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

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.
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PMID:Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma. 164 45

Over 30 epidemiologic studies have evaluated cancer risks associated with formaldehyde exposure. Excesses were reported for several sites, leukemia and cancers of the nasal cavities, nasopharynx, lung, and brain generating the greatest interest. The excesses of leukemia and brain and colon cancer found among professionals may not be related to formaldehyde exposure, since similar excesses were not observed among industrial workers. Inconsistencies among and within studies impede assigning formaldehyde a convincing causal role for the excesses of lung cancer found among industrial workers. A causal role for formaldehyde is the most probable for cancers of the nasopharynx and, to a less extent, the nasal cavities. Evidence of exposure-response relationships, the fact that direct contact with formaldehyde may occur at these upper respiratory sites, and the consistency of these findings with experimental studies make this assumption highly probable.
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PMID:Epidemiologic evidence on the relationship between formaldehyde exposure and cancer. 228 88

A suspicion of an excess cancer risk in automotive model shops prompted the Industrywide Studies Branch, NIOSH, to conduct a proportionate mortality study and an industrial hygiene characterization of operations in these shops. The mortality study showed a statistically significant excess proportion of deaths due to colon cancer and leukemia (for woodshops only). The materials used in the model shops include various natural woods, laminated woods, plastics, resins, varnishes, putties and paints. Personal breathing zone samples were collected for total and respirable dust, amines, various hydrocarbons (including styrene, and toluene), formaldehyde, and nitrosamines. Particle size distribution studies were conducted on the wood dust and bulk airborne samples of dusts were subjected to various mutagenicity test systems. Work practices, ventilation and general housekeeping were checked. Total wood dust samples ranged from 0.03 to 25 mg/m3 with an average around 1.0 mg/m3. The percent respirable dust ranged from 19 to 38% as measured with Andersen impactors. Solvent exposure samples ranged from non-detectable to about 10% of the OSHA Permissible Exposure Levels. Relevant recommendations for improvement of contaminant control were made.
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PMID:Industrial hygiene characterization of automotive wood model shops. 388 Jan 87

To evaluate the potential carcinogenic effects of formaldehyde, we examined the proportionate mortality experience of embalmers licensed to practice in California. Mortality was significantly elevated for total cancer, arteriosclerotic heart disease, and suicide, whereas significant deficits were noted in mortality from diseases of the respiratory and genitourinary systems. Deaths from cancers of the brain, colon, and prostate and leukemia were significantly higher than expected. No increased mortality was seen for cancers of the respiratory tract, including the nasal passages, where an effect might be expected based on animal studies. A parallel mortality survey of embalmers from New York State showed similar findings, with excesses of brain tumors, leukemia, colon cancer, arteriosclerotic heart disease, and cirrhosis. Further investigation is needed to determine whether any of these outcomes is related to formaldehyde exposure.
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PMID:Cancer and other causes of death among embalmers. 646 19

The mechanism is discussed by which certain nitrosamines induce esophageal papillomas and squamous cancer in rats, and some evidence is presented for the view that nitrosamines also induce the same cancer in humans, especially in China and South Africa. Studies on the metabolism of nitrosamines by cytochrome P450 isozymes in rat and human esophagus, including the activation reactions of formaldehyde and pentaldehyde formation from methyl-n-amylnitrosamine (MNAN), are reviewed. These reactions are catalyzed by microsomes from the rat and human esophagus, probably because these microsomes contain specific cytochrome P450 isozymes. Evidence is reviewed for the occurrence of nitrosamines related to MNAN in fungus-infected corn. The incidence of esophageal adenocarcinoma is rising in Western countries. The precursor lesion, Barrett's esophagus, is associated with colon cancer, suggesting a role for bile salts in the induction of the esophageal tumor. Studies are described in which rats were subjected to esophago-duodenostomy (joining the duodenum to the esophagus) and then treated with nitrosamines that normally induce esophageal squamous cancer. Adenocarcinomas of the lower esophagus were induced as well as Barrett's esophagus (under one set of conditions). Feeding a high-fat diet with this system increased the incidence of esophageal adenocarcinoma. This tumor was not induced when the operation was changed to esophago-gastroplasty (widening the lower esophageal sphincter). These results support a role of reflux of duodenal contents (including bile and pancreatic juice) rather than of gastric contents in the etiology of human esophageal adenocarcinoma.
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PMID:Metabolism of carcinogenic nitrosamines in the rat and human esophagus and induction of esophageal adenocarcinoma in rats. 811 18

Extrapulmonary tuberculosis is more frequent in hemodialysis patients than in the general population but intestinal localization is an unusual presentation of this infectious disease. We report a 60 year old patient on regular hemodialysis with intestinal tuberculosis masquerading as colon cancer. The patient presented with rectal bleeding, abdominal pain and fever and the radiological findings were compatible with ileocecal carcinoma. After surgery histological examination showed non-caseating granulomas but mycobacterial culture was not available. We performed a colonoscopy and obtained a biopsy of colonic mucosa for culture and other analyses. We identified acid-fast bacilli with Ziehl-Neelsen staining of formaldehyde preserved, paraffin-embedded tissue from the hemicolectomy and the colonic mucosal biopsy. Treatment with isoniazid, rifampicin and pyrazinamide for nine months was successful and well tolerated. Intestinal tuberculosis is a rare entity that we must keep in mind in a patient with abdominal pain, unexplained fever, digestive bleeding and particularly with a positive tuberculin reaction. When culture is not possible we can obtain intestinal samples by colonoscopy and use appropriate staining of paraffin-embedded tissues.
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PMID:[Ileocecal tuberculosis during hemodialysis simulating carcinoma of the colon]. 1147 13

In addition to its action as a topoisomerase II poison, mitoxantrone is activated by formaldehyde to bind DNA, forming DNA-adducts specifically at 5'CpG and CpA sequences, with an enhancement of adducts at methylated CpG sites. The butyric acid prodrug, AN-9 (pivaloyloxymethyl butyrate), releases formaldehyde upon cellular hydrolysis and our previous studies have shown that mitoxantrone acts synergistically with AN-9 in cytotoxicity assays. In this paper, we investigated the impact of methylation levels in the cell on mitoxantrone-induced cytotoxicity using the colon cancer cell line HCT116 and its derived DNA methyltransferase (DNMT) 1 and DNMT 3a knockout (DKO8) cell line. We found that decreased methylation levels in the DNMT-null cells led to at least a 2-fold reduction in mitoxantrone-induced cytotoxicity. Next, we studied the impact of mitox-antrone alone, and in combination with AN-9, on hypermethylated genes and their mRNA expression in breast cancer cells. Using methylation-specific PCR and RT-PCR, we found that mitoxantrone treatment of breast cancer cell lines resulted in demethylation of the 14.3.3s, Cyclin D2 and ERa genes, followed by re-expression of their mRNA. The effect of mitoxantrone on re-expression of key genes involved in cell cycle regulation, and ensuing death of the cells may be an additional, previously undiscovered mechanism of action of mitoxantrone.
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PMID:Mitoxantrone mediates demethylation and reexpression of cyclin d2, estrogen receptor and 14.3.3sigma in breast cancer cells. 1287 62

The adenomatous polyposis coli gene (APC gene) originally was identified as a tumor suppressor gene in colon cancer. We reported previously that APC is mutated and/or deleted in primary oral squamous cell carcinoma (OSCC) tissues and suggested that loss of APC function contributes to carcinogenesis in the oral region. In this study, we examined 50 OSCC tissue samples, which had been fixed in 10% buffered formaldehyde solution and embedded in paraffin, and eight cell lines, which were derived from OSCC, to analyze the expression level of the APC gene. Significant down-regulation of APC was detected by immunohistochemistry in 15 (30.0%) of 50 tissue samples and by the reverse transcriptase-polymerase chain reaction in five (62.5%) of eight cell lines. We then investigated the status of APC gene promoter methylation and restoration of the APC gene mRNA. Hypermethylation of the APC promoter CpG island was detected in two of eight (25%) OSCC-derived cell lines, and APC gene mRNA was restored in all OSCC-derived cell lines showing down-regulation of gene expression (n=5) after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Thus, the contribution of down-regulated APC expression to the development of human OSCC was about 30%, and hypermethylation of the gene promoter CpG island was confirmed to be a significant mechanism of inactivation of the APC gene in oral carcinogenesis.
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PMID:Status of reduced expression and hypermethylation of the APC tumor suppressor gene in human oral squamous cell carcinoma. 1575 20

The mechanism of doxorubicin is compared with that of doxazolidine, a doxorubicin-formaldehyde conjugate. The IC(50) for growth inhibition of 67 human cancer cell lines, but not cardiomyocytes, is 32-fold lower with doxazolidine than with doxorubicin. Growth inhibition by doxazolidine correlates better with growth inhibition by DNA cross-linking agents than with growth inhibition by doxorubicin. Doxorubicin induces G2/M arrest in HCT-116 colon cancer cells and HL-60 leukemia cells through a well-documented topoisomerase II dependent mechanism. Doxazolidine fails to induce a G2/M arrest in HCT-116 cells but induces apoptosis 4-fold better than doxorubicin. The IC(50) for doxazolidine growth inhibition of HL-60/MX2 cells, a topoisomerase II deficient derivative of HL-60 cells, is 1420-fold lower than the IC(50) for doxorubicin, and doxazolidine induces apoptosis 15-fold better. Further, doxazolidine has little effect in a topoisomerase II activity assay. These data indicate that doxorubicin and doxazolidine induce apoptosis via different mechanisms and doxazolidine cytotoxicity is topoisomerase II independent.
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PMID:Doxazolidine induction of apoptosis by a topoisomerase II independent mechanism. 1769 16

New and more potent prodrugs of the 5-fluorouracyl family derived by hydroxymethylation or acyloxymethylation of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione (tegafur, 1) are described. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity, and anticancer activities in vitro and in vivo, superior to those of tegafur. 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1 H,3 H)-pyrimidinedione (tegafur, 1), the oral prodrug of 5-FU, has been widely used for treatment of gastrointestinal malignancies with modest efficacy. The aim of this study was to develop and characterize new and more potent prodrugs of the 5-FU family derived by hydroxymethylation or acyloxymethylation of tegafur. Comparison between the effect of tegafur and the new prodrugs on the viability of a variety of cancer cell lines showed that the IC50 and IC90 values of the novel prodrugs were 5-10-fold lower than those of tegafur. While significant differences between the IC50 values of tegafur were observed between the sensitive HT-29 and the resistant LS-1034 colon cancer cell lines, the prodrugs affected them to a similar degree, suggesting that they overcame drug resistance. The increased potency of the prodrugs could be attributed to the antiproliferative contribution imparted by formaldehyde and butyric acid, released upon metabolic degradation. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity and anticancer activities in vitro and in vivo, superior to those of tegafur.
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PMID:Novel prodrugs of tegafur that display improved anticancer activity and antiangiogenic properties. 1816 51


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