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  • Kamper Sweeney posted an update 23 hours, 5 minutes ago

    We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today’s standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today’s standard of care will require an accounting of an individual’s androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.

    Obtaining a natural breast mound shape contributes profoundly to a symmetrical and successful outcome in breast reconstruction.

    This paper describes a new and efficient technique that enhances breast projection with natural ptosis in delayed breast reconstruction using abdominal free flaps, and compares it to the standard methods employed nowadays.

    The charts of all patients who underwent delayed breast reconstruction using free abdominal perforator flaps were reviewed between 2007-2017. Three methods of breast reconstruction were compared undermining, de-epithelialization and the “Hug flap”. In the newly described technique the caudal mastectomy skin was de-epithelialized and then the medial and lateral thirds were undermined and folded over to cover the central part (hug flap). 570 free abdominal flaps were performed in 490 patients for delayed breast reconstruction (410 unilateral breast reconstructions and 80 bilateral reconstructions).

    The de-epithelization technique was the most commonly used (3east symmetry.In vitro maturation (IVM) is an assisted reproduction technique with reduced hormone-related side-effects. Several attempts to implement IVM in routine practice have failed, primarily due to its relatively low efficiency compared with conventional in vitro fertilization (IVF). Recently, capacitation (CAPA)-IVM-a novel two-step IVM method-has improved the embryology outcomes through synchronizing the oocyte nuclear and cytoplasmic maturation. However, the efficiency gap between CAPA-IVM and conventional IVF is still noticeable especially in the numerical production of good quality embryos. Considering the importance of glucose for oocyte competence, its metabolization is studied within both in vivo and CAPA-IVM matured mouse cumulus-oocyte-complexes (COCs) through direct measurements in both cellular compartments, from transcriptional and translational perspectives, to reveal metabolic shortcomings within the CAPA-IVM COCs. SNDX-5613 These results confirmed that within in vivo COC, cumulus cells (CCs) are highly glycolytic, whereas oocytes, with low glycolytic activity, are deviating their glucose towards pentose phosphate pathway. No significant differences were observed in the CAPA-IVM oocytes compared with their in vivo counterparts. However, their CCs exhibited a precocious increase of glycolytic activity during the pre-maturation culture step and activity was decreased during the IVM step. Here, specific alterations in mouse COC glucose metabolism due to CAPA-IVM culture were characterized using direct measurements for the first time. Present data show that, while CAPA-IVM CCs are able to utilize glucose, their ability to support oocytes during final maturation is impaired. Future CAPA-IVM optimization strategies could focus on adjusting culture media energy substrate concentrations and/or implementing co-culture strategies.Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1 0.61; 95% confidence interval 0.45, 0.82; Ptrend less then 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged less then 65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.

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