Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble arylsulfatase (EC 3.1.6.1) is present in the body fluids of man in the form of two isoenzymes, arylsulfatase A and B, which reportedly are useful biochemical markers for certain types of malignancy. However, rapid assay of the individual isoenzymes is extremely difficult; procedures based on differential inhibition or activation of the isoenzymes in a mixture yield only semiquantitative results. A feature of these isoenzymes is their inhibition by some common anions (notably phosphate) at physiologic concentrations. The isoenzymes can be separated by anion-exchange chromatography, the B isoenzyme being eluted in the void volume and the A isoenzyme and the anionic inhibitors retarded. Lead is used to sequester phosphate, enabling measurement of A in the salt-eluted fraction. Using this technique, we have found significant elevations of B in the sera of patients with colorectal cancer. The potential of rapid, chromatographic separation coupled with continuous monitoring for arylsulfatase activity is discussed.
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PMID:Separation and analysis of arylsulfatase isoenzymes in body fluids of man. 2 85

The interaction of analogs of L-aspartic acid with adenylosuccinic acid synthetase, L-asparagine synthetase, and L-aspartic acid transcarbamylase is discussed. Each of these enzymes is of critical importance in the economy of certain types of tumor cells. L-Alanosine, a new antitumor antibiotic, is shown to be accepted as a substrate by the enzymes of de novo purine biosynthesis which ordinarily use L-aspartic acid as a substrate; as a consequence of this interaction, an anabolite is thought to be produced which impairs the formation of adenine nucleotides by inhibiting adenylosuccinate synthetase, leading to an interruption in DNA synthesis. Homoserine-beta-adenylate, guanidinosuccinic acid, and PA2LA [3-(phosphonacetylamido)-L-alanine] are shown to be inhibitors of L-asparagine synthetase from murine lymphoblasts; each of these analogs of L-aspartic acid exhibits novel structural properties which can be used by synthetic chemists in the design of molecules with an even greater ability to block the biosynthesis of L-asparagine. Certain aspects of the mechanism of action of PALA (N-phosphonacetyl-L-aspartic acid) were examined. This agent, which is a potent inhibitor of mammalian L-aspartic acid transcarbamylase, is capable of stimulating the homologous enzyme from Escherichia coli under certain circumstances. In vivo the duration of inhibition produced by this agent is shown to be unusually protracted; for example, L-aspartic acid transcarbamylase in mouse liver remains at 30% of treatment levels for greater than or equal to 20 days after a single therapeutic dose of PALA. This long-lasting effect reflects either sluggish synthesis of new enzyme molecules in this organ or shuttling of the inhibitor from old to new molecules. It is suggested that new and still more potent analogs of L-aspartic acid be sought, and that they be screened, inter alia, against these target enzymes.
Cancer Treat Rep 1979 Jun
PMID:Analogs of L-aspartic acid in chemotherapy for cancer. 3 3

The substitution reaction products of N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and the N-sulfate (potassium salt) of N-hydroxy-4-acetyl-aminobiphenyl (N-OSO3K-AABP) with DNA from calf thymus were determined after reaction in buffered solutions of 0.10 M NaCl at pH values from 4--9. In the case of N-AcO-AAF, the ratio of N-(guanin-8-yl)-2-acetylaminofluorene (N-(guanine-8-yl)-AAF) to 3-(guanin-N2-yl)-2-acetylaminofluorene (3-(guanin-N2-yl)-AAF) increased 2.2 times over the entire pH range studied, starting at pH 9. With the N-OSO3K-AABP, the total substitution of guanine was much lower (22--34 times) as compared with N-AcO-AAF, and the ratio of N-(guanin-8-yl)-4-acetylaminobiphenyl to 3-(guanin-N2-yl)-4-acetylaminobiphenyl was not affected by a change in pH of the reaction medium. As expected, heat-denatured DNA reacted more extensively with both esters, but an increase in substitution was much more pronounced for the biphenyl derivative (9 times) than for the fluorene compound (2.8 times). Degradation, denaturation or interstrand cross-linking of DNA were not observed under the reaction conditions employed.
Cancer Lett 1979 Jul
PMID:Effect of pH on the ratio of substitution products in DNA after reaction with the carcinogen N-acetoxy-2-acetylaminofluorene. 3 1

Rabbit lymphosarcoma tissues contain 70 S RNA and RNA-directed DNA polymerase encapsulated in particulate components that band in the density region of type C RNA viruses. RNA-directed DNA polymerase associated with the particles could be distinguished from cellular DNA polymerases by salt elution from phosphocellulose. The enzyme preferred the template primers poly(rA)-(dT)12-18 and poly(rC)-(dG)12-18 over other synthetic template primers and also utilized viral 70 S RNA as template; these properties are not observed with the known cellular DNA polymerases.
Cancer Res 1976 Dec
PMID:Presence of a high-molecular-weight RNA and RNA-directed DNA polymerase in rabbit hereditary lymphosarcoma. 6 26

In an unconventional assay system (MEM Test) Caspary & Field claimed in 1971 to have detected lymphocyte sensitization to a common tumour antigen in all patients with cancer. There was no evidence of histogenetic specificity to the reaction and their conclusions are in direct contradiction to those of all workers who have studied the cytotoxic activity of lymphocytes on tumour cells. To improve the specificity of the test system, another type of tumour antigen was used in MEM Test incubation. Tumour-associated antigens were prepared according to the hypertonic salt extraction method introduced by Reisfeld, Leonard, Meltzer et al. As shown by the results, information could be gained concerning the existence of a malignant tumour and its location.
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PMID:Determination of cell mediated immunity against tumour associated antigens in patients of ENT. 8 6

The results of bile analysis showed differences in the bile salt pattern of Caucasians and Nigerians, whose dietary habits differ mainly in dietary fibre composition. The Nigerian bile appears to contain less deoxycholate, but more cholate and a larger total pool of bile salts. These findings would seem to lend biochemical support for the epidemiological evidence concerning the uncommon occurrence of cholesterol gallstones and large bowel cancer in Nigeria as, indeed, in the less economically developed contries, where the dietary habits have not undergone comparable revolutionary changes of Western civilization, which have removed cellulose fibre from the diet in the process of industrial refinery.
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PMID:The dietary fibre theory and bile salt pattern in Nigerians. 10 34

The covalent conjugation of fatty acid to a tumor cell membrane preparation transformed it from an antigen that enhanced tumor growth to one that suppressed it. A crude cell membrane preparation was made by sequential hypertonic and hypotonic salt extraction of tumor cells from a fibrosarcoma induced in hamsters by simian virus 40. The membranes were chemically conjugated with dodecanoic anhydride in 0.5 M carbonate buffer (pH 9.0). Injection of unmodified membranes 10 days before transplantation of live tumor cells produced clear-cut enhancement of the tumor growth rate. In contrast, injection of lipid-conjugated membranes in a similar dose and protocol suppressed tumor growth. The lymphoid proliferative reactions to the tumor cells as demonstrated by the histology of both the tumor and regional lymph nodes were consistent with the hypothesis that unmodified membranes stimulated the production of antibody which participated in the enhancement of tumor growth, and that lipid-conjugated membranes stimulated the production of cell-mediated immunity which suppressed this growth.
J Natl Cancer Inst 1975 May
PMID:Immunization with a lipid-conjugated membrane antigen to suppress growth of a fibrosarcoma induced by simian virus 40. 16 7

Nuclear proteins of rat liver and rat ascites hepatoma were fractionated by extraction in solutions of different salt concentration and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The difference between the electrophorograms of the different fractions of nuclear proteins isolated from liver and from hepatoma was found in the bands which have the same electrophoretic mobility as the main proteins of informofers and are extracted from nuclei at salt concentrations which extract informofers. These changes in the electrophoretic patterns of proteins with the solubility and mobility of the proteins of informofers could be related to the defective processing of heterogeneous nuclear RNA in the hepatoma. In addition the identity of electrophorograms of nuclear proteins isolated from liver and from hepatoma and the identity of most bands in the electrophorograms of nuclear proteins which are soluble in 0.35 M NaCl and chromosomal proteins which are not soluble at this salt concentration support the notion that these nonhistone nuclear proteins which can be identified as the major bands in electrophorograms of chromosomal proteins are not the specific regulators of gene expression.
Int J Cancer 1975 Aug 15
PMID:Nuclear proteins of rat liver and of an aminoazo-dye-induced hepatoma. 16 62

Linear sucrose gradient analyses reveal that all estrogen-induced and -dependent primary renal tumor cytosols examined contain an 8 S and variable amounts of 4 S receptor in low ionic buffer concentrations. Similar results were obtained with extracts of primary metastases of these tumors. Sucrose gradients containing high salt (0.4 M KCl) convert the 8 S receptor in both the hamster renal tumor and uterus to a 4 to 5 S complex. Scatchard plot analysis reveals that the renal tumor cytosol estradiol-receptor complex has a Ka of 1.7 X 10(9) M-1 and 9.2 X 10(-10) M binding sites. Competition for the tritiated 17beta-estradiol binding sites in the renal tumor was similar to that in the uterus with respect to estrogenic compounds. Nonestrogenic steroids exhibited minimal competition at the same concentrations or higher. Substitution in the ring structure, particularly in position 3 of the phenolic A-ring, resulted in a considerable loss in the ability of such compounds to compete for these receptors. Aniestrogens were effective competitors for these estrogen receptors only at higher concentrations relative to the tritiated estradiol.
Cancer Res 1976 Mar
PMID:Receptor characteristics of specific estrogen binding in the renal adenocarcinoma of the golden hamster. 17 53

Ten aminoacyl transfer RNA's prepared from human malignant trophoblastic cells (BeWo line) were compared with the corresponding aminoacyl transfer RNA's from normal human chorionic tissue by cochromatography on a RPC-5 column. Phenylalanyl transfer RNA (Phe-tRNA) of BeWo cells had, in addition to the single species of Phe-tRNA found in normal chorionic tissues, an early eluting component. When Phe-tRNA from the chorion was exposed to mild acid, which selectively excises the Y base, it eluted in the same position as the early eluting Phe-tRNA of BeWo cells. Therefore, the BeWo Phe-tRNA is partially undermodified. Tyrosyl transfer RNA of BeWo cells exhibited a broad-based peak which eluted later than the normal and probably consists of two or more tyrosyl transfer RNA's. Seryl transfer RNA of BeWo cells showed two peaks of acceptor activity, while seryl transfer RNA of normal chorion had a third peak that eluted at a higher salt concentration. In addition, in an early eluting methionyl and lysyl transfer RNA and in a late eluting arginyl transfer RNA from BeWo cells and normal charion, quantitative alterations were detected. The remaining four transfer RNA's, leucyl, aspartyl, valyl, and histidyl, from the two sources did not show any significant differences in elution profiles. These alterations of the chromatographic profile appeared to be due to new or altered species of transfer RNA. They were not due to differences in the aminoacyl transfer RNA synthetase. The transfer RNA methyltransferase capacity of the enzymes from BeWo cells was 2-fold higher than that of the enzymes extracted from the chorion.
Cancer Res 1976 Aug
PMID:Changes in transfer RNA's in human malignant trophoblastic cells (BeWo line). 17 10


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