Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling.

Understanding the regulatory mechanisms unique to breast cancer stem cells (BCSCs) is required to control breast cancer metastasis. We found that phthalates promote BCSCs in human breast cancer cell cultures and xenograft tumors. A toxic phthalate, benzyl butyl phthalate (BBP), activated aryl hydrocarbon receptor in breast cancer cells to stimulate sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling and enhance formation of metastasis-initiating BCSCs.

Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells.

Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells.

Curcumin Suppresses Phthalate-Induced Metastasis and the Proportion of Cancer Stem Cell (CSC)-like Cells via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma.

Recent evidence indicating that phthalates promote cancer development, including cell proliferation, migration, and invasion, has raised public health concerns. Here, we show that bis(2-ethylhexyl) phthalate promotes the migration, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma cells. In addition, bis(2-ethylhexyl) phthalate increased the proportion of cancer stem cell (CSC)-like cells and stemness maintenance in vitro as well as tumor growth and metastasis in vivo.

HDAC inhibitors target HDAC5, upregulate microRNA-125a-5p, and induce apoptosis in breast cancer cells.

Histone deacetylase inhibitors (HDACi) are novel clinical anticancer drugs that inhibit HDAC gene expression and induce cell apoptosis in human cancers. Nevertheless, the detailed mechanism or the downstream HDAC targets by which HDACi mediates apoptosis in human breast cancer cells remains unclear. Here, we show that HDACi reduce tumorigenesis and induce intrinsic apoptosis of human breast cancer cells through the microRNA miR-125a-5p in vivo and in vitro.

miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis.

Identifying stably expressed tumor markers that can be used easily to detect cancer is currently an important area of cancer research. By using miRNA microarray, we identified 20 differentially expressed miRNAs in serum samples of breast cancer patients. Expression of miR-125a-5p was relatively lower in patients with shorter survival compared to long-term survivors.

Benzyl butyl phthalate induces migration, invasion, and angiogenesis of Huh7 hepatocellular carcinoma cells through nongenomic AhR/G-protein signaling.

Background: The widespread use of phthalates as plasticizers has raised public health concerns regarding their adverse effects, including an association with cancer. Although animal investigations have suggested an association between phthalate exposure and hepatocellular carcinoma, the mechanisms are unknown.

Methods: The hepatocellular carcinoma cell line Huh7 was treated with benzyl butyl phthalate (BBP), and then analyzed by total internal reflection fluorescence microscopy, confocal microscopy and double immunogold transmission electron microscopy.

miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis.

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients.

Ectopic pregnancy-derived human trophoblastic stem cells regenerate dopaminergic nigrostriatal pathway to treat parkinsonian rats.

Background: Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD); however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies.

n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP), on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d). A total of 473 genes were upregulated, and 468 were downregulated.

Phthalates stimulate the epithelial to mesenchymal transition through an HDAC6-dependent mechanism in human breast epithelial stem cells.

Phthalates are environmental hormone-like molecules that are associated with breast cancer risk and are involved in metastasis, a process that requires the epithelial-mesenchymal transition (EMT). However, few studies have addressed the potential effects of phthalates on stem cells. Here we tested the hypothesis that phthalates such as butyl benzyl phthalate and di-n-butyl phthalate induce EMT in R2d cells, a stem cell-derived human breast epithelial cell line that is responsive to estradiol for tumor development.

Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway.

The environmentally present group of chemical phthalates, or phthalate esters, has been recognized as a rising threat to public health, including cancer. While most studies have addressed the estrogenic effects of phthalates in malignancies of the breast and the prostate, little is known about their role in the etiology of hormone-independent cancer. Here we show that treatments with the phthalates n-butyl benzyl phthalate (BBP) and dibutyl phthalate (DBP) at 1 μM induced proliferation (BBP, 3.

Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma.

Objective: To elucidate the role of interleukin-1β (IL-1β) on cyclooxygenase-2 (COX-2) expression and invasion of endometrioma-derived ectopic endometrial mesenchymal stem cells (EN-MSCs) and to develop an organoid method to study the invasive ability of endometrial cells.

Design: Gene expression and cell functions.

Setting: Kaohsiung Medical University, Kaohsiung, Taiwan.

Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model.

Objective: To elucidate the role of endometrial stem-progenitor cells in the etiology of endometriosis and to develop an animal model to study the invasion ability of endometrial cells.

Design: Gene expression and cell function studies were designed.

Setting: Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Increasing CD44+/CD24(-) tumor stem cells, and upregulation of COX-2 and HDAC6, as major functions of HER2 in breast tumorigenesis.

Background: Cancer cells are believed to arise primarily from stem cells. CD44+/CD24(-) have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood.

Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway.

Scope: In this study we first report the antimigration, antiinvasive effect of glabridin, a flavonoid obtained from licorice, in MDA-MB-231 human breast adenocarcinoma cells.

Methods And Results: Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of MDA-MB-231 cells. In addition, glabridin also blocked human umbilical vein endothelial cells (HUVEC) migration and decreased MDA-MB-231-mediated angiogenesis.

Modulation of tumorigenesis and oestrogen receptor-alpha expression by cell culture conditions in a stem cell-derived breast epithelial cell line.

Background Information: The common phenotypes of cancer and stem cells suggest that cancers arise from stem cells. Oestrogen is one of the few most important determinants of breast cancer, as shown by several lines of convincing evidence. We have previously reported a human breast epithelial cell type (Type 1 HBEC) with stem cell characteristics and ER alpha (oestrogen receptor alpha) expression.

The concentrations of visfatin in the follicular fluids of women undergoing controlled ovarian stimulation are correlated to the number of oocytes retrieved.

Objective: To compare the concentrations of visfatin in the plasma with those in follicular fluid of women undergoing controlled ovarian stimulation and to discover their correlation to the number of oocytes retrieved. Further, to examine whether FSH or hCG affects the expression of visfatin and whether visfatin affects COX-2 expression in cultured granulosa luteal (GL) cells.

Design: A clinical and in vitro study.

A functional promoter polymorphism in interleukin-10 gene influences susceptibility to endometriosis.

Objective: To investigate the involvement of inflammation in the development of endometriosis.

Design: Case-control study to investigate the association between endometriosis and four inflammation-related genes: interleukin (IL)-6, IL-10, IL-1 beta, and cyclooxygenase-2.

Setting: University hospital.

Mifepristone attenuates human chorionic gonadotropin-induced extracellular signal-regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells.

Objective: To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction.

Design: An in vitro study.

Setting: University hospital.

Leptin suppresses human chorionic gonadotropin-induced cyclooxygenase-2 expression and prostaglandin production in cultured human granulose luteal cells.

Objective: In a previous study, we demonstrated that high leptin levels at the time of human chorionic gonadotropin (hCG) injection impaired the pregnancy rate for women undergoing in vitro fertilization. In this study we examine leptin's effect on prostaglandin formation and cyclooxygenase (COX) expression induced by hCG in human granulose luteal (GL) cells.

Methods: Human GL cells were obtained from women undergoing ovarian hyperstimulation.

In vitro effects of arecoline on sperm motility and cyclooxygenase-2 expression.

Semen samples were obtained from 30 volunteers who had never consumed betel quid. Swim-up spermatozoa from the 30 seminal samples of non-betel quid chewers and also non-smokers, usually not exposed to passive smoking, were treated in vitro with arecoline at different concentrations to evaluate the action of these drugs on sperm motility. Highly motile sperms were collected and divided into 5 equal fractions.

Effect of oral conjugated equine estrogen combined with medroxyprogesterone acetate on plasma homocysteine levels in postmenopausal women.

Conjugated equine estrogen alone or combined with medroxyprogesterone acetate lowered homocysteine levels in postmenopausal women. Regardless of the dosage of progestin used, there was no impact on homocysteine metabolism after 3 years of therapy.

Atrial natriuretic peptide inhibits ovarian functions in female mice.

Objective: To investigate the effects of atrial natriuretic peptide (ANP) on ovarian regulation in mice through intraperitoneal administration.

Study Design: Forty-two ICR strain female mice were divided into seven groups, including one control. Each mouse received ovarian hyperstimulation.

Differential expression of manganese containing superoxide dismutase in patients with breast cancer in Taiwan.

This study used Western blot analysis to measure the expression of superoxide dismutases (Mn-SOD and Cu/Zn-SOD) in breast cancer tissues from 57 patients. Mn-SOD expression in the breast cancer tissues averaged 1.5-fold higher than in the adjacent tumor-free tissues (p <0.

Chronic administration of atrial natriuretic peptide reduces testosterone production of testes in mice.

The purpose of the present study was to examine the effect of the long-term administration of human atrial natriuretic peptide (ANP) on testosterone production in male mice. Twenty-five mice received ANP (20 ng/hour/g body weight) for 7 days via mini-osmotic pump, and the other group (n = 25) received twice-daily intraperitoneal injections. After death, levels of follicle-stimulating hormone, luteinizing hormone (LH), and testosterone in plasma, pituitary gland, and testis were measured by radioimmunoassay.