Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity.

A Recurrent ADPRHL1 Germline Mutation Activates PARP1 and Confers Prostate Cancer Risk in African American Families.

Unlabelled: African American (AA) families have the highest risk of prostate cancer. However, the genetic factors contributing to prostate cancer susceptibility in AA families remain poorly understood. We performed whole-exome sequencing of one affected and one unaffected brother in an AA family with hereditary prostate cancer.

Deleterious effects of formalin-fixation and delays to fixation on RNA and miRNA-Seq profiles.

The National Cancer Institute conducted the Biospecimen Pre-analytical Variables (BPV) study to determine the effects of formalin fixation and delay to fixation (DTF) on the analysis of nucleic acids. By performing whole transcriptome sequencing and small RNA profiling on matched snap-frozen and FFPE specimens exposed to different delays to fixation, this study aimed to determine acceptable delays to fixation and proper workflow for accurate and reliable Next-Generation Sequencing (NGS) analysis of FFPE specimens. In comparison to snap-freezing, formalin fixation changed the relative proportions of intronic/exonic/untranslated RNA captured by RNA-seq for most genes.

'Cut from the same cloth': Shared microsatellite variants among cancers link to ectodermal tissues-neural tube and crest cells.

The pluripotent cells of the embryonic ectodermal tissues are known to be a precursor for multiple tumor types. The adaptability of these cells is a trait exploited by cancer. We previously described cancer-associated microsatellite loci (CAML) shared between glioblastoma (GBM) and lower-grade gliomas.

Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

Background: Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.

Large scale comparison of non-human sequences in human sequencing data.

Several studies have demonstrated that unmapped reads in next generation sequencing data could be used to identify infectious agents or structural variants, but there has been no intensive effort to analyze and classify all non-human sequences found in individual large data sets. To identify commonality in non-human sequences by infectious agents and putative contamination events, we analyzed non-human sequences in 150 genomic sequencing data files from the 1000 Genomes Project and observed that 0.13% of reads on average showed similarities to non-human genomes.

Somatic intronic microsatellite loci differentiate glioblastoma from lower-grade gliomas.

Genomic studies of glioma sub-types have amassed new disease specific mutations, yet these only partially explain how mutations are linked to predisposition or progression. We hypothesized that microsatellite variation could expand the understanding of glioma etiology. Furthermore, germline markers for gliomas are typically undetectable; therefore we also hypothesize that the predictability of cancer-associated microsatellite loci in germline DNA may support the current hypothesis of a glioma cell of origin.

The dynamic exome: acquired variants as individuals age.

A singular genome used for inference into population-based studies is a standard method in genomics. Recent studies show that spontaneous genomic variants can propagate into new generations and these changes can contribute to individual cell aging with environmental and evolutionary elements contributing to cumulative genomic variation. However, the contribution of aging to genomic changes in tissue samples remains uncharacterized.

Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes.

Although the connection between cancer and cigarette smoke is well established, nicotine is not characterized as a carcinogen. Here, we used exome sequencing to identify nicotine and oxidative stress-induced somatic mutations in normal human epithelial cells and its correlation with cancer. We identified over 6,400 SNVs, indels and microsatellites in each of the stress exposed cells relative to the control, of which, 2,159 were consistently observed at all nicotine doses.

Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study.

Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. We used Illumina® Next Generation Sequencing (NGS) technology to gain unbiased biological insight into the transcriptome of normal epithelial cells (MCF-10A) to nicotine exposure. We generated expression data from 54,699 transcripts using triplicates of control and nicotine stressed cells.

ReviSTER: an automated pipeline to revise misaligned reads to simple tandem repeats.

Motivation: Simple tandem repeats are highly variable genetic elements and widespread in genomes of many organisms. Next-generation sequencing technologies have enabled a robust comparison of large numbers of simple tandem repeat loci; however, analysis of their variation using traditional sequence analysis approaches still remains limiting and problematic due to variants occurring in repeat sequences confusing alignment programs into mapping sequence reads to incorrect loci when the sequence reads are significantly different from the reference sequence.

Results: We have developed a program, ReviSTER, which is an automated pipeline using a 'local mapping reference reconstruction method' to revise mismapped or partially misaligned reads at simple tandem repeat loci.

Systematic study to evaluate anti-diabetic potential of Amaranthus spinosus on type-1 and type-2 diabetes.

The present study was designed to systematically investigate the antidiabetic potential of Amaranthus spinosus leaves which are traditionally known to have various medicinal properties and used for the treatment of diabetes mellitus. The ethanolic extract of leaves of Amaranthus spinosus was administered (150, 300 and 450 mg/kg bw) to type-1 and type-2 diabetic rats. Standard drugs, glibenclamide and metformin were used as a positive control for comparison.

Improved variation calling via an iterative backbone remapping and local assembly method for bacterial genomes.

Sequencing data analysis remains limiting and problematic, especially for low complexity repeat sequences and transposon elements due to inherent sequencing errors and short sequence read lengths. We have developed a program, ReviSeq, which uses a hybrid method composed of iterative remapping and local assembly upon a bacterial sequence backbone. Application of this method to six Brucella suis field isolates compared to the newly revised B.

Inactivation of androgen-induced regulator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis.

Androgen signaling through androgen receptor (AR) is critical for prostate tumorigenesis. Given that AR-mediated gene regulation is enhanced by AR coregulators, inactivation of those coregulators is emerging as a promising therapy for prostate cancer (PCa). Here, we show that the N-acetyltransferase arrest-defect 1 protein (ARD1) functions as a unique AR regulator in PCa cells.

HEF1, a novel target of Wnt signaling, promotes colonic cell migration and cancer progression.

Misregulation of the canonical Wnt/β-catenin pathway and aberrant activation of Wnt signaling target genes are common in colorectal cancer (CRC) and contribute to cancer progression. Altered expression of human enhancer of filamentation 1 (HEF1; also known as NEDD9 or Cas-L) has been implicated in progression of melanoma, breast, and CRC. However, the regulation of HEF1 and the role of HEF1 in CRC tumorigenesis are not fully understood.

Leucas cephalotes regulates carbohydrate and lipid metabolism and improves antioxidant status in IDDM and NIDDM rats.

Ethnopharmacological Relevance: Leucas cephalotes (Roth.) Spreng. (Laminaceae) is an ayurvedic traditional medicinal plant used in India, Nepal and Pakistan to treat several ailments including diabetes.

Preliminary study on antihyperglycemic and antihyperlipaemic effects of Butea monosperma in NIDDM rats.

Oral administration of the ethanolic extract of the Butea monosperma seeds (300 mg/kg b.w.) exhibited significant antidiabetic, hypolipaemic and antiperoxidative effects in non-insulin dependent diabetes mellitus rats.

Antihyperglycemic and hypolipidemic effects of Costus speciosus in alloxan induced diabetic rats.

Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. In the present study, the antihyperglycemic, antihyperlipemic and antioxidant potency of an ethanol extract of Costus speciosus root was investigated in alloxan-induced diabetic male (Charles Foster) rats. Four groups of alloxan diabetic rats (n = 6) were administered orally with different doses of Costus speciosus root extract (150, 300 and 450 mg/kg BW) and a standard drug, glibenclamide (600 microg/kg BW), for 4 weeks.