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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BD-II and BD-IX male and female rats received weekly subcutaneous (s.c.) injections of 15 mg/kg 1,2-dimethylhydrazine dihydrochloride (DMH) beginning at either 35, 120 or 210 days of age and continuing for 20 weeks. Control animals received only the DMH vehicle. Additional BD-II and BD-IX male and female rats of the three age groups were gonadectomized at 21, 106 and 196 days. Beginning 14 days after gonadectomy, the rats received 15 mg/kg of DMH by s.c. injection once a week for 20 weeks. Animals were sacrificed 35 weeks after the initial DMH injection. Control rats of the appropriate age and sex did not develop colon tumors. BD-IX rats are apparently more sensitive to DMH than BD-II rats. The incidence of DMH-induced cancer is less in females than in males in both the BD-II and BD-IX animals. Gonadectomy does not affect cancer incidence in either BD-II males or females nor in the BD-IX females but reduced the incidence in BD-IX males exposed initially at either 120 or 210 days. Administration of androgen to castrate BD-IX males (120-day-old group) increases the incidence of colon cancer to that approaching the intact animal but has little effect in the BD-II castrate male. These data suggest a genetically influenced susceptibility to DMH-induced colon carcinogenesis between BD-II and BD-IX rats. Furthermore, a sex difference is evident in both BD lines but age appears to be a factor only in older BD-IX females. Apparently, androgens influence DMH-induced tumorigenesis in BD-IX males only if the initial exposure of DMH occurs after sexual maturity.
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PMID:Influence of gonadal hormones and age on 1,2-dimethylhydrazine-induced colon carcinogenesis. 92 91

Hereditary adenomatosis of the colon and rectum (ACR) and its Gardner's syndrome variant, an autosomal dominant trait, indicate a propensity for neoplasia. The present study describes the growth abnormalities of cultured human skin fibroblasts derived from normal-appearing cutaneous biopsies of ACR genotypes and a portion of the clinically asymptomatic ACR progeny, first filial generation, and their differential susceptibility to transformation by Kirsten murine sarcoma virus. These skin fibroblasts, but not cells derived from unaffected individuals, showed lack of contact inhibition, decreased serum requirement for growth, elevated levels of plasminogen activator, and alterations in the intracellular distribution of actin cables; they did not, however, grow in the absence of anchorage, nor did they form palpable tumors in congenitally athymic BALB/c nu/nu mice, and they were normal with regard to cholesterol feedback regulation. Skin fibroblasts from ACR subjects were 100- to 1000-fold more susceptible to transformation by the Kirsten murine sarcoma virus than were normal cells. The virally transformed skin fibroblasts were anchorage-independent and formed tumors in athymic mice. These growth abnormalities represent steps in the changing phenotypic expression of cells undergoing neoplastic transformation. Identification of abnormal expressions associated with oncogenesis may facilitate their use as diagnostic indices for the detection of latent forms of colon cancer in man.
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PMID:Phenotypic markers in human skin fibroblasts as possible diagnostic indices of hereditary adenomatosis of the colon and rectum. 92 93

The three ras genes code for proteins with a putative role in cellular signal transduction. They belong to a larger family of small guanosine-triphosphate (GTP)-binding proteins. The ras proteins acquire transforming activity when amino acids are substituted at one of a few specific sites, as a result of a point mutation in the gene. In about one third of adenocarcinomas of the lung, a K-ras mutation is present in codon 12 of the gene. Patients with early stages of K-ras mutation-positive tumors have a very unfavorable prognosis, even if apparently radical resection of the tumor has taken place. K-ras mutations are very rare among nonsmokers, and it is reasonable to assume that carcinogens in tobacco smoke directly cause the mutation. The types of ras mutations found in lung cancer are different from those in gastrointestinal malignancies. Colon cancer is mainly associated with mutations leading to substitution of the normal glycine at amino acid position 12 of K-ras by either valine or aspartic acid, and mutations in N-ras are not exceptional. In contrast, the predominant mutation in lung cancer leads to substitution of cysteine in codon 12. Several other members of the ras gene superfamily are also expressed in human lung cancer, but a possible relationship with lung tumorigenesis remains to be established.
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PMID:The ras gene family in human non-small-cell lung cancer. 132 34

Mutations of proto-oncogenes and tumor-suppressor genes lead to neoplastic development. Some germline mutations of these genes increase the tumor susceptibility of their carriers, but the relationship between genes controlling tumor susceptibility and the known oncogenes and tumor-suppressor genes remains unelucidated. Moreover, as tumor susceptibility in mouse is controlled by multiple genes, their identification has been virtually impossible. We therefore developed a new system, the recombinant congenic strains (RCS), which separates individual susceptibility genes into different RC strains, thus facilitating their analysis. To map genes controlling the development of colon cancer, we used the Balb/c-c-STS (CcS/Dem) RC strains. Owing to several unidentified genes, Balb/cHeA mice are relatively resistant and STS/A mice highly susceptible to 1,2-dimethylhydrazine-(DMH)-induced colon adenocarcinomas. Each CcS/Dem strain carries a different subset of about 12.5% of genes of the STS strain on the Balb/c background, and individual STS susceptibility genes became segregated into different RC strains. Using CcS-19, one of the highly susceptible RC strains, we mapped a novel colon tumor susceptibility gene, Scc-1, different from the oncogenes and tumor-suppressor genes known to be involved in colon tumorigenesis, in the vicinity of CD44 (Ly-24, Pgp-1) on chromosome 2. The mapping of the Scc-1 gene indicates that the RCS system can be used to map and study the presently unknown genes which control cancer development.
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PMID:Scc-1, a novel colon cancer susceptibility gene in the mouse: linkage to CD44 (Ly-24, Pgp-1) on chromosome 2. 134 18

Tumorigenesis is a heterogeneous process that occurs over a relatively long time span, progressing from a single cell through intermediate stages to give rise to a tumour that becomes more aggressive over time. Recent discoveries have begun to define the molecular events that underlie this progression in breast and colon cancer.
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PMID:Genetic basis of cancer. 136 53

Epidemiological and experimental studies have shown that increased intake of plant foods and decreased meat consumption are correlated with a decreased risk for colon cancer. Many components of plant foods are suggested to mitigate colon carcinogenesis, including vitamins, minerals, and dietary fiber. Phytosterols are a common component of plant foods consumed in relatively large quantities by vegetarians, who are at lower risk for colon cancer development than individuals on a Western diet low in phytosterols. In addition, phytosterols have been shown experimentally to inhibit colon cancer development. Dietary cholesterol, although structurally similar to the phytosterols, is correlated etiologically to the incidence of colon cancer, with changes in serum cholesterol levels and fecal bile acid profiles suggested to increase susceptibility to colon tumorigenesis. The objective of this paper is to discuss the effect of dietary phytosterols on cholesterol and bile acid metabolism and how these effects may lead to a decreased risk for colon cancer development.
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PMID:The role of dietary phytosterols in colon carcinogenesis. 140 45

Since it was first suggested that high dietary fat is a risk factor in colon cancer, there have been several studies to test this hypothesis. Epidemiologic studies suggested a positive association between dietary fat and colon cancer. Laboratory animal model studies demonstrated that not only the amount of fat, but also types of fat differing in fatty acid composition are important determining factors in colon tumor development. Chemically-induced colon tumor incidence was increased in rats fed the semipurified diets containing 23% corn oil, safflower oil, lard or beef tallow (high-fat) as compared to those fed 5% corn oil, safflower oil, lard or beef tallow diets (low-fat). Diets containing 23% coconut oil, olive oil or fish oil, or high-fat diets containing varying levels of trans fat, had no colon tumor-enhancing effect compared to their respective low fat diets. The stage at which the effect of dietary fat is exerted appears to be mostly during the post-initiation phase of colon carcinogenesis. Lack of a colon tumor enhancing effect of dietary fish oil is observed both during the initiation and postinitiation phases. The mechanisms by which various dietary fats increase colon carcinogenesis are not fully understood. In most instances, however, the high-fat diet appears to enhance tumorigenesis through elevation of agents, such as secondary bile acids, that act as promoters of tumor development. Lack of colon tumor promotion by dietary fish oil and trans fat appears to be mediated through their effect on mucosal ornithine decarboxylase activity, colonic secondary bile acids and/or prostaglandin synthesis.
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PMID:Dietary fat and colon cancer: animal model studies. 143

Tumorigenesis is thought to be a multistep process in which genetic alterations accumulate to bring about the neoplastic phenotype. Colorectal tumors appear to arise as a result of the mutational activation of oncogenes coupled with the inactivation of several tumor suppressor genes. We have found frequent allelic deletions of specific portions of chromosomes 5, 17, and 18 which presumably harbor suppressor genes. The target of allelic loss events on chromosome 17 has been shown to be the p53 gene, which is frequently mutated not only in colon cancer but in several other tumor types as well. Candidate suppressor genes have also recently been identified on chromosomes 18 and 5. The DCC gene on chromosome 18q encodes a protein with significant sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. Alterations of this gene may interfere with normal cell growth and differentiation by disrupting cell-cell or cell-substrate interactions. Two genes (MCC and APC) on chromosome 5q have also recently been identified and partially cloned. These genes are located in a region tightly linked to familial adenomatous polyposis (FAP). While MCC mutations have been found only in sporadic colon tumors, APC mutations have been identified in sporadic tumors as well as the germline of patients with FAP. Studies are currently in progress to increase our understanding of how alterations of these genes affect colorectal tumor cell growth.
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PMID:Suppressor gene alterations in the colorectal adenoma-carcinoma sequence. 146 93

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
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PMID:Oncogenesis in ovarian cancer. 150 89

We have been studying a rat model of colon cancer in which tumors are induced by direct application of N-methyl-N-nitrosourea (MNU) to discrete areas of the colonic mucosa for a limited period of time. Activation of the ras genes by point mutation has been observed in many experimental tumors, including tumors induced by MNU. To detect potential activating point mutations in the H-ras and K-ras oncogenes in MNU-induced rat colon tumors, DNA samples from 40 adenomas, nine carcinomas, and 14 histologically normal tissue samples from 14 rats--as well as from 16 foci induced on NIH3T3 cells by tumor DNAs--were amplified by the polymerase chain reaction and hybridized with allele-specific oligonucleotide probes. No H-ras point mutations were observed in any of these samples. We did detect K-ras point mutations, however, in four primary tumours--one adenoma (2.5%) and three carcinomas (33%); these mutations were all G----A transitions at the second nucleotide of codons 12 and 13. The absence of detectable ras mutations from the majority of tumors suggests that, in contrast to other animal models utilizing MNU, tumorigenesis in MNU-induced rat colon tumors may predominantly involve activation of genes other than ras.
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PMID:K-ras oncogene mutations in rat colon tumors induced by N-methyl-N-nitrosourea. 173 72


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