Intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome via activating macrophage-angiogenesis-related androgen signaling

The development of polycystic ovary syndrome(PCOS)is closely related to the chronic inflammatory and obese.Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling,but the underlying mechanisms have not been clarified.In this study,we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate liposome.Then,the offspring rat macrophage phenotype in offspring female rat adipose tissue,and levels of testosterone,angiogenic factors(PDGF and VEGF)and inflammatory factors(TNF-αand MCP-1)were investigated.By coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells(ECs),the mobility of adipocytes,and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide,NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996.It was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity,increased size and reduced number of subcutaneous and intra-abdominal adipocytes,and increased secretion of TNF-αand MCP-1 in female rats in the offspring.Eliminating macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen,and reduced TNF-αand MCP-1.Macrophages promoted mobility of adipocytes,and inhibited proliferation,migration,tube formation of ECs under hyperandrogenic condition,which were significantly inhibited by Apalutamide,JSH-23 and LY3214996.Thus,intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.

Non-viral targeted delivery system mediates transfection of thymidine kinase gene of herpes simplex virus into ovarian cancer cells:a comparison between one time and continuous mediation

Objective： To compare the transferring efficiency and killing effects of one time and continuous mediation with GE7, a non-viral targeted delivery system, in transfection of thymidine kinase gene of herpes simplex virus （HSV-tk） into ovarian cancer cells. Methods： GE7 was used to prepare recombinants with β-galactosidase （β-gal） and HSVI-tk; the recombinants were then used to transfect human ovarian cancer line CaOV3 once and continuously. β-gal staining was used to compare the efficiencies of one time and continuous mediation with GE7 system. Ganciclovior （GCV） was introduced into HSVI-tk transfected ovarian cells. Through drawing the cell growth curve and flow cytometry, the killing effects of GCV on once and continuously GE7/HSVI-tk transfected cells were observed. Results： We found that the one time and continuous exogenous gene transfer efficiencies were about 80% and 85%, respectively. When 1 μg/mL GCV was used to treat ovarian cell transfected with HSVI-tk gene, growth inhibiting rates of ovarian cells of one time and continuous transferring were 82% and 90%, respectively; their apoptosis indices were 15 and 30, respectively. Under same GCV concentration, continuous mediation of GE7/pCMV-tk transfection into ovarian cancer cells had more significant inhibitory effect than one time mediation （P 〈 0.05）. Conclusion： Compared with one time mediation, continuous mediation of transfection with GE7 gene delivery system has higher efficiency. Continuous mediation of GE7/HSVI-tk/GCV therapeutic gene system has more powerful killing effect.

A retrospective clinical study of patients with pregnancy-associated breast cancer among multiple centers in China (CSBrS-008)

Background:Pregnancy-associated breast cancer(PABC)is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth.With the rapid social development and the adjustment of reproductive policies in China,the average age of females at first childbirth is increasing,which is expected to lead to an increase in the incidence of PABC.This study aimed to accumulate clinical experience and to investigate and summarize the prevalence,diagnosis,and treatment of PABC based on large multicenter samples in China.Methods:According to the Chinese Society of Breast Surgery,a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified.The pregnancy status,clinicopathological features,comprehensive treatment methods,and outcomes were retrospectively analyzed.Survival curves were plotted using the Kaplan-Meier method.Results:A total of 164 patients of PABC accounted for 0.30%of the total number of cases in the same period;of which,83 patients were diagnosed during pregnancy and 81 patients during lactation.The median age of PABC was 33 years(24–47 years).Stage Ⅰ patients accounted for 9.1%(15/164),stage Ⅱ 54.9%(90/164),stage Ⅲ 24.4%(40/164),and stage Ⅳ 2.4%(4/164).About 9.1%(15/164)of patients were luminal A.Luminal B patients accounted the most(43.3%[71/164]).About 15.2%(25/164)of patients were human epidermal growth factor receptor 2(Her-2)overexpression and 18.9%(31/164)of patients were triple-negative breast cancer.For pregnancy breast cancer,36.1%(30/83)of patients received direct surgery and 20.5%(17/83)received chemotherapy during pregnancy.About 31.3%(26/83)chose abortion or induction of labor.The median follow-up time was 36 months(3–59 months);11.0%(18/164)patients had local recurrence or distant metastasis and 3.0%(5/164)died.Conclusions:It is safe and feasible to standardize surgery and chemotherapy for PABC.