UMLS:C0027651 - FACTA Search

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

Contents of 22 amino acids in hepatoma with surrounding and distant liver parenchyma resected from 10 pathologically proven patients were determined using high performance liquid chromatography. Analysis of the results showed that the contents of total amino acids and essential amino acids in hepatoma tissues were much higher than those in the surrounding and distant liver parenchyma. The contents of 11 amino acids, including glutamic acid, asparagine, glutamine, serine, histidine, arginine, tryptophan, methionine, leucine, isoleucine and lysine were higher than those in the surrounding and/or distant liver parenchyma. There was no statistically significant difference of amino acid contents between the surrounding and distant liver parenchyma. Most amino acid contents which increased in hepatoma tissues were positively correlated with tumor volume and/or serum gamma-glutamyl transpeptidase activity. These results suggested that hepatoma tissues can selectively take up the necessary amino acids which fail to be produced by the cancer tissues as raw material for synthesis of protein. The faster the hepatoma grows, the greater the need for amino acidosis. This study may be helpful to the application of imbalanced amino acid for correction of metabolic disturbances in hepatoma patients.
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PMID:[Changes in amino acid contents in hepatocellular carcinoma tissues]. 257 11

In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L-glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP-producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells.
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PMID:[Chemical modification of anti-cancer drugs to increase their affinity to tumor antigens]. 258 Apr 85

2-Amino-6-methyldipyrido[1,2-a:3',2'-d]limidazole, a potent bacterial mutagen from glutamic acid pyrolysate, when given to male CDF1 mice at a concentration of 0.05% in the diet induced blood vessel tumors characterized histopathologically. These hemangioendothelial sarcomas showed positive alkaline phosphatase activity histochemically and Weibel-Palade bodies ultrastructurally. Neoplasms were predilective for brown adipose tissue and foci of atypical cells, not peliosis-like lesions, appear to be an early stage in tumor development.
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PMID:Hemangioendothelial sarcoma in brown adipose tissue of mouse induced by carcinogenic heterocyclic amine, Glu-P-1. 262 66

The structure-function relationship of several recombinant human alpha interferons (IFN-alpha) (IFN-alpha 1, IFN-alpha 2, IFN-alpha 4, IFN-alpha 7, IFN-alpha 2/alpha 1 and IFN-delta 4 alpha 1) was investigated with respect to their ability to augment natural killer (NK) cytotoxicity of human peripheral blood mononuclear cells (PBMC) against hemopoietic tumor cell lines. Although all these IFNs significantly augmented NK cytotoxicity against the K562, Daudi and U937 targets, significant quantitave differences were observed in their ability to augment NK. INF-alpha 4, IFN-alpha 2 and IFN-alpha 2/alpha 1 were able to augment NK at low concentrations (less than 0.1 ng/ml), whereas IFN-alpha 7, IFN-alpha 1 and IFN-delta 4 alpha 1 required significantly higher concentrations (3 ng/ml or higher). The cumulative rank order of INFs on the basis of NK augmenting ability was found to be: IFN-alpha 4 approximately IFN-alpha 2 approximately IFN-alpha 2/alpha 1 greater than IFN-alpha 7 greater than IFN-alpha 1 approximately IFN-delta 4 alpha 1. To determine synergism or potentiation in the ability of IFNs to augment NK cytotoxicity, we investigated the effect of simultaneous, sequential and reversed order of treatment of human PBMC by these IFNs. Such potentiation or synergism was not observed. In addition, all these IFNs were able to augment NK cytotoxicity against targets from malignant melanoma cell lines. IFN-alpha 7 augmented regularly and reproducibly NK cytotoxicity in 15 of 19 normal donors examined (79%). This augmentation was blocked by an anti-IFN-alpha antibody. Concentrations of IFN-alpha 7 as low as 0.06 ng/ml were able significantly to augment NK cytotoxicity of PBMC after incubation for one hour at 37 degrees C. In contrast to these findings, IFN-alpha J, an interferon similar to IFN-alpha 7, has been report to be incapable of augmenting NK cytotoxicity and also of interfering with augmentation of NK by other IFNs. Sequential treatment of PBMC first with IFN-alpha 7 and then with other interferons did not prevent the augmentation of NK. Similarly, simultaneous treatment with IFN-alpha 7 and other interferons did not prevent augmentation of NK. In both treatments IFN-alpha J has been reported to prevent augmentation of NK. IFN alpha J and IFN-alpha 7 differ only by one amino acid, at position 107, where a lysine in IFN-alpha J has been replaced by a glutamic acid in the IFN-alpha 7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of natural killer cytotoxicity by recombinant alpha interferons. Augmentation by IFN-alpha 7, an interferon similar to IFN-alpha J. 281 13

The constituent amino acids of reduced glutathione (GSH), GSH itself, and D-alpha-tocopherol inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermis in vivo and in vitro. The inhibitory effects of cysteine (Cys), GSH and D-alpha-tocopherol on ODC induction were proportional to their abilities to decrease the incidence of skin tumors in the initiation-promotion protocol. Moreover, the ability of the constituent amino acids of GSH and GSH to inhibit TPA-induced ODC activity correlated well with their ability to increase the ratio of GSH/oxidized glutathione (GSSG) in isolated epidermal cells. In vitro, various treatments with 1 mM GSH, 1 mM glutamic acid (Glu), 1 mM glycine (Gly), 0.4 mM Cys and/or 0.2 mM cystine (CysCys) inhibited dramatically the sharp decline in the intracellular ratio of GSH/GSSG caused by 0.1 microM TPA. Since the inhibitory effects of Cys on both the decrease in the ratio of GSH/GSSG and the induction of ODC activity by TPA were greatly reduced by the inhibitors of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase, it is suggested that some of the inhibitory effects of Glu, Cys and Gly on tumor promotion could result from their interference with the metabolism of the tripeptide GSH, a natural antioxidant which inhibits chemical carcinogenesis. The free radical scavenger D-alpha-tocopherol, which did not alter directly the intracellular ratio of GSH/GSSG, also prevented completely the decrease in the ratio of GSH/GSSG caused by TPA. These results, therefore, suggest that GSH level-raising agents and other antioxidants might inhibit by diverse means the effects of TPA on GSH metabolism and skin tumor promotion.
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PMID:Inhibitory effects of glutathione level-raising agents and D-alpha-tocopherol on ornithine decarboxylase induction and mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 285 27

Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrate a link between the individual plasma glutamate level and the individual immunological reactivity as measured by mitogenic responses. This correlation has been analyzed in 39 colorectal carcinoma patients, 40 oat cell carcinoma patients, 24 large cell lung carcinoma patients, and 31 apparently healthy persons (blood donors). Blood cells from all three groups of tumor patients in comparison with cells from healthy persons produced markedly reduced mitogenic responses against PWM, and all three groups of tumor patients had on average significantly elevated plasma glutamic acid concentrations. Our analysis revealed a linear regression of the logarithm of the individual plasma glutamate levels (before therapeutic treatment) on the logarithm of the corresponding mitogenic reactivity against PWM for the entire population of 134 persons tested (correlation coefficient -0.80; level of significance P less than 0.00001). A statistically significant linear correlation with a similar regression equation was also observed in the group of the healthy blood donors (n = 31; correlation coefficient -0.56; P less than 0.01), indicating that this correlation is universal and not dependent on the presence of a tumor. Mitogenically stimulated murine lymphocyte cultures revealed an inverse correlation between glutamate concentration and cell proliferation in response to the mitogens PHA and PWM.
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PMID:Plasma glutamate concentration and lymphocyte activity. 289 10

The rat neu oncogene encodes a cell surface glycoprotein, p185, that possesses tyrosine kinase activity. The p185 polypeptide exhibits structural similarity to the epidermal growth factor receptor (EGFR) at both the deduced amino acid and nucleic acid level. However, the neu oncogene and the gene encoding the EGFR have been shown to reside on distinct chromosomes. Comparative analysis of the sequences of the normal neu cDNA and of the neu cDNA from neuroblastomas has revealed a single point mutation leading to a valine-to-glutamic acid substitution in the transmembrane anchoring domain. This mutation converts the neu gene to a transforming gene in rodents. In humans, the gene is called ERBB2 (also NGL and HER2), and amplification and over-expression of its products have been detected in certain tumors. The rat embryonal fibroblast cell line (Rat-1) appears to express both EGFR and cellular p185 polypeptides. We have found that EGF stimulates the phosphorylation of p185 in these cells at tyrosine as well as serine and threonine residues in a specific and dose-dependent manner. This activity occurs even though radiolabeled EGF cannot bind to immunopurified p185. The EGF effect is apparently unique since platelet-derived growth factor, insulin, and transforming growth factor beta all fail to phosphorylate p185 at tyrosine. The EGF-induced effect requires interaction of the EGFR and its cognate ligand because cell lines that lack EGFR cannot be shown to phosphorylate p185, even when exposed to large amounts of EGF. Oncogenic rodent p185 and the human p185 homologue ERBB2 that is overexpressed in human breast tumor cells also can be shown to become phosphorylated on tyrosine residues by the action of EGF. Collectively, these data demonstrate that EGF mediates phosphorylation of p185 at tyrosine as well as serine/threonine through cellular kinases by a receptor-specific mechanism.
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PMID:Phosphorylation process induced by epidermal growth factor alters the oncogenic and cellular neu (NGL) gene products. 289 89

Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations.
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PMID:Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat. 289 15

(6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)-cyclohexanone and [4-(tert-butyloxycarbonyl)benzyl]triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid and (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithin e. Compound 1 was found to be a good substrate for partially purified mouse liver folypolyglutamate synthetase (FPGS), with a Michaelis constant (Km = 15 microM) comparable to that reported for the reduced folate substrate (6S)-5,6,7,8-tetrahydropteroyl-L-glutamic acid and for (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid (DDATHF). However, in striking contrast to DDATHF, which is potently cytotoxic, 1 failed to inhibit tumor cell growth in culture at concentrations of up to 100 microM. These results suggested that the NH at position 8 of DDATHF is important for cytotoxic activity but not for polyglutamylation. Just as 1 was a good substrate for FPGS, the ornithine analogue 2 proved to be among the more potent competitive inhibitors of this enzyme discovered to date, with a Ki,s of 10 microM. While the binding affinity of 2 was lower than that reported for 5,6,7,8-tetrahydropteroyl-L-ornithine (H4PteOrn), very substantial FPGS inhibition was observed even though N5,N8, and N10 in H4PteOrn were replaced by carbon. Binding to FPGS thus appears to be tolerant of bioisosteric replacements made simultaneously in ring B and the bridge region. Neither 1 nor 2 was active in preventing cell growth in culture at concentrations of up 100 microM. The N delta-hemiphthaloyl derivative of 2, synthesized as a potential prodrug, was also inactive.
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PMID:(6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydrofolate and 6(R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithine as potential antifolates and antitumor agents. 291 20

A type IV collagenolytic metalloproteinase secreted by human monocytes/macrophages has been isolated and characterized. Monocytes isolated from peripheral blood and cultured in vitro exhibited a high type IV collagenolytic activity during the first and second day, but such activity declined markedly over subsequent days. Type IV collagenolytic activity was also transiently elaborated by macrophages isolated from (a) bronchioalveolar lavage of patients with pulmonary sarcoidosis, (b) primary human colostrum, and (c) peritoneal lavage of a patient with peritonitis. In contrast, macrophages isolated from the bronchioalveolar lavage of normal individuals, or from noninflammatory peritoneal fluids, failed to exhibit type IV collagenolytic activity. A type IV collagenolytic neutral proteinase was purified from macrophages isolated from inflammatory peritoneal fluid. The proteinase has a mass of 67 kDa on gel electrophoresis and is not altered in its migration under reducing conditions. It produces a characteristic 1/4-3/4 cleavage of type IV collagen, and its activity is abolished by treatment with EDTA but not phenylmethanesulfonyl fluoride. The isoelectric pH of the proteinase is 5.2 as judged by two-dimensional gel electrophoresis. The amino acid composition of the proteinase was notable for a high content of serine, glutamic acid, glycine, and alanine and no detectable hydroxyproline, cysteine, or methionine residues. The carbohydrate content of the proteinase was 11.2%, and galactose was the most abundant monosaccharide (8.7%) released following acid hydrolysis, followed by glucose (1.3%), mannose (1.2%), and trace amounts of fucose and galactosamine. Such a type IV collagenolytic protease may play an important role during the traversal of the vascular basement membrane by extravasating monocytes. The biochemical characteristics and biologic function of the macrophage proteinase may be similar or identical to the type IV collagenolytic proteinase identified in metastatic tumor cells.
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PMID:Transient expression of type IV collagenolytic metalloproteinase by human mononuclear phagocytes. 300 12

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