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.     

Qualitative and Quantitative analysis of 3D predicted arachidonate 15-lipoxygenase-B (15-LOX-2) from Homo sapiens

15-Lipoxygenase-2 protein has been reported to play an important role in normal development of prostate, lung, skin, and cornea tissues. It behaves as a suppressor of prostate cancer development by restricting cell cycle progression and implicating a possible protective role against tumor formation. On the basis of the above report, we selected 15-LOX-2 protein to study the structural classification and functional relationship with associated protein network at computational level. Sequence alignment and protein functional study shows that it contains a highly conserved LOX motif. PLAT domain with PF01477 and LH2 domain with PF00305 were successfully observed. Arachidonate 5-lipoxygenase (PDB ID: 3O8Y) was selected as a template with 42% identity. 3D structure was successfully predicted and verified. Qualitative analysis suggests that the predicted model was reliable and stable with best quality. Quantitative study shows that the model contained expected volume and area with best resolution. Predicted and best evaluated model has been successfully deposited to PMDB database with PMDB ID PM0078035. Active site identification revealed GLU(369), ALA(370), LEU(371), THR(372), HIS(373), LEU(374), HIS(376), SER(377), HIS(378), THR(385), LEU(389), HIS(394), PHE(399), LYS(400), LEU(401), ILE(403) and PRO(404) residues may play a major role during protein-protein, protein-drug and protein-cofactor interactions. STRING database result indicated that IL (4), GPX (2 and 4), PPARG, PTGS (1 and 2), CYP (2J2, 2C8, 4A11 and 2B6), PLA (2G2A, 2G4A, 2G1B and 2G6) and A LOX (5, 15, 12 and 12B) members from their respective gene families have network based functional association with 15-LOX-2.     

Antioxidant activity of the phenol rich fractions of leaves of Chukrasia tabularis A. Juss

The present study was designed to explore the antioxidant potential of chloroform, ethyl acetate, n-butanol and water fractions of 80% methanol extract of leaves Chukrasia tabularis by 2,2'-diphenyl-1-picrylhydrazyl (DPPH), deoxyribose degradation (non-site specific and site specific), reducing power and DNA nicking assays. The different fractions showed significant activities in all the free radical scavenging tests and these findings have also shown direct relationship between antioxidant activity and phenolic content. Among the fractions, ethyl acetate fraction exhibited highest inhibition of 93.14%, 89.99%, 87.04% in DPPH, non-site specific and site specific deoxyribose degradation assays, respectively and 91.20% reduction of ferricyanide to give Prussian blue coloured complex in reducing power assay at maximum concentration tested. This preliminary study indicates the antioxidant activity of the leaves of Chukrasia tabularis, and moreover the results showed correlation with the amount of phenolic content present in different fractions.     

A cure‐rate model for Q‐learning: Estimating an adaptive immunosuppressant treatment strategy for allogeneic hematopoietic cell transplant patients

Cancers treated by transplantation are often curative, but immunosuppressive drugs are required to prevent and (if needed) to treat graft‐versus‐host disease. Estimation of an optimal adaptive treatment strategy when treatment at either one of two stages of treatment may lead to a cure has not yet been considered. Using a sample of 9563 patients treated for blood and bone cancers by allogeneic hematopoietic cell transplantation drawn from the Center for Blood and Marrow Transplant Research database, we provide a case study of a novel approach to Q‐learning for survival data in the presence of a potentially curative treatment, and demonstrate the results differ substantially from an implementation of Q‐learning that fails to account for the cure‐rate.     

Variability in structural carbohydrates and in vitro digestibility of forages. 4. Fenugreek (Trigonella foenum-graecum)

The chemical composition of ten genotypes of fenugreek, with and without a pretreatment with neutral detergent, has been determined together with dry matter digestibility in vitro. Preliminary extraction with neutral detergent lowered the percentage yield of acid detergent fibre and about 84% of this decrease was observed in the reduction of cellulose level.Dry matter digestibility in vitro was significantly correlated with acid detergent and cellulose when sequential extraction was done. It was considered necessary to use sequential analysis to determine the chemical composition of fenugreek forage.