Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

Abstract

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.

FastProject: A Tool for Low-Dimensional Analysis of Single-Cell RNA-Seq Data

“…While hypoxic regions are characteristic in solid tumors [25], this inverse correlation is surprising and possibly aligned with the up-regulation of angiogenetic markers in mesenchymal glioblastoma tumors [22]. Finally, we see a strong negative correlation with a signature of response to the PPARγ agonist rosiglitazone, which aligns with previous observations of beneficial effects PPARγ agonists have in glioblastoma [26,27,28].…”

miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1β

“…However, the PGC-1b protein family were found high expressed in all kinds of solid tumors. 31,32 Our data manifested that PGC-1b expression level was also elevated when IGF-1 R was overexpressed ( Figure 5D). Further detection suggested the inhibitor of Akt could suppress the PGC-1b expression even when IGF-1 R was transfected ( Figure 5D), which was also validated in breast cancer.…”

Glioblastoma Cell Migration is Directed by Electrical Signals

“…However, PI3K inhibition with LY294002 did not affect cathodal migration, although BEZ235 abolished directed migration, which may be non-specifically accrued to its duel activity on PI3K/mTOR and more efficient downregulation of Akt [49,50]. addition to anti-proliferative, pro-differentiation of GSC and pro-apoptotic effects reported previously [52]. Such findings need to be recapitulated in animal models of GBM to determine whether tumour infiltration can be reversed.…”