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

The role of leucine andalanine aminopeptidases is stidued in three different biologic systems: experimental wound healing in the rat, experimental carrageenan induced intraderman granulomas in the rat, and human laryngeal carcinomas. The wound healing experiments indicate that the proliferating granulation tissue has high quantities of aminopeptidases activity which is residing primarily intracellularly in granulocytes, macrophages, mast cells fibroblasts, and new budding vessels. The quantititave levels of tissue aminopeptidases correlate positively with the degree of cellularity of the wound and fibroblastic activity. Some aminopeptidases (isoenzymes) are secreted or released by the fibroblasts in be blood serum. Starch gel electrophoretic analysis demonstrates thses with different concentrations and migration rates. Two are probably released or secreted into the serum, and th third is membranous bound in the cytoplasm (lysosomal). The carrageenan intradermal granuloma demonstrates a different inflammatory reaction which is rich in macrophages and produces a different pattern of aminopeptidases activity. Macrophages produce a high tissue level of aminopeptidase activity which is intracellular bound and not readily leached out into the serum. Gel electrophoresis studies of aminopeptidases produced by the granuloma demonstrate that the tissue bound enzyme is the main component. In addition, there appears to be a mechanism, which is not understood, for specific induction or activation of lysosomal proteolytic and carbohydrase enzymes. This mechanism is dependent on the nature of composition of the injuring agent. Laryngeal carcinomas demonstrate high tissue homogenate levels and normal serum levels of aminopeptidase activities. These enzymes are located in the tumor stroma. They are not directly related to tumor invasiveness but to the degree of stromal proliferation. The tumor stroma behaves as though it were a non-healing wound constantly secreted proteolytic enzymes (aminopeptidases). A major problem that needs to be resolved is to find the operating mechanism by which malignant cells interact with their constantly proliferating fibroblastic stroma.
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PMID:The role of aminopeptidases in inflammatory and neoplastic tissues. 95 Aug 61

Lymphocyte-stimulated protein synthesis (SPS) in response to human tumor-associated antigens was assessed by measuring [3H]leucine incorporation. Correlation of SPS with other in vivo and in vitro response was demonstrated by immunizing normal subjects with keyhole limpet hemocyanin and testing sequentially frozen lymphocytes and serum samples. One week after immunization, lymphocytes from normal subjects demonstrated increased SPS to keyhole limpet hemocyanin. This correlated with the appearance of delayed cutaneous hypersensitivity responses and preceded detection of hemagglutinating antibodies and increases in lymphocyte [3H]thymidine incorporation. There was no difference in the reactivity of fresh and viable frozen lymphocytes, and as few as 5X 10(5) lymphocytes/microtiter plate well could be used. Tumor-associated antigens were prepared from four lung carcinomas, six sarcomas, and six melanomas, using 3 M KCI extraction. Lymphocyte responses to both autologous and allogeneic tumor extracts were observed. Five of 15 patients demonstrated significant SPS to autologous tumor antigens. Fourteen of 20 lung cancer patients responded to lung cancer antigen, whereas only 11 of 41 patients with other tumors and 3 of 19 normal subjects reacted. Significantly, more lung cancer patients reacted to the tumor extract than to an extract of uninvolved lung from the same patient. Twenty-one of 42 melanoma patients responded to melanoma antigen. Ten of 33 patients with other tumors and 3 of 24 normal subjects reacted to the melanoma extract. Eight of 30 melanoma patients reacted to an extract of muscle from the same donor as was the melanoma antigen. Tumor-associated antigenic activity of 3 M KCI extracts can therefore be detected by measuring lymphocyte [3h]leucine incorporation.
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PMID:A rapid assay for stimulation of human lymphocytes by tumor-associated antigens. 97 69

Activities of hydrolytic enzymes on the surface of monkey kidney, canine kidney, L. FM3A and various tumor cells were determined and compared with those in the cell homogenate. Although aminopeptidase (EC 3.4.11.-) activities were always detected on the surface membrane in mammalian cells, trypsin, chymotrypsin and elastase activities were not detected while slight glycosidase activity was detected in a suspension of cultured cells. The activities of alanine-, leucine-, methionine- and phenylalanine-aminopeptidases were rather high but aminopeptidase A, proline-, valine-, glycyl propline dipeptidyl-and glycyl propyl leucine-tripeptidyl-aminopeptidases showed relatively low activities. Aminopeptidase activity was also demonstrated in the isolated membrane fractions. The specific activities of enzymes in these membrane fractions were not significantly greater than in cell homogenate so it was concluded that these enzyme activities were rather loosely bound to the cell membrane. Further evidence for the localization of the aminopeptidase activities on the cell surface was obtained by using glass-bead-bound substrate and detecting the release of the terminal residues. When bestatin, a specific inhibitor against aminopeptidase B and leucine aminopeptidase, was included in the assay system for the enzyme activities on the cell surface, the enzymes were commonly inhibited in all types of cells.
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PMID:Aminopeptidase activities on the surface of mammalian cells. 99 Mar 9

The production of tumor-specific cell-mediated cytotoxicity following in vitro sensitization of C57BL spleen cells against a syngeneic 3LL Lewis lung carcinoma was studied. Lymphocytes were sensitized on monolayers of the tumor cells for 4-5 days. The cytotoxicity was assayed by measuring the reduction in 3H-leucine and 3H-thymidine incorporation by target cells after interaction with the sensitized lymphocytes. Spleen lymphocytes sensitized on monolayers of 3LL tumor cells caused a high extent of lysis; such cells tested on C57BL or C3H fibroblast targets evoked only a low level of cytotoxicity. C57BL spleen cells sensitized on C57BL fibroblasts caused a low level of cytotoxicity when tested on a 3LL target. Thus cytotoxicity appeared to be tumor specific. The reduced incorporation into protein and DNA of target tumor cells caused by the sensitized lymphocytes was a measure of cell injury, which was more sensitive than direct cell count or uptake of 51CR. Lymphocytes from syngeneic tumor-bearing mice, tested 13-25 days after tumor inoculation, did not manifest in vitro cytotoxicity. On the contrary, such lymphocytes sometimes appeared to have a promoting effect on the tumor cells.
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PMID:Specific cytotoxicity in vitro of lymphocytes sensitized in culture against tumor cells. 99 7

The chromatographic elution profiles of 15 aminoacyl tRNA's from dependent and independent mammary tumors of GR mice have been studied using the reversed phase chromatography (RPC 5). The seryl tRNA from the dependent tumor displayed three isoacceptor peaks while only two isoacceptor peaks were observed in the case of the independent tumor when the tRNA's were charged in the presence of the GR mice liver enzyme. Charging of the tRNA's with radioactive leucine by homologous and heterologous enzyme revealed major differences in the leucyl isoacceptor species. The homologous dependent tumor system charges five leucyl tRNA species while the independent system only charges four. The leucyl tRNA from the dependent tumor has a new peak which is only recognized by its own enzyme, but this peak is either suppressed or completely absent in the independent tumor.
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PMID:Transfer RNA and aminoacyl tRNA synthetases in hormone dependent and independent mammary tumors of GR mice: II. Isoacceptor tRNA's in hormone dependent and independent mammary tumors of GR mice. 101 41

Rates of incorporation of thymidine and uridine, but not leucine, decrease markedly in L1210 (V) cells within 1 hour of incubation in DULBECCO'S medium containing 10% serum. 2-Mercaptoethanol (2-ME) after a latent period of more than 5 hours causes an increase in nucleotide incorporation. Bovine serum albumin can substitute for serum in the medium, but a higher concentration of 2-ME is required for growth. After charcoal treatment of the albumin less 2-ME is required. These experiments suggest that inhibition of the tumor cells is caused by a serum factor whose effect is antagonized by the thiol.
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PMID:Studies of the mechanism of growth promotion of lymphoma cells by 2-mercaptoethanol in vitro. 105 63

Tumoral secretions and pathophysiology of diarrhea were studied in 1 patient with pancreatic cholera. High concentrations of vasoactive intestinal peptide were found in both systemic blood and tumoral extracts, together with increased plasma levels of calcitonin and protaglandins E and Falpha. Gastric inhibitory peptide and gastrointestinal and pancreatic hormones were absent from the tumor, except for small amounts of glucagon, and their blood levels were normal. Decreased basal but normal pentagastrin-stimulated gastric acid secretion, normal basal and secretin-stimulated pancreatic secretion, increased volume of gallbladder bile with high bicarbonate, and low bile salt concentrations were observed, but the electrolyte content and flow rate of fluid passing the duodenojejunal junction were within normal limits. Small intestine was found to be the origin of the water and electrolyte fasting losses. Jejunum was the site of bicarbonate secretion. Jejunal glucose and leucine-stimulated water and sodium transports were also strikingly decreased, whereas the absorption rates of the sugar and amino acid were normal. Colon reabsorbed high amounts of water and sodium but increased potassium losses. Biological effects of vasoactive intestinal peptide may explain most of the patient's upper digestive secretion abnormalities and small intestinal function impairments, whereas secondary aldosteronism might explain the modified colonic function.
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PMID:Pancreatic cholera. Sudies on tumoral secretions and pathophysiology of diarrhea. 109 88

Curve-fitting procedures indicated that exo-2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) modified V and Km for one of two systems serving for histidine transport into the S37 ascites tumor cells. When this system was obliterated by leucine in the medium, BCH had no effect on histidine transport. Curve-fitting procedures similarly suggest N-methyl-alpha-aminoisobutyric acid affected the Km and V values for the other histidine-transporting system and that carboxymethylhistidine (His(Cm)) inhibited both transport systems. His(Cm) further inhibited histidine uptake into leucine-inhibited cells. Km and V values were altered simultaneously in the presence of several inhibitory analogs. Alanine methyl ester markedly inhibited high-concentration histidine uptake, whereas leucine methyl ester markedly inhibited low-concentration histidine uptake. The present results confirm earlier suggestions that our high c system is Christensen's A system and our low c system his L system. We also confirm a very high degree of specificity of N-methyl-alpha-aminoisobutyric acid for the A or high c system, and of BCH for the L or low c system. We suggest the utility of combining two approaches to the study of transport system properties; use of specific analogs and modification of biphasic plots. We demonstrate that the carboxyl group is not a prerequisite molecular feature for inhibitory interaction with the A or L system.
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PMID:Biphasic kinetic plots and specific analogs distinguishing and describing amino acid transport sites in S37 ascites tumor cells. 113 29

Lymphocyte responses to lung carcinoma-associated antigens were assessed by measuring 3H-leucine incorporation in 20 lung cancer patients, 37 patients with other neoplasms, and 20 normal subjects. Antigens were prepared from 9 lung carcinomas by means of 3M KCl extraction. Fifteen of 20 lung cancer patients showed increased leucine incorporation to one or more tumor antigens, whereas only 5 of 20 normal subjects responded. Lymphocyte responses to both autologous and allogeneic tumor extracts were observed. Eighteen lung cancer patients were tested with the most reactive antigen and 13 responded. Seven of 37 patients with other neoplasms and 2 of 18 normal subjects reacted to this antigen. Significantly more lung cancer patients reacted to the tumor extract than to an extract of uninvolved lung from the same patient. The reactivity of lymphocytes from lung cancer patients clinically free of disease was significantly greater than that of patients with disseminated disease. Extraction of lung carcinomas with 3M KCl is a useful technique for solubilizing tumor-associated antigens (TAA). Antigenic activity may be followed in vitro by measuring lymphocyte 3H-leucine incorporation.
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PMID:Lymphocyte responses of lung cancer patients to tumor-associated antigen measured by leucine incorporation. 117 75

The effect of estrogen on synthesis of glucose-6-phosphate dehydrogenase (D-Glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49) in the R3230AC mammary adenocarcinoma of ovariectomized Fischer rats was investigated. Enzyme synthesis was estimated by techniques using immunochemica precipitation and isolation of enzyme protein from tissues of rats that had been given radioactive leucine prior to sacrifice. The antibody-enzyme complex was dissociated and glucose-6-phosphate dehydrogenase was isolated after electrophoresis on sodium dodecyl sulfate-acrylamide gels. Administration of estradiol-17beta produced a two-fold increase in glucose-6-phosphate dehydrogenase activity, which was preceded by a five-fold increase in specific synthesis of glucose-6-phosphate dehydrogenase in R3230AC tumors. At least a 15-fold increase in enzyme synthesis was observed in the uterus. The rate of enzyme degradation (t 1/2) in the tumor was estimated at 17 h. These data indicate that the estrogen-induced increase in glucose-6-phosphate dehydrogenase activity was due to a de novo increase in enzyme synthesis.
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PMID:Effect of estrogen on synthesis of glucose-6-phosphate dehydrogenase in R3230AC mammary tumors and uteri. 118 4


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