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)

A glycoprotein with a molecular weight of 62 000 has been isolated from a tumor-cell line, A549, and purified to homogeneity by gel chromatography. The glycoprotein contained sialic acid, galactose, mannose, N-acetylglucosamine and a relatively high amount of glutamic acid and proline. The data indicated that the overall composition of this glycoprotein was different from that of the glycoprotein of Mr 62 000 isolated from lung lavage of patients with alveolar proteinosis. The glycoprotein did not react with the antiserum raised against glycoprotein of Mr 62 000 isolated from lung lavage of patients with alveolar proteinosis.
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PMID:Characterization of a glycoprotein isolated from a continuous tumor-cell line of human lung carcinoma. 631 68

Each of nine mammary carcinomas induced by a single injection of nitroso-methylurea into 50-day-old Buf/N female rats, contained a transforming H-ras-1 gene. Molecular characterization of one of the genes revealed that the twelfth codon was GAA instead of GGA of the normal allele, encoding glutamic acid in place of glycine. These results indicate that chemical carcinogenesis represents an adequate model to study the role of transforming ras genes in human neoplasia.
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PMID:Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations. 631 12

The synthesis of an 8-deazafolate analogue of the intermediate in the methylation of 2'-deoxyuridylate is described. Alkylation of diethyl 5,6,7,8-tetrahydro-8-deazafolate with 3'-O-acetyl-5-(bromomethyl)-2'-deoxyuridine 5'-[bis-(trichlorethyl) phosphate], followed by removal of the trichloroethyl groups with a Zn/Cu couple and mild saponification, gave the target inhibitor N-[4-[[[2-amino-3,4,5,6,7, 8-hexahydro-4-oxo-5-[(2'-deoxyuridin-5-yl)methyl]-pyrido[3,2-d] pyrimidin-6-yl]methyl]amino]benzoyl]-L-glutamic acid 5'-monophosphate. The free nucleoside and the 5'-(methyl phosphate) diester were similarly prepared. Each of these reactions yielded a pair of diastereoisomers about C-6 of the reduced deazafolate in approximately a 1:1 ratio. These diastereoisomeric mixtures were evaluated as inhibitors of thymidylate synthetase derived from human tumor (HeLa) cells. The 5'-monophosphate was a potent inhibitor, competitive with respect to both 2'-deoxyuridylate (Ki = 0.06 microM) and tetrahydrofolate (Ki = 0.25 microM). In contrast, the nucleoside and the nucleotide methyl ester were poorer inhibitors by more than 3 orders of magnitude, attesting to the importance of the anionic function at the nucleoside 5'-position in the affinity of an inhibitor for the enzyme active site.
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PMID:A potent multisubstrate analogue inhibitor of human thymidylate synthetase. 650 2

We have compared the effects of several amino acid treatments on the induction of ornithine decarboxylase activity and the accumulation of putrescine, spermidine, and spermine by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo and in vitro. Incubation of isolated epidermal cells with mM concentrations of glycine, asparagine, glutamic acid, canavanine, arginine, and/or lysine inhibited dramatically the induction of ornithine decarboxylase activity by the tumor promoter. These remarkable inhibitory effects were concentration-dependent and additive. Arginine and its analog, canavanine, inhibited to the same degree TPA-induced ornithine decarboxylase activity, and potentiated to the same extent the inhibitory effects of glutamic acid, asparagine, and glycine on this enzyme. However, the inhibitory effects of arginine and canavanine were not additive. Similar alterations of tumor promoter-induced epidermal ornithine decarboxylase activity were observed in vivo when 62.5 mumol of the amino acids were injected i.p. 2 h before the topical application of 8.5 nmol of TPA to mouse skin. The results suggest the possibility that treatments with glycine, asparagine, glutamic acid, and arginine, the amino acids that were the most effective in inhibiting the tumor promoter-induced accumulation of polyamines in vivo, may reduce the tumor-promoting ability of TPA.
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PMID:Effects of amino acid treatments on 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis in vivo and in vitro. 664 98

The synthesis of poly-gamma-glutamyl derivatives of 7-hydroxymethotrexate (7-OH-4-NH2-10-CH3-pteroyl-glutamic acid (PteGlu1] was evaluated by direct hydroxylation of the tetraglutamyl derivative of methotrexate (4-NH2-10-CH3-PteGlu4) by a cell-free preparation of rabbit liver aldehyde oxidase and by polyglutamylation of 7-OH-methotrexate in Ehrlich ascites tumor cells in vitro. The polyglutamyl derivatives of 7-OH-methotrexate rapidly accumulate in cells to the 7-OH-4-NH2-10-CH3-PteGlu4. While 7-OH-methotrexate monoglutamate does not bind to dihydrofolate reductase, 7-OH-4-NH2-10-CH3-PteGlu4 does bind to the enzyme as established by gel filtration analysis of cell extracts and by use of purified dihydrofolate reductase from Ehrlich cells. Within cells, the rate of formation of 7-OH-methotrexate polyglutamyl derivatives exceeds that for methotrexate by a factor of 2.7 at comparable free monoglutamyl substrate levels, suggesting that 7-OH-methotrexate may be a better substrate than methotrexate for the folylpolyglutamate synthetase. 7-OH-methotrexate slows the rate of methotrexate polyglutamylation in cells, a consequence of the inhibition of methotrexate transport with reduced methotrexate substrate available for polyglutamylation. When 7-OH-methotrexate polyglutamyl derivatives were accumulated inside the cells following which extracellular 7-OH-methotrexate was removed, the monoglutamate, and to a lesser extent the diglutamate, exited the cells whereas the majority of the longer polyglutamyl derivatives were retained and continued to be metabolized to higher forms. These studies suggest that 7-OH-methotrexate and its polyglutamyl derivatives may play a role in modulating methotrexate action, either by their own inhibitory effects on folate-dependent enzymes or by their effects on methotrexate transport and metabolism within cells.
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PMID:Synthesis and properties of 7-hydroxymethotrexate polyglutamyl derivatives in Ehrlich ascites tumor cells in vitro. 671 37

Thalidomide metabolites inhibited the attachment of tumor cells to concanavalin A coated polyethylene surfaces. Thalidomide, itself, was non-inhibitory. Thalidomide activation to inhibitory products required hepatic microsomes, an NADPH-generating system, and molecular oxygen. Production of inhibitory metabolites was unaffected by either epoxide hydrolase or 1,2-epoxy-3,3,3-trichloropropane (TCPO), an inhibitor of epoxide hydrolase endogenous to hepatic S9 fraction. Therefore, the attachment inhibitor was probably not an arene oxide. Inhibition was not accompanied by cytotoxicity, as judged by trypan blue exclusion. Although uninduced hepatic microsomes from mice, rats and dogs had similar abilities to activate thalidomide, microsomes from Aroclor 1254 induced rats were relatively inactive in the system. Inhibitory metabolites were generated from the thalidomide analogues EM8 , EM12 , EM16 , EM87 , EM136 , EM255 , E350 , phthalimide, phthalimido-phthalimide, indan, 1- indanone and 1,3- indandione . Glutarimide , glutamic acid and phthalic acid did not activate to inhibitory products.
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PMID:Teratogen metabolism: activation of thalidomide and thalidomide analogues to products that inhibit the attachment of cells to concanavalin A coated plastic surfaces. 673 64

The effect of supplementation of dietary gluten with its first and second limiting amino acids (lysine and threonine) on food intake and growth was examined in normal and Walker 256 carcinosarcoma-bearing male, Sprague-Dawley rats. Two diets were used. Diet G had 16.4% gluten and diet GLT had (%): gluten 15, L-lysine.HCl 1, and L-threonine, 0.4 Normal and tumor-bearing animals (7) were fed each diet from day 7 until day 20 post-transplant of the tumor bearers. Food intake in the tumor-bearers was lower than that of controls (P < 0.01) from day 10 post-transplant. Normal animals fed diet GLT ate more than those fed diet G throughout the experiment. A similar effect of protein quality on the food intake of tumor-bearers was seen until day 15 post-transplant; thereafter, food intake of tumor-bearers was similar on both diets. Tumor-bearing animals had lower (P < 0.01) protein and lipid contents than controls on both diets. Diet had no effect on tumor weight or content of protein, lipid, DNA or RNA. Protein and lipid contents of hosts and controls on diet GLT were higher (P < 0.5) than for their counterparts on diet G.
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PMID:Protein quality, food intake and growth in normal and Walker 256 carcinosarcoma-bearing rats. 677 44

Carbodiimide-mediated condensation of 4-amino-4-deoxy-N10-methylpteroic acid (APA) with several alkyl, aralkyl, and aryl amines, in the presence or absence of N-hydroxysuccinimide, was employed in order to prepare new lipid-soluble bis(amide) derivatives of methotrexate (MTX) as potential prodrugs. MTX dianilide was likewise prepared, in comparable yield, from APA and L-glutamic acid dianilide via the mixed carboxylic--carbonic anhydride method. Dihydrazide and bis(N-methylhydrazide) derivatives of MTX were formed readily from MTX diethyl ester. However, reaction with hydroxylamine led to MTX gamma-monohydroxamic acid as the sole isolated product. The bis adduct appears to form, but is unstable during workup. The identity of the product was confirmed by independent mixed anhydride synthesis from APA and the gamma-monohydroxamate of L-glutamic acid. Treatment of MTX dimethyl ester with N,N-dimethylhydrazine unexpectedly yielded MTX gamma-monomethyl ester. MTX dianilide was active against L1210 leukemia in mice, with a +155% increase in life span at a dose of 160 mg/kg given ip in 10% Tween 80 on a q3d X 3 schedule. The bis(p-chlorobenzylamide), bis(p-methoxybenzylamide), and dihydrazide were also active against L1210 leukemia in vivo, but to a lesser extent than the dianilide. The gamma-monohydroxamic acid derivative showed activity (+111% ILS at 40 mg/kg) similar to that of MTX and was found to bind to a partially purified dihydrofolate reductase preparation from L1210 cells with an ID50 of 0.005 microM as compared to 0.007 microM for MTX. In vivo experiments in mice indicated that the pharmacokinetic properties of this compound and of MTX are similar but failed to demonstrate any advantage over MTX in terms of selective uptake into tumor (sc implanted P388 leukemia) or improved penetration of the central nervous system. The activities of the dianilide, bis(benzylamide), and dihydrazide derivatives in vivo are of interest in view of their low toxicity relative to MTX against cells in culture, which suggests that these derivatives are probably acting as prodrugs in the intact animal.
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PMID:Methotrexate analogues. 13. Chemical and pharmacological studies on amide, hydrazide, and hydroxamic acid derivatives of the glutamate side chain. 678 99

A proteoglycan was isolated from ascites fluid produced by a rat yolk sac tumor. The glycosaminoglycan chains of the proteoglycan are all sensitive to digestion with chondroitinase ABC and about 90% are sensitive to chondroitinase AC. The proteoglycan contains 5% protein. Amino acid analysis revealed a high content of serine and glycine which together constitute 37% of the amino acids. Glutamic acid (glutamine) and aspartic acid (asparagine) are also abundant. Galactosamine accounts for 97% of the hexosamine and the remainder is glucosamine. These characteristics indicate that the glycosaminoglycan side chains of this proteoglycan are predominantly chondroitin sulfate with a smaller amount of dermatan sulfate. Antibodies to the proteoglycan were prepared by immunization of a rabbit with purified alkali-treated proteoglycan. Affinity-purified antibodies from the antiserum immunoprecipitated (35S)sulfate-labeled radioactivity from culture media of the yolk sac tumor cells known to contain chondroitin sulfate proteoglycan. This binding was inhibited by the intact purified proteoglycan but not by proteoglycan treated with papain, suggesting dependence of the reactivity of the antibodies on integrity of the protein part of the proteoglycan. Immunofluorescence of the cultured yolk sac tumor cells revealed localization of immune reactive proteoglycans at the cell surface.
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PMID:Isolation of a chondroitin sulfate proteoglycan from a rat yolk sac tumor and immunochemical demonstration of its cell surface localization. 679 88

A DNA-binding protein with a molecular weight of 64,000 (64DP) has been found in elevated concentrations in the serum of patients with malignant diseases. 64DP has been found to be different from any previously described tumor markers, such as AFP, CEA, and C3DP. The results obtained with column SDS - polyacrylamide gel electrophoresis are as follows. 64DP is normally present in the serum at the concentration of 48 +/- 26 micrograms/ml (n = 49). The mean value of 64DP in 96 patients with untreated malignant disease was 167 +/- 67 micrograms/ml, whereas in 41 patients with nonneoplastic disease it was 61 +/- 23 micrograms/ml. No organ or tissue specificity seems to be required for malignant neoplasms to result in elevated serum 64DP concentrations. The clinical stage of the disease does no have much effect on the levels of 64DP and, even with histologically proven early lesions, the patients showed elevated levels of serum 64DP. Following successful surgical resection, 64DP tends to fall toward the normal value. Purification of 64DP was performed and its physicochemical properties have been defined. 64DP is a glycoprotein present in the alpha1-globulin fraction and it is rich in leucine, glutamic acid, and aspartic acid in its amino acid composition. More recently, using purified 64DP preparation, a single radial immunodiffusion assay system has been developed. According to the results of this method, the diagnostic accuracy of 64DP appears to be somewhat low and even marginal for certain types of commonly encountered surgical malignancies. Studies concerning the discrepancy between the results obtained by the two assay methods are now in progress.
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PMID:The role of a serum DNA-binding protein (64DP) in the diagnosis of malignant neoplasms. 680 49


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