Objectives: Expression of uPA mRNA is massively up-regulated in the stroma of poorly differentiated ovarian tumors. We hypothesized that this expression was induced by paracrine signals from the epithelial tumor cells, and established an in vitro model of ovarian cancer microenvironment to study intercellular cross-talk.
Methods: ES-2 clear cell carcinoma cells were grown in tissue culture inserts in a double-chamber system with fibroblastic stromal LEP cells embedded in Matrigel.
Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).
View Article and Find Full Text PDFBackground: Monoamines play important roles in decidualization, implantation, immune modulation and inflammation. Furthermore, monoamines are potent vasoactive mediators that regulate blood flow and capillary permeability. Regulation of the uterine blood flow is important both during menstruation and pregnancy.
View Article and Find Full Text PDFThe non-neuronal monoamine transporters (OCT1, OCT2, EMT, and PMAT) play a key role in the clearance of monoamines from extracellular compartments. In a previous report we described endometrial distribution and cyclic variation of the vesicular monoamine transporter (VMAT2) mRNA and the neuronal norepinephrine transporter (NET) mRNA. In the present study we used in situ hybridization, real-time PCR and immunohistochemistry to reveal tissue distribution and cyclic variation of mRNA for the non-neuronal monoamine transporters in the human endometrium and early pregnancy decidua.
View Article and Find Full Text PDFCellular reuptake of monoamines, which is mediated by cell membrane transporters, is followed by accumulation in vesicles by vesicular monoamine transporters (VMAT). The aim of this study was to demonstrate the presence of functional monoamine transporters with high affinity for histamine in human endometrial tissue, since histamine has been implicated as a paracrine signal during endometrial decidualization and embryo implantation. In situ hybridization with (35)S-labelled cRNA probes was used for detection of the organic cationic transporter-2 (OCT-2), the extraneuronal monoamine transporter (EMT), and VMAT-2 in cryosections of normal human endometrial tissue.
View Article and Find Full Text PDFThis study was designed to assess the predictive value of an MTT (3-[4,5-dimethylthiazol-2,5-diphenyl] tetrazolium bromide) in vitro assay for the evaluation of leukemic cell resistance/sensitivity to cytotoxic drugs, and to compare these results with clinical and laboratory parameters in cases of childhood acute lymphoblastic leukemia (ALL).The chemoresistance of leukemic cells was ascertained by means of an MTT assay in 32 previously untreated children with ALL. The children were treated using the protocol ALL-BFM 90.
View Article and Find Full Text PDFCellular screening of various synthetic triterpenoid compounds formally derived from lupane has identified a number of analogues as potential anticancer drug candidates. Here we describe the synthesis and structure-activity relationships of betulin and betulinic acid derivatives containing an E-ring modified with different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup-18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane systems, as well as des-E-lupane derivatives, were prepared from the readily available natural pentacyclic triterpene betulin using oxidative procedures.
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