Norio Takamoto

Down-regulation of pregnane X receptor contributes to cell growth inhibition and apoptosis by anticancer agents in endometrial cancer cells.

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of drug-metabolizing enzymes, cytochrome P450 3A (CYP3A) family, and members of the drug transporter family, including multiple drug resistance 1 (MDR1). We demonstrated previously that steroid/xenobiotic metabolism by tumor tissue through the PXR-CYP3A pathway might play an important role in endometrial cancer and that PXR ligands enhance PXR-mediated transcription in a ligand- and promoter-dependent fashion, leading to differential regulation of individual PXR targets, especially CYP3A4 and MDR1. In this study, we investigated the potential contribution of PXR down-regulation by RNA interference toward the augmentation of drug sensitivity and the overcoming of drug resistance. We observed the protein levels of both CYP3A4 and MDR1 in PXR small interfering RNA (siRNA)-transfected cells were not increased in the presence of PXR ligands, paclitaxel, cisplatin, estradiol, or medroxyprogesterone acetate (MPA) compared with control siRNA-transfected cells. There was no PXR-mediated transactivation or augmentation of transcription by coactivators in the presence of these ligands. We then found that PXR down-regulation caused a significant increase in cell growth inhibition and enhancement of apoptosis in the presence of the anticancer agents, paclitaxel, cisplatin, and MPA. Finally, we demonstrated that PXR overexpression caused a significant decrease in cell growth inhibition and inhibited apoptosis in the presence of paclitaxel or cisplatin. These data suggest that PXR down-regulation could be a novel therapeutic approach for the augmentation of sensitivity to anticancer agents, or to overcome resistance to them, in the treatment of endometrial cancer.

Elevated level of serum retinol‐binding protein 4 in pregnancy‐induced hypertension

Aim:  Recent progress in adiposcience has revealed several important adipose‐tissue‐originated factors, so‐called adipokines. Retinol‐binding protein 4 (RBP4), a protein expressed and secreted by adipocytes, has been identified as a novel regulator of insulin resistance. Physiological insulin resistance occurs during the pregnancy of mammals to accommodate fetal growth, and it has been suggested that insulin resistance and hyperinsulinemia might also be associated with pregnancy‐induced hypertension (PIH). In order to shed light on the role of RBP4 during pregnancy, we attempted to assess RBP4 levels during pregnancy. Fetal growth could be affected by aberrant regulation of RBP4 levels in fetal circulation per se, so we examined the RBP4 levels in cord blood samples of growth restricted cases.

Malignant Melanoma of the Uterine Cervix: A Case Report

We present case of a 57‐year‐old Japanese woman a 9 cm‐size primary malignant melanoma of the uterine cervix. MRI demonstrated a low‐signal T1‐weighted spin echo image and hyperperfusion indicated by Gd‐DTPA enhancement. The sequence! analysis of the MTS1/CDK4I gene revealed no deletion or mutation. The results of cytological, pathological, and electron microscopy tests are also presented.

Effects of intermittent high glucose on BeWo choriocarcinoma cells in culture

Aim:  The aim of this study was to investigate the cellular effects of intermittent high glucose on the human BeWo placental choriocarcinoma cell line, used as a model of the effects of glucose fluctuation in diabetic pregnancies.