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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organ specific tumor metastasis is thought in part to require the ability of metastatic cells to respond to target-organ-associated growth factors or to avoid the effects of target organ associated growth inhibitors. We previously found that murine and rat liver-conditioned media inhibited the growth of the poorly-liver metastasizing murine RAW117-P large-cell lymphoma cells more than their highly liver-metastasizing RAW117-H10 counterparts. Using a six step chromatographic procedure, the major RAW117-P cell proliferation inhibitor from a rat liver extract was purified. The factor displayed a Mr of approximately 35,000 and an isoelectric point > 8.5. This material inhibited the growth of many cells at high concentration; however, in dose-response studies it displayed a higher IC50 for highly-liver metastatic murine RAW117-H10 lymphoma and human KM12SM colon carcinoma cells than for their poorly-liver metastatic counterparts. Attempts to identify the growth inhibitor led to the supplementation of tissue culture inhibitor assays with various components, including excess amino acids, and this was found to completely abrogate the factor's activity. Specifically, the addition of excess arginine resulted in the complete cellular recovery from inhibitor exposure. This tentatively identified the liver growth inhibitor as the enzyme arginase, a Mr approximately 10,000 multisubunit protein. A microtiter plate-based assay for arginase was developed and the purification repeated using human liver as a source of activity and the human KM12C colon carcinoma line as a target. The growth inhibitory and arginase activities were found to co-purify, identifying the factor as arginase. Highly-metastatic cells displayed no ability to preferentially inactivate or inhibit the activity of arginase, but they did they display slightly greater amounts of intracellular arginine. The liver is a major site of arginase localization as the enzyme is required for the functioning of the urea cycle. The results indicate that certain liver-colonizing tumor cells can escape, to a degree, the proliferation-damping effects of arginine depletion.
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PMID:Partial purification of a liver-derived tumor cell growth inhibitor that differentially inhibits poorly-liver metastasizing cell lines: identification as an active subunit of arginase. 1159 8

The metabolic NO pathway, catalyzed by the enzyme NO synthase in macrophages, is a key defense element against viruses and tumors. However, arginase is an other enzyme able to metabolize the substrate L-arginine, and the two enzymes are alternatively regulated by Th1 and Th2 cytokines in murine macrophages. Marek's disease is characterized by strong immunosuppression and development of T-cell lymphomas in chickens. Inoculation of the very virulent strain of MDV RB-1B induced strong and long-lasting arginase macrophage-dependent activity, which was inhibited by L-norvaline in vitro, but induced low NO production in monocytes and splenocytes from highly susceptible B(13)/B(13) chickens. By contrast, in B(21)/B(21) chickens genetically resistant to tumor development, RB-1B induced a weak and transient increase in arginase activity and strong NO production. The vaccinal HVT strain did not induce any arginase activity in monocytes or splenocytes. Moreover, vaccination with HVT prevented tumor appearance after RB-1B challenge and increase in arginase activity, but favored NO production in susceptible chickens. Differential expression of NO synthase and arginase was modulated in chicken macrophages, with IFN-gamma and LPS being strong inducers of both, depending on the type of macrophage, and TGF-beta 1 and PGE(2) stimulating only arginase activity. This increase in arginase activity in macrophages from chickens inoculated with Marek's disease virus might thus be due to a direct effect of the virus on macrophages, possibly through viral products, or to indirect effects on the cytokine balance.
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PMID:Resistance and susceptibility to Marek's disease: nitric oxide synthase/arginase activity balance. 1190 Sep 57

Investigations on the influence of the parasympathetic nervous system via muscarinic signaling in tumor progression have produced contradictory evidence. We investigated the expression of muscarinic acetylcholine receptors (mAchR) and their intracellular transduction pathways, in two murine mammary adenocarcinoma cell lines, LM3 and LM2 in comparison with the normal murine mammary epithelial cell line: NMuMG. Saturation binding assays with the tritiated muscarinic antagonist quinuclidinyl benzilate ([3H]-QNB) indicate that LM3 cells express higher amounts of mAchR than LM2 cells. Muscarinic receptor activation with carbachol (CARB) enhanced basal production of citrulline to a greater extent in LM3 cells than in LM2 cells. The nitric oxide synthase (NOS) inhibitor, NGmono-methyl-L-arginine (L-NMMA), blunted this effect only in LM3 cells while in LM2 cells the action of CARB was blocked by Nomega hydroxy-L-arginine (L-OH-Arg), which is known to inhibit the arginase pathway. Atropine blocks the action of CARB in both cell lines. Additionally, mAchR activation stimulates prostaglandin E2 (PGE2) synthesis only in LM2 cells. NMuMG cells show detectable basal amounts of nitric oxide and PGE2, but they did not respond to CARB. Binding experiments confirm the absence of mAchR in these cells. The findings indicate that mAchR expression in tumor cells, and its control on arginine metabolism, via NOS/arginase, and on PGE2 synthesis by COX activation, could be a switch on mechanism that might lead mammary cells from normal to malignant phenotype. Moreover, mAchR coupling to distinct effectors might be associated with differences in aggressiveness of tumor cells.
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PMID:Nitric oxide synthase, arginase and cyclooxygenase are involved in muscarinic receptor activation in different murine mammary adenocarcinoma cell lines. 1201 84

Arginase activity was measured in serum and biopsy from healthy individuals and colorectal cancer patients. Arginase activity in tumor samples (87 +/- 7.7 U/g tissue) was significantly higher than in controls (40.7 +/- 3.3 U/g tissue). However, serum arginase activity did not show any significant change in both groups. Finally, the micromethod used to quantify arginase activity in this study is superior to other methods because it has increased sensitivity, requires less sample, and is less time-consuming. Arginase differences are significant, according to the t-test (P<0.05)
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PMID:Diagnostic performance of arginase activity in colorectal cancer. 1204 90

Neovascularization, an essential step for tumor progression and metastasis development, can be modulated by the presence of macrophages (Mps) in the tumor microenvironment. The ability of Mps to regulate the angiogenicity of the LMM3 tumor cell line was studied. Peritoneal Mps from LMM3 tumor-bearing mice (TMps) potentiate in vivo LMM3 angiogenicity. These results were confirmed by CD31 immunoblotting assays. The activity of TMps depended on nitric oxide synthase (NOS) and arginase (A) activity. By immunoblotting we evidenced that AI and AII isoforms were up-regulated in TMps while the inducible and neuronal NOS isoforms were highly expressed in normal Mps. TMps might positively modulate tumor growth by stimulating angiogenic cascade mainly through polyamine synthesis.
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PMID:Arginine metabolic pathways involved in the modulation of tumor-induced angiogenesis by macrophages. 1245 93

L-Arginine (Arg) is classified as an essential amino acid for birds, carnivores and young mammals and a conditionally essential amino acid for adults. It is converted by arginase to L-ornithine, a precursor of polyamines and urea, which is important in the urea cycle. Arg serves as a precursor for creatine, which plays an essential role in the energy metabolism of muscle, nerve and testis and accounts for Arg catabolism and for the synthesis of agmatine and proteins. Via its ability to increase growth hormone secretion it influences immune function. Depending on nutritional status and developmental stage, normal plasma Arg concentrations in humans and animals range from 95 to 250 micromol/l. Systemic or oral Arg administration has been shown to improve cardiovascular function and reduce myocardial ischemia in coronary artery disease patients. It reduces blood pressure and renal vascular resistance in essential hypertensive patients with normal or insufficient renal function. Although Arg plasma concentrations are not altered in hypercholesterolemic individuals, oral or intravenous Arg administration can reverse endothelial dysfunction in hypercholesterolemic patients and in cigarette smokers. The main importance of Arg is attributed to its role as a precursor for the synthesis of nitric oxide (NO), a free radical molecule that is synthesized in all mammalian cells from L-Arg by NO synthase (NOS). NO appears to be a major form of the endothelium-derived relaxing factor (EDRF). NO and EDRF share similar chemical and pharmacological properties and are derived from the oxidation of a terminal guanidine group of L-Arg. Various mechanisms have been implicated in the defect in vascular relaxation. These include, increased diffusional barrier for NO, L-Arg depletion, altered levels of reactive oxygen, inactivation of NO by superoxide anions (O2-). The independent reactions of O2-, NO and their reaction yielding peroxynitrite are critical in the initiation and maintenance of the atherosclerotic state and contribute to the defect in vasorelaxation. NO also plays a role as a neurotransmitter, mediator of immune response and as signaling molecule. The NO synthesized by iNOS in macrophages contributes to their cytotoxic activity against tumor cells, bacteria and protozoa. Our aim here is to review on some amino acids with high functional priority such as Arg and to define their effective activity in human health and pathologies.
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PMID:I. Arginine. 1248 80

The present study investigated the ability of the arginine analog L-NAME (N(omega)-Nitro-L-arginine methyl ester) to modulate the activity of arginase. L-NAME inhibited the activity of arginase in lysates from rat colon cancer cells and liver. It also inhibited the arginase activity of tumor cells in culture. Furthermore, in vivo treatment of rats with L-NAME inhibited arginase activity in tumor nodules and liver, and the effect persisted after treatment ceased. The effect of L-NAME on arginase requires consideration when it is used in vivo in animal models with the aim of inhibiting endothelial NO-synthase, another enzyme using arginine as substrate.
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PMID:Arginase activity is inhibited by L-NAME, both in vitro and in vivo. 1253 Apr 80

Most of the mice bearing a s.c. BW-Sp3 lymphoma tumor mount a CD8(+) T cell-mediated response resulting in tumor regression. Nonetheless, tumor progression occurs in some of the recipients and is associated with CTL inactivity. We demonstrated that T cell-activating APC were induced in regressors whereas T cell suppressive myeloid cells predominated in the spleen of progressors. Indeed, in vitro depletion of either the adherent or the CD11b(+) populations restored T cell cytotoxicity and proliferation in these mice. This CTL inhibition was cell-to-cell contact-dependent but not mediated by NO. However, the same progressor suppressive cells prevented the activity of in vitro-restimulated CTLs derived from regressors in a cell-to-cell contact and NO-dependent fashion. Thus, either the NO-dependent or -independent suppressive pathway prevailed, depending on the target CTL population. In addition, the suppressive population expressed a high arginase activity, suggesting an association of the suppressive phenotype with alternatively activated (M2) myeloid cells. However, the high arginase activity is not directly involved in the suppressive process. Our results provide new insights for myeloid cell-mediated CTL inhibition during cancer progression.
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PMID:Nitric oxide-independent CTL suppression during tumor progression: association with arginase-producing (M2) myeloid cells. 1273 51

The activities of the enzymes arginase and rhodanese were examined in homogenates of 13 mouse cell strains and 2 human cell strains after long cultivation of the cells in vitro. Three strains of mouse liver origin showed both high arginase and rhodanese activities in keeping with activities of the tissue of origin. Two strains of cells of human epithelial origin, HeLa and epidermis, were found to have high rhodanese activity but low arginase activity, the skin being almost devoid of it. Seven mouse fibroblast strains or substrains had moderate rhodanese activity and all except one of the strains had low arginase activity. Two of the fibroblast strains tested, NCTC 1745 and NCTC 2050, were derived from a single cell of a tumor appearing after injection of the high tumor producing strain NCTC 1742 into a mouse. The strain 1745 had 20 times and the strain 2050 had 400 times the arginase activity of the parent strain of cells. The findings imply a considerable biochemical variation in the three strains. Three mouse mammary carcinoma clones were devoid of arginase activity, but had considerable rhodanese activity.
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PMID:The arginase and rhodanese activities of certain cell strains after long cultivation in vitro. 1358 50

BACKGROUND: Arginine metabolism in tumor cell lines can be influenced by various cytokines, including recombinant human interferon-gamma (rIFN-gamma), a cytokine that shows promising clinical activity in epithelial ovarian cancer (EOC). METHODS: We examined EOC cell lines for the expression of arginase in an enzymatic assay and for transcripts of arginase I and II, inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO) by reverse transcription-polymerase chain reaction. The effects of rIFN-gamma on arginase activity and on tumor cell growth inhibition were determined by measuring [3H]thymidine uptake. RESULTS: Elevated arginase activity was detected in 5 of 8 tumor cell lines, and analysis at the transcriptional level showed that arginase II was involved but arginase I was not. rIFN-gamma reduced arginase activity in 3 EOC cell lines but increased activity in the 2008 cell line and its platinum-resistant subline, 2008.C13. iNOS transcripts were not detected in rIFN-gamma-treated or untreated cell lines. In contrast, IDO activity was induced or increased by rIFN-gamma. Suppression of arginase activity by rIFN-gamma in certain cell lines suggested that such inhibition might contribute to its antiproliferative effects. However, supplementation of the medium with polyamine pathway products did not interfere with the growth-inhibitory effects of rIFN-gamma EOC cells. CONCLUSIONS: Increased arginase activity, specifically identified with arginase II, is present in most of the tested EOC cell lines. rIFN-gamma inhibits or stimulates arginase activity in certain EOC cell lines, though the decrease in arginase activity does not appear to be associated with the in vitro antiproliferative activity of rIFN-gamma. Since cells within the stroma of EOC tissues could also contribute to arginine metabolism following treatment with rIFN-gamma or rIFN-gamma-inducers, it would be helpful to examine these effects in vivo.
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PMID:rIFN-gamma-mediated growth suppression of platinum-sensitive and -resistant ovarian tumor cell lines not dependent upon arginase inhibition. 1457 12


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