Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective.

Seasonally Related Disruption of Metabolism by Environmental Contaminants in Male Goldfish ().

Endocrine disrupting chemicals mimic or disrupt action of the natural hormones, adversely impacting hormonal function as well as cardiovascular, reproductive, and metabolic health. Goldfish are seasonal breeders with an annual reproductive cycle regulated by neuroendocrine signaling which involves allocation of metabolic energy to sustain growth and reproduction. We hypothesize that seasonal changes in physiology alter overall vulnerability of goldfish to metabolic perturbation induced by environmental contaminants.

Considerations for the Safe Operation of Schools During the Coronavirus Pandemic.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its post-acute sequelae, the impact of remote learning or periods of quarantine on education and well-being of children, and the contribution of schools to viral circulation in the community. The risk for infections that may occur within schools is related to the incidence of SARS-CoV-2 infections within the local community.

Effects of systemic inflammation on relapse in early breast cancer.

Chronic inflammation has been a proposed mechanism of resistance to aromatase inhibitors in breast cancer. Stratifying by HER2 status, a matched case-control study from the Wellness After Breast Cancer-II cohort was performed to assess whether or not elevated serum inflammatory biomarkers (C-Reactive protein [CRP], interleukin-6 [IL-6], and serum amyloid A [SAA]) and/or the presence of a high-risk IL-6 promoter genotype were associated with recurrence of hormone receptor positive (HR+) early breast cancer. Estrogen levels were also measured and correlated with biomarkers and disease outcomes.

Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock.

Endocrine disrupting chemicals (EDCs) are endocrine-active chemical pollutants that disrupt reproductive, neuroendocrine, cardiovascular and metabolic health across species. The circadian clock is a transcriptional oscillator responsible for entraining 24-hour rhythms of physiology, behavior and metabolism. Extensive bidirectional cross talk exists between circadian and endocrine systems and circadian rhythmicity is present at all levels of endocrine control, from synthesis and release of hormones, to sensitivity of target tissues to hormone action.

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen.

The Women's Health Initiative studies reported that the menopausal hormone therapy (MHT) regimen containing conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer incidence. These observations suggest the possibility that CEE might exert unique actions on breast and also suggest the need to eliminate the progestogen from MHT regimens. A MHT regimen called a tissue selective estrogen complex (TSEC), containing CEE plus bazedoxifene (BZA), to avoid the need for a progestogen, was developed and FDA approved.

Validation of highly sensitive simultaneous targeted and untargeted analysis of keto-steroids by Girard P derivatization and stable isotope dilution-liquid chromatography-high resolution mass spectrometry.

A multiplexed quantitative method for the analysis of three major unconjugated steroids in human serum by stable isotope dilution liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed and validated on a Q Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer. This quantification utilized isotope dilution and Girard P derivatization on the keto-groups of testosterone (T), androstenedione (AD) and dehydroepiandrosterone (DHEA) to improve ionization efficiency using electrospray ionization. Major isomeric compounds to T and DHEA; the inactive epimer of testosterone (epiT), and the metabolite of AD, 5α-androstanedione (5α-AD) were completely resolved on a biphenyl column within an 18min method.

Analysis of estrogens and androgens in postmenopausal serum and plasma by liquid chromatography-mass spectrometry.

Liquid chromatography-selected reaction monitoring/mass spectrometry-based methodology has evolved to the point where accurate analyses of trace levels of estrogens and androgens in postmenopausal serum and plasma can be accomplished with high precision and accuracy. A suite of derivatization procedures has been developed, which together with modern mass spectrometry instrumentation provide investigators with robust and sensitive methodology. Pre-ionized derivatives are proving to be useful as they are not subject to suppression of the electrospray signal.