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

Sites of inflammation with prominent macrophage infiltration, such as wounds and certain tumors, are uniquely deficient in free arginine. The effects of arginine availability on macrophage physiology were investigated. When cultured in media containing less than 0.1 mM L-arginine, rat resident peritoneal macrophages exhibited enhanced spreading, tumor cytotoxicity, superoxide production, phagocytosis, and protein synthesis. Thus, arginine concentrations similar to those found in sites of inflammation can augment macrophage functions, while those found in plasma (approximately 0.1 mM) and in commonly used culture media (0.4 to 1.2 mM) are inhibitory. Culture in homoarginine, but not D-arginine, ornithine, citrulline, urea, histidine, or lysine also inhibited macrophage tumor cytotoxicity, indicating the specificity of the effect. In contrast to resident macrophages, the tumor cytotoxicity of peritoneal macrophages obtained after C. parvum injection was suppressed by culture in arginine-deficient media. However, L-arginine-deficient media enhanced all other activation-associated functions in C. parvum-elicited macrophages as in resident cells. Arginine-free wound fluid promoted resident macrophage tumoricidal activity when compared with rat serum, and again, the addition of L-arginine was inhibitory. The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation.
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PMID:Regulation of macrophage functions by L-arginine. 253 41

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 preparation for functional analyses, a study of the binding of H-2Kb-specific monoclonal antibodies (mAb) to formaldehyde (FOR)-fixed H-2b spleen or tumor cells revealed that three of nine mAb tested had lost reactivity with the FOR-fixed cells, whereas the reactivity of the other mAb generally did not diminish. Comparison of the reactivity of these mAb on untreated H-2Kbm mutant cells and on FOR-treated H-2Kb cells suggests that for three mAb the total loss of reactivity on the latter could be a consequence of the alteration by FOR of lysine 89, which is substituted by alanine in mutant bm3. H-2Kb-specific alloreactive polyclonal or monoclonal CTL, all of which had retained reactivity with bm3 target cells, had also retained reactivity with FOR-fixed H-2b cells as indicated by cold target inhibition studies. The H-2Kb-specific CTL were probably reactive with "conformational" determinants of H-2Kb, which are dependent on the integrity of both the alpha 1 and the alpha 2 domains of the H-2Kb molecule. Results are compatible with FOR treatment selectively affecting a serological determinant in the alpha 1 domain without affecting conformational-type CTL determinants.
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PMID:Selective destruction by formaldehyde fixation of an H-2Kb serological determinant involving lysine 89 without loss of T-cell reactivity. 258 Jul 85

In an attempt to better define the immunological reactivity of patients with malignant melanoma, the electrophoretic mobility of lymphocytes and their reactivity were studied in poly-L-lysine agglutination and in nucleolar test. Blood samples were examined before treatment and repeatedly after surgical removal of the tumor. A microagglutination test induced by poly-L-lysine was used for the detection of sensitized lymphocytes in peripheral blood of melanoma patients. The number of positive results was increasing with the progression of the disease. After incubation with poly-L-lysine the electrophoretic mobility of lymphocytes was changed in melanoma patients. The nucleolar test was used for the study of quantitative and morphological changes of the nucleoli in lymphocytes. Elevated values of the nucleolar coefficient and an increased number of active nucleoli provided evidence on the higher immunological reactivity of melanoma patients. The decline in the number of lymphocytes with ring-shaped nucleoli, signaling immunologic exhaustion, are of prognostic value. Lymphocytes were assayed also for the presence of receptors for sheep erythrocytes (E active and total rosettes) and C3d component of complement (EAC rosettes). The reported findings may be used to advantage in evaluating the immunological reactivity of melanoma patients.
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PMID:[Immunologic parameters in patients with malignant melanoma]. 262 50

We have previously demonstrated that incubation with IL-2 can induce ADCC activity in murine cells and that this activity was mediated by asialo GM1+, FcR+ cells. In the present study we show that the cytokines IFN-alpha and IFN-gamma, TNF-alpha, and IL-1 alpha are unable to induce antibody-dependent cellular cytotoxicity (ADCC) in murine cells; however, TNF-alpha and IL-1 alpha could substantially augment the ADCC induced by IL-2. IL-1 increased the IL-2-induced ADCC activity in a dose-dependent fashion and in cells isolated from the thymus and spleen. The precursors of the ADCC induced by the combination of IL-1 and IL-2 were asialo GM1+ cells, similar to the precursor cells of IL-2-induced ADCC. The effect of IL-1 and TNF on ADCC was not the result of an increase in the FcR density on the cell surface or the result of an increase in the number of FcR+ cells although IL-1 increased the recovery of viable cells in culture. The main effect of IL-1 and TNF was the enhancement of the lytic ability of the IL-2 cultured cells as indicated by increased intra-cellular benzyloxycarbonyl L-lysine thiobenzylester-esterase activity. These results suggest that lymphokines such as IL-1 and TNF may synergize with IL-2 in the induction of ADCC and could thus potentially be useful for the immunotherapy of established tumors when combined with the administration of specific anti-tumor antibodies.
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PMID:The effect of various cytokines on the in vitro induction of antibody-dependent cellular cytotoxicity in murine cells. Enhancement of IL-2-induced antibody-dependent cellular cytotoxicity activity by IL-1 and tumor necrosis factor-alpha. 264 49

The levels of several tumor associated proteases, including plasminogen activators (PA), are elevated in many malignant tumors compared to their benign tumor counterparts. Extracellular matrix degradation mediated by PA may facilitate tumor cell invasion and metastasis. To assess whether PA content correlates with the aggressive phenotype in prostate cancer, we studied these activators in the PC-3 human prostate cell line and PC-3CALN, an aggressive in vivo derived variant cell line. Enzymatic assays using H-D-val-leu-lys-pNA (S-2251) as substrate and peroxidase-anti-peroxidase immunohistochemical techniques were used. In an in vitro chemoinvasion assay, the PC-3CALN variant cell line demonstrated significantly greater invasive behavior than the unselected, parental PC-3 line. The activity of PA secreted by PC-3CALN cells was 3.5 times greater than that of PC-3 cells (p less than 0.01). PC-3 metastases obtained following intrasplenic injection of PC-3 cells had greater PA activities than the corresponding primary tumors. Immunohistochemical studies of PC-3 tumors demonstrated preferential localization of urokinase-type PA to areas of apparent tumor cell invasion. These data suggest a correlation between PA and the aggressive phenotype in this model of human prostate cancer. PA, in particular u-PA, may play a role in the migration and invasion of prostate cancer cells and provide a marker of the aggressive phenotype.
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PMID:Plasminogen activators in human prostate cancer cell lines and tumors: correlation with the aggressive phenotype. 265 23

Tumor cells can be induced to differentiate in vitro by biochemical manipulation of their culture environment. In the studies described here, the effects of medium conditioned by human retinal pigmented epithelial (RPE) cells on Y79 human retinoblastoma cells have been examined. RPE-conditioned medium in conjunction with laminin and a poly-D-lysine substratum is observed to induce neuronal differentiation of Y79 cells. The cells extend long cellular processes and exhibit immunologically detectable neurotypic properties. In contrast, control Y79 cells not exposed to medium conditioned by RPE cells exhibit only infrequent neuronal phenotypes. This response of Y79 cells to RPE-conditioned medium indicates that factors secreted by RPE cells can act as inducers of neuronal differentiation in retinoblastoma cells and suggest that such factors may be of importance in the development and differentiation of the neural retina.
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PMID:Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. 266 19

The purpose of this study was to examine the activity and associated kinetic parameters of epidermal protein kinase C (PKC) following stimulation by sn-1,2-dioctanoylglycerol (DIC8) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and to examine the relationship between levels of epidermal PKC activity and the induction of ornithine decarboxylase by these agents, utilizing various stocks and strains of mice. Importantly, the mouse strains and stock used in this study have known differing susceptibilities to undergo TPA-induced tumor promotion: the CD-1 stock and the DBA/2 strain (both sensitive to TPA-induced tumor promotion) and the C57BL/6 strain (resistant to TPA-induced tumor promotion). TPA-stimulated protein kinase C activity was measured in the 10(5)g supernatant fraction of epidermal homogenates using lysine-rich histone as a phosphate acceptor substrate. The maximal velocities for TPA-stimulated epidermal PKC activity in CD-1, DBA/2 and C57BL/6 were 0.28, 0.29 and 0.27 nmol PO4-histone/mg 10(5)g protein/min, respectively. TPA-stimulated epidermal PKC from CD-1, DBA/2 and C57BL/6 had similar theoretical Vmax values and the apparent concentrations of TPA yielding half-maximal stimulation of PKC were also similar. DiC8-stimulated PKC activity to a greater Vmax; however, the concentration required to yield half-maximal stimulation of PKC was one thousand times greater than that of TPA. There were no strain differences in these parameters when the enzyme was stimulated with DiC8. Thus, the levels of epidermal PKC activity in CD-1, DBA/2 and C57BL/6 mice exhibit no strain differences when stimulated by TPA or DiC8 using lysine-rich histone as a phosphate acceptor substrate. Since sn-1,2-diacylglycerols are known effective inducers of epidermal ornithine decarboxylase (ODC) activity, the induction of epidermal ODC was examined in each mouse strain 5 h after topical application of 2 nmol TPA, 5 nmol TPA or 2.5 mumol DiC8. After topical treatment with TPA, C57BL/6 demonstrated an unexpected 2- and 4-fold increase in ODC activity over CD-1 and DBA/2 mice. After treatment with DiC8, C57BL/6 demonstrated a 6- and 10-fold increase in ODC activity over CD-1 and DBA/2, respectively. Thus, the resistant strain (C57BL/6) demonstrated a 'hyperinducibility' of epidermal ODC activity by TPA or DiC8. The time course for the induction of epidermal ODC was examined in each strain, and at every time point measured (3-15 h), the C57BL/6 strain exhibited this 'hyperinducibility' of ODC relative to the other strains. Epidermal DNA synthesis was stimulated to a similar extent in C57BL/6 and CD-1 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of epidermal protein kinase C activity, ornithine decarboxylase induction and DNA synthesis stimulated by TPA or dioctanoylglycerol in mouse strains with differing susceptibility to TPA-induced tumor promotion. 270 40

sn-1,2-Didecanoylglycerol, a synthetic lipid second messenger and model diacylglycerol, was evaluated as a complete skin tumor promoter in CD-1 mice. In addition, sn-1,2-dioctanoylglycerol, sn-1,2-didecanoylglycerol, the second stage tumor promoter mezerein, and the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for their ability to stimulate epidermal protein kinase C activity in vitro. All four compounds stimulated epidermal protein kinase C activity utilizing lysine-rich histone as the phosphate acceptor substrate. sn-1,2-Dioctanoylglycerol and sn-1,2-didecanoylglycerol stimulated epidermal protein kinase C activity to a maximum velocity similar to that obtained when the enzyme was stimulated with TPA; however, about 1000 times greater concentration of the sn-1,2-diacylglycerols was required. sn-1,2-Didecanoylglycerol was evaluated as a complete skin tumor promoter in CD-1 mice utilizing a dosing regimen demonstrated to produce epidermal hyperplasia. Mice were initiated with 200 nmol 7,12-dimethylbenz[a]anthracene. One week later the mice received twice daily topical applications of 1 nmol TPA, 2 mumol sn-1,2-didecanoylglycerol or 5 mumol sn-1,2-didecanoylglycerol, 5 days/week. Additional initiated mice received twice weekly topical applications of 2 or 5 nmol TPA. Initiated mice treated with 5 nmol TPA twice weekly or with 1 nmol TPA twice daily for 5 days/week (cumulative weekly doses of 10 nmol TPA) responded similarly, based on the tumor incidence and the average number of tumors per mouse. Initiated mice treated with 2 or 5 mumol sn-1,2-didecanoylglycerol twice daily developed tumors in a dose-dependent manner. Initiated mice treated with 5 mumol sn-1,2-didecanoylglycerol twice daily developed many tumors, and at 20 weeks there was a 74% tumor incidence and an average of 6.0 tumors/mouse. At 20 weeks, 24% of the initiated mice treated with 2 mumol sn-1,2-didecanoylglycerol twice daily developed tumors, with an average of 1.1 tumors/mouse. Mice which were not initiated but treated twice daily with 5 mumol sn-1,2-didecanoylglycerol for 20 weeks did not develop any tumors. These data demonstrate that the representative synthetic lipid second messenger sn-1,2-didecanoylglycerol, like TPA, is a complete tumor promoter in DMBA-initiated mouse skin.
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PMID:Synthetic lipid second messenger sn-1,2-didecanoylglycerol: a complete tumor promoter in mouse skin. 274 35

Anti-tumor monoclonal antibodies were cross-linked to the anti-CD3 T-cell antibody OKT3 by the use of the heterobifunctional cross-linker succinimidyl-3-(2-pyridyldithio)propionate. Derivatized monoclonal antibodies, heterodimers, and homodimers were resolved by analytical isoelectric focusing in polyacrylamide gels containing 1% Triton X-100. Isoelectric points of the derivatized antibodies were lower than native antibodies, consistent with lysine derivatization. Antibodies derivatized with 2-iminothiolane were equivalent or slightly higher in pI compared with native antibodies. Heterodimers focused in microheterogeneous bands between the pI extremes of the parent derivatized antibodies. The isoelectric points of homodimers were lower than those of parental antibodies and could be distinguished from heterodimers. Reduced and alkylated heterodimers were resolved into their constituent antibodies by isoelectric focusing.
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PMID:Isoelectric focusing of cross-linked monoclonal antibody heterodimers, homodimers and derivatized monoclonal antibodies. 275 54


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