Acyl-coenzyme A: cholesterol acyltransferase inhibitor Avasimibe affect survival and proliferation of glioma tumor cell lines.

Glioblastoma is the most common primary brain tumor in adults and one of its hallmarks is resistance to apoptosis. Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular membrane-bound enzyme that uses cholesterol and long chain fatty acyl-CoA as substrates to produce cholesteryl esters. The presence of cholesteryl esters in glioblastoma may be related to vascular and/or cell neoplastic proliferation in the tumor mass, two prerequisites for tumor cell growth. ACAT activity has been detected in glioblastoma cell homogenates. The present study is the first report on the effect of Avasimibe, a specific inhibitor of ACAT, on glioma cell lines (U87, A172 and GL261). Our results showed that Avasimibe inhibited ACAT-1 expression and cholesterol ester synthesis in glioma cell lines. Moreover, Avasimibe inhibited the growth of the cells by inducing cell cycle arrest and induced apoptosis as a result of caspase-8 and caspase-3 activation. Also, Our findings provide proof of principle that targeting ACAT-1 with the inhibitor Avasimibe could be an efficient therapy in the treatment of glioblastoma.

A Combination of Systemic and Intracranial Anti-CD25 Immunotherapy Elicits a Long-Time Survival in Murine Model of Glioma.

Abrogating the suppression of glioma-infiltrating Tregs in the periphery and the central nervous system is essential to successful glioma rejection. We sought to improve the immune response in glioma-bearing mice, by investigating new strategies using the anti-CD25 immunotherapy. We found a complete long-term survival of glioma-bearing mice treated with a combination of systemic and intracranial anti-CD25 mAb immunotherapy as compared to systemic administration of anti-CD25 mAb. In addition, the group of mice that had been cured by the combined anti-CD25 mAb showed long-term survival without late tumor relapse when challenged with the GL261 glioma. The antitumor immune response was investigated by analysis of antitumor immune response (CTL). Results showed that the use of the combined injections of anti-CD25 mAb induced efficient targeting of Tregs expansion inside and outside of the brain and altered Tregs trafficking in the bone marrow and brain areas where antitumor immunity was primed.