Assessing the antitumor effects of metformin on ovarian clear cell carcinoma.

Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase in some cell lines and suppressed phosphorylation of the mammalian target of rapamycin in a particular cell line. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase in a particular cell line. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin.

Caesarean Section of Multifetal Pregnancy.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 0/7 and 38 6/7 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long U -shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.

Contraction-associated proteins expression by human uterine smooth muscle cells depends on maternal serum and progranulin associated with gestational weight gain.

Pregnant women with obesity are at increased risk of parturition dysfunction; however, the biological mechanism has remained unknown. We hypothesized that molecules circulating in the serum of pregnant women with obesity may induce the aberrant expression of contraction-associated proteins (CAPs), leading to insufficient uterine contractions. This study aimed to investigate the effects of maternal serum on CAPs expression by human uterine smooth muscle cells (UtSMCs) and elucidate the influence of maternal obesity. Blood samples were collected from singleton pregnant women at 36-41 weeks of gestation before the onset of labor. UtSMCs were incubated in the serum, and the mRNA expressions of PTGFR, OXTR, GJA1, and PTGS2 were examined by RT-PCR. Progranulin (PGRN) is a circulating glycoprotein associated with insulin resistance characterized by the accumulation of visceral fat. The serum PGRN levels of the samples were measured by ELISA. After incubated with PGRN (100-1,000 ng/mL), mRNA expression of PTGFR, OXTR, and GJA1 and protein expression of CX43 were examined by RT-PCR and western blotting, respectively. The mRNA expressions of PTGFR, OXTR, and GJA1 showed significantly negative correlations with gestational weight gain (GWG). Serum PGRN levels showed a significantly positive correlation with GWG. High levels of PGRN suppressed the mRNA expression of GJA1 and the protein expression of CX43. The change in maternal serum induced by GWG suppressed the CAPs expression by UtSMCs. PGRN is one of the factors in the serum responsible for inhibiting the expression of CX43.