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)

Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.
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PMID:Effects of cysteine upon tumor cells. 2 29

A specific collagenase (EC 3.4.24.3) has been found and purified from serum-free culture medium of 11095 epidermoid carcinoma of rat prostate. The molecular weight of this collagenase was estimated at 71 000 and the pH optimum was approx. 7. At 26 degrees C, the collagenase cleaved collagen at a site 3/4 the length from the N-terminus. At 37 degrees C, this collagenase degraded collagen to smaller peptides. The enzyme activity was inhibited by serum, cysteine and EDTA, but not by protease inhibitors. The presence of collagenase in rat tumor tissue suggests that this enzyme might play a significant role in tissue invasion by cancer cells.
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PMID:Collagenase activity in cultures of rat prostate carcinoma. 3 9

This paper reports that the ionophore-induced slow-reacting substance (SRS) from mast cell tumor leukocytes is a member of a group of compounds called leukotrienes. Briefly, murine mastocytoma cells treated with calcium ionophore produced a SRS that caused guinea pig ileum to contract. This response could be reversed by an SRS antagonist, FPL 55712. Based on osotope incorporation experiments, spectrophotometry, and chemical degradation analyses, the SRS was identified. It is a cysteine-containing derivative of 5-hydroxy-7,9,11,14-icosatetraenoic acid, which was attached in a thioether linkage at C-6. The SRS was structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. The leukotrienes have the common feature of the presence of a conjugated triene. Leukotriene A is an intermediate in the formation of leukotriene B, and is proposed to be the precursor also of leukotriene C, the SRS chemically identified in this paper.
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PMID:Leukotriene C: a slow-reacting substance from murine mastocytoma cells. 4 Dec 40

Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.
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PMID:Tumor antigen and acid phosphatase isoenzyme in prostatic cancer. 4 19

The structure and antigenic characteristics of a human k, IgG myeloma protein that formed half-molecules were analyzed. Most of the myeloma protein found in the patient's serum and urine consisted to two chain 4.3S half-molecules. A small amount of four chain 7S myeloma protein was, however, found in the serum and was apparently formed by the same clone of tumor cells. Polyacrylamide gel electrophoresis in 8 M urea and 1% sodium dodecyl sulfate and analytical ultracentrifugation in 6 M guanidine of the fully reduced and alkylated half-molecule indicated that this myeloma protein had a heavy chain of a smaller molecular weight (approximately 45,000) than that of normal gamma chains, Except for this apparent deletion, the heavy chain resembled gamma1 chains. The amino acid composition of the peptides containing the half-cysteine residues forming the interchain disulfide bonds, the glycopeptide of the Fc fragment and the COOH-terminal structure were similar if not identical with the analogous structures of gamma1 chains. No Fc fragment could be prepared because the Fc portion of the heavy chain of the myeloma protein was extremely susceptible to degradation with papain. After mild reduction and alkylation, the 7S myeloma protein dissociated into half-molecules, indicating a lack of noncovalent interactions in the Fc fragment that are present in all classes of human immunoglogulins and are responsible for the formation ofFc dimers. The half-molecule was antigenically deficient in the Fc fragment. It failed to precipitate with anti-Fc fragment antisera in double gel diffusion tests and inhibited a Fc-anti-Fc fragment binding reaction weakly and incompletely. The half-molecule and the 7S protein had the same genetic markers on the first and second homology region of the gamma chain. The half-molecule lacked, however, the corresponding markers on the third homology region, These findings suggest that this myeloma protein had a deletion in the gamma chain which was probably located in third homology region and was likely the structural abnormality responsible for the lack of noncovalent interaction in the Fc fragment and absence of most of the antigenic determinants characteristic of gamma chains.
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PMID:Human myeloma IgG half-molecules. Structural and antigenic analyses,. 5 83

Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, in contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. Methylglyoxal and hpe are potent carcinostatic agents in vitro but relatively ineffective in vivo. Both aldehydes have a short half-life in vivo which may explain their poor carcinostatic properties when administered other than peritumorally. Several possibilities of increasing the effective half-life were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration of an inhibitor of glyoxalase I, (iii) administration of aldehyde-cysteine adducts, and (iv continuous intravenous infusion. Methylglyoxal (36 mg/kg i.p., twice daily) was slightly less effective in inhibiting the growth of the solid form of Ehrlich carcinoma than a dose of 72 mg/kg (inj. 1); 36 mg/kg (inj. 2) 46.2% compared to 51%. The aldehyde was more effective aginst the ascitic form of the tumour, with 99.76% inhibition of growth after giving 72 mg/kg twice daily for five days followed by 36 mg/kg for five days. The glyoxalase I inhibitor S-(p-bromobenzyl)-glutathione didnot significantly enhance the activity of methylglyoxal against the solid form of the tumour. Nicotinamide (1% w/v in the drink) was similarily inactive. Methylglyoxal in combination with nicotinamide was significantly more effect (P less than 0.05) than methylglyoxal alone (36 mg/kg, twice daily) in inhibiting the growth of the ascitic tumour. Methylglyoxal-N-acetyl-L-cysteine was four times less toxic than methylglyoxalalone but was marginally less effective against the ascitic form of the tumour. Doses of these adducts equivalent to 144 mg/kg per day of methylglyoxal were more effective P less than 0.05) than the optimal regime of methylglyoxal in inhibiting the solid tumour (67.5% inhibition compared to 51%). Treatment of mice bearing the ascitic form of Sarcoma 180 with five daily doses (i.p.) of an HPE-cysteine adduct equivalent to a dose of HPE alone of 32-256 mg/kg per day significantly increased survival time by comparison with controls. The adduct was 2-3 times more effective, dose-for-dose, than HPE alone in inhibiting tumour growth. Purified buffered methylglyoxal has an LD50 on continuous infusion into the right lateral tail vein in mice of more than 3.0 mg/g per day (seven days at 2.8 ml/day). Local oedema followed by tail necrosis occurs at doses in excess of 0.25-0.5 mg/g per day in mice bearing the solid forms of the syngeneic tumours: squamous carcinoma D; lymphosarcoma 1 (WH/Ht mice); and spontaneous mammary D5056 (CBA/CA mice). A maximum tumour volume growth delay of 3.4 days at Day 17 (P less than 0.001) after transplantation was observed after infusion of 0.5 mg/g per day methylglyoxal on Days 11-17 in the CBA/CA D40 syngeneic mammary tumour. Tumour regrowth after termination of therapy eliminated the significant difference between control and methylglyoxal-treated tumours by Day 27. Methylglyoxal infusion (0...
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PMID:Carcinostatic activity of methylglyoxal and related substances in tumour-bearing mice. 15 13

Helenalin and tenulin injected into CF1 male mice bearing Ehrlich ascites tumors inhibit DNA synthesis and DNA polymerase enzymatic activity in the tumor cells. Helenalin inhibited protein synthesis. Both drugs increased the concentration of adenosine 3',5'-monophosphate, and interfered with glycolytic and mitochondrial energy processes. Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro indicate that the cyclopentenone-bearing sesquiterpene lactone and related compounds do not alkylate puring bases of nucleic acids but rather undergo a Michael-type addition reaction with the sulfhydryl groups of reduced glutathione and l-cysteine. Thus, the inhibition of cellular enzyme activities and metabolism that has been observed with these drugs might be explained by the occurrence of a Michael-type teaction.
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PMID:Sesquiterpene antitumor agents: inhibitors of cellular metabolism. 19 9

The nucleotide sequence of the segment of simian virus 40 DNA between standard map positions 0.53 and 0.65, i.e., approximately half of the restriction fragment Hind A, is reported. This segment is located near the beginning of the early region and is transcribed counterclockwise. There is a potential initiating ATG signal at 13 nucleotides from the Hind C-Hind A junction in the strand with the same polarity as the early mRNA. From this signal on, an open reading frame is present which would allow the synthesis of a polypeptide of 174 amino acids until a TAA termination codon is reached at nucleotide 602 (map position 0.547). This polypeptide, revealed by the DNA sequence, corresponds almost certainly to small-t antigen. Correlation of the deduced amino acid sequence with the NH(2)-terminal sequences of small-t and large-T (tumor) antigens of simian virus 40, as established by Paucha et al. [Paucha, E., Mellor, A., Harvey, R., Smith, A. E., Hewick, R. M. & Waterfield, M. D. (1978) [Proc. Natl. Acad. Sci. USA 75, 2165-2169], strongly argues that both proteins are indeed initiated at the ATG triplet. Because the DNA region between 0.547 and 0.534 is blocked for translation in all three reading frames by multiple termination condons, we conclude that the large-T antigen must be coded for by two noncontiguous DNA segments: the segment from 0.65 to around 0.60, which small-t and large-T antigens share, and another segment starting at some point after position 0.534 and continuing counterclockwise until it terminates at map position 0.174. Small-t antigen is methionine-rich and has a remarkably high number of cysteine residues clustered mainly in its COOH-terminal half. It is rich in both basic and acidic residues, the former being slightly in excess.
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PMID:Nucleotide sequence of the simian virus 40 small-t gene. 20 55

Three human malignant melanomas were cultured in pure populations and one tumor was cloned into melanotic and amelanotic cell lines. In the homogenates of these cultured cells, specific collagenase activities were demonstrated by isotope release from 14C-labeled collagen, disc electrophoresis, and specific cleavage of collagen molecules as demonstrated in the segment long spacing form. No significant collagenase activity was observed in the culture media. Interestingly, early cultures had a high collagenase activity in the cells and as they were successively subcultured, the activity diminished. Cysteine completely inhibited the degradation of tropocollagen as determined by disc electrophoresis and EDTA partially inhibited the degradation. It is concluded that human malignant melanoma cells produce a specific collagenase in vitro which can be extracted in early culture directly from the homogenate.
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PMID:Collagenolytic activities of cultured human malignant melanoma cells. 21 92

In experimental animals, a systemic treatment with thiols of the mercaptoalkylamine type has affected all of five solid tumors so far investigated. (Three of the tumors were transplanted into the strain of origin.) There was either inhibition of growth or "oncodieresis," i.e., a necrosis and sloughing of tumors conducive to full recovery and repair. Mercaptoalkylamines and derivatives of the type used in our experiments are known to bind to cellular sites by a two-point attachment involving both thiol and amino groups. One of these compounds, cysteamine, was active in its native, unsubstituted form, but did not bring about oncodieresis when either the amino or thiol group, or both, were alkylated. Mercaptopropylamine, the 3-carbon homolog of cysteamine, was less active. Cystamine, a disulfide dimer of cysteamine that has no free reactive sulfhydryl, did not induce any reaction. Thioglycerol, lacking a terminal amino group, had only negligible activity. Rejection was much more striking when treatment was started on the day of inoculation than when started 7 days later. Male mice rejected better than females. Results were inferior when tow of the agents were given simultaneously or together with other radioprotectants, such as L-cysteine, glutathione, dimethyl sulfoxide, or reserpine. Tumor rejection was enhanced when the phosphorylated thioyls, S-2-(3-aminopropylamino)ethylphosphorothioic acid or S-(2-ethylguanidine)phosphorothioci acid, were given simultaneously with the radioprotective serotonin, but there was no synergy of serotonin with the nonphosphorylated compounds S-2-aminoethylisothiouronium bromide or cysteamine. Serotonin alone did not affect the tumors.
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PMID:Tumor rejection in experimental animals treated with radioprotective thiols. 23 35


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