Volume 1 (4). June 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:
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In this issue
IMAGES IN GLIOMA RESEARCH: Myxoma virus infection promotes NK lysis of glioma cells. Glioma microvesicles Dying endothelial cell stimulates glioma cell proliferation Neuro-oncology practives in Australia Neuro-oncology practives in China Transferrin-conjugated doxorubicin-based nanoparticles A new practical scoring system for glioblastoma may predict survival RETRACTION: Antiglioma activity of curcumin-loaded lipid nanoparticles

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IMAGES IN GLIOMAS RESEARCH Abstract: Myxoma virus (MYXV) is a well-established oncolytic agent against different types of tumors. MYXV is also known for its immunomodulatory properties in down-regulating major histocompatibility complex (MHC) I surface expression (via the M153R gene product, a viral E3-ubiquitin ligase) and suppressing T cell killing of infected target cells. MHC I down-regulation, however, favors NK cell activation. Brain tumors including gliomas are characterized by high MHC I expression with impaired NK activity. We thus hypothesized that MYXV infection of glioma cells will promote NK cell-mediated recognition and killing of gliomas. We infected human gliomas with MYXV and evaluated their susceptibility to NK cell-mediated cytotoxicity. MYXV enhanced NK cell-mediated killing of glioma cells (U87 cells, MYXV vs. Mock: 51.73% vs. 28.63%, P=.0001, t test; U251 cells, MYXV vs. Mock: 40.4% vs. 20.03%, P .0007, t test). Using MYXV M153R targeted knockout (designated vMyx-M153KO) to infect gliomas, we demonstrate that M153R was responsible for reduced expression of MHC I on gliomas and enhanced NK cell-mediated antiglioma activity (U87 cells, MYXV vs. vMyx-M153KO: 51.73% vs. 25.17%, P=.0002, t test; U251 cells, MYXV vs. vMyx-M153KO: 40.4% vs. 19.27, P=.0013, t test). Consequently, NK cell-mediated lysis of established human glioma tumors in CB-17 SCID mice was accelerated with improved mouse survival (log-rank P=.0072). These results demonstrate the potential for combining MYXV with NK cells to effectively kill malignant gliomas.

Immunohistochemistry performed on paraffin sections of mice brains with established U87 tumors that were treated with indicated viruses for 48 h. Hematoxylin and Eosin (H&E) stain shows tumor, with the arrows indicating tumor location in the brain. Brown M-T7 stain represents MYXV early protein staining within the tumor. Photomicrographs were magnified 25X and 200X. FROM: Ogbomo H, Zemp FJ, Lun X, Zhang J, Stack D, Rahman MM, McFadden G, Mody CH, Forsyth PA. Myxoma virus infection promotes NK lysis of malignant gliomas in vitro and in vivo. PLoS One. 2013 Jun 10;8(6):e66825

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GLIOMAS.ORG NEWSLETTERS TUMOR BIOLOGY Glioma microvesicles carry selectively packaged coding and noncoding RNAs Oncology patterns of care study. Asia Pac J Clin Oncol. 2013 May 29. doi: 10.1111/ajco.12079. [Epub ahead of print] PMID: 23714694

A study found that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. When brain microvascular endothelial cells were exposed for short-term to glioma microvesicles gene expression changes in the endothelial cells that cannot be fully explained by direct delivery of transcripts were observed. These results hightlight the increasing complexity of the interactions between glioma cells and their local environment that are critical determinants of brain tumor growth, infiltration and neovascularisation.
Li CC, Eaton SA, Young PE, Lee M, Shuttleworth R, Humphreys DT, Grau GE, Combes V, Bebawy M, Gong J, Brammah S, Buckland ME, Suter CM. Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells. RNA Biol. 2013 Jun 17;10(8).

Chemotherapy for gliomas in mainland China

Chemotherapy is currently the standard treatment modality for malignant gliomas and is usually administered by the Department of Neurosurgery. Studies on chemotherapy for gliomas began in the 1970s in mainland China but well-designed randomized controlled trials (RCTs) are rare. Oral or intravenous administration was found in 55.7% of studies, followed by intraarterial (26.7%) and interstitial (15.7%) chemotherapy. Nitrosoureas were the most frequently used chemotherapeutic agents, as found in 133 studies (63.3%). Since 2003, 56 studies on temozolomide (TMZ) have been published.. There is a need to carry out high-quality multicenter RCTs on chemotherapy for gliomas.
Sai K, Yang QY, Shen D, Chen ZP. Chemotherapy for gliomas in mainland China: An overview. Oncol Lett. 2013 May;5(5):1448-1452. Epub 2013 Mar 19. PMID: 23761809 [PubMed]

Dying endothelial cells stimulate proliferation of malignant glioma cells

Apoptotic cells may have a compensatory effect on the proliferation of neighboring cells. By coculturing glioma cell lines with dying ECs under various conditions a study showed evidence that dying vascular endothelial cells (ECs) facilitate glioma cell growth via a caspase 3-mediated pathway. Calciumindependent phospholipase A2 (iPLA2) and Prostaglandin E2 (PGE2), downstream effectors effector of the caspase 3-iPLA2 signaling pathway are involved. Blocking this compensatory proliferation effecgs during tumor therapy may be a promising approach for improving the prognosis of these malignant tumors.
Mao P, Smith L, Xie W, Wang M. Dying endothelial cells stimulate proliferation of malignant glioma cells via a caspase 3-mediated pathway. Oncol Lett. 2013 May;5(5):1615-1620.

NANOPHARMACOLOGY Transferrin-Modified Doxorubicin-Loaded Biodegradable Nanoparticles

NEURO-ONCOLOGY PRACTICE Neuro-oncology practices in Australia Doxorubicin

A survey of 28 Australia cancer centres showed that treatment protocols are virtually identical for patients with an initial diagnosis of glioblastoma multiforme (GBM). Variation was found for older or less fit patients. 70% of patients received chemotherapy at recurrence, usually modified schedule temozolomide. 50% of the cancer centers offered bevacizumab. For anaplastic astrocytoma (AA), most clinicians offer radiotherapy alone but 30% would use radiotherapy with concurrent and adjuvant temozolomide. 50% of clinicians continued to use prophylactic anticonvulsants; 25% do not prescribe prophylactic antibiotics during chemoradiotherapy and 50% would continue anti-coagulation therapy indefinitely for thromboembolism.

A novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Doxorubicin (Dox) was developed and tested for glioma treatment using C6 glioma intracranial implant rat model as experimental model. The Nanoparticles were conjugated to Transferrin (Tf) specifically target the NP to glioma. The average diameter of Tf-NP-Dox was 100nm with 32 Tf molecules on the surface. Tf-NP-Dox demonstrated much stronger cytotoxicity to C6 glioma cells compared to NP-Dox or Dox. Thus, Tf-NP-Dox is a potential nano-scale drug delivery system for glioma chemotherapy.
Liu G, Mao J, Jiang Z, Sun T, Hu Y, Jiang Z, Zhang C, Dong J, Huang Q, Lan Q. Transferrin-Modified Doxorubicin-Loaded Biodegradable Nanoparticles Exhibit Enhanced Efficacy in Treating Brain GliomaBearing Rats. Cancer Biother Radiopharm. 2013 Jun 20

Chen JY, Hovey E, Rosenthal M, Livingstone A, Simes J. Neurooncology practices in Australia: A Cooperative Group for Neuro__________________________________________________________________________________________________________________________ Volume 1 (4), June 2013. www.gliomas.org

GLIOMAS.ORG NEWSLETTERS II Anticancer Drugs NEUROSURGERY A new practical scoring system for glioblastoma may predict survival Meeting 22-23 August, 2013 Stockholm, Sweden

A new scale was devised to predict the survival of patients with recurrent glioblastoma. A 3-tier scale (scoring range, 0-2 points) composed of additive scores for the Karnofsky performance status (KPS) (0 for KPS 70 and 1 for KPS < 70) and ependymal involvement (0 for no enhancement and 1 for enhancement of the ventricle wall in the magnetic resonance imaging) significantly distinguished groups with good (0 points; median survival, 18.0 months), intermediate (1 point; median survival, 10.0 months), and poor prognoses (2 points; median survival, 4.0 months). The new scale was successfully applied to the validation cohort of patients showing distinct prognosis among the groups (median survivals of 11.0, 9.0, and 4.0 months for the 0-, 1-, and 2-point groups, respectively). The devised scale was validated with a separate set of 96 patients from 3 different institutes.
Park CK, Kim JH, Nam DH, Kim CY, Chung SB, Kim YH, Seol HJ, Kim TM, Choi SH, Lee SH, Heo DS, Kim IH, Kim DG, Jung HW. A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma. Neuro Oncol. 2013 Jun 25. [Epub ahead of print]

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

RETRACTION Antiglioma activity of curcumin-loaded lipid nanoparticles

The following article has been retracted at the request of the Editor-in-Chief citing unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia: Kundu P, Mohanty C, Sahoo SK Antiglioma activity of curcuminloaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy. Acta Biomater. 2012 Jul;8(7):2670-87. doi: 10.1016/j.actbio.2012.03.048
Kundu P, Mohanty C, Sahoo SK. Retraction. Retraction notice to "Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy" [Acta Biomaterialia 8 (2012) 2670-2687]. Acta Biomater. 2013 Jun;9(6):7074.

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