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 simian virus 40 large tumor antigen (T-ag) is found in both the nuclei (nT-ag) and plasma membranes (mT-ag) of simian virus 40-infected or -transformed cells. It is not known how newly synthesized T-ag molecules are recognized, sorted, and transported to their ultimate subcellular destinations. One possibility is that these events depend upon structural differences between nT-ag and mT-ag. To test this possibility, we compared the structures of nT-ag and mT-ag from simian virus 40-infected cells. No differences between the two forms of T-ag were detected by migration in polyacrylamide gels, by Staphylococcus aureus V8 partial proteolytic mapping of methionine- or proline-containing peptides, or by two-dimensional tryptic peptide mapping of methionine-containing peptides. The carboxy-terminal, methionine-containing tryptic peptide was identified in the two-dimensional maps and was shown to be identical in nT-ag and mT-ag. Thus, a structural basis for the recognition and differential localization of T-ags could not be demonstrated. The carboxy terminus of the T-ag encoded by mutant dlA2413 is derived from the alternate open reading frame of the simian virus 40 early region, in analogy with the theoretical early gene product, T*-ag. We used this mutant to identify peptides unique to T*-ag. None of these peptides were detected in maps of mT-ag; only wild-type T-ag-specific peptides were found. These findings suggest that T*-ag does not represent the membrane-associated form of T-ag, but that mT-ag is encoded within the same reading frame used for nT-ag.
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PMID:Absence of a structural basis for intracellular recognition and differential localization of nuclear and plasma membrane-associated forms of simian virus 40 large tumor antigen. 302 27

The human p53 tumor antigen comprises several physically distinct proteins. Two p53 proteins, separable by polyacrylamide gel electrophoresis, are expressed by the human transformed cell line SV-80. The individual cDNAs which code for these proteins were isolated and constructed into the SP6 transcription vector. The proteins encoded by these clones were identified by in vitro transcription with the SP6 vector and translation in a cell-free system. p53-H-1 and p53-H-19 cDNA clones code for the faster- and slower-migrating p53 protein species, respectively, of SV-80. The in vitro-expressed proteins of p53-H-1 and p53-H-19 had the same antigenic determinants and were structurally indistinguishable from their in vivo counterparts. By expressing defined restricted cDNA fragments in vitro, the region of heterogeneity between the respective cDNAs was located at the 5' end of the cDNAs. Exchanging the 5' fragments of interest and expressing the chimeric clones in vitro confirmed that the DNA heterogeneity was responsible for the difference in the electrophoretic mobility of these proteins. The sequences of the two cDNAs revealed a single base pair difference (G versus C) in the coding region of the clones. This sequence difference resulted in an arginine being coded for in clone p53-H-1 and a proline being coded for at the equivalent position in clone p53-H-19. This variation accounted for the change in the electrophoretic mobility of the individual p53 protein species.
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PMID:Molecular basis for heterogeneity of the human p53 protein. 302 64

It was previously shown that the administration of dexamethasone (Dex) to mice bearing mammary adenocarcinoma caused the collagen content of the tumor capsule to be decreased by 50%, but collagenase and other neutral protease activities of the tumor were the same as in the controls. These events occurred with distinctly increased tumor invasion and metastasis. The present communication reports on the characterization of capsule collagen and the effects of agents [vitamin A (VA) and Dex] on capsule collagen metabolism and presents further evidence concerning the possible mechanisms by which the collagen content of the capsule was decreased in the Dex-treated hosts. The collagen extracted from capsules of untreated controls and mice (C3H/HeJ) treated with VA or Dex was primarily type I, as judged by the migration of protein bands in sodium dodecylsulfate-polyacrylamide gel electrophoresis and by patterns of elution peaks from an octadecyl C-18 column. The amino acid compositions of type I collagen of the capsule of treated and untreated controls were similar but not identical to those of mouse skin and guinea pig skin type I collagens. The specific activity of intracellular free [14C] proline, the extent of hydroxylation of [14C]proline residues of collagen, and the specific activity of [14C]hydroxyproline and proline in each case were similar in treated and in untreated controls. These results suggest that the observed 45% decrease in the conversion of [14C]proline into protein-bound [14C]hydroxyproline of the Dex-treated hosts apparently was due to decreased collagen synthesis. The data also suggest that the most critical effects of Dex on tumor invasion and metastasis appeared to occur at an early stage before full formation of the collagenous extracellular matrix.
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PMID:Effects of vitamin A and dexamethasone on capsule collagen metabolism in mouse mammary adenocarcinoma. 302 97

The extracellular matrix of the dermis is subject to severe alterations during tumor promotion with phorbol esters in mouse skin. The metabolic changes also involve general stimulation of protein synthesis and most specifically an increase of collagen synthesis. During chronic treatment with the tumor promoting phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) increased protein synthesis was observed that did not occur during treatment with the non-promoting mitogens 4-O-methyl-TPA and Ca-ionophore A 23187. Relative collagen synthesis measured as the ratio of radioactivities in hydroxyproline and proline or as the proportion of total radioactivity in pepsin resistant material was elevated, too, but not sufficiently to substitute for TPA-induced collagen loss. In contrast collagen degradation caused by the non-promoting irritant A 23187 is followed by an immediate, substantial increase of collagen synthesis. When TPA treatment was discontinued after a few applications insufficient for tumor development rapid resynthesis of collagen took place. Therefore we assume that continued phorbol ester application not only caused connective tissue damage but also prevents the repair of that damage. This effect seems to be promoter specific and contributes to the disruption of dermal-epidermal interactions during tumor promotion.
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PMID:Chronic 12-O-tetradecanoylphorbol-13-acetate treatment prevents restoration of collagen loss associated with its inflammatory effect on mouse skin. 310 8

Kinins in the ascitic fluid from a patient with gastric cancer were purified by gel filtration and reversed-phase high-performance liquid chromatography (HPLC). Two fractions (fractions I and II) showed kinin activity. Fraction I did not correspond to either bradykinin or other known kinins, whereas fraction II corresponded to bradykinin. Fraction I contained 8 amino acid residues from bradykinin minus 1 proline plus 1 additional hydroxyproline. Sequence analysis of fraction I showed that the proline at the third amino acid residue of bradykinin was replaced by hydroxyproline. The retention time of fraction I on reversed-phase HPLC was exactly the same as that of synthetic [hydroxyprolyl3]bradykinin (Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg) and was distinguishable from des-Pro3-bradykinin. Thus, these results demonstrate for the first time the presence of [hydroxyprolyl3]bradykinin in vivo. This is also the first report of the presence of bradykinin in human tumor ascites.
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PMID:Purification and identification of [hydroxyprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer. 318 82

We characterized the effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on osteoblast function and DNA synthesis in 21-day-old fetal rat calvaria maintained in organ culture. Protein synthesis was determined by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein (NCP), respectively. Alkaline phosphatase activity was assessed as the release of p-nitrophenol from p-nitrophenol phosphate. DNA synthesis was determined by the incorporation of [3H]thymidine into acid-insoluble bone and total DNA content. PMA at 3-100 ng/ml (4-133 nM) caused a dose-related inhibition of collagen synthesis that was observed 6 hours after adding PMA to calvaria. PMA inhibited collagen synthesis in the osteoblast-rich central bone of calvaria but did not alter collagen synthesis in the periosteum. There was little effect of PMA on noncollagen protein synthesis in the central bone or periosteum. Phorbol esters that do not promote tumor formation in vivo did not alter collagen synthesis in calvaria. PMA stimulated prostaglandin E2 (PGE2) production in calvaria, but indomethacin did not alter the inhibitory effect of PMA on bone collagen synthesis. PMA decreased alkaline phosphatase activity measured after 48 hr of culture and increased the incorporation of [3H]thymidine into bone and DNA content after 96 hr of culture. These data indicate that PMA inhibits collagen synthesis and alkaline phosphatase activity, while stimulating DNA synthesis, suggesting that activation of protein kinase C might regulate osteoblast function and bone cell replication.
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PMID:Inhibition of bone collagen synthesis by the tumor promoter phorbol 12-myristate 13-acetate. 321 12

Better in vitro models are needed to elucidate the mechanisms underlying tissue destruction by human tumor cells. To address this matter recently isolated and characterized human ovarian carcinoma cell lines derived from either primary tumors, ascitic effusions or metastatic growths were plated in direct contact with extracellular matrix (ECM) previously deposited on culture dishes by bovine corneal endothelial cells. Light and electron microscopy of four of the five ovarian tumor cell lines demonstrated morphologic digestion with penetration of ECM by tumor cell microvilli, along with associated rarefaction. The ability of these same ovarian tumor cell lines to solubilize specific carbohydrate and protein moieties present in intact ECM was assessed with the use of metabolically prelabeled ECM employing tritiated fucose, galactose, glucosamine and proline. Results from these studies corroborated morphologic observations in which four of the five tumor cell lines tested extensively solubilized radiolabeled ECM. The kinetics of radiolabel release from ECM illustrated that three of the four invasive tumors released [3H]fucose, [3H]glucosamine and [3H]proline at high rates. Normal human ovarian fibroblasts and mesothelial cells were observed to be unable to digest ECM and this was consistent with their inability to release radiolabeled material from prelabeled ECM. The results from these studies suggest that some ovarian carcinomas have the ability to degrade basement membrane components. Knowledge regarding the mechanisms responsible for tissue degradation may eventually lead to the development of new chemotherapeutic modalities designed to restrict tumor cell invasion, growth and metastasis.
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PMID:In vitro degradation of extracellular matrix by human ovarian carcinoma cells. 329 49

Antitumor effects of carboplatin and iproplatin, a second-generation cisplatin analog were studied using cisplatin sensitive human urinary bladder (NM-B-1) and prostatic cancers (PRO-1) grown in nude mice. Both NM-B-1 and PRO-1 were sensitive to carboplatin and iproplatin. The tumor-regression effect of carboplatin at the fourfold dose of cisplatin was comparable to that of cisplatin. Iproplatin at the eight to sixteen times dose of cisplatin showed a comparable tumor regression to cisplatin. The range of effective dose was wider in carboplatin than cisplatin and that of iproplatin was not so wide as cisplatin.
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PMID:[Antitumor effect of carboplatin and iproplatin on human urinary bladder and prostatic cancers grown in nude mice]. 331 5

It has been proposed that proteases secreted by cancer cells facilitate metastasis by degrading extracellular matrix. Estrogen receptor-positive breast cancer cells secrete a Mr 52,000 pro-cath-D under estrogen stimulation, whereas this protease is produced constitutively by estrogen receptor-negative cancer cells. We report on the degradation in vitro of extracellular matrix by purified Mr 52,000 cathepsin D (cath-D) and by conditioned media prepared from different cell lines. The purified Mr 52,000 pro-cath-D was autoactivated at pH 4.5 into a Mr 51,000 cath-D and found to digest the extracellular matrix of endothelial bovine corneal cells labeled with [3H]proline or [35S]methionine. Culture medium conditioned by estrogen-treated MCF7 cells had a similar effect at pH 4.5 but not at pH 7.4. Matrix degradation was totally inhibited by pepstatin. Other breast cancer cells (BT20, MDA-MB231, T47D cells, etc.) and other cancer cells also secreted a pepstatin-sensitive proteinase able to degrade extracellular matrix. By contrast, the U2 variant of MCF7 cells, which lacks the Mr 52,000 cath-D gene, and the nontumoral epithelial mammary cells secreted a negligible amount of this proteinase. In all conditioned media, the pepstatin-dependent extracellular matrix degrading activity was highly correlated to the Mr 52,000 cath-D concentration measured by immunoenzymatic assay. We conclude that the Mr 52,000 cath-D is the major acidic protease secreted by mammary cancer cells. We suggest that this protease may degrade basement membrane and consequently facilitate tumor invasion when it is released in an acidic microenvironment.
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PMID:In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. 337 11

The effect on the mucosa of sodium nitrite that enters the colon from the ileum or transmucosally from the circulation is unknown. Isolated colonic mucosal cells and Roux-en-Y colostomies were used to test whether high doses of sodium nitrite (5-40 mM) had any harmful histological or inhibitory metabolic actions on the mucosa. Luminal instillation of 40 mM NaNO2 (3 ml/24 hr) for 7-14 days produced no microscopic changes in the mucosa either of damage (ulceration, mucus cell depletion) or of new growth (dysplasia, neoplasia). Beta oxidation of bacterial fatty acids (n-butyrate) by colonic epithelial cells in rat and man was enhanced by 50% (P less than 0.001) with 10 mM NaNO2, while oxidation of glucose and amino acid (proline) was not affected. Sodium nitrite significantly depressed ketogenesis (P less than 0.001) by the colonic mucosa of rat and man. In conclusion, sodium nitrite in the presence of bacteria has no damaging effect on the colonic mucosa but causes selective stimulation of fatty acid oxidation in the colonic mucosa of rat and man.
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PMID:Specific metabolic effect of sodium nitrite on fat metabolism by mucosal cells of the colon. 348


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