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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 clon