Different Oncogenes and Reproductive Histories Shape the Progression of Distinct Premalignant Clones in Multistage Mouse Breast Cancer Models.

A remote carcinogen exposure can predispose to breast cancer onset decades later, suggesting that carcinogen-induced mutations generate long-lived premalignant clones. How subsequent events influence the progression of specific premalignant clones remains poorly understood. Herein, multistage mouse models of mammary carcinogenesis were generated by combining chemical carcinogen exposure [using 7,12-dimethylbenzanthracene (DMBA)] with transgenes that enable inducible expression of one of two clinically relevant mammary oncogenes: c-MYC (MYC) or PIK3CA (PIK).

Age and 17β-Estradiol (E) Facilitate Nuclear Export and Argonaute Loading of microRNAs in the Female Brain.

Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17β-estradiol (E), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone replacement therapy is only effective within a narrow window of time surrounding the menopausal transition.

Nab-Paclitaxel and Gemcitabine as First-Line Treatment of Metastatic Ampullary Adenocarcinoma with a Novel RNA Fusion and Mutation.

Ampullary adenocarcinoma is a rare malignancy that lacks standard systemic treatment. We describe a case of recurrent metastatic ampullary adenocarcinoma of the pancreaticobiliary subtype treated with nanoparticle albumin-bound (nab)-paclitaxel and gemcitabine as first-line treatment. This report also highlights the molecular profile of the ampullary adenocarcinoma and circulating tumor DNA (ctDNA).

17β-Estradiol Regulates miR-9-5p and miR-9-3p Stability and Function in the Aged Female Rat Brain.

Clinical studies demonstrated that the ovarian hormone 17β-estradiol (E) is neuroprotective within a narrow window of time following menopause, suggesting that there is a biological switch in E action that is temporally dependent. However, the molecular mechanisms mediating this temporal switch have not been determined. Our previous studies focused on microRNAs (miRNA) as one potential molecular mediator and showed that E differentially regulated a subset of mature miRNAs which was dependent on age and the length of time following E deprivation.

Epigenomic control of gonadotrophin-releasing hormone neurone development and hypogonadotrophic hypogonadism.

Mammalian reproductive success depends on gonadotrophin-releasing hormone (GnRH) neurones to stimulate gonadotrophin secretion from the anterior pituitary and activate gonadal steroidogenesis and gametogenesis. Genetic screening studies in patients diagnosed with Kallmann syndrome (KS), a congenital form of hypogonadotrophic hypogonadism (CHH), identified several causal mutations, including those in the fibroblast growth factor (FGF) system. This signalling pathway regulates neuroendocrine progenitor cell proliferation, fate specification and cell survival.