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

Tiazofurin and 8-Cl-cAMP are novel chemotherapeutic agents shown to be effective against various cancer cells in vitro and in vivo. They act through distinct mechanisms that might modulate the signal transduction pathway, which causes growth inhibition, differentiation and down-regulation of c-ras and c-myc oncogene expression. We examined the effects of tiazofurin and 8-Cl-cAMP on colony formation of HT-29 human colon cancer and BxPC-3 and PANC-1 human pancreatic cancer cell lines. The IC50 of 8-Cl-cAMP was 0.1 and 0.2 microM in the pancreatic and colon cancer cell lines, respectively, and tiazofurin yielded IC50s from 4 (PANC-1) to 18 microM (HT-29). Simultaneous incubation with 8-Cl-cAMP and tiazofurin had additive effects on the inhibition of colony formation in the three examined cell lines. These results indicate possible clinical usefulness of a combination of tiazofurin and 8-Cl-cAMP in the treatment of colon and pancreatic carcinomas.
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PMID:Action of tiazofurin and 8-Cl-cAMP in human colon and pancreatic cancer cells. 136 29

In addition to being regulated by a complex array of cis- and trans-acting factors, c-myc protooncogene expression may be modulated by antisense RNA transcripts. Our previous studies have determined that depletion of intracellular polyamines by alpha-difluoromethylornithine results in a marked decrease in the transcription of the human c-myc gene. Because of reports that antisense transcription occurs in the 5' and 3' regions of this gene, we used a genomic clone of the human c-myc gene to ascertain whether polyamine depletion might induce an antisense RNA transcript. These studies demonstrate that polyamine depletion of the human colon cancer cell line COLO 320 results in induction of an endogenous RNA transcript with high homology to the antisense strand of the second intervening sequence (PvuII-RsaI) of the c-myc gene. Furthermore, during such depletion, steady state levels of this transcript vary inversely to the sense direction c-myc RNA. RNase protection studies suggest that the antisense transcript may arise from a different gene locus than the c-myc gene. To further identify the origins of this RNA, a cDNA library was generated from size-selected RNA and screened with c-myc sequences. A 438-base pair cDNA was isolated with approximately 85% homology, to a 285-base region in the second intron of the c-myc gene. Computer homology analysis further reveals that a 120-base region within this cDNA also has approximately 85% homology to the antisense strands of a number of genes, including the growth-related genes, N-myc, p53, and thymidine kinase. These studies provide the initial characterization of an endogenous antisense RNA transcript which could influence cell growth by modulating the expression of c-myc and other genes.
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PMID:Characterization of an endogenous RNA transcript with homology to the antisense strand of the human c-myc gene. 137 45

The mitogenic role of estradiol on the growth of colon cancer was examined in mice. Sham-operated or ovariectomized mice were injected with cancer cells and received estradiol treatment. Tumor growth was noted: tumor weights were higher in female than male mice. The growth of the tumors was least in ovariectomized mice and highest in estradiol-treated ovariectomized mice. Tumor messenger RNA (mRNA) levels for ornithine decarboxylase (ODC) and proto-oncogenes c-myc, c-fos, and H-ras were examined. Two transcripts (2.2 and 2.7 kilobase pairs) of ODC were observed. The steady-state mRNA levels for ODC paralleled the changes observed in the weight of the tumors in all groups of animals. Less dramatic changes were observed in c-myc mRNA levels. No significant differences were observed in the mRNA levels for H-ras and c-fos. It thus appears likely that an increase in the ODC mRNA levels and, to a lesser extent, an increase in c-myc mRNA levels may be some of the important mechanisms by which estradiol mediates its growth effects on colon cancer cells in vivo.
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PMID:Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. 145 76

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

Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.
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PMID:Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer. 169 76

Ras gene family (c-Ha, Ki, N ras) and c-myc proto-oncogenes were analyzed in seven colonic and three gastric adenomatous polyps obtained from a patient with Turcot's syndrome. The rearrangement and amplification as well as overexpression of c-Ha ras gene in one colonic adenomatous polyp were determined. The amplified c-Ha ras gene in this polyp revealed larger fragments of BamHI, PstI and SacI than those in the normal colonic mucosa from the same patient. But, such abnormalities were not observed in other polyps. No abnormalities of c-Ki ras, c-N ras or c-myc gene were observed in any polyps. These results suggest that the alternations of c-Ha ras gene in this patient may not be responsible for the adenomatous change, but may be related to the transition from adenoma to carcinoma of the colon.
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PMID:Rearrangement, amplification and overexpression of c-Ha Ras gene in premalignant lesion of Turcot's syndrome. 170 48

In order to understand the cellular events associated with cell death after the formation of topoisomerase II-DNA cleavable complexes, we compared the induction of endonucleolytic DNA fragmentation by etoposide and its more potent analog, teniposide (VM-26) in the human cell lines HT-29 and HL-60. A new filter-binding assay is described, which allows rapid quantification of nonprotein-linked DNA fragmentation involved in apoptosis. Both cell lines showed similar loss of colony formation ability following 30 min of treatment with various VM-26 concentrations even though the initial topoisomerase II-mediated DNA single-strand break frequency was higher in HL-60 cells. DNA repair studies following drug removal indicated that VM-26-induced DNA breaks reversed rapidly and completely in HT-29 cells, while in HL-60 cells, the initial lesions persisted at and above 5 microM VM-26. In both cell lines, topoisomerase II cleavage complexes, as measured by DNA-protein cross-links by alkaline elution, reversed rapidly and completely within 2-3 h. Secondary DNA fragmentation resembling chromatin endonucleolytic cleavage by apoptosis could be detected in HL-60 cells 3 h after VM-26 or etoposide treatment but not in HT-29 cells. Secondary DNA fragmentation was also induced in the human colon cancer cell lines COLO 320, which have c-myc amplification. Since HL-60 cells also have c-myc amplification and HT-29 do not, it is possible that c-myc overexpression may be involved in secondary DNA fragmentation. Finally, our results indicate heterogeneity of cell death mechanisms after exposure to topoisomerase II inhibitors among human cancer cell lines.
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PMID:Differential induction of secondary DNA fragmentation by topoisomerase II inhibitors in human tumor cell lines with amplified c-myc expression. 193 88

Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented.
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PMID:Oncogenes and suppressor genes: their involvement in colon cancer. 222 91

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. 228 1

The biosynthesis of the polyamines, putrescine, spermidine and spermine, is temporally linked with expression of many growth related genes. Our previous studies have shown that generalized polyamine depletion of the human colon cancer cell line COLO 320 by 2-difluoromethylornithine is associated with decreased transcription of the c-myc, c-fos, and ornithine decarboxylase (ODC) genes. In the current study, the role of individual polyamines was further defined by the use of a specific inhibitor of spermidine synthase, S-adenosyl-1,8, diamino-3-thio-octane (AdoDATO), and a spermine analogue, N1,N12 bis(ethyl)spermine. Our data demonstrate that depletion of spermidine results in a 60-90% decrease in c-myc mRNA steady state levels. In contrast, c-fos mRNA levels are decreased only when both spermidine and spermine are diminished. Furthermore, ODC mRNA levels are increased when all polyamines are decreased by DFMO, but are unaffected by a selective reduction in intracellular spermidine levels by AdoDATO. These studies suggest that individual polyamines may have a selective role in the expression of specific growth related genes.
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PMID:Modulation of growth gene expression by selective alteration of polyamines in human colon carcinoma cells. 251 47


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