Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile polyps (JP) are the most common colonic tumor in children. Although considered benign, malignant transformation has been reported in JP. Ornithine decarboxylase (ODC) and tyrosine kinase (TyK) enzymes are markers for a rapid cell proliferation index. DNA aneuploidy score and p53 gene expression are late malignant changes seen in patients with colon cancer. In this study, we investigated ODC and TyK activities as well as DNA aneuploidy score and p53 expression in juvenile polyps compared with the adjacent normal colonic mucosa. Results showed that ODC was significantly increased in JP compared with the adjacent normal colonic mucosa. TyK activity was increased in 3/5 polyps and decreased in 2/5 polyps compared with the mucosa. Mean TyK activity was higher in JP compared with normal mucosa but did not reach significance (707 and 632 pmol/mg pmol, respectively). Moreover, changes in phosphorylization of TyK proteins was also observed in JP but not in normal mucosa. JP had a normal DNA aneuploidy score and showed no expression of p53 gene. We conclude that JP do not express p53 gene and aneuploidy but had higher activity of ODC and TyK enzymes, suggesting a higher stage of cell proliferation.
 ...
PMID:Ornithine decarboxylase and tyrosine kinase activity in juvenile polyps of childhood. 855 12

The predisposition to colon cancer is multigenetically controlled in animals and probably also in humans. We have analyzed the multigenic control of susceptibility to 1,2-dimethylhydrazine-induced colon tumors in mice by using a set of 20 homozygous CcS/Dem recombinant congenic strains, each of which contains a different random subset of approximately 12.5% of genes from the susceptible strain STS/A and 87.5% of genes from the relatively resistant strain BALB/cHeA. Some CcS/Dem strains received the alleles from the susceptible strain STS/A at one or more of the multiple colon tumor susceptibility loci and are susceptible, whereas others are resistant. Linkage analysis shows that these susceptibility genes are different from the mouse homologs of the genes known to be somatically mutated in human colon cancer (KRAS2, TP53, DCC, MCC, APC, MSH2, and probably also MLH1). Different subsets of genes control tumor numbers and size. Two colon cancer susceptibility genes, Scc1 and Scc2, map to mouse chromosome 2. The Scc1 locus has been mapped to a narrow region of 2.4 centimorgans (90% confidence interval).
 ...
PMID:Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different from the genes known to be somatically mutated in colon cancer. 857 18

DNA single-strand conformational polymorphism (SSCP) analysis is widely used for detection of point mutations in clinical specimens. Performing SSCP analysis with cRNA instead of DNA has been shown to improve mutation detection frequency. RNA can exist in numerous meta-stable conformations, which appear as patterns of bands on nondenaturing electrophoresis gels. Single base mutations can cause not only mobility shifts of major bands, but also loss of some conformations and appearance of new conformations. Unique RNA SSCP patterns associated with specific base sequences in many cases allow visual identification of point mutations. However, in some cases, the RNA SSCP pattern of a single base change in a sequence is not sufficiently different for a positive identification of the mutation. Improvement in the detection capability of RNA SSCP was obtained by adding 3'-deoxynucleotides to the transcription reaction. The presence of chain-terminating nucleotides in the transcription reaction formed numerous new RNA fragments, thereby generating complex band patterns ("bar codes") unique to each RNA sequence. This method was applied to analyzing p53 mutations in patients with colon cancer.
 ...
PMID:Identification of mutations by RNA conformational polymorphism "bar code" analysis. 859 93

Experimental studies in rodents using chemical carcinogens and viral oncogenes show a high susceptibility to malignant transformation. Analytical epidemiological studies have revealed an increased risk of human brain tumor development in association with certain occupations but, with the exception of therapeutic X-irradiation, attempts to identify a specific exposure or causative environmental agent have so far been unsuccessful. Thus, endogenous mutations and genetic factors may play a more important role. This view is supported by recent studies on the nature of DNA alterations in human brain tumors. More than 70% of p53 mutations observed during glioma progression are G:C-->A:T transitions, predominantly at CpG sites, i.e. likely to be produced by deamination of 5-mcC or related spontaneous mechanisms. No specific mutations or mutational hot spots were found which could be suggestive of environmental carcinogens operative in the etiology of human brain tumors. A similar pattern of mutation is found in colon cancer, sarcomas, and lymphomas, i.e. neoplasms with largely unknown etiology. This is similarly true for p53 germline mutations which again show a strong preference for G:C-->A:T transitions at CpG sites.
 ...
PMID:Genetic and environmental factors in the etiology of human brain tumors. 859 15

The role of apoptosis in colon cancer was investigated in terms of control of growth and expression on p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.
 ...
PMID:Apoptosis of colon cancer: comparison with Ki-67 proliferative activity and expression of p53. 860 65

Loss of heterozygosity (LOH) occurring on various chromosomes has been described in the majority of human tumors and its targets are believed to be tumor suppressor genes. Although allelic deletion of the p53 gene (over 60%) has been frequently observed in gastric cancer, as well as in other human malignancies, LOH of other tumor suppressor genes is still discrepant in gastric cancer. To our knowledge, simultaneous analysis of LOH using PCR in adenomatous polyposis coli (APC), deleted in colon cancer (DCC), and retinoblastoma susceptibility (Rb) genes has not yet been reported in sporadic gastric cancer. We examined 21 advanced gastric cancers (12 intestinal type and 9 diffuse type) for LOH at the APC, DCC, and Rb loci using PCR. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing PCR at polymorphic sites within the genes. LOH occurred in 30% of informative cases at APC, in 27% of informative cases at DCC, and in 30% of informative cases at Rb. Thirty-three percent of tumors informative at all loci (fully informative) lost heterozygosity at all three loci. There were no significant differences among histologic types in the prevalence of LOH at any locus and no correlations between losses involving APC, DCC, and Rb genes. These data suggest that inactivation of APC, DCC, and Rb is involved in the development and progression of some human gastric cancers regardless of histologic type.
 ...
PMID:Loss of heterozygosity of multiple tumor suppressor genes in human gastric cancers by polymerase chain reaction. 860 93

A number of oligonucleotides were designed to bind through Hoogsteen triple helix or Watson-Crick hydrogen bonds to the p53 consensus sequence homology localized within the human nontranscribed rRNA spacer region. The oligomers, which bind in vitro to the consensus sequence homology, function as p53 analogues in cells deficient in wild-type p53 protein. Oligomers suppress proliferation of human colon cancer cells by three to eightfold, but only suppress proliferation of normal human mesangial cells or lung fibroblasts by less than 50%. On the basis of these studies, p53 analogues may be used therapeutically to selectively modify proliferation of transformed cells.
 ...
PMID:Suppression of cellular proliferation using p53 DNA recognition site-related oligonucleotides. 861 76

A great deal of the energy and time of a cell is invested in DNA repair activities. The first step in DNA repair pathways is recognition of the lesion on the DNA. The classical lesion-recognizing proteins interact with other repair proteins to form multiprotein complexes most notable of which are those that function in Nucleotide Excision Repair (NER). Proteins involved in lesion recognition include HMG1 and 2 recognizing cisplatin adducts but also maintaining active nucleosome structures and interacting with loops in cruciforms; HMG-box nuclear proteins; XPA and XPC lacking in xeroderma pigmentosum patients and involved in lesion recognition during NER; p53 recognizing strand breaks and insertion/deletion mismatches and causing arrest in the cell cycle; MSH2 mismatch repair protein identified as the human colon cancer gene product; and others including the transcription factor YB-1 that binds to depurinated DNA with a higher affinity compared with undamaged DNA. Other type of lesion-recognizing proteins are also repair enzymes like the O(6)-methylguanine-DNA methyltransferase and DNA glycosylases. Lesion recognition is an important process and might be the rate-limiting step in the overall repair process.
 ...
PMID:DNA lesion-recognizing proteins and the p53 connection. 861 13

p53 induction and cell cycle arrest occur following DNA damage, possibly to allow repair prior to replication. p21WAF1/CIP1, a cyclin-cyclin-dependent kinase inhibitor and proliferating cell nuclear antigen-interacting protein, is induced by p53 and mediates the cell cycle arrest. To investigate a role for p21 in DNA repair in vivo, we studied the expression of in vitro damaged reporter DNA transfected into p21 +/+ or -/- HCT116 human colon cancer cells. Introduction of UV-damaged or cisplatinum-damaged cytomegalovirus-driven beta-galactosidase reporter DNA into tumor cells revealed a significant decrease (2-5-fold) in reporter expression in p21 -/- versus +/+ cells. In the absence of DNA damage, there was a significant increase (2-3-fold) in the number of 6-TG-resistant colonies derived from p21 -/- versus +/+ cells. Reintroduction of wild-type p21, but not a p21 C-terminal truncation mutant which lacks the proliferating cell nuclear antigen interaction domain, stimulated (2-3-fold) the repair capacity of the p21-deficient cells. We conclude that p21 deficiency is associated with a defect in DNA repair, which could lead to an increased sensitivity of tumor cells to DNA damage.
 ...
PMID:Repair Defect in p21 WAF1/CIP1 -/- human cancer cells. 862 93

C --> T transitions at CpG sites are the most prevalent mutations found in the p53 tumor suppressor gene in human colon tumors and in the germline (Li-Fraumeni syndrome). All of the mutational hot spots are methylated to 5-methylcytosine, and it has been hypothesized that the majority of these mutations are caused by spontaneous hydrolytic deamination of this base to thymine. We have previously reported that bacterial methyltransferases induce transition mutations at CpG sites by increasing the deamination rate of C --> U when the concentration of the methyl group donor S-adenosylmethionine (AdoMet) drops below its Km, suggesting an alternative mechanism to create these mutations. Unrepaired uracil pairs with adenine during replication, completing the C --> T transition mutation. To determine whether this mechanism could contribute to the development of human colon cancer, we examined the level of DNA (cytosine-5)-methyltransferase (MTase) expression, the concentration of AdoMet, and the activity of uracil-DNA glycosylase in human colon tissues, and searched for the presence of mutations in the MTase gene. Using reverse transcription-PCR methods, we found that average MTase mRNA expression levels were only 3.7-fold elevated in tumor tissues compared with surrounding normal mucosa from the same patient. Also, no mutations were found in conserved regions of the gene in 10 tumors sequenced. High-performance liquid chromatographic analysis of extracts from the same tissues showed that AdoMet concentrations were not reduced below the Km value for the mammalian enzyme, and the concentration ratio of AdoMet:S-adenosylhomocysteine, the breakdown product of AdoMet and the competitive MTase inhibitor, did not differ significantly. Finally, extracts from the tumor tissue efficiently removed uracil from DNA. Therefore, biochemical conditions favoring a mutagenic pathway of C --> U --> T were not found in a target tissue known to undergo a high rate of C --> T transitions at CpG sites.
 ...
PMID:Mechanisms for the involvement of DNA methylation in colon carcinogenesis. 862 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>