Social Isolation Activates Dormant Mammary Tumors, and Modifies Inflammatory and Mitochondrial Metabolic Pathways in the Rat Mammary Gland.

Although multifactorial in origin, one of the most impactful consequences of social isolation is an increase in breast cancer mortality. How this happens is unknown, but many studies have shown that social isolation increases circulating inflammatory cytokines and impairs mitochondrial metabolism. Using a preclinical Sprague Dawley rat model of estrogen receptor-positive breast cancer, we investigated whether social isolation impairs the response to tamoxifen therapy and increases the risk of tumors emerging from dormancy, and thus their recurrence. We also studied which signaling pathways in the mammary glands may be affected by social isolation in tamoxifen treated rats, and whether an anti-inflammatory herbal mixture blocks the effects of social isolation. Social isolation increased the risk of dormant mammary tumor recurrence after tamoxifen therapy. The elevated recurrence risk was associated with changes in multiple signaling pathways including an upregulation of IL6/JAK/STAT3 signaling in the mammary glands and tumors and suppression of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In addition, social isolation increased the expression of receptor for advanced glycation end-products (RAGE), consistent with impaired insulin sensitivity and weight gain linked to social isolation. In socially isolated animals, the herbal product inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling, suppressed the expression of RAGE ligands S100a8 and S100a9, and prevented the increase in recurrence of dormant mammary tumors. Increased breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following the completion of hormone therapy using interventions that simultaneously target several different pathways including inflammatory and mitochondrial metabolism pathways.

Stress biomarkers in medical students participating in a mind body medicine skills program.

Georgetown University School of Medicine offers an elective Mind-Body Medicine Skills (MBMS) course to medical students to promote self-care and self-awareness. Participating medical students reported better management of academic stress and well-being than non-participants. In this study, we sought to assess the stress-reducing effects of MBMS by measuring physiological changes in first-year medical students. Saliva samples were collected before (January, time 1 (T1)-pre-intervention) and upon completion of the course (May, time 2 (T2p)-post-intervention), as well as from non-participating medical students (May, time 2 (T2c)-control). The T2p and T2c collections coincided with the period of final examinations. Cortisol, dehydroepiandrosterone-sulfate (DHEA-S), testosterone and secretory immunoglobulin A (sIgA) were measured. The mean morning salivary cortisol at T2p was 97% of the mean at baseline T1 which was significantly lower than for T2c (2.4) (95% confidence interval (CI) 0.57-1.60, P = .001); DHEA-S showed similar pattern as cortisol where the T2p levels were significantly lower than T2c (P < .001) in both morning and evening collections. Testosterone ratio at T2p (0.85) was also lower than T2c (1.6) (95% CI 0.53-1.3, P = .01). sIgA levels were not statistically different. On direct comparison, the T2c and T2p means were significantly different for all cortisol, DHEA-S and testosterone values. Participants maintained their hormonal balance within the normal range throughout the academic semester while the control group showed significantly increased levels, probably exacerbated by the end of the semester exam stress. To our knowledge, this is the first study to assess the physiologic benefits of a MBMS program in medical students.