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GLIOMAS.ORG

NEWSLETTER

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Volume 1 (3), June 2013.

www.gliomas.org

GLIOMAS.ORG NEWSLETTERSis a short electronic

newsletter periodically released by e-mail as a PDF file to sub-

scribers 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.

Each issue of GLIOMAS NEWSLETTERS is the result of a broad

screening of the literature in free (e.g. pubmed) or subscription

based (e.g. ISI) databases and journals. Interaction with the

industry and academic institutions guarantee the early release

of relevant information for patients and professionals.

The highlights of important studies are briefly summarized in a

friendly medical language. Each summary is convenient cited

(Reference) at the bottom of the summary to allow anyone

interested to quickly find the original source.

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staff and patients.

In this issueIMAGES 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 immunomodulatoryproperties in down-regulating major histocompatibility complex (MHC) I surface expression (via the M153R gene product, a viral E3-ubiquitin ligase) andsuppressing T cell killing of infected target cells. MHC I down-regulation, however, favors NK cell activation. Brain tumors including gliomas are charac-terized by high MHC I expression with impaired NK activity. We thus hypothesized that MYXV infection of glioma cells will promote NK cell-mediatedrecognition 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 ofestablished 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. Hema-toxylin and Eosin (H&E) stain shows tumor, with the arrows indicating tumor location in the brain. Brown M-T7 stain represents MYXV early proteinstaining 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 ofmalignant gliomas in vitro and in vivo. PLoS One. 2013 Jun 10;8(6):e66825

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TUMOR BIOLOGY

Glioma microvesicles carry selectively packaged coding andnoncoding RNAs

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 microvascu-

lar endothelial cells were exposed for short-term to gliomamicrovesicles gene expression changes in the endothelial cells

that cannot be fully explained by direct delivery of transcripts

were observed. These results hightlight the increasing complex-

ity of the interactions between glioma cells and their local envi-

ronment 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 andnoncoding RNAs which alter gene expression in recipient cells.

RNA Biol. 2013 Jun 17;10(8).

Dying endothelial cells stimulate proliferation of malignantglioma cells

Apoptotic cells may have a compensatory effect on the prolif-

eration of neighboring cells. By coculturing glioma cell lines

with dying ECs under various conditions a study showed evi-

dence that dying vascular endothelial cells (ECs) facilitate

glioma cell growth via a caspase 3-mediated pathway. Calcium-

independent 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 tu-

mors.

Mao P, Smith L, Xie W, Wang M. Dying endothelial cells stimulateproliferation of malignant glioma cells via a caspase 3-mediated path-way. Oncol Lett. 2013 May;5(5):1615-1620.

NEURO-ONCOLOGY PRACTICE

Neuro-oncology practices in Australia

A survey of 28 Australia cancer centres showed that treatment

protocols are virtually identical for patients with an initial diag-

nosis of glioblastoma multiforme (GBM). Variation was found

for older or less fit patients. 70% of patients received chemo-

therapy at recurrence, usually modified schedule temo-

zolomide. 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 prophylac-

tic antibiotics during chemoradiotherapy and 50% would con-

tinue anti-coagulation therapy indefinitely for thromboem-

bolism.

Chen JY, Hovey E, Rosenthal M, Livingstone A, Simes J. Neuro-oncology practices in Australia: A Cooperative Group for Neuro-

Oncology patterns of care study. Asia Pac J Clin Oncol. 2013 May 29.

doi: 10.1111/ajco.12079. [Epub ahead of print] PMID: 23714694

Chemotherapy for gliomas in mainland China

Chemotherapy is currently the standard treatment modality for

malignant gliomas and is usually administered by the Depart-

ment of Neurosurgery. Studies on chemotherapy for gliomasbegan in the 1970s in mainland China but well-designed ran-

domized controlled trials (RCTs) are rare. Oral or intravenous

administration was found in 55.7% of studies, followed by intra-

arterial (26.7%) and interstitial (15.7%) chemotherapy. Nitro-

soureas 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 inmainland China: An overview. Oncol Lett. 2013 May;5(5):1448-1452.Epub 2013 Mar 19. PMID: 23761809 [PubMed]

NANOPHARMACOLOGY

Transferrin-Modified Doxorubicin-Loaded BiodegradableNanoparticles

Doxorubicin

A novel nano-scale drug delivery system employing biodegrad-

able 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) specificallytarget the NP to glioma. The average diameter of Tf-NP-Dox

was 100 nm 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, HuangQ, Lan Q. Transferrin-Modified Doxorubicin-Loaded Biodegradable

Nanoparticles Exhibit Enhanced Efficacy in Treating Brain Glioma-Bearing Rats. Cancer Biother Radiopharm. 2013 Jun 20

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NEUROSURGERY

A new practical scoring system for glioblastoma may predictsurvival

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 ependymalinvolvement (0 for no enhancement and 1 for enhancement of

the ventricle wall in the magnetic resonance imaging) signifi-

cantly distinguished groups with good (0 points; median sur-

vival, 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 differ-

ent 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 . Apractical scoring system to determine whether to proceed with surgicalresection in recurrent glioblastoma. Neuro Oncol. 2013 Jun 25. [Epub

ahead of print]

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 curcumin-

loaded 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 "An-

tiglioma activity of curcumin-loaded lipid nanoparticles and its en-hanced bioavailability in brain tissue for effective glioblastoma therapy"[Acta Biomaterialia 8 (2012) 2670-2687]. Acta Biomater. 2013Jun;9(6):7074.

II Anticancer Drugs

Meeting

22-23 August, 2013

Stockholm, Sweden

Confirmed Speakers from

US

GermanyFrance

UK

Sweden

Egypt

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Japan

Saudi Arabia

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and other countries will pre-

sent their work

www.anticancerdrugs.org/2013

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