Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunotherapies, although promising in preclinical studies, have not yet enhanced the survival of patients with glioblastomas. To further understand the immunobiology of glioblastomas in clinical settings, we examined 53 cytokine or cytokine receptor transcripts in 12 human glioblastomas and 6 human glioblastoma cell lines and correlated the findings with the degree of inflammation. Multi-probe RNase protection assays were used to examine Th1, Th2, and Th3 cytokine and cytokine receptor expression. Th2 [interleukin (IL)-6, leukemia inhibitory factor and oncostatin M] and Th3 (transforming growth factor-beta1, 2, 3) cytokine and their receptor transcripts were strongly expressed in almost all glioblastomas and glioma cell lines. Two other Th2 cytokine receptor subunit transcripts (IL-4Ralpha and IL-13Ralpha) were also commonly detected. In contrast, although Th1 cytokine receptors tumor necrosis factor (TNF) RI, interferon (IFN)-gammaRalpha, IFN-gammaRbeta, were detected, their cytokines (IFN-gamma, TNF-alpha, lymphotoxin-alpha) were not. Transcripts for IL-2 family cytokine (IL-2, IL-7, IL-9, IL-15) and receptors (IL-2Ralpha, IL-2Rbeta, gammac, IL-7Ralpha, IL-9Ralpha, IL15Ralpha) and IL-12 family cytokine (IL-12p40) and receptors (IL-12Rbeta1 and IL-12beta2) were essentially absent in both tumors and cell lines. Immunohistochemical methods showed sparse T lymphocyte infiltrates and numerous microglia in the glioblastomas. This pattern indicates an 'immunosuppressive status' in glioblastomas and could account for the failure of immunotherapy in such tumors.
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PMID:Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation. 1181 Jan 84

Heparin-binding epidermal growth factor (HB-EGF) is a recently identified member of the EGF growth factor family found to be expressed in the uterus of both mouse and human at the time of implantation. In the present study, we investigated the expression patterns of HB-EGF in normal cycling endometrium and compared its expression with the fertility-associated endometrial epithelial biomarkers alpha(v)beta(3) integrin, leukemia inhibitory factor (LIF) and homeobox gene, HOXA-10. RNase protection assay (RPA) using RNA made from endometrium collected from different phases of the menstrual cycle demonstrated increased HB-EGF expression during the mid-secretory phase, a pattern similar to, but slightly preceding the expression of alpha(v)beta(3) integrin and HOXA-10. In vitro studies demonstrated stimulation of HB-EGF expression by estradiol-17beta (E(2)) and progesterone (P(4)) alone or in combination in stromal cells. Combined treatment with E(2) + P(4) was, however, required to stimulate epithelial HB-EGF expression. In vitro experiments demonstrated the ability of HB-EGF to stimulate epithelial expression of the key endometrial proteins including LIF, HOXA-10, and the beta(3) integrin subunit. Each has previously been demonstrated to be an important epithelial biomarker expressed during the implantation window. In addition, conditioned media from endometrial stromal cells treated with E(2) + P(4) + relaxin mimicked the stimulatory effect of HB-EGF on epithelial expression of the beta(3) integrin subunit. The stimulatory effect of the stromal-conditioned medium was blocked by antibodies that neutralize a known receptor for HB-EGF. These data suggest that uterine receptivity may be regulated in part by the stromal-derived HB-EGF.
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PMID:Regulated expression of heparin-binding EGF-like growth factor (HB-EGF) in the human endometrium: a potential paracrine role during implantation. 1211 77

An adequate endometrial glucose metabolism, mediated by facilitative glucose transporter molecules (GLUT), is an essential part of endometrial differentiation and decidualization to provide a nutritional and receptive milieu. In human endometrium, only the GLUT1 and GLUT3 isoforms are expressed, whereas glucose transporters, involved in insulin-dependent glucose uptake (GLUT2, GLUT4, GLUT8), could not be detected. Messenger RNA expression, analyzed by RNase protection assay, of both isoforms increased in total endometrium throughout the secretory phase and in decidua. Analysis of mRNA expression in isolated epithelial cells, stromal cells, and CD45 positive leukocytes revealed that increase of GLUT1 expression was due to increasing stromal expression, whereas increase of GLUT3 was due to its expression in CD45-positive immune cells. In vitro, GLUT1 and GLUT3 were not directly regulated by 17beta-estradiol, progesterone, or IL-1beta, IL-6, and leukemia inhibitory factor, but GLUT1 mRNA increased progressively in stromal cells, decidualized in vitro. Inhibition of glucose transporters by cytochalasin B reduced stromal glucose uptake and stromal decidualization. In idiopathic infertile patients, GLUT1 expression in midsecretory endometrium was suppressed. The suppression was caused by reduced stromal expression. Our results suggest stromal GLUT to play a role in the regulation of endometrial function and be compromised in the preparation of the endometrium for the implanting embryo.
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PMID:Glucose transporter proteins (GLUT) in human endometrium: expression, regulation, and function throughout the menstrual cycle and in early pregnancy. 1291 84


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