Overexpression of estrogen receptor-alpha gene suppresses gap junctional intercellular communication in endometrial carcinoma cells.

Stimulation of the endometrium by estrogens without the differentiating effect of progestins is the primary etiological factor associated with the development of endometrial hyperplasia and adenocarcinoma. However, the correlation between sex steroids and gap junctional intercellular communication (GJIC), which is considered to play an important role in the control of cell growth and differentiation, is not well known in endometrial carcinoma. In this study, we focused on the influence of estrogen and its receptor in connexin (Cx) expression and GJIC in endometrial carcinoma cells, established stable clone IK-ER1 overexpressing ER-alpha to transfect the expression vector and analysed them in various hormonal conditions. The growth of IK-ER1 was accelerated by 17beta-estradiol and the acceleration of the 5-bromo-25-deoxyuridine labeling index was observed. GJIC was assayed by scoring the number of dye-coupled cells after microinjection of single cells with Lucifer-Yellow, and subcellular localization of Cx26 and Cx32 was analysed by immunocytochemistry. In the presence of estradiol, dye-coupled cells of IK-ER1 were significantly reduced compared to those without estradiol and the reduction was completely inhibited by adding ICI182.780, a pure antiestrogen substrate. Cxs were detected as only small spots by immunocytochemistry, and Western blotting showed that the expression was decreased. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and suppressing GJIC via suppression of the expression of Cxs in endometrial carcinogenesis.

Impact of prepregnant body mass index and maternal weight gain on the risk of pregnancy complications in Japanese women.

BACKGROUND: To analyze the association of pregnancy complications with prepregnant body mass index and weight gain during pregnancy in Japanese women. METHODS: A retrospective cohort study was conducted with 21,718 Japanese women with a singleton pregnancy. Pregnant women were grouped by prepregnant body mass index and evaluated for association with pregnancy complications using multivariate logistic regression analysis. The women in each body mass index group were then divided into groups by weight gain during pregnancy using intervals of 0.05 kg/week to analyze the relationship between the weight gain and pregnancy complications by multivariate logistic regression association analysis. RESULTS: In both nulliparous and parous women, the least pregnancy complications were found among women with medium prepregnant body mass indexes (18-23.9). Significant risks of pregnancy complications were associated with low (< 18) and high (> or = 24) prepregnant body mass indexes, particularly high prepregnant body mass indexes. In nulliparous women, the optimal weight gain was 0.25-0.4 kg/week for low (< 18) prepregnant body mass index, 0.20-0.30 kg/week for medium (18-23.9) prepregnant body mass index, and > or = 0.05 kg/week for high (> or = 24) prepregnant body mass index. In parous women, the corresponding values were > or = 0.20, 0.20-0.30, and 0.05-0.30 kg/week. CONCLUSIONS: Japanese women with prepregnant body mass indexes from 18 to 23.9 are least associated with pregnancy complications, although there is a broad range of prepregnant body mass indexes associated with few pregnancy complications. Optimal weight gain is roughly inversely related to prepregnant body mass index.

Changed expression of heat shock proteins in various pathological findings in placentas with intrauterine fetal growth restriction.

Heat shock proteins (HSPs) are activated in the cells of most organisms in response to sublethal heat shock and other stressors. It has been reported that HSP27, HSP60, HSP70, and HSP90 are expressed in normal human placenta, and it was thought that these HSPs play a role in the demonstration of cell viability and function. In this study, we performed an immunohistochemical (IHC) study of these HSPs for 27 placentas that had complicated intrauterine fetal growth restriction (IUGR) and compared the IHC findings with the pathological findings. To quantify HSP27, HSP60, HSP70, and HSP90, immunoreacted cells in the chorionic villi, syncytiotrophoblasts (ST), and cytotrophoblasts (CT) were counted. In thrombus, excessive syncytial knots, and avascular villi, the expression of HSPs was higher in the pathological sections compared to control in both ST and CT. In contrast, all HSPs decreased in both ST and CT around the infarction region. The data suggested that chorionic villi cells locally responded to some stresses, e.g., hypoxia and increase or decrease in the expression of HSPs. Although the villous cells around the infarction histologically appear viable, they may have received lethal damage, and as a result the expression of HSPs was decreased. These results are expected to improve our understanding of the pathological findings of IUGR in placentas, including the quality, damage, and function of the chorionic villi.

Correlation between responsiveness of neoadjuvant chemotherapy and apoptosis-associated proteins for cervical adenocarcinoma.

OBJECTIVE: Adenocarcinoma of the uterine cervix appears to be increasing in prevalence and it has been suggested that these tumors tend to be less sensitive to radiation therapy and to chemotherapy than squamous carcinomas. In the present study, 29 patients with locally advanced cervical adenocarcinoma (bulky IB-IVB) were treated with neoadjuvant chemotherapy (NAC) using cisplatin, aclacinomycin-A and mitomycin-C, followed by radical surgery or irradiation. METHODS: To predict the prognosis and response to the chemotherapy, the expression of apoptosis associated-proteins, p53, p21WAF1/CIP1, Bcl-2 and activated caspase-3 was evaluated for tumor samples by immunohistochemistry. RESULTS: Of the analyzed clinicopathological factors, the overexpression of p53 was frequently observed in endocervical-type adenocarcinoma, nonresponders to chemotherapy and the grade 0 histologic effect of the chemotherapy. Positive staining of Bcl-2 was frequently observed in the early stage and had a better prognosis than for patients with the negative staining; however, there was no correlation between responders and nonresponders to chemotherapy. The expression of p21WAF1/CIP1 and caspase-3 was not correlated to the clinicopathological factors. CONCLUSION: In this study, the overexpression of p53 was found to be a factor to predict the chemoresistance and positive expression of Bcl-2 indicated as a better prognostic value. For p21WAF1/CIP1 and caspase-3, further analysis is necessary.