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)

The M27 and H59 variants of Lewis lung carcinoma differ in their responsiveness to the chemotactic elastin peptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG). M27 cells, selected for metastasis to lung, are highly responsive to a positive gradient of VGVAPG. H59 cells, selected for metastasis to liver, do not migrate in response to VGVAPG. Although both cell types bind radiolabeled VGVAPG, Scatchard analysis of 125I-Tyr-VGVAPG binding reveals that M27 cells bind the chemoattractant with a Kd of 2.7 nM, whereas nonresponsive H59 cells bind the peptide with a Kd of 67 nM. These findings indicate that the failure of H59 cells to migrate in response to VGVAPG may be due to the reduced affinity of their VGVAPG receptors. Both receptor affinity and chemotactic responsiveness to VGVAPG can be modulated in each of these two tumor cell lines by the levels of active membrane-associated protein kinase C. Treatment of nonresponsive H59 cells with 12-O-tetradecanoylphorbol 13-acetate increases the level of membrane-bound protein kinase C activity with a concomitant increase in VGVAPG binding affinity and induction of chemotactic responsiveness to VGVAPG. Treatment of M27 cells with the protein kinase C inhibitor, staurosporine, reduces VGVAPG binding affinity and abrogates the chemotactic response. We conclude that chemotactic responsiveness of M27 and H59 tumor cells is dependent upon high VGVAPG receptor affinity, which is strongly correlated to high levels of membrane-bound protein kinase C activity.
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PMID:Membrane-bound protein kinase C modulates receptor affinity and chemotactic responsiveness of Lewis lung carcinoma sublines to an elastin-derived peptide. 254 74

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.
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PMID:Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6. 254 7

Products of glutamine metabolism were examined in the MC-29 virus-induced chicken hepatoma mitochondria incubated in vitro. Glutamine oxidation proceeded in the tumor mitochondria exclusively via a pathway involving glutamic-oxalacetic transaminase. Malate stimulated aspartate production from glutamine, while pyruvate exerted suppressive effect on aspartate production with little alanine formation. The mitochondria of this hepatoma are unique in that the metabolic pattern and response to malate and pyruvate are essentially inconsistent with those reported in normal cells as well as those proposed by Moreadith and Lehninger in various tumor cells.
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PMID:End products of glutamine oxidation in MC-29 virus-induced chicken hepatoma mitochondria. 257 53

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

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.
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PMID:Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. 264 81

Tumor-induced alterations in insulin sensitivity and glucose metabolism were investigated by examining the effect of glucose and insulin infusions in 72-h-starved tumor-bearing (TB) rats. Following glucose infusion, the rate of glucose disappearance from the blood was similar in TB and non-tumor-bearing (NTB) rats, even though insulin concentrations were lower in TB rats. Blood lactate was increased in TB rats prior to treatment and increased immediately following glucose infusion. Insulin alone decreased blood glucose in NTB but not TB rats. When insulin was infused together with glucose, the rate of glucose disappearance increased similarly in both TB and NTB rats. The immediate increase in blood lactate seen in TB rats following glucose infusion was not apparent in the TB rats receiving insulin and glucose. TB rats infused with glucose and insulin showed a greater rise in blood alanine concentrations, compared with all other infusion regimens. While ketone body concentrations decreased in both TB and NTB rats in response to the different infusion regimens, plasma free fatty acids in TB rats were not decreased by insulin and glucose treatments. TB rats therefore not only have decreased insulin release, but adipose tissue is also less sensitive to insulin action. In vivo studies using 2-deoxy[U-14C]glucose showed that glucose uptake by the muscle and adipose tissue, but not the tumor, was significantly increased by the infusion of insulin, thereby demonstrating one of the mechanisms by which insulin may act to conserve host tissue.
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PMID:Metabolic response to insulin and glucose infusions in starved tumor-bearing rats. 267 52

The hepatic response to glucagon was investigated in five groups of animals: (1) controls; (2) excess growth hormone (GH; tumor-bearing); (3) streptozotocin-induced diabetic; (4) cortisol-treated, and (5) insulin-treated animals. Blood samples were collected from the animal models and hepatocytes were prepared and used for glucagon-binding studies and studies of total glucose production, gluconeogenesis and glycogen determinations. Glucagon binding was elevated in GH-tumor-bearing and cortisol-treated hepatocytes but lower in hepatocytes from diabetic animals. Basal total glucose production wash higher in hepatocytes from diabetic rats but not changed in hepatocytes from GH-tumor-bearing, insulin-treated or cortisol-treated animals. Glucagon significantly stimulated total glucose production in hepatocytes from control, insulin-treated and cortisol-treated but not diabetic and GH tumor models. Gluconeogenesis as evaluated by alanine conversion to glucose was significantly increased in hepatocytes from diabetic and cortisol-treated animals and was significantly lower in hepatocytes from GH-tumor-bearing animals. Glucagon failed to significantly stimulate gluconeogenesis in hepatocytes from diabetic and tumor-bearing animals. Hepatic glycogen content was significantly decreased in diabetic and GH-tumor-bearing animals but not changed in insulin-treated and cortisol-treated animals. We conclude that increased glucagon binding was not always correlated with an increase in glucagon-stimulated glycogenolysis, gluconeogenesis or increased sensitivity to glucagon. Persistent hyperinsulinism may effectively suppress glucagon- or cortisol-stimulated pathways.
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PMID:Regulation of the hepatic response to glucagon: role of insulin, growth hormone and cortisol. 269 9

Middle ear meningioma is a very rare tumor. Less than twenty cases have been reported in the world literature and most of these cases report only a short period of follow-up care. This case is interesting not only for its rarity but also because of the opportunity of a follow-up of fifteen years.
Ala Med 1989 May
PMID:Middle ear meningioma: case report. 274 60

Fourteen derivatives of sparsomycin (1) were synthesized. Six of them were prepared following a novel synthetic route starting from the L-amino acid alanine. Some physicochemical properties, viz. lipophilicity and water solubility, of selected derivatives were measured. The biological activity was tested in vitro in cell-free protein synthesis inhibition assays, in bacterial and tumor cell growth inhibition assays, and in the L1210 leukemia in vivo model in mice. Also for selected drugs the acute toxicity in mice was determined. Ribosomes from both an eukaryotic and a prokaryotic organism were used in the protein synthesis inhibition systems. A linear correlation between the lipophilicity parameters measured was observed. Water solubility and drug toxicity in mice were found to be linearly correlated with lipophilicity. All the derivatives studied are more lipophilic than 1. The deshydroxysparsomycin analogues (30-33) showed an interesting phenomenon: increase in hydrophobicity was accompanied by a considerable increase in water solubility. We found that an increase in hydrophobicity of the drug as a result of replacing the SMe group of 1 with larger alkylthio groups causes an increase in the biological activity of the drug. However, not only the hydrophobicity but also shape and size of the substituent are important; in the homologous series 1-9-10-11-12, 21-22-23-24, and 30-31-32-33, highest protein synthesis inhibitory and in vitro cytostatic activity is found with compounds 11, 23, and 32, respectively, and in comparison with the highly active n-butyl compound 10, the isomeric tert-butyl compound 13 is rather inactive. Polar substituents replacing the SMe group, i.e. Cl in 17 and 35, also render the molecule inactive. Substituting the bivalent sulfur atom for a methylene group decreases the drug's activity. This effect can be compensated for by increasing the length of the alkylsulfinyl side chain. The agreement between the results derived from cell-free and "in vivo" tests is good. The assays using ribosomes of bacterial and eukaryotic organisms give similar results although the latter seem to be more sensitive to changes in hydrophobicity of the drug. Our results confirm the presence of a hydrophobic region at the peptidyl transferase center of the ribosome; the interaction of sparsomycin with this region is more pronounced in the eukaryotic particles. The sparsomycin analogues 11, 23, and 30 show the highest antitumor activity against L1210 leukemia in mice, their median T/C values are 386, 330, and 216%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lipophilic analogues of sparsomycin as strong inhibitors of protein synthesis and tumor growth: a structure-activity relationship study. 275 19

Lipoprotein from the outer membrane of Escherichia coli and the synthetically prepared lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 derived from the N-terminus of lipoprotein constitute potent macrophage and polyclonal B-lymphocyte activators. The compounds have also been shown to induce tumor cytotoxicity in murine bone marrow-derived macrophages (BMDM). Bone marrow stem cells were cultured in the presence of colony-stimulating factor 1 to yield BMDM of 98 to 99% purity at day 8. After stimulation with the lipopeptides on days 4, 6, 8 and 10 of bone marrow culture, the cytotoxic effect of BMDM on the tumor cell line L929 was determined in a [3H]thymidine release assay. Maximum tumor cytotoxicity was found on day 8 with an optimal effector/target-cell ratio of 10:1, and a duration of lipopeptide stimulation of 4 h. The supernatants of lipopeptide stimulated BMDM also showed cytotoxic activity that could be inhibited by antiserum against tumor necrosis factor alpha. The effects of the lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 were comparable or superior to those exerted by lipopolysaccharide. Our results demonstrate that synthetic lipopeptides are potent activators for murine BMDM and may therefore prove to be an important tool for the elucidation of the role of macrophages in the host defence mechanisms against tumor cells.
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PMID:Induction of tumor cytotoxicity in murine bone marrow-derived macrophages by two synthetic lipopeptide analogues. 277 84


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