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Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n=60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The renin-angiotensin system (RAS) and inflammation may play a decisive role in hypertensive end organ damage (EOD) including left ventricular (LV) hypertrophy and vascular remodeling. It is not clear whether the local RAS and inflammatory factors are involved in hypertensive EOD, and which RAS or inflammatory factors (systematic or local) is more important in EOD. Hemodynamics, cardiovascular hypertrophy, angiotensin II (Ang II) concentration and inflammatory factors in spontaneously hypertensive rats (SHR) were measured. mRNA expression of tissue RAS and inflammatory factors in SHR was assayed by real-time PCR. The independent effects and relative importance of hemodynamic factors and mRNA expression of RAS and inflammatory factors in local tissue on cardiovascular hypertrophy were assessed by stepwise multivariate regression analysis. It was found that blood pressure (BP), blood pressure variability, circulating Ang II, inflammatory factors, cardiac and aortic gene expressions of all the components of RAS and some inflammatory factors were elevated, and baroreflex sensitivity (BRS) was decreased in SHR. Changes of mRNA expressions of RAS components and inflammatory factors was unidirectional in the heart and aorta in SHR. It is the tissue RAS, rather the circulating RAS and inflammatory factors, that contributed to hypertensive cardiovascular hypertrophy. Statistically, LV hypertrophy was mainly determined by diastolic blood pressure and the cardiac angiotensin-converting enzyme gene expression, and aortic hypertrophy was mainly correlated with baroreflex sensitivity.