Ellis Hayley Patricia, Kurian Kathreena Mary
School of Cellular and Molecular Medicine, University of Bristol , Bristol , UK.
Brain Tumour Research Group, Institute of Clinical Neuroscience, University of Bristol , Bristol , UK.
Front Oncol. 2014 Mar 14;4:52. doi: 10.3389/fonc.2014.00052. eCollection 2014.
Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral medications for type 2 diabetes, certain agonists carry the risk for congestive heart failure, myocardial infarction, cardiovascular disease, bone loss, weight gain, and fluid retention as side-effects. The nuclear receptor transcription factor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of refractory high grade glioma.
多形性胶质母细胞瘤（GBM）是最常见的原发性中枢神经系统肿瘤，总体生存率极低，5年后仅有10%的患者存活。有有趣的初步证据表明，接受过氧化物酶体增殖物激活受体γ（PPARγ）激动剂（一类抗糖尿病的噻唑烷二酮类药物）治疗的糖尿病患者，胶质母细胞瘤的中位生存期有所延长。尽管噻唑烷二酮类药物是治疗2型糖尿病的有效口服药物，但某些激动剂有导致充血性心力衰竭、心肌梗死、心血管疾病、骨质流失、体重增加和液体潴留等副作用的风险。已发现核受体转录因子PPARγ在高级别胶质瘤中表达，其激活已显示对人和大鼠胶质瘤细胞系有多种抗肿瘤作用，并且在某些情况下，在正常星形胶质细胞中还观察到抗氧化酶有额外的保护性增加。目前，尚无关于使用PPARγ激动剂治疗胶质瘤患者的临床试验正在进行。本综述阐述了评估PPARγ激动剂作为难治性高级别胶质瘤新型辅助治疗药物潜力的理由。
