Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.

miR-506: a regulator of chemo-sensitivity through suppression of the RAD51-homologous recombination axis

Ovarian carcinoma is the most lethal gynecologic malignancy. Resistance to platinum is considered the major problem afecting prognosis. Our recent study established that micro RNA-506(mi R-506) expression was closely associated with progression-free survival and overall survival in two independent patient cohorts totaling 598 epithelial ovarian cancer cases. Further functional study demonstrated that mi R-506 could augment the response to cisplatin and olaparib through targeting RAD51 and suppressing homologous recombination in a panel of ovarian cancer cell lines. Systemic delivery of mi R-506 in an orthotopic ovarian cancer mouse model signiicantly augmented the cisplatin response, thus recapitulating the clinical observation. Therefore, mi R-506 plays a functionally important role in homologous recombination and has important therapeutic value for sensitizing cancer cells to chemotherapy, especially in chemo-resistant patients with attenuated expression of mi R-506.

Ovarian cancer presenting with hypercalcemia:two cases with similar manifestations but different mechanisms

Hypercalcemia presenting in ovarian cancer is uncommon in the clinic.Here,two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported,with a review of the literature.The laboratory findings and stepwise clinical investigations of these two cases differed,indicating distinct underlying causes of hypercalcemia.In case one,the serum levels and immunostaining for parathyroid hormone-related protein(PTHr P)verified humoral hypercalcemia of malignancy(HHM).In case two,the high level of parathyroid hormone(PTH)and the scintigraphy scan showing parathyroid gland adenoma confirmed primary hyperparathyroidism-induced hypercalcemia.Both patients received optimal cytoreductive operation and adjuvant chemotherapy but showed different outcomes respectively.This article focused on differential diagnosis of ovarian cancerassociated hypercalcemia,by stepwise imaging and laboratory investigation,and the appropriate therapy should be considered based on the different etiologies.

Prevalence of Reproductive Tract Infections and Association with Human Papillomavirus Infection Among Reproductive-Age Women—Six Tertiary Hospitals,China,June 2021-December 2022

Summary What is already known about this topic?Previous studies have indicated a possible association between reproductive tract infections(RTIs)and highrisk human papillomavirus(HPV)infection,but the evidence is still inconclusive.What is added by this report?This multicenter study found significantly higher positive rates of HPV,including general HPV,highrisk HPV.

子宫内膜息肉临床诊疗路径

子宫内膜息肉是常见的子宫内膜良性病变之一,可发生于青春期后的任何年龄,患病率随年龄增加而增高,其常见症状为异常子宫出血、不孕,或无明显症状。本临床诊疗路径以循证医学证据为基础,以临床规范诊疗为目的,建立从子宫内膜息肉高危因素的识别、临床诊断、病理分型到治疗再到患者的长期管理、宣教的诊疗流程路径,给予临床医师共识性的指导建议,旨在为广大妇产科医师提供子宫内膜息肉临床诊疗的可行性和规范性流程。