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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic progression of colorectal epithelial cells from benign adenomas to malignant carcinomas appears to result from a series of genetic alterations involving both oncogenes and tumor suppressor genes. This progression was recently found to be associated with expression of splice variant isoforms of CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this study we examined the relationship of CD44 expression to somatic genetic events in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13 and overexpression of p53 protein as a marker of gene mutation. Among 22 small adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras mutation. CD44 was absent in the other 2 small adenomas positive for K-ras mutation or p53 overexpression. In contrast to the early expression of CD44 in small adenomas, mutations of K-ras and p53 were detected preferentially in large adenomas and late-stage adenomas containing carcinoma. The frequent expression of CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests that activation of CD44 gene expression is related to earlier events in the adenoma-carcinoma sequence, possibly cell activation and proliferation following APC gene mutation or alteration of DNA methylation.
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PMID:CD44 expression in colorectal adenomas is an early event occurring prior to K-ras and p53 gene mutation. 751 84

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)
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PMID:[Etiology of colorectal cancer]. 755 83

Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and also shown to be associated with the development of esophageal and lung cancers. To determine if these genes are also involved in the development of gastric cancer, 79 primary human gastric cancers were examined for loss of heterozygosity of APC or MCC or both. Loss of APC was detected in 20% of 15 informative differentiated cases, but not in 20 informative undifferentiated cases, while loss of MCC occurred in 23.5% of 17 informative undifferentiated cases, but not in 19 informative differentiated cases. These data suggest that loss of heterozygosity of APC/MCC gene is involved in the development of gastric carcinomas, and that distinctly different molecular mechanism(s) may be responsible for the development of differentiated and undifferentiated gastric carcinomas.
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PMID:Loss of heterozygosity of APC/MCC gene in differentiated and undifferentiated gastric carcinomas in Taiwan. 758 53

The APC (age-period-cohort analysis) model makes the assumption that the mortality mij in a given age-group and year is the (simple) product of three factors: an age-related factor ai, one period-related factor bj and one (birth) cohort-related factor Ck: mij = eai x ebj x eck. By taking the natural logarithm, a linear model results which can be treated with fairly standard statistics techniques: ln (mij) = ai+bj+ck. The mij data from observation data are used to estimate alpha, beta(a), beta(b), beta(c) by linear regression method. The value of EXP (beta) is to estimate the effect of each variable. The APC model is consistent with carcinogenesis modeling of molecular biology on tumour. The results of APC analysis for cervical cancer, male and female stomach cancer show that the risk factors have been changed. In fact, the risk factors of cervical cancer have been decreased since liberation, and the risk factor of stomach was increased in the first period of sixty's. The analytic method used in this paper will benefit the study on epidemiology and etiology of cancer.
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PMID:[An analysis of relationship between mortality of cancer and age-period-cohort]. 758 97

Epidemiological studies and animal experiments show an association of dietary intake of fish oils and low incidence of several types of cancers. The active ingredients of fish oils appear to be polyunsaturated fatty acids of omega-3 type such as eicosapentaenoic acid and docosahexaenoic acid (DHA). We have investigated chemopreventive effects of DHA on mouse intestinal polyposis using adenomatous polyposis coli (Apc) gene knockout mice. Damage to the human APC gene is responsible for not only familial adenomatous polyposis but also many sporadic cancers of the entire digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed gene knockout mice containing a truncation mutation in the Apc gene at codon 716 (Apc delta 716). The heterozygous mice developed numerous intestinal polyps, and all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating the loss of heterozygosity [Oshima et al. (1995), Proc. Natl Acad. Sci. USA, 92, 4482-4486]. We fed Apc delta 716 heterozygotes with AIN-76A purified diet containing 3% DHA for 7 weeks, and scored the number and size of intestinal polyps. Average DHA intakes per day were 4.1 and 4.3 g/kg body wt for males and females, respectively. DHA-fed females had only 31% of polyps compared with the control females that developed about 220 polyps, whereas DHA-fed females showed no significant decrease in the polyp number. As for the polyp size, the proportion of larger polyps decreased more significantly in females than in males. This is the first demonstration that DHA inhibits intestinal polyposis induced by an Apc mutation at both its formation and growth.
Carcinogenesis 1995 Nov
PMID:Effects of docosahexaenoic acid (DHA) on intestinal polyp development in Apc delta 716 knockout mice. 758 74

The mutation and deletion of APC, MCC genes in human esophageal cancer were analyzed by PCR amplification and direct sequencing assay. In PCR amplification analysis, one of 10 cases of esophageal cancer was found to have APC gene deletion in exon 11; one of 10 cases of EC was found to have MCC gene deletion in exon 12; one case of EC was found to have MCC gene deletion in exon 12. One of adjacent non-tumor tissue was also found to have deletion at exon 12 of MCC. In PCR direct sequencing analysis, two of 10 cases of EC were found to contain APC gene mutation in exon 11, two of 7 cases of EC were found to contain MCC genes mutation in exon 12. The results confirmed that mutation of APC and MCC genes exists in human esophageal cancer. It gives new clues to the understanding of carcinogenesis of human esophageal cancer. The mechanism of mutation or deletion of APC and MCC genes in EC needs further study.
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PMID:[Mutation of tumor suppressor genes APC and MCC in human esophageal cancer]. 765 96

Results of epidemiological studies have shown that nitrosamine-induced carcinogensis is involved in esophageal cancer in China. In order to demonstrate the mechanism at molecular level, Multiple tumor suppressor genes Rb, p53, APC and MCC in human fetus esophageal epithelium treated with NMBzA (in vitro) for 24 hours or three weeks and esophageal carcinoma induced by NMBzA were analyzed with PCR amplification and direct sequencing. In PCR amplification analysis. Rb, p53, APC and MCC deletions in esophageal carcinoma of human fetus induced by NMBzA were found, but no deletions of these genes was demonstrated in NMBzA-treated human fetal esophageal epithelium. PCR direct sequencing analysis revealed mutation of p53, Rb and MCC genes in human fetal esophageal epithelium treated with NMBzA for three weeks. The results first confirmed (in vitro) that nitrosamine can cause mutations and deletions of multiple tumor suppressor genes in human esophageal epithelium. The mutations of tumor suppressor genes in nitrosamine-induced esophageal carcinoma may occur in the early stage, while deletions in late stage of carcinogenesis.
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PMID:[Multiple tumor suppressor genes in esophageal carcinoma induced in human fetus esophageal epithelium by NMBzA]. 765 18

We screened 30 gastric adenomas and 72 gastric adenocarcinomas for four genetic alterations (mutations of the K-ras, APC, and p53 genes and loss of heterozygosity at the DCC genetic locus) which are known to occur during colorectal tumourigenesis. We used polymerase chain reaction (PCR) single-strand conformation polymorphism analysis to detect mutations. Loss of heterozygosity (LOH) at the DCC locus was ascertained directly by performing PCR on the variable number of tandem repeats within the gene. Mutations of the K-ras gene were not detected in any gastric adenoma or carcinoma. APC mutations were detected in 20 per cent (6/30) of the adenomas but in only 1.4 per cent (1/72) of the carcinomas. In contrast, the p53 gene was frequently mutated in carcinomas (35 per cent; 25/72), but not in adenomas. LOH at the DCC locus was a frequent occurrence in carcinomas (58 per cent; 11/19 informative cases) but was infrequent in adenomas (14 per cent; 1/7). Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas. The considerable differences in the incidences of genetic alterations between gastric adenoma and carcinoma indicate that the sequential development of gastric carcinoma from adenoma is uncommon in gastric carcinogenesis.
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PMID:The sequential accumulation of genetic alterations characteristic of the colorectal adenoma-carcinoma sequence does not occur between gastric adenoma and adenocarcinoma. 869 30

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

The objective of this study is to develop a hypothesis about the carcinogenesis of breast cancer from a descriptive analysis. This study is an application of the age-period-cohort model (APC model) on the mortality rate of breast cancer in Taiwan over the period from 1964 to 1991. Age-specific and age-adjusted mortality rates are described and then age, period, and cohort effects are separately analysed. (Female) breast cancer mortality data in Taiwan from 1964 to 1991 were abstracted from the annual reports of the Taiwan Provincial Department of Health. The population data in Taiwan from 1964 to 1991 were abstracted from the demographic data in Taiwan compiled by the Ministry of Interior, R.O.C. The results show that both age-adjusted and age-specific mortality rates of breast cancer are increasing over the study period and with birth cohorts. The bimodal pattern becomes more apparent in later periods. The Clemmensen's hook is five years later both in the descriptive study and the APC analysis. The findings suggest a possible role of later life overnutrition as the major period effed (promoter) and a change in reproductive behavior as the cohort effect (initiator). The application of the APC model also denotes the possible role of later life overnutrition and a change in reproductive behavior after the birth cohort of 1929. These findings may help us develop hypotheses of carcinogenesis of breast cancer.
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PMID:Age-period-cohort analysis of breast cancer mortality. 776 32


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