NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells

Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells

Metabolic and cardiovascular responses during sub-maximal exercise in humans after 14 days of head-down tilt bed rest and inactivity

VO(2), f (H), Q, SV, [Hb], C(a)O(2), QaO(2), MAP and R (P) were measured in 10 young subjects at rest and during exercise at 50, 100 and 150 W before and after 14 days of head-down tilt bed rest (HDTBR) and of ambulatory (AMB) control period. f (H) was 18 and 8% higher after HDTBR and AMB, respectively. SV dropped by 15% both after HDTBR and AMB, whereas Q did not change. After HDTBR, C(a)O(2) decreased at rest (-8%) and at 50 W (-5%), whereas QaO(2) did not change; MAP was 14 and 6% lower at rest and at 100 W and R (P) decreased by 23% only at rest. Changes in f (H) and SV were larger after HDTBR than after AMB. These results show that, notwithstanding the drop of SV, moderate-intensity dynamic exercise elicited a normal pressure response after 14 days of HDTBR