Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,2-Diglycerides with long-chain fatty acid residues related to nutritional fat (LCDGs) specifically affect growth and urokinase secretion in human colonic tumor cells, but not in normal mucosa. This allows them to advance and enhance carcinogenesis in the colon and rectum. SW480 colon carcinoma cells are LCDG sensitive in the same way as primary colonic tumor cells and have therefore been used as a model system to study the mechanism of LCDG action and to search for inhibitors of tumor development in the colon. Using this model system, we have shown that the effects of LCDGs are transmitted by protein kinase C and abolished by downregulation of the enzyme. Retinol, retinoic acid, and beta-carotene in nanomolar concentrations inhibit LCDG-induced growth and urokinase secretion and block stimulation of protein kinase C. Although retinol and retinoic acid at higher concentrations also display stimulatory activity, beta-carotene does not. At 100 nM, a concentration that can easily be reached in the plasma of humans, beta-carotene reduces LCDG-induced urokinase secretion about 50%. Inasmuch as beta-carotene does not have side effects due to intrinsic activities and storage effects, beta-carotene and foods rich in carotenes could be useful in the prevention of colorectal cancer.
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PMID:Retinoids inhibit protein kinase C-dependent transduction of 1,2-diglyceride signals in human colonic tumor cells. 805 26

Development of colon carcinomas appears to be associated with inactivation of multiple tumour suppressor genes. Cytogenetic and DNA analyses of colon carcinomas have detected a high frequency of chromosome 1p deletion, which suggests the presence of a tumour suppressor gene. We therefore introduced normal human chromosome 1 into colon carcinoma COKFu cells, through microcell hybridization. Six clones of hybrid cells containing normal chromosome 1 were obtained, four of which had a small fragment of the introduced chromosome 1, including 1p36-34. The morphology of hybrid cells with chromosome 1 markedly altered to a flat shape. The cloning efficiency of all six hybrid cells in soft agar was significantly reduced, and the tumourigenicity in athymic nude mice was completely suppressed. Hybrid cells containing only the region of 1p36-34, as well as those containing intact chromosome 1, showed suppressed transformed phenotype. Furthermore, several tumourigenic revertant cells were obtained from the hybrid cells. These revertant cells had a morphology similar to that of COKFu cells, and were found to have lost the 1p36 region from the introduced chromosome 1. These results indicate that a normal chromosome 1p36 carries a tumour suppressor gene for colon carcinogenesis.
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PMID:Suppression of tumourigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. 810 48

The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, beta 2-glycoprotein I, ovine submaxillaris mucin, and the gangliosides GM1, GM2, GM3 and GD1a. Because of their possible relevance for metastasis, precursors of Le(a) and Le(x) antigens, too, were employed, namely neoglycolipids produced by coupling LcOse4 or NeoLcOse4 oligosaccharides to L-alpha-phosphatidyl-ethanol-amine-dipalmitoyl. Our data indicate that human colorectal tumor tissue contains two highly active sialyltransferase enzymes, which are only weakly expressed in normal mucosa. These are a N-glycan-specific alpha 2,6-sialyltransferase, which was significantly increased in metastasizing tumors, and a Gal beta 1,3Gal-NAc-specific sialyltransferase, which was increased in tumors of early stages. A shift to enhanced alpha 2,6-sialylation of membrane glycoproteins during carcinogenesis was demonstrated by lectin ELISA analysis of magneto-bead separated tumor cells. Quantitative determination of specific sialyltransferase activities may be a sensitive tool for detection and monitoring of colon carcinoma.
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PMID:Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors. 819

Allyl isothiocyanate, a constituent of mustard and certain vegetables found in the human diet, was tested for cytotoxic and cytostatic effects in HT29 human colon carcinoma cells in vitro. For an exposure time of 24 h, allyl isothiocyanate exhibited a Dq of 0.32 microgram/ml and a D0 of 0.74 micrograms/ml. Following detransformation of the cells by treatment with sodium butyrate or dimethylformamide the cells became more resistant to the cytotoxic effects of allyl isothiocyanate, the Dq increasing to 0.74 microgram/ml and the D0 to 0.96 microgram/ml (with butyrate) or 0.84 microgram/ml (with dimethylformamide). At the Dq value for detransformed cells the survival of the control cells was reduced to 56%. Allyl isothiocyanate was also found to be less cytostatic to the mass growth of detransformed populations in that daily doses of 1.6 micrograms/ml over a week reduced the final number of detransformed cells relative to untreated cultures by < 25% whilst growth of the transformed cultures was reduced by > 60%. Given this increased sensitivity of the cells to allyl isothiocyanate when in the transformed state, it is hypothesized that, when consumed in the human diet, this compound may protect against the development of colorectal cancer by selectively inhibiting the growth of transformed cell clones within the gastrointestinal mucosa.
Carcinogenesis 1993 Oct
PMID:Allyl isothiocyanate is selectively toxic to transformed cells of the human colorectal tumour line HT29. 822 57

In areas of the world where hepatitis B and aflatoxin ingestion are common, alterations of the p53 tumor suppressor gene have frequently been reported in hepatocellular carcinoma (HCC). In particular, G-to-T transversions at codon 249 of the p53 gene have been consistently observed in hepatocellular carcinomas in China and sub-Saharan Africa. The goal of this study was to determine the frequency and relationship of p53 gene alterations and hepatitis B in formalin-fixed, paraffin-embedded HCCs resected in the United States. Since immunoreactivity for p53 correlates closely with the presence of missense mutations in the p53 gene, we performed immunohistochemical staining with the monoclonal antibody PAb1801. Only seven of 37 cases (19%) demonstrated nuclear accumulation of p53 gene product, in contrast to 10 of 20 cases (50%) of colon carcinoma metastatic to the liver. Staining was not observed in seven liver cell adenomas, 10 cases of focal nodular hyperplasia, or eight cases of cirrhosis. DNA was extracted from formalin-fixed paraffin sections for additional analysis with use of the polymerase chain reaction (PCR). G-to-T transversions of the third nucleotide of codon 249 were demonstrated in only four of 37 cases (11%), three of which had stained with PAb1801. Of 13 patients for whom there was information about a restriction fragment length polymorphism (RFLP) for BstUI within the fourth exon of the p53 gene, allelic loss of p53 was demonstrated in only two cases (15%), both of which stained with PAb1801. Because of previous reports specifically associating hepatitis B with p53 mutations in HCC, we performed nested PCR for hepatitis B virus DNA. Five of 37 cases (14%) contained hepatitis B virus DNA, two of which stained diffusely for p53 and three of which had codon 249 mutations. Our findings indicate that alterations in the p53 gene, particularly at codon 249, are uncommon in HCCs in the United States, and when present are associated with hepatitis B. Since hepatitis B is infrequently associated with HCC in our patient population, the role of p53 alterations in hepatocellular carcinogenesis may not be as significant as in other parts of the world where hepatitis B and aflatoxin are more prevalent.
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PMID:Hepatitis B and alterations of the p53 tumor suppressor gene in hepatocellular carcinoma. 823 31

Colorectal carcinogenesis is a multistep process that is accompanied by accumulation of changes in proto-oncogenes and tumor-suppressor genes. APC/MCC, RAS, DCC, p53 mutations and/or allelic losses, hyperexpression of c-MYC and RB genes, as well as other genomic alterations appear at characteristic stages of tumor development and are observed in most neoplasms. However, consideration of each of these abnormalities leaves many unanswered questions. The striking data on recurrent amplification of the RB tumor-suppressor gene as well as suppressive activities of protein kinase C and activated RAS genes, at least in some colon carcinoma cell lines, suggest the unusual effects of some signalling pathways in colonic epithelial cells. The results obtained to date indicate that distinct sets of genetic changes may underlie the development of colorectal tumors.
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PMID:Genetic events responsible for colorectal tumorigenesis: achievements and challenges. 824 74

Patients with diabetes frequently suffer from various postoperative complications, especially infection. Diabetic patients also have a high incidence of uterine endometrial cancer. The nature of the intrauterine bacterial flora may be related to both infection and carcinogenesis. Therefore, identification of the intrauterine bacterial flora in diabetic patients may be useful. Bacteria were detected in the uterine endometrial cavity of 100% of ten diabetic patients with myoma uteri. However, among 20 non-diabetic control patients with myoma uteri, only three 15% harbored bacteria. Members of the Enterobacteriaceae (Escherichia coli, Proteus spp., Enterobacter cloacae, and Klebsiella pneumoniae) were the predominant bacteria. We speculate that bacterial products contribute to carcinogenesis, as has been proposed for colon carcinoma. Antimicrobial agents active against Enterobacteriaceae should be used to prevent postoperative infections in gynecologic procedures in diabetic patients.
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PMID:Bacterial flora detected of the uterine endometrial cavity of diabetic patients with myoma uteri. 836 May 20

Recent identification of genetic alterations in colon polyps and tumors has allowed construction of a hypothesis for the molecular basis of colon carcinogenesis. The consistency of observed genetic changes has inspired enthusiastic anticipation of new diagnostic tools and interventions for colon cancer. Appropriate animal models are crucial to the testing of molecular postulates as well as the development of markers and therapies for colon carcinogenesis. We discuss herein the various animal models that are currently used for the study of colon cancer as well as those that hold promise for the future. The contributions, drawbacks, and potential uses for the chemical carcinogen model, the multiple intestinal neoplasia model, transgenic animals, and the reconstruction model in the study of colon carcinoma are presented.
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PMID:Animal models for colon carcinogenesis. 850 67

The development of human colon carcinomas is associated with a number of genetic alterations. A high frequency of deletion of the short arm of chromosome 8 at a late stage of colon carcinogenesis was detected by DNA analysis of colon carcinomas, which suggests the presence of a tumor suppressor gene. We therefore, introduced normal human chromosome 8 into colon carcinoma cells that showed allele loss on 8p21, through microcell hybridization. Five clones of hybrid cells were obtained from independent experiments. Three hybrids exhibited morphological alteration and suppressed tumorigenicity in the subcutis of nude mice, but the other two did not. The difference between the two types of hybrids was the region of the introduced normal chromosome 8: Three hybrids exhibiting morphological alteration and suppressed tumorigenicity had the entire region of the introduced chromosome 8, whereas the other two, exhibiting no change, lacked 8p12-pter from the introduced chromosome. Furthermore, the invasiveness of the hybrids with suppressed tumorigenicity was reduced to one-fifth of that of the parental cells. These results indicate that 8p12-pter carries a gene that contributes to suppression of both tumorigenicity and invasiveness of colon carcinomas.
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PMID:Suppression of tumorigenicity and invasiveness of colon carcinoma cells by introduction of normal chromosome 8p12-pter. 857 Feb 18

The progression of human malignancies is thought to involve the inactivation or loss of tumor suppressor genes. Previous studies have suggested that inactivation of tumor suppressor genes on chromosomes 5q, 17p, 18q, and 8p play a role in the development of colorectal carcinoma. However, chromosome 3p at the von Hippel-Lindau disease (VHL) gene locus (3p25-26) has not been previously implicated in the development or progression of sporadic colorectal carcinoma. The authors have analyzed VHL gene alterations on chromosome 3p in sporadic human colon carcinomas and adenomas using modified microdissection techniques. These techniques allow for procurement and analysis of selected subpopulations of cells from both paraffin-embedded and frozen human tumor specimens. VHL disease gene deletion was detected by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis in microdissected colon carcinoma specimens. Allelic loss of VHL gene was detected in 7 of 11 (64%) informative patients who underwent colectomy for primary sporadic colon carcinoma. However, no allelic loss of VHL gene was shown in colonic adenomas of eight informative patients. These results indicate that VHL disease gene deletion frequently occurs in sporadic colon carcinoma. Because this deletion was not present in adenomas, VHL gene may play a role in colonic carcinogenesis and represent a relatively late event in colonic neoplasia progression. Additionally, microdissection of tissue sections may be especially useful in detecting allelic loss in PCR-based studies of infiltrating tumors, particularly when the tumor cells represent a relatively small percentage of the total cell population.
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PMID:von Hippel-Lindau disease gene deletion detected in microdissected sporadic human colon carcinoma specimens. 861 56


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