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Prostate cancer is a heterogeneous disease and optimum gene targeting treatment is often impermissible. We aim to determine the intratumoral genomic heterogeneity of prostate cancer and explore candidate genes for targeted therapy. Exome sequencing was performed on 37 samples from 16 patients with prostate cancer. Somatic variant analysis, copy number variant (CNV) analysis, clonal evolution analysis and variant spectrum analysis were used to study the intratumoral genomic heterogeneity and genetic characteristics of metastatic prostate cancer. Our study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden (TMB), variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures. Moreover, we identified several common genetic characteristics of prostate cancer. Alterations of DNA damage repair genes, RTK/RAS pathway associated gene RASGRF1 and autophagy gene EPG5 may be involved in tumorigenesis in prostate cancer. CNV burden and DNA damage repair (DDR) genes may be associated with metastasis of prostate cancer. What's new? Prostate cancer is a heterogeneous disease, making the development of gene targeting therapies difficult. This study confirmed the high intratumoral genetic heterogeneity of prostate cancer in the number of shared variants, tumor mutation and copy number variation (CNV) burden, weighted genome instability index, clonal evolutionary process, and variant spectrum as well as variant genes, CNV profiles, and mutational signatures. The authors could however identify several common genetic characteristics of prostate cancer. Thus, RASGRF1 and EPG5 may be involved in the tumorigenesis of prostate cancer. Furthermore, the CNV burden and DNA damage repair genes may be associated with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Aims Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. Methods At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. Conclusions The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A simple and efficient route for the preparation of terphenyl derivatives via palladium-catalyzed sequential directed C-H arylation/Suzuki-Miyaura in 'one-pot' has been developed. 4,4′-(Cyclohexane-1,1-diyl)diphenol is an essential ligand. This reaction can tolerate a series of functional groups and provides the terphenyl derivatives in moderate to good yield. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Pd/C-catalyzed Suzuki-Miyaura cross-coupling between aryl bromides and arylboronic acids in 50% methanol aqueous solution proceeded smoothly in the presence of 18-crown-6. Various aryl bromides bearing electron-withdrawing groups and electron-donating groups coupled with arylboronic acid in high yields. In addition, the catalyst could be recycled five times without loss of activity. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]