Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumor genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumors in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5–15% of myeloid, kidney, colon and prostate cancers. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We performed fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identified six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants were bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression were positively correlated in prostate tumors. TET2 is expressed in normal prostate tissue and reduced in a subset of tumors from the Cancer Genome Atlas (TCGA). Small interfering RNA (siRNA)-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration, and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine (hmC) proximal to KLK3. A gene co-expression network identified using TCGA prostate tumor RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signaling. Decreased TET2 mRNA expression in TCGA PCa tumors is strongly associated with reduced patient survival indicating reduced expression in tumors maybe an informative biomarker of disease progression and perhaps metastatic disease.
Hydrochemical evaluation of groundwater has been conducted in Bankura I and II Blocks to analyze and determining groundwater quality in the area. Thirty-six groundwater samples were analyzed for their physical and chemical properties using standard laboratory methods. The constituents have the following ranges in the water: pH 6.4-8. ). Sodium adsorption ratio (SAR), soluble sodium percentage (SSP), residual sodium carbonate (RSC), magnesium adsorption ratio (MAR), total hardness (TH), and permeability index (PI) were calculated as derived parameters, to investigate the ionic toxicity. Concerned chemical parameters when plotted in the U.S. Salinity diagram indicate that waters are of C 1 -S 1 , C 2 -S 1 and C 3 -S 1 types, i.e., low salinity and low sodium which is good for irrigation. The values of Sodium Adsorption Ratio indicate that the groundwater of the area falls under the category of low sodium hazard. So, there is neither salinity nor toxicity problem of irrigation water, and hence the ground water can safely be used for long-term irrigation. The chemical parameters when plotted in Piper's trilinear diagram are found to concentrate in the central and west central part of the diamond-shaped field. Based on the analytical results, groundwater in the area is found to be generally fresh and hard to very hard. ). According to Gibbs diagrams samples fall in the rock dominance field and the chemical quality of groundwater is related to the lithology of the area. The alkaline earth elements (Ca and Mg) occur in greater abundance than alkaline elements (Na and K). A comparative study of our analytical results with the WHO standards of drinking water indicate that the present waters are also good for drinking purposes.
Gold nanoclusters (Au NCs) have become a promising nanomaterial for cancer therapy because of their biocompatibility and fluorescent properties. In this study, the effect of ultrasmall protein-stabilized 2 nm Au NCs on six types of mammalian cells (fibroblasts, B-lymphocytes, glioblastoma, neuroblastoma, and two types of prostate cancer cells) under electromagnetic radiation is investigated. Cellular association of Au NCs in vitro is concentration-dependent, and Au NCs have low intrinsic toxicity. However, when Au NC-incubated cells are exposed to a 1 GHz electromagnetic field (microwave radiation), cell viability significantly decreases, thus demonstrating that Au NCs exhibit specific microwave-dependent cytotoxicity, likely resulting from localized heating. Upon i.v. injection in mice, Au NCs are still present at 24 h post administration. Considering the specific microwave-dependent cytotoxicity and low intrinsic toxicity, our work suggests the potential of Au NCs as effective and safe nanomedicines for cancer therapy.
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