Subtype-Specific Surface Proteins on Adipose Tissue Macrophages and Their Association to Obesity-Induced Insulin Resistance.

A chronic low-grade inflammation, originating in the adipose tissue, is considered a driver of obesity-associated insulin resistance. Macrophage composition in white adipose tissue is believed to contribute to the pathogenesis of metabolic diseases, but a detailed characterization of pro- and anti-inflammatory adipose tissue macrophages (ATMs) in human obesity and how they are distributed in visceral- and subcutaneous adipose depots is lacking. In this study, we performed a surface proteome screening of pro- and anti-inflammatory ATMs in both subcutaneous- (SAT) and visceral adipose tissue (VAT) and evaluated their relationship with systemic insulin resistance. From the proteomics screen we found novel surface proteins specific to M1-like- and M2-like macrophages, and we identified depot-specific immunophenotypes in SAT and VAT. Furthermore, we found that insulin resistance, assessed by HOMA-IR, was positively associated with a relative increase in pro-inflammatory M1-like macrophages in both SAT and VAT.

Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database.

PURPOSE: Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring. METHODS: Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC-MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation. RESULTS: At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4'-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation. CONCLUSIONS: This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data.