Volume 1 (5). July 2013.

GLIOMAS.ORG NEWSLETTER
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GLIOMAS.ORG NEWSLETTERS is a short electronic newsletter periodically released by e-mail as a PDF file to subscribers who want to keep updated on the latest advances on glioma research including but not limited to:
DRUGS & CHEMOTHERAPY NEURORADIOLOGY NEUROIMAGING NEUROSURGERY NEUROPHARMACOLOGY NANOMEDICINE GLIOMA BIOLOGY CLINICAL STUDIES related to the diagnosis, treatment and prognosis of glioma patients. GLIOMAS.ORG. An International Consortium

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In this issue
IMAGES IN GLIOMA RESEARCH: AVAglio study design. Glioma rat model for surgical technique evaluation BCL2A1 is a Potential Biomarker for Postoperative Seizure Control Salvianolic Acid B Induces Apoptosis in Human Glioma U87 Cells Activation of the phosphorylation of ATM contributes to radioresistance of glioma stem cells A spliceosome protein is essential for glioma stem cell viability Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir Webinar Recording Optic Gliomas

_____________________________________________________________________________________________________________________________ Volume 1 (5), July 2013. www.gliomas.org

GLIOMAS.ORG NEWSLETTERS

IMAGES IN GLIOMAS RESEARCH

Glioblastoma (GBM) or grade IV glioma is the most common primary brain tumor in adults. Standard treatment median overall survival (OS) is only 14-15 months and less than 10% of patients will survive 5 years after diagnosis. There is no standard treatment in recurrent GBM and OS ranges from 3 to 9 months. GBM is 1 of the most vascularized human tumors and GBM cells produce vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF, has demonstrated activity in vitro and in phase II trials in relapse, as well as in 1 phase III trial as first line therapy. Bevacizumab also improves quality of life for patients suffering GBM. This paper reviews the mechanism of action of bevacizumab, its metabolism and pharmacokinetic profile. It summarizes the clinical studies in recurrent and newly diagnosed GBM, its potential side effects and complications and its place in therapy.

AVAglio study design. From: Gil-Gil MJ, Mesia C, Rey M, Bruna J. Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol. 2013 Jun 6;7:123-35.

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GLIOMAS.ORG NEWSLETTERS NEUROSURGERY Glioma rat model for surgical technique evaluation DNA DAMAGE RESPONSE Activation of the phosphorylation of ATM contributes to radioresistance of glioma stem cells

A glioma rat model consisting of the C6 cell line and SpragueDawley rats as recipients could be a well-suited model to investigate surgical techniques and their impact on tumour therapy. However, the site of transplantation of the glioma cells, the preparation of cell grafts and the technique of tumour growth evaluation is of utmost importance to achieve reliable results .
Keiner D, Heimann A, Kronfeld A, Sommer C, Mueller-Forell W, Kempski O, Oertel J. Towards a glioma model for surgical technique evaluation in the rat. Br J Neurosurg. 2013

Activated downstream efectors of ataxia telangiectasia mutated (ATM) were found to be higher in glioma stem cells (GSCs) compared to glioma cells (GCs). CSCs were more resistant to radiation compared to GCs. Inhibition of ATM could significantly reduce the radioresistance of GSCs and GCs. ATM may represent a source of radioresistance in GSCs and a target of improved radiosensitivity of GSCs.
Zhou W, Sun M, Li GH, Wu YZ, Wang Y, Jin F, Zhang YY, Yang L, Wang DL. Activation of the phosphorylation of ATM contributes to radioresistance of glioma stem cells. Oncol Rep. 2013 Jul 11. doi: 10.3892/or.2013.2614.

BIOMARKERS BCL2A1 is a Potential Biomarker for Postoperative Seizure Control

B-cell lymphoma 2 proteins (BCL2) are important cell death regulators, whose main function is to control the release of cytochrome c from mitochondria in the intrinsic apoptotic pathway. A homologous protein, BCL2-related protein A1 (BCL2A1) that is overexpressed in a variety of cancer cells, was proven to be a novel marker associated with seizure prognosis in patients with low-grade gliomas (LGGs).
You G, Feng L, Yan W, Zhang W, Wang YZ, Li SW, Li SW, Li GL, Song YJ, Kang CS, You YP, Jiang T. BCL2A1 is a Potential Biomarker for Postoperative Seizure Control in Patients with Low-grade Gliomas. CNS Neurosci Ther. 2013

GLIOMA STEM CELLS A spliceosome protein is essential for glioma stem cell viability

The PHD finger protein 5A (PHF5A), which encodes a component of the U2 small nuclear ribonucleoprotein (snRNP) splicing complex, as a gene specifically required for the viability of GSCs but not normal neural stem cells (NSCs). PHF5Amediated exon recognition is selectively required for GSC viability and tumor formation.
[No authors listed] A spliceosome protein is essential for glioma stem cell viability. Cancer Discov. 2013 Jul;3(7):OF22. doi: 10.1158/21598290.CD-RW2013-105. Epub 2013 May 16. PMID: 23847366. Comment on: Hubert CG, Bradley RK, Ding Y, Toledo CM, Herman J, Skutt-Kakaria K, Girard EJ, Davison J, Berndt J, Corrin P, Hardcastle J, Basom R, Delrow JJ, Webb T, Pollard SM, Lee J, Olson JM, Paddison PJ. Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A. Genes Dev. 2013 May 1;27(9):1032-45. doi: 10.1101/gad.212548.112. PMID: 23651857

TRADITIONAL CHINESE MEDICINE Salvianolic Acid B Induces Apoptosis in Human Glioma U87 Cells

NEUROIMAGING & NEUROSURGERY Salvianolic acid B Structure Awake language mapping and 3-Tesla intraoperative MRIguided volumetric resection

Salvianolic acid B (SalB), the main water-soluble bioactive compounds isolated from the traditional Chinese medical herb Danshen significantly decreased cell viability of U87 cells in a dose- and time-dependent manner. SalB also enhanced the intracellular ROS generation and induced apoptotic cell death in U87 cells. SalB can be considered as a potential effective and safe natural anticancer agent for glioma prevention and treatment glioma.
Wang ZS, Luo P, Dai SH, Liu ZB, Zheng XR, Chen T. Salvianolic Acid B Induces Apoptosis in Human Glioma U87 Cells Through p38Mediated ROS Generation. Cell Mol Neurobiol. 2013 Jul 11. [Epub ahead of print] PMID: 23842993

Two technologies awake surgery and intraoperative MRI (iMRI usually used independently for the optimization and the maximal safe resection of gliomas were combined by a Chinese team. The study involved 30 patients and showed a potential utility. It was reported to be safe and.
Lu J, Wu J, Yao C, Zhuang D, Qiu T, Hu X, Zhang J, Gong X, Liang W, Mao Y, Zhou L. Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas. J Clin Neurosci. 2013 Jul 10. doi:pii: S0967-5868(13)00068-4. 10.1016/j.jocn.2012.10.042. [Epub ahead of print] PMID: 23850046

GENE THERAPY (PHASE III CLINICAL STUDY) __________________________________________________________________________________________________________________________ Volume 1 (5), July 2013. www.gliomas.org

GLIOMAS.ORG NEWSLETTERS Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir

II Anticancer Drugs Meeting 22-23 August, 2013 Stockholm, Sweden

Ganciclovir Structure

A team in Germany assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme (herpes-simplex-virus thymidine kinase; sitimagene ceradenovec) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma. The use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme, although the intervention did not improve overall survival
Westphal M, Yl-Herttuala S, Martin J, Warnke P, Menei P, Eckland D, Kinley J, Kay R, Ram Z; for the ASPECT Study Group. Adenovirusmediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Jul 11. doi:pii: S1470-2045(13)70274-2. 10.1016/S14702045(13)70274-2. [Epub ahead of print] PMID: 23850491

Confirmed Speakers from US Germany France UK Sweden Egypt Australia Israel Japan Saudi Arabia Mexico Russia and other countries will present their work

www.anticancerdrugs.org/2013

NEWS Webinar Recording Optic Gliomas

The Neurofibromatosis Network presented this webinar on optic gliomas in neurofibromatosis type 1 in May of 2012. The speaker was Dr. Robert Listernick, the director of the NF clinic at Luries Childrens Hospital in Chicago.placebo. View the video at the link shown below.
Source: http://www.nfmidwest.org/webinar-recording-optic-gliomas/

_____________________________________________________________________________________________________________________________ Volume 1 (5), July 2013. www.gliomas.org