Lactam類, Pyridone類, ならびに関連化合物74種の抗腫瘍性について

Seventy-four compounds related to lactams and pyridones were synthesized and their anti-tumor activity was examined using Ehrlich carcinoma cells. 4-(2-Piperidyl) butyric acid hydrochloride was found to have some anti-tumor effect on the solid type of Ehrlich carcinoma cells, but no other substances were found to be effective. Correlation between the anti-tumor activity and structure of the tested compounds still remains uncertain

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Reduction of Serum Ubiquinol-10 and Ubiquinone-10 Levels by Atorvastatin in Hypercholesterolemic Patients

This find is registered at Portable Antiquities of the Netherlands with number PAN-0002281

High frequency of a retinoid X receptor gamma gene variant in familial combined hyperlipidemia that associates with atherogenic dyslipidemia

Objective - The genetic background of familial combined hyperlipidemia (FCHL) has not been fully clarified. Because several nuclear receptors play pivotal roles in lipid metabolism, we tested the hypothesis that genetic variants of nuclear receptors contribute to FCHL. Methods and Results - We screened all the coding regions of the PPAR alpha, PPAR gamma 2, PPAR delta, FXR, LXR alpha, and RXR gamma genes in 180 hyperlipidemic patients including 60 FCHL probands. Clinical characteristics of the identified variants were evaluated in other 175 patients suspected of coronary disease. We identified PPAR alpha Asp140Asn and Gly395Glu, PPAR gamma 2 Pro12Ala, RXR gamma Gly14Ser, and FXR -1g - > t variants. Only RXR gamma Ser14 was more frequent in FCHL (15%, P <0.05) than in other primary hyperlipidemia (4%) and in controls (5%). Among patients suspected of coronary disease, we identified 9 RXR gamma Ser14 carriers, who showed increased triglycerides (1.62 +/- 0.82 versus 1.91 +/- 0.42 [mean +/- SD] mmol/L, P <0.05), decreased HDL-cholesterol (1.32 +/- 0.41 versus 1.04 +/- 0.26, P <0.05), and decreased post-heparin plasma lipoprotein lipase protein levels (222 +/- 85 versus 149 +/- 38 ng/mL, P <0.01). In vitro, RXR gamma Ser14 showed significantly stronger repression of the lipoprotein lipase promoter than RXR gamma Gly14. Conclusion - These findings suggest that RXR gamma contributes to the genetic background of FCHL