach. In addition, systemic release of miRNAs also positions them as attractive tools for non-invasive cancer diagnosis and prognosis. This review initially looks at differentially expressed miRNAs in GBMs. Our focus will next be directed towards circulating miRNAs and how these molecules could be leveraged for cancer diagnosis as well as for the assessment of patient response to chemotherapeutic treatments. Finally, we discuss the primary strategies utilized  in the development of miRNA-focused therapeutics and summarize preclinical results gathered in GBMs to date.

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[825]

TÍTULO / TITLE:  - Fine needle aspiration cytology of primary sphenoid sinus esthesioneuroblastoma metastatic to the skin.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Avicenna J Med. 2012 Jan;2(1):15-8. doi: 10.4103/2231-0770.94806.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2231-0770.94806

AUTORES / AUTHORS:  - Akinfolarin J; Jazaerly T; Jones K; Abu-Hamdan M; Lonardo F; Folbe A; Giorgadze T

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Wayne State University, Detroit Medical Center, Detroit, MI, USA.

RESUMEN / SUMMARY:  - Esthesioneuroblastoma (ENB) is a rare tumor derived from olfactory neuroepithelium. ENB in a site outside of where olfactory epithelium exists is exceedingly rare with only five cases of ENB isolated to the sphenoid sinuses described in the literature to date. To the best of our knowledge, a skin metastasis of ENB outside the head and neck region has not been reported. We present an unusual case of a 33-year-old male diagnosed with primary sphenoid sinus ENB, who underwent surgical resection of the tumor followed by chemoradiation. About 5 months later, the patient developed a dermal mass in the  sternal region, clinically suspicious for metastasis. Fine needle aspiration (FNA) revealed a tumor with morphological features and immunophenotype consistent with the metastasis from patient’s known primary sphenoid sinus ENB. Our case demonstrates that the skin may be a rare site of a metastatic ENB, and FNA is a cost-effective and reliable diagnostic method of a suspected cutaneous metastasis.

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[826]

TÍTULO / TITLE:  - Neuro-oncology: Everolimus for astrocytoma in tuberous sclerosis complex.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Nat Rev Neurol. 2012 Dec 11;9(1):6. doi: 10.1038/nrneurol.2012.257. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2012.257

AUTORES / AUTHORS:  - Kingwell K

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[827]

TÍTULO / TITLE:  - A rare posterior cranial fossa tumor.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Cancer Res Ther. 2012 Oct;8(4):644-6. doi: 10.4103/0973-1482.106587.

            ●● Enlace al texto completo (gratuito o de pago) 4103/0973-1482.106587

AUTORES / AUTHORS:  - Nandeesh BN; Chabra MS; Babu MK; Chand AK

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, St. John’s Medical College, Bangalore, Karnataka, India.

RESUMEN / SUMMARY:  - Among tumors of the central nervous system, tumors of the mixed glioneuronal type form an important recognized subset. Some of the examples for mixed glioneuronal  tumors include gangliocytoma, dysembryoplastic neuroepithelial tumor (DNT), ganglioglioma, anaplastic ganglioglioma, and central neurocytoma. The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a new entity that has only slowly emerged in the literature due to its prior classification with other low-grade mixed glial and neuronal tumors. These tumors are relatively infrequent lesions, and therefore, they can be challenging to diagnose for the practicing pathologist. This is a rare biphasic tumor with clearly defined neurocytic and glial components. The tumor is found exclusively in the posterior  fossa, where it arises in the midline, usually occupying a substantial fraction of the fourth ventricle, and it is observed by magnetic resonance imaging (MRI) as a circumscribed, solid mass with heterogeneous contrast enhancement. We describe here a case of RGNT occurring in a 22-year-old male.

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[828]

TÍTULO / TITLE:  - Role of GalNAc4S-6ST in Astrocytic Tumor Progression.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2013;8(1):e54278. doi: 10.1371/journal.pone.0054278. Epub 2013 Jan 17.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054278

AUTORES / AUTHORS:  - Kobayashi T; Yan H; Kurahashi Y; Ito Y; Maeda H; Tada T; Hongo K; Nakayama J

INSTITUCIÓN / INSTITUTION:  - Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan ; Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan.

RESUMEN / SUMMARY:  - N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) is the sulfotransferase responsible for biosynthesis of highly sulfated chondroitin sulfate CS-E. Although involvements of CS-E in neuronal cell functions have been  extensively analyzed, the role of GalNAc4S-6ST in astrocytic tumor progression remains unknown. Here, we reveal that GalNAc4S-6ST transcripts were detected in astrocytic tumors derived from all 30 patients examined using quantitative reverse transcription-PCR analysis. Patients with high GalNAc4S-6ST mRNA expression had significantly worse outcome compared with patients with low expression, and multivariate survival analysis disclosed that GalNAc4S-6ST is an  independent poor prognostic factor for astrocytic tumors. We then tested whether  CS-E enhanced haptotaxic migration of glioblastoma U251-MG cells that endogenously express both the CS-E’s scaffold tyrosine phosphatase zeta (PTPzeta) and GalNAc4S-6ST, in the presence of CS-E’s preferred ligands, pleiotrophin (PTN) or midkine (MK), using a modified Boyden chamber method. Haptotaxic stimulation of cell migration by PTN was most robust on control siRNA-transfected U251-MG cells, while that enhancing effect was cancelled following transduction of GalNAc4S-6ST siRNA. Similar results were obtained using MK, suggesting that both  PTN and MK enhance migration of U251-MG cells by binding to CS-E. We also found that PTPzeta as well as PTN and MK were frequently expressed in astrocytic tumor  cells. Thus, our findings indicate that GalNAc4S-6ST mRNA expressed by astrocytic tumor cells is associated with poor patient prognosis likely by enhancing CS-E-mediated tumor cell motility in the presence of PTN and/or MK.

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[829]

TÍTULO / TITLE:  - The Supraorbital Eyebrow Craniotomy for Removal of Intra-axial Frontal Brain Tumors: A Technical Note.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World Neurosurg. 2013 Jan 23. pii: S1878-8750(12)01340-X. doi: 10.1016/j.wneu.2012.11.051.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.wneu.2012.11.051

AUTORES / AUTHORS:  - Ditzel Filho LF; McLaughlin N; Bresson D; Solari D; Kassam AB; Kelly DF

INSTITUCIÓN / INSTITUTION:  - Brain Tumor Center, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA, USA.

RESUMEN / SUMMARY:  - OBJECTIVE: The supraorbital (SO) “eyebrow” craniotomy is commonly used to remove  extra-axial frontal fossa and parasellar tumors such as meningiomas and craniopharyngiomas. Herein we present the utility and selection criteria for the  SO approach to resect intra-axial frontal brain lesions. METHODS: All consecutive patients who underwent a SO craniotomy for an intra-axial lesion were retrospectively analyzed for lesion location, pathology, extent of resection, operative times, length of stay and complications. RESULTS: Over 28 months, 10 patients (mean age 67.6 years, 7 female) underwent 11 SO procedures to resect intra-axial brain lesions. Pathology included metastatic carcinoma (n=7), glioma  (n=2) and radiation necrosis (n=1). The mean distance of the shortest trajectory  to the lesion was 2.4 mm. Gross total or near total removal was achieved in 80% of the cases. Median length of hospital stay was 3 days (range 2 - 6 days), and was 2 days for patients admitted electively for SO craniotomy. There were no new  neurological deficits, post-operative hematomas or CSF leaks. CONCLUSION: The SO  “eyebrow” craniotomy is a safe and effective keyhole method to remove intra-axial frontal lobe lesions, particularly those of the frontal pole and orbito-frontal region, allowing for minimal disruption of normal brain parenchyma, and promoting a rapid recovery and relatively short hospital stay. Metastatic tumors and select gliomas in this area are most amenable to this approach. Deeper intra-axial tumors can also be effectively accessed via this route with excellent clinical outcomes.

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[830]

TÍTULO / TITLE:  - Primary diffuse large B cell lymphoma of the cranial vault.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Iran J Radiol. 2012 Jun;9(2):88-92. doi: 10.5812/iranjradiol.7734. Epub 2012 Jun  30.

            ●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.7734

AUTORES / AUTHORS:  - Rezaei-Kalantari K; Samimi K; Jafari M; Karimi MA; Ansari K; Davoodi M; Nabi-Meybodi M; Gorjian M

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Hazrat Rasoul-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.

RESUMEN / SUMMARY:  - Primary non-Hodgkin’s lymphoma of the cranial vault is extremely rare. This case  report presents a 42-year-old man with a painless subcutaneous scalp mass which extended intracranially associated with recent mild headache. Initial computed tomography and magnetic resonance imaging revealed two lesions emanating from the skull. Biopsy revealed a diagnosis of diffuse large B cell lymphoma (DLBCL). A thorough work-up revealed no other point of involvement. This case is concerned about considering lymphoma in the differential diagnosis of calvarial lesions with both intra- and extra cranial extensions but without obvious intervening bony destruction.

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[831]

TÍTULO / TITLE:  - Encephalocraniocutaneous Lipomatosis without Neurologic Anomalies.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Dermatol. 2012 Nov;24(4):476-8. doi: 10.5021/ad.2012.24.4.476. Epub 2012 Nov  8.

            ●● Enlace al texto completo (gratuito o de pago) 5021/ad.2012.24.4.476

AUTORES / AUTHORS:  - Kim DH; Park SB; Lee Y; Im M; Seo YJ; Choi SH; Lee JH

INSTITUCIÓN / INSTITUTION:  - Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.

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[832]

TÍTULO / TITLE:  - GATA4 and DcR1 methylation in glioblastomas.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Diagn Pathol. 2013 Jan 15;8(1):7.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-7

AUTORES / AUTHORS:  - Vaitkiene P; Skiriute D; Skauminas K; Tamasauskas A

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Epigenetic silencing of tumor suppressor genes plays important role in gliomagenesis. Recently, GATA4 and DcR1 were suggested to be a  tumor suppressor genes involved in tumorigenesis in various types of human cancers. However, up to now the methylation frequency of GATA4 and DcR1 genes has not been determined in glioblastoma. In this study, we investigated methylation of GATA4 and DcR1 promoters and their association with patient prognosis in glioblastoma. METHODS: Methylation status of GATA4 and DcR1 promoters was investigated by methylation specific PCR in 99 glioblastoma patients. Statistical analyses were conducted to investigate the association between clinical variables and overall survival time. RESULTS: GATA4 and DcR1 were aberrantly methylated in  23.2% and 27.6% of glioblastoma tumors, but not in normal brain. GATA4 promoter hypermethylation showed significant association with patients age (p = 0.027). Relationship between genes promoter methylation and glioblastoma patient survival was not determined. CONCLUSIONS: The present work demonstrated that GATA4 and DcR1 promoter hypermethylation is tumor specific event in glioblastoma but they promoter methylation cannot be considered as a prognostic marker of glioblastoma  survival. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/1381170351801852.

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[833]

TÍTULO / TITLE:  - BRAF-Mediated Regulation of mTOR Drives Gliomagenesis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Jan;3(1):OF21. doi: 10.1158/2159-8290.CD-RW2012-209. Epub 2012 Nov 21.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2012-209

RESUMEN / SUMMARY:  - The f-BRAF fusion protein enhances NSC growth and gliomagenesis in a cell-type-specific manner.

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[834]

TÍTULO / TITLE:  - Leptomeningeal carcinomatosis from ethmoid sinus adenocarcinoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Dec 26. pii: S1879-7296(12)00103-2.  doi: 10.1016/j.anorl.2012.07.004.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.anorl.2012.07.004

AUTORES / AUTHORS:  - Espitalier F; Michel G; Mourrain-Langlois E; Lebouvier T; Bord E; Ferron C; Malard O

INSTITUCIÓN / INSTITUTION:  - Service d’ORL et Chirurgie Cervico-Faciale, CHU de Nantes, Hotel Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. Electronic address: florent.espitalier@chu-nantes.fr.

RESUMEN / SUMMARY:  - INTRODUCTION: Adenocarcinoma of the ethmoid is an aggressive tumor, with potential extension to surrounding structures. Leptomeningeal extension is a rarely reported entity. CASE REPORT: A carpenter, aged 55, developed multifocal cranial nerve-related symptoms 1week after resection of adenocarcinoma of the ethmoid, evolving towards deteriorated general health status and death 10weeks later. Brain MRI showed diffuse contrast enhancement of the cranial nerves, and repeated cerebrospinal fluid (CSF) examination found increased protein concentration associated with decreased glucose concentration, without malignant  cells. The diagnosis of carcinomatous meningitis was based on the association of  clinical, CSF and brain MRI data. DISCUSSION/CONCLUSION: Leptomeningeal dissemination of adenocarcinoma of the ethmoid is rare; diagnosis is guided by clinical signs. MRI reveals neurological spread, but the presence of malignant cells in the CSF is sufficient for diagnosis. Due to poor prognosis, the only currently available treatments are palliative.

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[835]

TÍTULO / TITLE:  - Dural Metastases of a Glioblastoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Clin Neuroradiol. 2012 Dec 23.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00062-012-0192-8

AUTORES / AUTHORS:  - Lettau M; Jedrusik P; Laible M

INSTITUCIÓN / INSTITUTION:  - Division of Neuroradiology, Department of Neurosurgery, University of Freiburg Medical Center, Breisacher Strasse 64, 79106, Freiburg, Germany, michael_lettau@gmx.de.

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[836]

TÍTULO / TITLE:  - Malignant glioma with angiocentric features.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurosurg Pediatr. 2012 Dec 14.

            ●● Enlace al texto completo (gratuito o de pago) 3171/2012.11.PEDS12234

AUTORES / AUTHORS:  - Lu JQ; Patel S; Wilson BA; Pugh J; Mehta V

INSTITUCIÓN / INSTITUTION:  - Departments of Laboratory Medicine and Pathology.

RESUMEN / SUMMARY:  - Angiocentric glioma is a recently recognized benign brain tumor with unknown histogenesis. Most of these tumors are mitotically low in activity in accord with their benign clinical course. However, increased mitotic activity has been noted  in several cases, one of which had an ultimately fatal outcome. Here, the authors present a tumor showing angiocentric glioma and glioblastoma-like features, with  recurrence of the lower-grade component after radiotherapy. A 15-year-old boy presented with a 3-month history of progressive left-sided weakness and headache. Magnetic resonance imaging showed a large heterogeneous mass in the right frontal lobe, with mild post-Gd enhancement. A gross-total resection was obtained. Histopathological examination of the resected tissue revealed a tumor with 2 distinct appearances: 1) a mildly to moderately cellular infiltrating tumor with  angiocentric glioma characteristics, and 2) a markedly cellular glioblastoma-like tissue with necrosis and microvascular proliferation. The patient received a course of postoperative radiotherapy to 59.4 Gy in 33 fractions administered over the course of 6.5 weeks, but his tumor recurred 4 months after resection. A second resection was then performed. The recurrent tumor exhibited radiation-induced changes and persistent characteristics of angiocentric glioma,  but it had fewer malignant features; the mitotic activity was lower, and there was no necrosis or microvascular proliferation. The findings in this case, along  with those in several previously reported cases, suggest that angiocentric gliomas may have a malignant variant or malignant transformation. Angiocentric gliomas with malignant features tend to recur, for which surgical intervention followed by radiotherapy and chemotherapy should be offered as a therapeutic option.

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[837]

TÍTULO / TITLE:  - Iatrogenic intradural lumbosacral cyst following epiduroscopy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Korean Neurosurg Soc. 2012 Nov;52(5):491-4. doi: 10.3340/jkns.2012.52.5.491. Epub 2012 Nov 30.

            ●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2012.52.5.491

AUTORES / AUTHORS:  - Ryu KS; Rathi NK; Kim G; Park CK

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Seoul St. Mary’s Hospital, The Catholic University College of Medicine, Seoul, Korea.

RESUMEN / SUMMARY:  - We report a rare complication of iatrogenic spinal intradural following minimally invasive extradural endoscopic procedues in the lumbo-sacral spines. To our knowledge, intradural cyst following epiduroscopy has not been reported in the literature. A 65-year-old woman with back pain related with previous lumbar disc  surgery underwent endoscopic epidural neuroplasty and nerve block, but her back pain much aggravated after this procedure. Postoperative magnetic resonance imaging revealed a large intradural cyst from S1-2 to L2-3 displacing the nerve roots anteriorly. On T1 and T2-weighted image, the signal within the cyst had the same intensity as cerebrospinal fluid. The patient underwent partial laminectomy  of L5 and intradural exploration, and fenestration of the cystic wall was accomplished. During operation, the communication between the cyst and subarachnoid space was not identified, and the content of the cyst was the same as that of cerebrospinal fluid. Postoperatively, the pain attenuated immediately. Incidental durotomy which occurred during advancing the endoscope through epidural space may be the cause of formation of the intradural cyst. Intrdural cyst should be considered, if a patient complains of new symptoms such as aggravation of back pain after epiduroscopy. Surgical treatment, simple fenestration of the cyst may lead to improved outcome. All the procedures using epiduroscopy should be performed with caution.

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[838]

TÍTULO / TITLE:  - An Antiviral NK-Cell Response Impairs Glioblastoma Virotherapy.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Discov. 2013 Jan;3(1):OF19. doi: 10.1158/2159-8290.CD-RW2012-219. Epub 2012 Dec 6.

            ●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2012-219

RESUMEN / SUMMARY:  - An NK-cell-mediated immune response reduces the efficacy of oncolytic HSV glioblastoma therapy.

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[839]

TÍTULO / TITLE:  - Diffuse intrinsic pontine glioma: poised for progress.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Front Oncol. 2012;2:205. doi: 10.3389/fonc.2012.00205. Epub 2012 Dec 28.

            ●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2012.00205

AUTORES / AUTHORS:  - Warren KE

INSTITUCIÓN / INSTITUTION:  - Pediatric Neuro-Oncology Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health Bethesda, MD, USA.

RESUMEN / SUMMARY:  - Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be  similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the  stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies.

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[840]

TÍTULO / TITLE:  - A huge malignant peripheral nerve sheath tumor with hepatic metastasis arising from retroperitoneal ganglioneuroma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2013 Jan;5(1):123-126. Epub 2012 Oct 10.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.961

AUTORES / AUTHORS:  - Meng ZH; Yang YS; Cheng KL; Chen GQ; Wang LP; Li W

INSTITUCIÓN / INSTITUTION:  - Departments of Hepatobiliary-Pancreatic Surgery.

RESUMEN / SUMMARY:  - Ganglioneuromas (GNs) are the rarest and most benign of the neuroblastic tumors.  We experienced a case of huge retroperitoneal GN which differentiated into malignant peripheral nerve sheath tumors (MPNST) with hepatic metastasis. The tumor was located in the upper right quarter of the abdomen and pressed the right lobe of the liver, which was initially misdiagnosed as a liver carcinoma. The tumor shared blood supply with the right liver lob and had rich blood supplies from the abdominal aorta, renal artery and hepatic artery. It was also associated with skin pigment and recurrence shortly following resection. Our finding demonstrated that MPNST is a potent invasive malignant tumor and metastasis earlier with very poor prognosis.

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[841]

TÍTULO / TITLE:  - Retroperitoneal ganglioneuroma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - APSP J Case Rep. 2013 Jan;4(1):8. Epub 2013 Jan 1.

AUTORES / AUTHORS:  - Singh J; Kr Priyadarshi V; Kumar Pandey P; Kr Vijay M; Kumar Pal D; Kundu A

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Institute of Postgraduate Medical Education and Research,  Kolkata. India.

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[842]

TÍTULO / TITLE:  - A rare presentation of craniopharyngioma: delayed puberty.

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 http://bmj.com/search.dtl 

            ●● Cita: British Medical J. (BMJ): <> Case Rep. 2012 Nov 28;2012. pii: bcr2012007519. doi: 10.1136/bcr-2012-007519.

            ●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007519

AUTORES / AUTHORS:  - Inci MF; Ozkan F; Bozkurt S; Demir CF

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Sutcu Imam University Medical School, Kahramanmaras, Turkey. drfatihinci@gmail.com

RESUMEN / SUMMARY:  - Craniopharyngiomas are the most frequently encountered suprasellar tumours in children. Owing to the slow growth rate of these tumours, they are often quite large before becoming symptomatic. They are more common among children and older  adults (55-74 years). Depending upon the direction of growth and tumour size, craniopharyngiomas can affect the hypothalamus, pituitary stalk, optic nerves and chiasm and carotid arteries. Compression of these neural and vascular structures  frequently precipitates endocrine disorders, visual loss and an increased intracranial pressure. Hypopituitarism leading to a delayed puberty is a rare presentation of craniopharyngioma. The diagnosis of craniopharyngioma is usually  made with the classic radiological imaging features based on CT and MRI.

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[843]

TÍTULO / TITLE:  - Ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - World J Clin Oncol. 2012 Dec 10;3(12):155-8. doi: 10.5306/wjco.v3.i12.155.

            ●● Enlace al texto completo (gratuito o de pago) 5306/wjco.v3.i12.155

AUTORES / AUTHORS:  - Hayama S; Ohmi M; Yonemori A; Yamabuki T; Inomata H; Nihei K; Hirano S

INSTITUCIÓN / INSTITUTION:  - Satoshi Hayama, Makoto Ohmi, Atsuya Yonemori, Takumi Yamabuki, Hitoshi Inomata, Kazuyoshi Nihei, Department of Surgery, Kushiro Red Cross Hospital, 21-14 Shineicyo, Kushiro, Hokkaido 085-8512, Japan.

RESUMEN / SUMMARY:  - We discuss an extremely rare case of ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma. Radiological examinations showed a cystic tumor sandwiched between the pancreas and left kidney. Surgery was scheduled because the tumor seemed to have originated from the pancreas. En-block resection of the tumor with distal pancreatectomy, splenectomy, and left adrenalectomy was  performed. In terms of macroscopic appearance, the tumor mainly consisted of a unilocular cystic mass, but the presence of a smaller, solid mass was also noted  within the tumor. Histopathologic examination confirmed that the cystic mass was  consistent with a mature cystic teratoma of the retroperitoneum, and in addition, a ganglioneuroblastoma was evident in the solid component. Histopathologically, the ganglioneuroblastomatous area was intimately associated with dermoid tissue of the mature cystic teratoma, thus this case was diagnosed to be a mature cystic teratoma with malignant transformation. To best of our knowledge, this is the first reported case of ganglioneuroblastoma arising in a mature cystic teratoma.

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[844]

TÍTULO / TITLE:  - Pituitary adenoma volumetry with 3D Slicer.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - PLoS One. 2012;7(12):e51788. doi: 10.1371/journal.pone.0051788. Epub 2012 Dec 11.

            ●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051788

AUTORES / AUTHORS:  - Egger J; Kapur T; Nimsky C; Kikinis R

INSTITUCIÓN / INSTITUTION:  - Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. egger@bwh.harvard.edu

RESUMEN / SUMMARY:  - In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and  performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97+/-3.39%.

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[845]

TÍTULO / TITLE:  - Arachnoid cyst of the velum interpositum originating from tela choroidea.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Surg Neurol Int. 2012;3:120. doi: 10.4103/2152-7806.102334. Epub 2012 Oct 13.

            ●● Enlace al texto completo (gratuito o de pago) 4103/2152-7806.102334

AUTORES / AUTHORS:  - Funaki T; Makino Y; Arakawa Y; Hojo M; Kunieda T; Takagi Y; Takahashi JC; Miyamoto S

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.

RESUMEN / SUMMARY:  - BACKGROUND: Arachnoid cysts originating from the velum interpositum are very rare, and their existence as a clinicopathologic entity remains controversial. We report a case of a patient with an arachnoid cyst of the velum interpositum presenting with memory disturbance, focusing on the anatomical origin of the lesion and the physiological mechanisms causing memory disturbance. CASE DESCRIPTION: A 65-year-old man with a large cystic lesion in the velum interpositum experienced progressive memory disturbance and enlargement of the lesion 6 months before referral to our institution. Neuropsychological evaluation on admission demonstrated severe memory disturbance. Radiological examination did not reveal hydrocephalus, but the bilateral fornices and thalami were compressed  by the cyst. The patient underwent endoscopic cystoventriculostomy via the frontal horn of the right lateral ventricle through a frontal burr hole. Histopathology of the sample was consistent with that of an arachnoid cyst, and the endoscopic findings suggested that the cyst originated from the tela choroidea, which covers the velum interpositum. The symptoms resolved after surgery with significant improvement in neuropsychological test scores. CONCLUSION: Arachnoid cysts of the velum interpositum are rare but distinct clinicopathologic entities that originate from the tela choroidea. The lesions can cause memory disturbance without hydrocephalus due to compression of the fornices and thalami, but this can be reversed by surgery.

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[846]

TÍTULO / TITLE:  - Stevens Johnson Syndrome-An Adverse Drug Reaction Occurred after Uncomplicated Removal of an Intracerebral Cavernous Hemangioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - J Neurol Surg A Cent Eur Neurosurg. 2013 Jan 14.

            ●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1330112

AUTORES / AUTHORS:  - Akhavan-Sigari R; Rohde V; Abili M

INSTITUCIÓN / INSTITUTION:  - Department of Neurosurgery, University Medical Center Gottingen, Georg-August-University Gottingen, Germany.

RESUMEN / SUMMARY:  - Background Toxic epidermal necrolysis (TEN) is a rare, severe adverse drug reaction. Steven-Johnson syndrome (SJS) represents the milder end of the spectrum. The exact pathogenesis of TEN and SJS is still unknown. Many drugs, including prednisolone, cyclosporin, and intravenous immunoglobulin (IVIG), have  been used in an attempt to halt the disease process. The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks.Case In this paper, we describe a young patient who underwent a total removal of an intracerebral cavernous hemangioma following development of SJS after taking phenytoin postoperatively.Conclusion We suggest that the practice of routine use of phenytoin following brain surgery should be re-evaluated because the treatment may be neither essential nor without side effects.

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[847]

TÍTULO / TITLE:  - Ganglioneuroma of the adrenal gland: a rare tumor in a rare location.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Oncol. 2012 Sep;5(3):487-9. doi: 10.1159/000342445. Epub 2012 Sep 4.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000342445

AUTORES / AUTHORS:  - Gilshtein H; Peled Z; Grunner S; Fischer D; Kakiashvili E; Kluger Y

INSTITUCIÓN / INSTITUTION:  - Division of Surgical Oncology, Department of General Surgery.

RESUMEN / SUMMARY:  - A 62-year-old man presented to his general practitioner complaining of non-specific back pain. He underwent a computerized tomography scan and magnetic  resonance imaging that revealed a large left adrenal mass. A thorough investigation of this mass revealed it to be a non-secreting tumor. At surgery, a large tumor of the left adrenal was found. The final pathology report revealed a  ganglioneuroma of the adrenal gland.

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[848]

TÍTULO / TITLE:  - Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Oncol Lett. 2012 Dec;4(6):1321-1324. Epub 2012 Sep 14.

            ●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.918

AUTORES / AUTHORS:  - Ma R; Zhang G; Wang H; Lv H; Fang F; Kang X

INSTITUCIÓN / INSTITUTION:  - Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Dongcheng, Beijing 100050;

RESUMEN / SUMMARY:  - Low-grade glioma is predisposed to progress to anaplastic astrocytoma and eventually secondary glioblastoma. The malignant transformation may involve the accumulation of multiple genetic alterations. The purpose of this study was to explore the role of miR-544 in glioma progression and discuss whether it may be a novel biomarker of malignant transformation. The expression of miR-544 was measured in a series of 198 glioma samples (63 low-grade glioma, 44 anaplastic astrocytoma and 91 glioblastoma tumors) using microarrays. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the expression levels of miR-544 in tissue and serum samples in an independent validated cohort (25 low-grade glioma, 21 anaplastic astrocytoma and 20 glioblastoma tumors). A Pearson correlation analysis was performed to examine the correlation between miR-544 levels of tissue and serum samples. Microarrays revealed that the expression levels of miR-544 decreased significantly in anaplastic gliomas (P<0.01) or glioblastoma (P<0.01) compared with low-grade gliomas. In an independent cohort of glioma patients, miR-544 exhibited a progression-associated downregulation in glioma tumors. The levels of miR-544 in serum samples tended to be lower in anaplastic and glioblastoma patients compared with low-grade gliomas, but with no significant difference. The Pearson correlation analysis revealed a weakly positive correlation between tissue and serum levels of miR-544. These data support a significant role for miR-544 aberration in the malignant transformation of glioma. The downregulation of miR-544 in tissue may be used as  a novel biomarker.

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