Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor

Enhanced mesenchymal expression of FGF10 led to the formation of multifocal PIN or prostate cancer. Inhibition of epithelial FGFR1 signaling using DN FGFR1 led to reversal of the cancer phenotype. A subset of the FGF10-induced carcinoma was serially transplantable. Paracrine FGF10 led to an increase in epithelial androgen receptor and synergized with cell-autonomous activated AKT. Our observations indicate that stromal FGF10 expression may facilitate the multifocal histology observed in prostate adenocarcinoma and suggest the FGF10/FGFR1 axis as a potential therapeutic target in treating hormone-sensitive or refractory prostate cancer. We also show that transient exposure to a paracrine growth factor may be sufficient for the initiation of oncogenic transformation.     

Accidental Inorganic Mercury Chloride Poisoning in a 2-Year Old Child

Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life threatening features and acute renal failure. A 2-year old well thriving child presented with alleged history of accidental ingestion of inorganic mercury chloride. He presented with evidence of corrosive trauma to the gastrointestinal tract mucosa, but with normal renal function at admission, which was managed with BAL and other supportive treatment. But he developed non-oliguric renal failure after admission, which also improved gradually. On follow-up, two months later, the patient’s renal function was normal; indicating that renal failure caused by acute inorganic mercury poisoning produced no permanent renal damage. We have hereby presented a case of mercury intoxication in a 2-year old child, with an excellent clinical improvement and normalization of laboratory results.     

Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation

Herein we describe a novel series of compounds from which varenicline (1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine) has been identified for smoking cessation. Neuronal nicotinic acetylcholine receptors (nAChRs) mediate the dependence-producing effects of nicotine. We have pursued alpha4beta2 nicotinic receptor partial agonists to inhibit dopaminergic activation produced by smoking while simultaneously providing relief from the craving and withdrawal syndrome that accompanies cessation attempts. Varenicline displays high alpha4beta2 nAChR affinity and the desired in vivo dopaminergic profile.     

Indole-3-carbinol induces apoptosis in AGS cancer cells via mitochondrial pathway

Indole-3-carbinol is produced from the cruciferous vegetables and broadly investigated for their various biological effects in in-vitro and in-vivo aspects. However, the anticancer activity of I3C and its molecular mechanisms have not been investigated in human adeno gastro carcinoma (AGS) cells. In our study of AGS cells, nuclear condensation was observed by 4′,6-diamidino-2-phenylindole (DAPI) staining, cell death was confirmed by a cell viability assay, and fragmented DNA was observed at the IC₅₀ dose by a DNA fragmentation assay. Apoptosis was evaluated by the qPCR technique. Treatment of the AGS cells with I3C at different concentrations has drastically decreased cell proliferation and differentiation. By releasing cytochrome-c from mitochondria in the intrinsic pathway, I3C prevents the multiplication of AGS cells and initiates apoptosis. The WST-1 assay result showed that I3C treatment against AGS cells had considerably reduced the viability of the cells. Furthermore, RT-qPCR showed the fold change among the expressed proteins compared with reference gene β-actin. Molecular docking revealed that I3C showed a strong binding affinity for the apoptotic protein 3DCY. The results show the caspase group of proteins contribute to the core of apoptotic machinery. I3C and its metabolites target a variety of components of cell-cycle control via distinct signaling pathways in light of the rapid development of tumors and oncogenesis. The translational significance of I3C and its metabolites in cancer is highlighted by their wide range of antitumor activity and low toxicity. Furthermore, the novel prodrug I3C, which has overlapping underlying mechanisms, could encourage new strategies to decrease oncogenesis.