The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract.

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

Therapeutic horseback riding in breast cancer survivors: a pilot study.

PURPOSE: To evaluate the physiologic and psychological effects of an equine-assisted therapy protocol (EAT) in breast cancer survivors. METHODS: Twenty women (mean age, 45.61±2.71 years) whose breast cancer treatment had concluded at least 6 months previously underwent a screening protocol to certify their eligibility to participate in noncompetitive sports. The patients were randomly assigned to an intervention group (n=10) or a control group (n=10). Intervention patients participated in a 16-week EAT protocol consisting of 2 hours of activity per week. All patients were tested before and after the intervention for maximal oxygen consumption (VO2max), fat mass percentage, total body water percentage, strength of principal muscular groups (measured on five weight-lifting machines [leg press, leg extension, leg curl, shoulder press, vertical traction]), and quality of life using the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire (FACIT-F). RESULTS: After intervention, the intervention group showed an improvement in VO2max (28.29%; p<.001), a decrease in fat mass percentage (change, -7.73%; p<0.002), an increase in total body water percentage (6.90%; p=0.027), and an increase in strength (leg press, 17.75% [p=0.018]; leg extension, 21.55% [p=0.005]; leg curl, 26.04% [p<0.001]; shoulder press, 49.72% [p=0.003]; vertical traction, 19.27% [p=0.002]). Furthermore, the increase in the three FACIT-F scores (FACIT-F trial outcome: 9.29% [p=0.010]; Functional Assessment of Cancer Therapy-General total score, 14.80% [p=0.022]; FACIT-F total score, 11.48% [p=0.004]) showed an increase in quality of life. No significant changes for any variable were found for the control group. CONCLUSIONS: EAT had positive effects on both physiologic and psychological measures, enhancing quality of life of breast cancer survivors. RESULTS suggest a new method for rehabilitation intervention strategies after cancer in a nonmedical environment.