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At least 55 records · Page 3Linked to original sources
PubMed2004

Progesterone-independent effects of human progesterone receptors (PRs) in estrogen receptor-positive breast cancer: PR isoform-specific gene regulation and tumor biology.

Progesterone receptors (PRs) are prognostic markers in breast cancers irrespective of the patient's progestational status. However, there are two PR isoforms, PR-A and PR-B, that are equimolar in the normal breast but dysregulated in advanced disease. Postmenopausal, tamoxifen-treated patients with estrogen receptor (ER)-positive, PR-A-rich tumors have much faster disease recurrence than patients with PR-B-rich tumors. To study the mechanisms we engineered ER+ breast cancer cells that express each PR isoform under control of an inducible promoter. We identified 79 genes regulated by progesterone (P), mainly by PR-B, and 51 genes regulated without progesterone, mainly by PR-A. Only nine genes were regulated with and without ligand, leading to definition of three classes: I) genes regulated only by liganded PR; II) genes regulated only by unliganded PR; III) genes regulated by both. Unliganded PR-A and PR-B differentially regulate genes that coordinate extracellular signaling pathways and influence tumor cell biology. Indeed, in the absence of P, compared with ER+/PR-B+ or PR- cells, ER+, PR-A+ cells exhibit an aggressive phenotype, are more adhesive to an extracellular matrix, and are more migratory. Additionally, unliganded PR-A and PR-B both inhibit cell growth and provoke resistance to Taxol-induced apoptosis. We propose that PR-A:PR-B ratios, even in the absence of P, influence the biology and treatment response of ER+ tumors, that PR-A isoforms are functionally dominant in P-deficient states, and that PR-A rich tumors are especially aggressive.

Apoptosis↗
PubMed2001

Stromal PRs mediate induction of 17beta-hydroxysteroid dehydrogenase type 2 expression in human endometrial epithelium: a paracrine mechanism for inactivation of E2.

Progesterone stimulates the expression of 17beta-hydroxysteroid dehydrogenase (HSD) type 2, which catalyzes the conversion of the potent estrogen, E2, to an inactive form, estrone, in epithelial cells of human endometrial tissue. Various effects of progesterone on uterine epithelium have recently been shown to be mediated by stromal PRs in mice. We describe herein a critical paracrine mechanism whereby progesterone induction of 17beta-HSD type 2 enzyme activity, transcript levels, and promoter activity in human endometrial epithelial cells are mediated primarily by PR in endometrial stromal cells. Medium conditioned with progestin-pretreated human endometrial stromal cells robustly increased 17beta-HSD type 2 enzyme activity (2-fold) and mRNA levels (13.2-fold) in Ishikawa malignant endometrial epithelial cells. In contrast, direct progestin treatment of Ishikawa epithelial cells gave rise to much smaller increases in enzyme activity (1.2-fold) and mRNA levels (4-fold). These results suggest that progesterone- dependent paracrine factors arising from stromal cells are primarily responsible for the induction of epithelial 17beta-HSD type 2 expression in the endometrium. We transfected serial deletion mutants of the -1,244 bp 5'-flanking region of the 17beta-HSD type 2 gene into Ishikawa cells. No progesterone response elements could be identified upstream of the 17beta-HSD type 2 promoter. Stromal PR-dependent induction of the 17beta-HSD type 2 promoter was mediated by a critical regulatory region mapped to the -200/-100 bp sequence. Direct treatment of Ishikawa cells with progestin gave rise to a maximal increase in the activity of -200 bp/Luciferase construct only by 1.2-fold, whereas medium conditioned by progestin-pretreated endometrial stromal cells increased promoter activity up to 2.4-fold in a time- and concentration-dependent manner. The stimulatory effect of medium conditioned by progestin-pretreated stromal cells was enhanced strikingly by increasing stromal cell PR levels with the addition of estrogen. This epithelial-stromal interaction was specific for endometrial epithelial cells, since 17beta-HSD type 2 could not be induced in malignant breast epithelial cells by media conditioned with progestin-treated breast or endometrial stromal cells. In conclusion, progesterone regulates the conversion of biologically active E2 to estrone by inducing the 17beta-HSD type 2 enzyme in human endometrial epithelium primarily via PR in stromal cells, which secrete factors that induce transcription mediated primarily by the -200/-100 bp 5'-regulatory region of the 17beta-HSD type 2 promoter.

17-Hydroxysteroid Dehydrogenases↗
PubMed2003

Dexanabinol: dexanabinone, HU 211, PA 50211, PRS 211007, sinnabidol.

Dexanabinol [HU 211, dexanabinone, sinnabidol, PA 50211, PRS 211007] is a synthetic, non-psychotropic tetrahydro-cannabinoid. Dexanabinol lacks cannabimimetic activity, and is a functional antagonist of the NMDA receptor with antioxidant and anti-tumour necrosis factor-alpha properties. Dexanabinol is in clinical trials for traumatic brain injury (head injuries), glaucoma and mild cognitive impairment, and is being investigated preclinically for its potential in the treatment of multiple sclerosis. Pharmos has a licensing agreement with the Hebrew University, Israel, and is seeking a partner for development and commercialisation of the dexanabinol family of compounds. The Financial Times (ft.com) reported in March 2001 that the market for brain trauma could be worth approximately 500 million US dollars, according to estimates by Pharmos. The company was said to have 26 million US dollars in capital at the time, most of which would be used taking dexanabinol through regulatory submission, according to the Financial Times.

Animals↗
PubMed1997

A software for the description of workplaces in the PRS system.

Workplace description is an operation indispensable for the identification of professional risks and, in fulfillment of that objective, can best be accomplished by listing the constituent tasks associated with each job. This article presents a software in Visual-Basic to be run on a portable micro-computer, which facilitates this process according to these aims. The occupational physician and safety engineer can make good use of the exposure database resulting from the application of this program. Job histories are built automatically, while workers with similar exposures are grouped together and job-exposure matrices are elaborated. This information, computerized, sorted and re-assembled, can then be used effectively for studies in the field of occupational epidemiology.

Epidemiologic Methods↗
PubMed1992

Roles of the pap- and prs-encoded adhesins in Escherichia coli adherence to human uroepithelial cells.

In this study, we reexamined the structural prerequisites for the attachment of P-fimbriated Escherichia coli to human urinary tract epithelial cells. The epithelial cells were obtained from A1P1 nonsecretor individuals, who express the globoseries of glycolipids without the ABH blood group determinants, and from A1P1 secretor individuals, who in addition express globo-A, a receptor for the prsJ96 adhesin. The wild-type E. coli strains J96, AD110, and IA2 and the recombinant clones HB101 papJ96, HB101 prsJ96, HB101 papIA2, and HB101 papAD110 were tested for binding. They expressed P fimbriae, as defined by P blood group-dependent agglutination of human erythrocytes of the globoseries, but differed in reactivity with galactose alpha 1-4galactose beta (Gal alpha 1-4Gal beta)-latex beads, isolated glycolipids of the globoseries, sheep erythrocytes, and uroepithelial cells. Three different patterns of binding were represented among the recombinant clones. HB101 papIA2 and HB101 papAD110 agglutinated sheep erythrocytes and Gal alpha 1-4Gal beta-latex beads and attached to both secretor and nonsecretor epithelial cells. HB101 prsJ96 agglutinated sheep erythrocytes, reacted poorly with Gal alpha 1-4Gal beta-latex beads, and attached to A1 secretor but not to A1 nonsecretor epithelial cells. HB101 papJ96 agglutinated Gal alpha 1-4Gal beta-latex beads but not sheep erythrocytes and attached poorly to human uroepithelial cells. The receptors relevant for adhesion were analyzed by inhibition with glycolipids in suspension. The sheep erythrocyte agglutination and attachment to secretor and nonsecretor epithelial cells of HB101 papIA2 and HB101 papAD110 were inhibited by globotetraosylceramide, while the Forssman glycolipid had no effect. The sheep erythrocyte reactivity and attachment to secretor epithelial cells of HB101 prsJ96 were inhibited by the Forssman glycolipid. These results permitted three conclusions. First, the expression of functionally active Gal alpha 1-4Gal beta-specific adhesins, as in HB101 papJ96, was not sufficient to make E. coli competent to attach to human uroepithelial cells. Attachment required P fimbriae of the papIA2 or papAD110 type. Second, the sheep erythrocyte reactivity of P-fimbriated strains could not be attributed solely to recognition of the Forssman glycolipid and may not be used to define the prsJ96-encoded phenotype. Third, the P-fimbrial adhesins which mediate secretor state-independent attachment to human uroepithelial cells recognized receptor epitopes provided by globotetraosylceramide.

Adhesins, Escherichia coli↗
PubMed1988

Mutation in the phosphoribosylpyrophosphate synthetase gene (prs) that results in simultaneous requirements for purine and pyrimidine nucleosides, nicotinamide nucleotide, histidine, and tryptophan in Escherichia coli.

A mutant of Escherichia coli harboring a temperature-labile phosphoribosylpyrophosphate (PRPP) synthetase was characterized. Despite the lack of a detectable PRPP pool or PRPP synthetase activity at 40 degrees C, the strain was fully viable at this temperature as long as guanosine, uridine, histidine, tryptophan, and nicotinamide mononucleotide were all added to the growth medium. Viability of the strain was dependent upon mutations in genes of the nucleoside salvage pathways that improved the utilization of exogenous nucleosides. The properties of the strain are those expected of a PRPP-less strain and suggest that PRPP synthetase is dispensable for E. coli.

Escherichia coli↗
PubMed2000

Phase variation of F165(1) (Prs-like) fimbriae from Escherichia coli causing septicaemia in animals.

Escherichia coli O115:F165 strains are associated with septicaemia in young pigs and synthesize fimbriae involved in virulence, designated as F165(1). F165(1) fimbriae belong to the P fimbrial family and are encoded by the foo gene cluster. The foo regulatory region of strain 5131 possesses characteristics similar to that of members of the P regulatory family, including papI and papB homologues, and two GATC sites separated by 102 bp, targets of differential Dam methylation. In wild-type strains, the synthesis of F165(1) is repressed by leucine and the fimbriae undergo phase variation. Immunofluorescence staining showed that phase variation of F165(1) results in a majority of cells (98%) in the ON phase, in contrast with phase variation of other members of this regulatory family, for which the majority of the cells are in the OFF state. Using a translational fusion in strain 5131 between phoA and fooA, encoding for the major structural subunit of F165(1), it was shown that leucine inhibits the OFF to ON switch and modulates the basal transcription of the foo operon.

Alanine↗
PubMed1992

Structure, aims and prospects of PRS in Germany.

The development of ERS as an offering in the outpatient services sector is based on the consideration that the proportion of elderly people in the total population has enormously increased during the last few years and will continue to increase until the year 2000. Besides the necessary inpatient institutions, it is absolutely necessary to offer outpatient services to meet the needs and requirements of elderly, sick and handicapped people. This is also intended by the legislative bodies which have established by law the priority of outpatient services. ERS represents an important element of this general conception. One cannot do this without high quality standards. Furthermore, ERS must always be offered in connection with other outpatient social services.

Aged↗