Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Correlations between radiocurability and kinetic parameters were investigated in four transplantable tumor types in WHT/Ht mice. The radiation dose to achieve 50% tumor control at 120 days after irradiation, i.e., TCD50/120, was 30 Gy for squamous cell carcinoma H, 32 Gy for squamous cell carcinoma NOS, 46 Gy for rhabdomyosarcoma KAS, and 63 Gy for fibrosarcoma YAS. The tumor cell kinetic parameters investigated were specific growth delay, volume doubling time, 125I-iododeoxyuridine (IUdR) uptake rate, and specific cell loss rate. The specific cell loss rate was defined as the ratio of cell loss rate in non-irradiated tumors to the rate in irradiated tumors, and was obtained by measuring the retention rate of radioactivity in the tumors. No correlations were found between specific growth delay, volume doubling time, 125I-IUdR uptake rate, and TCD50. However, the specific cell loss rate correlated with the TCD50. Therefore, the 125I-IUdR labeling method may be useful as an in situ predictive assay for tumor radiocurability.
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PMID:Single dose radiocurability of four murine solid tumors and a predictive assay for the curability in situ. 955 26

Prospective data on 1,360 consecutive inpatients referred to the consultation-liaison psychiatry service of 2 metropolitan general teaching hospitals and diagnoses as having a Depressive Illness Spectrum Disorder were collected by using the MICRO-CARES clinical database system. The distribution of DSM-III-R diagnoses was major depression (MD) 49%; dysthymia (DYS) 15%; organic or substance-induced mood disorder or depressive disorder not otherwise specified (ORG/NOS) 14%; and adjustment disorder with depressed mood (AD) 29%s. Antidepressants were prescribed in 59% of the MD cases, 40% of the DYS cases, 36% of the ORG/NOS cases, and 17% of the AD cases. In confirmed MD, antidepressants were prescribed in 69%, and significantly more often in those who were older, female, had a prior history of physical illness, had a neoplasm or a disorder of the nervous or musculoskeletal systems, had higher Axis IV scores, or were referred because of pain or terminal illness. The patients with confirmed MD prescribed antidepressants had a longer length of stay and were referred later than those not prescribed antidepressants. The results illustrate the importance of all the forms of depression in consultation-liaison psychiatry and the vigor with which all forms are treated.
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PMID:Consultation-liaison psychiatrists management of depression. 966 71

Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis. Inducible nitric oxide synthase (iNOS; NOS-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and regulators of epithelial cell growth. Expression levels of iNOS and COX-2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers. To determine the involvement of iNOS and COX-2 in Barrett's-associated neoplasia, we measured expression of these genes in metaplastic Barrett's and esophageal adenocarcinomas. We detected elevated iNOS and COX-2 mRNA levels in Barrett's mucosa compared with paired gastric control tissues in 16 of 21 (76%) and 17 of 21 (80%) patients, respectively (P < 0.001 for both genes). In esophageal adenocarcinomas, iNOS and COX-2 mRNA levels were increased in four of five and five of five cases, respectively. Furthermore, in 10 of 10 Barrett's patients, immunohistochemical staining for iNOS and COX-2 expression was strongly positive and higher than in matched gastric controls. Increased COX-2 expression was confirmed by Western blotting. These findings support the hypothesis that iNOS and COX-2 are involved early and often in Barrett's-associated neoplastic progression.
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PMID:Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. 967 48

The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock. The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway. The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes. iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself. In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury. Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion. Its cytoprotective role is best exemplified in a rodent model of endotoxemia. Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage. NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals. NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity. These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury. In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties.
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PMID:Inducible nitric oxide synthase in the liver: regulation and function. 972 29

The objective of this study was to elucidate the role and mechanism of nitric oxide (NO) synthase (NOS) in modulating the growth of the Caco-2 human colon carcinoma cell line. The two novel observations reported here are, first, that NG-hydroxy-L-arginine (NOHA) inhibits Caco-2 tumor cell proliferation, likely by inhibiting arginase activity, and, second, that NO causes cytostasis by mechanisms that might involve inhibition of ornithine decarboxylase (ODC) activity. Both arginase and ODC are enzymes involved in the conversion of arginine to polyamines required for cell proliferation. Cell growth was monitored by cell count, cell protein analysis, and DNA synthesis. NOHA (1-30 microM) and NO in the form of DETA/NO (1-30 microM) inhibited cell proliferation by 30-85%. The cytostatic effect of NOHA was prevented by addition of excess ornithine, putrescine, spermidine, or spermine to cell cultures, whereas the cytostatic effect of NO (DETA/NO) and alpha-difluoromethylornithine (ODC inhibitor) was unaffected by ornithine but was prevented by putrescine, spermidine, or spermine. The cytostatic effect of NOHA appeared to be independent of its conversion to NO, and the effect of NO appeared to be independent of cGMP. NOHA inhibited urea production by Caco-2 cells and inhibited arginase catalytic activity (85% at 3 microM), whereas NO (DEA/NO and SNAP) inhibited ODC activity (>/=60% at 30 microM) without affecting arginase activity. Coculture of Caco-2 cells with lipopolysaccharide/cytokine-activated rat aortic endothelial cells markedly slowed Caco-2 cell proliferation, and this was blocked by NOS inhibitors. These observations that NOHA and NO may inhibit sequential steps in the arginine-polyamine pathway suggest a novel biological role for NOS in the inhibition of cell proliferation of certain tumor cells and possibly other cell types.
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PMID:NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms. 975 58

Neovascularization, the growth and formation of capillary blood vessels, is an essential component of solid tumor growth and a critical step in metastasis. Tumor associated macrophages (TAMs) have several functions related to tumor biology including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define the TAM and microvessel density (MD) in human invasive breast carcinoma NOS and to correlate their values with lymph node status, tumor size, tumor grade and mitotic activity index (MAI), and, finally, to determine whether MD is connected with TAMs. A total number of 57 invasive breast carcinomas NOS were processed for immunohistochemical analysis using mAb to F-VIII to visualize endothelial cells and mAb to CD68 antigens for macrophages. Statistical analysis showed only a positive correlation between TAMs and MAI (p = 0.004). These results support the notion that intensity of tumor angiogenesis does not provide additional prognostic significance, while TAMs may play a positive role in breast cancer micro system since they regulate tumor proliferation.
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PMID:Comparison of microvessel density with tumor associated macrophages in invasive breast carcinoma. 985 92

Cellular nitric oxide (NO) synthesis determines whether NO has cytoprotective or cytotoxic effects at anatomic sites; thus it is important to identify potential NO synthase isoforms in tumor tissue and tumor cell lines which might be involved in tumor development or destruction. Incubation of human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, CaPan-2) with cytokines resulted in increased NO formation, indicating the existence of the NOS2 isoform. This was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, we identified the presence of the endothelium-derived NOS isoform 3 by RT-PCR analysis and immunohistochemistry in normal and pancreatic tumor biopsies. NOS3 was markedly overexpressed in the vasculature of the tumor tissue. RT-PCR analysis of tumor biopsies identified NOS isoform 2 mRNA in 60% of cases, but western blot analysis or immunohistochemistry scored negative for this isoform. It is noteworthy that the NOS enzyme activity in pancreatic tumor cell lines and tumor biopsies was inhibited by EGTA by approximately 30% and 65%, respectively. Our results suggest that increased endothelium-derived NOS isoform 3 expression in pancreatic adenocarcinomas regulates blood flow and is therefore involved in the vascularization and neovascularization of human pancreatic tumors.
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PMID:Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the vasculature of human pancreatic tumor biopsies. 992 50

Inducible nitric oxide synthase (iNOS) is overexpressed in colonic tumors of humans and also in rats treated with a colon carcinogen. iNOS appear to regulate cyclooxygenase-2 (COX-2) expression and production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to study the inhibitory effects of S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT) a selective iNOS-specific inhibitor, measured against formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). Beginning at 5 weeks of age, male F344 rats were fed experimental diets containing 0 or 50 p.p.m. of PBIT, or 2000 p.p.m. of curcumin (non-specific iNOS inhibitor). One week later, rats were injected s.c. with AOM (15 mg/kg body wt, once weekly for 2 weeks). At 17 weeks of age, all rats were killed, colons were evaluated for ACF formation and colonic mucosa was assayed for isoforms of COX and NOS activities. Both COX and iNOS activities in colonic mucosa of the AOM-treated rats were significantly induced. Importantly, 50 p.p.m. PBIT suppressed AOM-induced colonic ACF formation to 58% (P < 0.0001) and crypt multiplicity containing four or more crypts per focus to 78% (P < 0.0001); it also suppressed AOM-induced iNOS activity. Curcumin inhibited colonic ACF formation by 45% (P < 0.001). These observations suggest that iNOS may play a key regulatory role in colon carcinogenesis. Developing iNOS-specific inhibitors may provide a selective and safe chemopreventive strategy for colon cancer treatment.
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PMID:Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. 1022 93

It is well documented that nitric oxide (NO) is an effector molecule of macrophage-mediated tumor cell toxicity in vitro; however, little is known about the role of NO in the antitumor immune response in vivo. We have developed a treatment protocol using lipid A. We have investigated the effects of lipid A on inducible NO synthase (NOS II) expression and evolution inside tumors during the course of treatment. Lipid A (OM-174) treatment induced tumor regression in rats bearing established colon tumors. Furthermore, NO was synthesized and secreted inside the tumors of lipid A-treated rats, as demonstrated by the increase of NOS II mRNA and NOS II content in the tumors, as well as of NOS II activity and NO production. During treatment, NOS II was localized in tumor cells only. Lipid A had no direct effect on tumor cells in vitro, while the combination of interferon gamma (IFN-gamma) plus interleukin-1 beta (IL-1beta) induced production of NO by tumor cells which was cytostatic. The content of IFN-gamma and IL-1beta in tumors was enhanced during lipid A treatment; this is in agreement with an indirect effect of lipid A in vivo via the IFN-gamma and IL-1beta pathways.
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PMID:Expression of inducible nitric oxide synthase in tumors in relation with their regression induced by lipid A in rats. 1032 29

A 3-h exposure to NO donors (spermine-NO, DETA-NO, or SNAP), or to NOS II-expressing cells (activated macrophages or EMT6 cells) reversibly inhibited DNA synthesis in K562 tumor cells. In GSH-depleted K562 cells, cytostasis remained reversible when induced by DETA-NO or NOS II activity, but became irreversible after exposure to spermine-NO or SNAP. Only SNAP and spermine-NO efficiently inhibited GAPDH, an enzyme with a critical thiol, in GSH-depleted cells. Thus, the irreversible cytostasis induced in GSH-depleted cells by spermine-NO or SNAP can be tentatively attributed to S-nitrosating or oxidizing species derived from NO. However, these species did not contribute significantly to the early antiproliferative effects of macrophages. Ribonucleotide reductase, a key enzyme in DNA synthesis. has been shown to be inhibited by NO. Supplementation of the medium with deoxyribonucleosides to bypass RNR inhibition restored DNA synthesis in target cells exposed to DETA-NO and NO-producing cells, but was inefficient for GSH-depleted cells previously submitted to spermine-NO or SNAP. These cells also exhibited a persistent depletion of the dATP pool. In conclusion, GSH depletion reveals striking qualitative differences in the nature of the toxic effectors released by various NO sources, questioning the significance of S-nitrosating or oxidizing nitrogen oxides in NOS II-dependent cytostasis.
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PMID:Differential cytostatic effects of NO donors and NO producing cells. 1038 Dec


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