CXCR2 is a negative regulator of p21 in p53-dependent and independent manner via Akt-mediated Mdm2 in ovarian cancer.

Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood.

Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension.

Background/aims: To investigaterole of serotonin (5-HT) and serotonin transporter (5-HTT) in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH) and the effect of statins on regulating 5HT and 5-HTT.

Methods: A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day.

CXCR2-driven ovarian cancer progression involves upregulation of proinflammatory chemokines by potentiating NF-κB activation via EGFR-transactivated Akt signaling.

Ovarian cancer is an inflammation-associated malignancy with a high mortality rate. CXCR2 expressing ovarian cancers are aggressive with poorer outcomes. We therefore investigated molecular mechanisms involved in CXCR2-driven cancer progression by comparing CXCR2 positive and negative ovarian cancer cell lines.

Inhibitory effect of tumor suppressor p53 on proinflammatory chemokine expression in ovarian cancer cells by reducing proteasomal degradation of IκB.

Ovarian cancer, one of inflammation-associated cancers, is the fifth leading cause of cancer deaths among women. Inflammation in the tumor microenvironment is associated with peritoneal tumor dissemination and massive ascites, which contribute to high mortality in ovarian cancer. Tumor suppressor p53 is frequently deleted or mutated in aggressive and high-grade ovarian cancer, probably aggravating cancer progression and increasing mortality.

Protective cardiovascular and renal actions of vitamin D and estrogen.

Both basic science and clinical studies support the concept that vitamin D deficiency is involved in the pathogenesis of cardiovascular and renal diseases through its association with diabetes, obesity, and hypertension. Understanding the underlying mechanisms may provide a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases. This review explores the effect of vitamin D deficiency in the development of cardiovascular and renal diseases, and the role of vitamin D supplementation on cardiovascular outcomes.

Expression of adrenomedullin 2 (ADM2)/intermedin (IMD) in human placenta: role in trophoblast invasion and migration.

Calcitonin gene-related peptide (CALCB), amylin, and adrenomedullin (ADM) belong to a unique group of calcitonin (CALCA)/CALCB family peptides that have overlapping biological effects owing to their structure and cross-reactivity between receptors. CALCB and ADM are expressed in fetoplacental tissues and are important in maintaining normal placental function. Recently, ADM 2 (ADM2)/intermedin was identified as a novel CALCA/CALCB family peptide that functions through CALCB and ADM receptors.

Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development.

Recent studies have shown that homozygous knockout of gene for calcitonin gene-related peptide (CALCA) receptor component, calcitonin receptor-like receptor (CALCRL), led to extreme hydrops fetalis and embryonic death, underlining the critical role of CALCA in embryonic development and fetal growth. The present study was designed to determine the cellular localization of CALCA and its receptor components, CALCRL and receptor activity modifying protein 1 (RAMP1), at the human implantation site during early pregnancy; to assess whether CALCA regulates in vitro angiogenesis of human endothelial cells; and to examine whether CALCA can improve angiogenic imbalance in preeclamptic placental explants. Our studies demonstrated that both protein and mRNA for CALCA were expressed by the villous and extravillous trophoblasts and decidual cells in the first-trimester villous tissues.

Circulating calcitonin gene-related peptide and its placental origins in normotensive and preeclamptic pregnancies.

Objective: The present study was designed to determine plasma calcitonin gene-related peptide concentration in both maternal and fetal circulations in normotensive and pre-eclamptic pregnancies and investigate whether placenta is 1 of its origins.

Study Design: Maternal blood, cord blood, and villous tissue were collected from women in normotensive pregnancies and complicated with pre-eclampsia. Calcitonin gene-related peptide concentrations were determined by radioimmunoassay.

Calcitonin gene-related peptide stimulates human villous trophoblast cell differentiation in vitro.

Calcitonin gene-related peptide (CGRP) is a multifunctional peptide present in both maternal and fetal circulations in pregnancy. Its receptors have been identified on human trophoblast cells, but the role of CGRP in trophoblast differentiation remains unknown. This study was designed to determine the effect of CGRP on the differentiation of villous trophoblasts isolated from normal human term placentae.

Ca2+ signaling in human fetoplacental vasculature: effect of CGRP on umbilical vein smooth muscle cytosolic Ca2+ concentration.

CGRP is a potent vasodilator with increased levels in fetoplacental circulation during late pregnancy. We have recently demonstrated that acute CGRP exposure to fetoplacental vessels in vitro induced vascular relaxation, but the signaling pathway of CGRP in fetoplacental vasculature remains unclear. We hypothesized that CGRP relaxes fetoplacental vasculature via regulating smooth muscle cytosolic Ca2+ concentrations.

Adrenomedullin enhances invasion by trophoblast cell lines.

We have tested the hypothesis that adrenomedullin (ADM), a multifunctional peptide hormone, works as a trophoblast proinvasion factor. Our results showed that ADM receptor components-the mRNA and proteins of calcitonin receptor-like receptor (CALCRL) and receptor activity modifying proteins (RAMPs)-were expressed by human choriocarcinoma JAr cells and first-trimester cytotrophoblast HTR-8/SV neo cells. ADM stimulates both JAr and HTR-8/SV neo cell proliferation.

Evidence for decreased calcitonin gene-related peptide (CGRP) receptors and compromised responsiveness to CGRP of fetoplacental vessels in preeclamptic pregnancies.

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory peptide, and its concentration is increased in both maternal and fetal circulation during late pregnancy. The present study was designed to investigate the expression of CGRP receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity modifying protein 1 (RAMP1), and the relaxation response to CGRP in fetoplacental vessels from normotensive pregnant women and women with preeclampsia. Results showed that: 1) mRNA for both CRLR and RAMP1 was expressed in fetoplacental vessels from normal pregnancies; however, these mRNA expressions were substantially reduced in the vessels from preeclamptic women; 2) CRLR and RAMP1 proteins were abundantly expressed in the endothelium and smooth muscle layer of the fetoplacental vessels, as well as the trophoblast cells in normal placentas.

Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone.

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi.

Effects of steroid hormones on calcitonin gene-related peptide receptors in cultured human myometrium.

Objective: This study was designed to examine whether, with the use of human myometrial explants in culture, calcitonin gene-related peptide B receptors are regulated by steroid hormones.

Study Design: Myometrial tissues were obtained from the lower uterine segments from women in a nonpregnant state and pregnant women who were not in labor undergoing cesarean delivery (39.1 +/- 0.

Expression and regulation of calcitonin gene-related Peptide receptor in rat placentas.

Calcitonin gene-related peptide (CGRP), one of the most potent vasodilators known, exerts its biological action by interacting with its receptors. Recent reports suggest the existence of two types of CGRP receptors, CGRP-A and CGRP-B. The current study was designed to examine whether CGRP-B receptors are present in the rat placenta, and if they are, whether they are modulated by gestational age and by sex-steroid hormones.