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Glioblastoma and anti malarials

Hongxing Ye, Mantao Chen, Fei Cao, Hongguang Huang, Renya Zhan, Xiujue Zheng
BACKGROUND: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs...
September 20, 2016: BMC Neurology
Dieter Lemke, Hans-Werner Pledl, Markus Zorn, Manfred Jugold, Ed Green, Jonas Blaes, Sarah Löw, Anne Hertenstein, Martina Ott, Felix Sahm, Ann-Catherine Steffen, Markus Weiler, Frank Winkler, Michael Platten, Zhen Dong, Wolfgang Wick
Influencing cancer metabolism by lifestyle changes is an attractive strategy as - if effective - exercise-induced problems may be less severe than those induced by classical anti-cancer therapies. Pursuing this idea, clinical trials evaluated the benefit of e.g. different diets such as the ketogenic diet, intermittent caloric restriction and physical exercise (PE) in the primary and secondary prevention of different cancer types. PE proved to be beneficial in the context of breast and colon cancer.Glioblastoma has a dismal prognosis, with an average overall survival of about one year despite maximal safe resection, concomitant radiochemotherapy with temozolomide followed by adjuvant temozolomide therapy...
August 30, 2016: Oncotarget
Georg Karpel-Massler, Mike-Andrew Westhoff, Richard E Kast, Annika Dwucet, Lisa Nonnenmacher, C Rainer Wirtz, Klaus-Michael Debatin, Marc-Eric Halatsch
As chemotherapy with temozolomide is far from providing satisfactory clinical outcomes for patients with glioblastoma, more efficient drugs and drug combinations are urgently needed. The anti-malarial artesunate was previously shown to exert a profound cytotoxic effect on various tumor cell lines including those derived from glioblastoma. In the current study, we sought to examine the antiproliferative effect of a combination of temozolomide and artesunate on two different established human glioblastoma cell lines...
February 2014: Anti-cancer Agents in Medicinal Chemistry
Thomas Efferth, Tzutzuy Ramirez, Erich Gebhart, Marc-Eric Halatsch
New drugs and combination modalities for otherwise non-responsive brain tumors are urgently required. The anti-malarial artesunate (ART) and the EGFR tyrosine kinase inhibitor OSI-774 reveal profound cytotoxic activity. The effectiveness of a combination treatment and the underlying molecular determinants of cellular response are unknown. In the present investigation, we studied ART and OSI-774 in glioblastoma multiforme (GBM) cell lines. Supra-additive inhibition of cell growth was observed in U-87MG.DeltaEGFR cells transduced with a deletion-mutant constitutively active EGFR gene, while additive effects were present in cells transduced with wild-type EGFR (U-87MG...
May 1, 2004: Biochemical Pharmacology
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