Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancer. Three of the most frequently deleted chromosomal loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In order to detect loss of heterozygosity (LOH) within these genes in dysplastic and cancerous ulcerative colitis, we used an application of the polymerase chain reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and 13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at 2 or more loci, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was more common in left-sided neoplasms. These data suggest that allelic deletion of p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at least a subset of colonic dysplasias and carcinomas occurring in the setting of ulcerative colitis.
 ...
PMID:Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis. 134 56

Neoplastic progression in patients with chronic ulcerative colitis (UC) is characterized by the development of epithelial dysplasia, which is accompanied by genetic abnormalities that can be detected by flow cytometric and molecular biologic methods. Distribution of and correlation between histologic abnormalities, DNA content, and loss of heterozygosity for a p53 allele (p53 LOH) in the colons of nine UC patients were analyzed. Loss of a p53 allele was found in 85% (22/26) of biopsy specimens classified histologically as carcinoma, 63% (25/40) of biopsy specimens with high grade dysplasia, and 33% (7/21) of biopsy specimens with low grade dysplasia. Loss of heterozygosity for p53 was also found in 9% (5/57) of biopsy specimens indefinite for dysplasia and in 1/18 biopsy specimens negative for dysplasia, showing that this genetic change may occur early in the histological progression towards carcinoma. Aneuploid DNA contents were more common than p53 LOH in regions with negative, indefinite or low grade dysplastic histology; moreover, p53 LOH was detected only in aneuploid cells and not in diploid epithelium. Aneuploidy alone was not as specific a marker for the concomitant presence of dysplasia or carcinoma in a biopsy sample as aneuploidy combined with p53 LOH. These findings show that aneuploidy may precede both p53 LOH and epithelial dysplasia. Two UC patients' colons contained geographically separated clones of cells with different aneuploidies that also showed loss of different p53 alleles, suggesting that neoplasia may arise within different populations of cells in separate areas of the same colon.
 ...
PMID:Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. 850 Jul 56

Allelic deletions of the p53 gene previously were demonstrated by Southern hybridization to occur in high frequency in sporadic colon carcinomas and in a variety of other human tumors. We have examined the frequency of allelic loss of the p53 gene in carcinoma and dysplasia arising in patients with chronic ulcerative colitis who are heterozygous for the codon 72 polymorphism in exon 4 of the p53 gene. Cells derived from carcinoma and dysplasia specimens from 10 patients who were heterozygous at this locus were sorted by flow cytometry on the basis of DNA content. The p53 exon 4 region was amplified from diploid and aneuploid populations, via a polymerase chain reaction (PCR), and digested with BstUI. Three of three carcinomas, four of six dysplasias, and one patient who was indefinite for dysplasia demonstrated evidence of allelic loss of the p53 gene. Seven of ten cases of sporadic colon carcinoma, analyzed for comparative purposes, exhibited loss of a p53 allele. These results demonstrate that PCR analysis, followed by restriction endonuclease digestion of a polymorphic locus, can provide a rapid, definitive method for analyzing loss of heterozygosity in small numbers of cells from colonic mucosa. Such loss precedes cancer in ulcerative colitis and can be present in its earliest histologically identifiable precursor.
 ...
PMID:Frequent loss of a p53 allele in carcinomas and their precursors in ulcerative colitis. 204 25

The molecular mechanisms underlying premalignant gastrointestinal diseases, such as ulcerative colitis and Barrett's esophagus, remain unknown. For this reason, the expression of the protooncogene c-Ha-ras was studied in ulcerative colitis and Barrett's esophagus. Total cellular RNA was extracted from different regions of the gastrointestinal tract in these two diseases. Expression of c-Ha-ras was greater in proximal than in distal colon and undetectable in Barrett's esophagus. These regional differences in expression were not seen with the control gene beta-actin or with the protooncogenes c-myc and p53. In order to evaluate structural factors contributing to expression, amplification and methylation of c-Ha-ras DNA were studied in these tissues by Southern and slot blotting. No amplification of c-Ha-ras or six other protooncogenes was detected. These data suggest tissue-specific regulation of c-Ha-ras expression in the gastrointestinal tract in certain premalignant disease states.
 ...
PMID:Tissue-specific expression of c-Ha-ras in premalignant gastrointestinal mucosae. 255 32

Colorectal cancer affect the 15% of general population in developed countries. Cancer is a multistep process in which multiple genetic alterations must usually occur in several years. The premalignant step consists of one or multiple aberrant crypts due to hyperproliferation of cells and its shift from the deep third of the crypt to its surface. It has been suggested that abnormality in the APC gene is responsible for this. Furthermore, there exists DNA hypometilation, activation of the gene K-ras and ornithine decarboxylase activity. There is also a loss of MCC gene, that seems to interact with the APC gene. Entire alterations described make possible the Class I adenoma formation. This adenoma, needs the loss of the DCC gene (late stage in the carcinogenesis process), to become a Class II adenoma. The following alteration is deleted and mutation of the p53 gene. There is also an activation of the c-myc oncogene. These two genes are important mechanisms for the conversion of a benign adenoma to a malignant one, adenoma with in situ carcinoma or Class III adenoma. This type of adenoma becomes carcinoma and metastatic stage, throughout inactivation of several tumor suppressor genes. Besides the hereditary APC alteration and other acquired genetic changes as described above there are other associated genetics, antigenics, and enzymes that have an important role in the adenoma-carcinoma sequence. Several carcinogenic factors have been described which also contribute in the adenoma and carcinoma formation: ulcerative colitis, acromegaly, familial history of colonic neoplasia, certain professions, smoking and drinking, consumption of red or processed meat, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Etiology of colorectal cancer]. 755 83

A variety of premalignant lesions, including Barrett's esophagus, colonic polyps, ulcerative colitis, primary sclerosing cholangitis, intraductal mucin secreting papillomatosis are now well recognized and accessible to direct endoscopic assessment and biopsy or brushing. This review emphasizes the potential usefulness of genetic markers, in particular Ki-ras oncogene and p53 tumor suppressor gene mutations, in the endoscopic surveillance of these premalignant conditions. The adjunction of Ki-ras and p53 assays in material collected during endoscopic procedures may help the clinician detect earlier and with a higher accuracy neoplastic progression.
 ...
PMID:Use of genetic markers during endoscopic screening and follow-up of gastrointestinal precancerous lesions. 757 78

Numerous molecular genetic events occurring in the development of sporadic colorectal neoplasia have been previously defined. The most frequent genetic alterations are mutations of the APC, KRAS, and TP53 genes, as well as loss of the DCC gene and of the second TP53 allele. The data from several groups indicate that these genes play an important role in ulcerative colitis-associated dysplasias and cancer, as they do in sporadic colorectal adenomas and carcinomas. KRAS and TP53 mutations were detected in dysplasia, but also in villous regeneration and active colitis, and affect a subpopulation of the cells composing these lesions. We conclude that in histologically defined dysplasia, clones can be found that genetically represent precancerous lesions in ulcerative colitis. Seen in this way, part of the active colitis and villous regeneration lesions might be considered as preneoplastic. When present, KRAS mutation is an excellent genetic marker to map populations of preneoplastic cells.
 ...
PMID:Molecular genetics of dysplasia in ulcerative colitis. 757 15

Three p53 DNA polymorphisms (BstU I and Msp I restriction fragment length polymorphisms (RFLPs) in exon 4 and intron 6 respectively, and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patients with colorectal cancer and compared with patients with ulcerative colitis and healthy controls. There were only minor differences between patients with ulcerative colitis and controls, the only significant difference was observed in the distribution of BstU I-Msp I haplotypes. When single polymorphisms were studied, a significantly lower frequency of the 16 bp duplication was found in patients with colorectal cancer. The protective effect of the 16 bp duplication was more pronounced in haplotype combinations with the BstU I A1 and Msp I A1 alleles, whereas these alleles in combination with the 16 bp A1 allele (no duplication) were associated with an increased risk for colorectal cancer. The genotypic combination BstU I 2-1, 16 bp 1-I, Msp I 2-1 was found in 8.4% of cases among patients with colorectal cancer and 0.5% of cases in the controls (odds ratio = 18.8). The extended haplotype responsible for the high cancer risk of this genotype appears to be BstU I A1-16 bp A1-Msp I A1. The results of this study indicate that the haplotype approach to the identification of p53 germ line alleles associated with increased susceptibility to cancer is far more powerful than the analysis of single polymorphisms, since the capacity to identify germ line alleles predisposing to cancer should increase with the number of polymorphic sites included in the analysis.
 ...
PMID:P53 germ line haplotypes associated with increased risk for colorectal cancer. 761 78

1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 and 2) and p53 (exons 4-7) were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Of 18 adenomas and 38 adenocarcinomas induced in male F344 rats (52 tumors induced by 1-HA plus MAM acetate, three by 1-HA alone, and one by MAM acetate alone), no mutations in Ki-ras or p53 were detected under two conditions of PCR-SSCP analysis. Because human colon carcinomas from patients with ulcerative colitis have a very low incidence of Ki-ras mutation, this experimental system would be a good animal model of human colon carcinomas with ulcerative colitis and of human colon carcinomas without Ki-ras or p53 mutations.
 ...
PMID:No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate. 772 40

The frequency and timing of p53 inactivation in ulcerative colitis (UC)-associated tumorigenesis were investigated using immunohistochemistry (IHC) to detect p53 protein overexpression in 56 carcinomas and 40 dysplastic epithelia derived from 58 patients with UC undergoing colectomy for neoplasia. p53 DNA in 25 of the carcinomas also was evaluated by single-strand conformation polymorphism analysis (SSCP) to detect point mutations in exons 5-8 and by loss of heterozygosity analysis to detect allelic deletions. Point mutations were detected in 20 of the 25 carcinomas (80.0%) undergoing both IHC and DNA analysis. One carcinoma contained an allelic deletion but no mutations of the corresponding allele within the region tested. p53 overexpression occurred in 16 (76.2%) of the 21 carcinomas with point mutations and/or allelic deletions but not in any of those with wild type DNA. Of the 56 carcinomas evaluated by IHC, p53 overexpression occurred in 34 carcinomas (60.7%). The proportion of positive tumors was independent of stage, anatomic location, differentiation, and histological subtype. Overexpression was observed in nine of 20 dysplastic masses devoid of and situated remote from carcinoma (45.0%) and correlated positively with increasing grade of dysplasia (P < .025). In contrast, overexpression occurred in 16 of 20 dysplastic epithelia situated adjacent to carcinoma (80.0%) and correlated with overexpression by the corresponding carcinomas but not with the grade of dysplasia present (P = .013). It is concluded that p53 overexpression can be detected by IHC in most, although not all, UC-associated carcinomas with p53 mutations and/or allelic deletions. Based on this method, p53 overexpression occurs frequently in UC-associated carcinomas regardless of stage and pathological characteristics, in noncancerous dysplastic masses with high grade dysplasia, and in dysplasias of all grades situated adjacent to carcinomas. These findings implicate p53 inactivation in the progression from dysplasia to carcinoma in UC and suggest that its occurrence in dysplastic epithelium may be an independent marker of malignant potential.
 ...
PMID:p53 protein expression in ulcerative colitis-associated colorectal dysplasia and carcinoma. 792 12


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