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Simple Summary: The use of diverse omics platforms and small sample sizes in current studies of cancer chemoresistance limits consensus regarding the molecular mechanisms underlying chemoresistance and the applicability of those study findings. We built transcriptome data for chemotherapy-resistant breast cancer samples for two cohorts and conducted pathway and subpathway analyses that revealed the activation of several molecular pathways associated with chemoresistance in Cushing's syndrome, human papillomavirus infection, proteoglycans in cancer, fluid shear stress, and focal adhesion that have not been reported in the resistance of breast cancer to chemotherapy. However, analysis of a subset of triple-negative breast cancer samples revealed activation of the identical chemoresistance pathways. Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancers—one comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing's syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing's syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways. [ABSTRACT FROM AUTHOR]

Objective The goal of present study was to examine the influence of demographic characteristics, lifestyle, and metabolic factors on pressure-induced pain threshold. Design and Setting The study population comprised 2,517 healthy men at second-phase recruitment of a population-based cohort in China. The pressure pain threshold ( PPT) at two locations, triceps and inguinal lines, was obtained using a digital pressure algometer. Education and occupation, as well as lifestyle factors, were self-reported in a face-to-face interview. Blood lipid and fasting glucose were measured as a routine healthy check-up program. Results A lower PPT was found among men with younger age, higher level of education, and non-manual occupation. In addition, men with central obesity and moderate leisure time physical exercise were more sensitive to muscle mechanical stimuli. PPT was significantly correlated with high-density lipoprotein cholesterol (β for triceps = 0.064, and β for inguinal lines = 0.052) in a multivariate linear regression model, after controlling for multiple variables. Elevated PPT was also found among subjects with hyperglycemia (both P for triceps and inguinal lines <0.001) and excess drinking ( P for triceps = 0.005). Conclusions It is important for physicians and researchers to consider these variables when evaluating pain sensitivity in clinic and in research. The underling mechanisms between these factors and pressure pain perception are worthy of further exploration. [ABSTRACT FROM AUTHOR]