Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia, atypical hyperplasia, early-stage cancer and advanced cancer was 16.7%, 31.2%, 50.0%, and 32.2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of H-ras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G-->T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P < 0.05, P < 0.01, P < 0.01, respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.
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PMID:The role of ras gene mutation in gastric cancer and precancerous lesions. 1080 11

The first case of cancer in inflammatory bowel disease (IBD) was reported at The Mount Sinai Hospital in 1925 in a patient with ulcerative colitis (UC). In 1956, carcinoma of the jejunum was described in a patient with regional enteritis (Crohn's disease [CD]). IBD cancers are preceded by dysplasia, and the relative risk increases with duration of the IBD. CD cancers are more proximally distributed than are UC cancers. Both tend to occur at the site of the overt disease and both develop at earlier ages (47 UC, 50 CD) than in the de novo colorectal cancer (70 years). The absolute cumulative colon cancer frequencies (8% UC, 7% CD) are identical after 20 years, emphasizing the importance of regular surveillance in both types of IBD. Moreover, the increased risk of colon cancer exists in patients with CD even when CD is confined to the small bowel, and patients with IBD have increased risks of developing extraintestinal and reticuloendothelial tumors in both CD and UC, as well as ano-vulval and malignant melanoma in CD. Colitic colorectal cancers are often diffuse, extensive, multiple and right-sided with insidious presentation. The prognosis is no worse after operation than that of de novo colon cancer. Most small bowel cancers in CD are adenocarcinomas, rather than sarcomas, and present at a younger age, more diffusely and more distally than de novo cancers, usually making them undiagnosable at a curable early stage; indeed, two-thirds present with intestinal obstruction. Strictures of the colon are common in patients with IBD, and they have a 10-fold risk for colon cancer, 30-fold for UC, and 6-fold for CD. The risk increases with disease duration. The indications for surgery are absolute, relative and incidental, and the procedures include segmental resection, total proctocolectomy, subtotal colectomy and palliative procedures.
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PMID:Cancer in inflammatory bowel disease. 1082 8

The human GNAI2 gene coding for G protein, Galphai2, is located on chromosome 3p21 in proximity to the region where an inflammatory bowel disease (IBD) locus has been suggested. Galphai2-deficient mice develop a lethal diffuse colitis that resembles human ulcerative colitis (UC) and frequently progresses to colon adenocarcinoma. Furthermore, the human GNAI2 gene is subject to point mutations at certain positions, including three at codon 179, all of which have been reported in human endocrine tumors. In order to evaluate the possible involvement of this gene in IBD pathogenesis, we have examined GNAI2 codon 179 sequences in 28 familial IBD patients, including 13 UC, 15 Crohn's disease (CD), and 7 patients with colon cancer/dysplasia, from 12 multiplex IBD families. The wildtype codon 179, CGC for arginine, plus the first G of the codon 180 engender a sequence recognizable by the enzyme BstUI. Mutations, therefore, can result in the abrogation of BstUI digestion of polymerase chain reaction (PCR) products containing the codon 179. Using the PCR-restriction fragment length polymorphism technique, all 28 IBD patients, including those with colon cancer, and 14 non-IBD family members show a BstUI-cleavable PCR-banding pattern indicating the presence of wildtype codon 179. We conclude that, in the familial IBD and colon cancer/dysplasia patients studied, there is no detectable mutation in the codon 179 of the GNAI2 gene.
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PMID:Absence of GNAI2 codon 179 oncogene mutations in inflammatory bowel disease. 1083 69

Cyclooxygenase (COX) is a key enzyme in the synthesis of prostaglandins from arachidonic acid. Much evidence, including that from epidemiological and experimental studies, suggests that the inducible form of COX, COX-2, is increased in colon tumor tissues and is involved in colon cancer tumorigenesis. To determine the significance of COX-2 in tumorigenesis in the urinary bladder, the expression of COX-2 in transitional cell carcinoma and preneoplastic lesions of the bladder was examined. Tumor specificity of COX-2 immunoblotting was 100% in 12 of 35 (34%) tumors, but in 0 of the 10 normal urothelia samples. COX-2 expression was significantly correlated with tumor stage in 9 of 20 (45%) muscle-invasive (pT2-4) tumors and in 3 of 15 (20%) superficially invasive (pT1) tumors (P < 0.05). Immunohistochemical examination revealed that 13 of 14 (93%) samples of carcinoma in situ (CIS), which may be the precursor of muscle-invasive-type tumors, expressed COX-2, whereas 10 of 21 (48%) samples of dysplasia, which may be the precursor of both superficially invasive and muscle-invasive tumors, expressed COX-2. From the expression profile of COX-2 in these various urothelia, it is suggested that COX-2 is involved in the development of transitional cell carcinoma of the urinary bladder, especially that of muscle-invasive tumors via CIS. Furthermore, COX-2 may be a therapeutic target for CIS because of the high expression rate of COX-2 in CIS lesions.
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PMID:Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. 1087 95

It is well known that patients with long-standing inflammatory bowel disease (IBD), ulcerative colitis (UC) or Crohn's disease(CD) are at increased risk for developing colorectal cancer (CC). Before adenocarcinoma develops, the intestinal epithelium progress through a premalignant phase of dysplasia, which can be identified via mucosal biopsy and routine tissue histology. Surveillance colonoscopy and prophylactic colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Many physicians suggests that surveillance for extensive colitis should begin after 8 to 10 years of disease, and surveillance for left-sided colitis should begin after 15-20 years. Colonoscopy is recommended with frequent biopsies, at least every 10 cm in all four quadrants, and with biopsy of any suspicious lesion. The emerging field of colon cancer genetics has identified several important tumor markers that have potential to improve sensitivity for detection of early neoplasia.
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PMID:[Premalignant and malignant changes in idiopathic inflammatory bowel disease]. 1095 65

The human heparanase gene, an endo-beta-glucuronidase that cleaves heparan sulfate at specific intrachain sites, has recently been cloned and shown to function in tumor progression and metastatic spread. Antisense digoxigenin-labeled heparanase RNA probe and monoclonal anti-human heparanase antibodies were used to examine the expression of the heparanase gene and protein in normal, dysplastic, and neoplastic human colonic mucosa. To our knowledge, this is the first systematic study of heparanase expression in human colon cancer. Both the heparanase gene and protein were expressed at early stages of neoplasia, already at the stage of adenoma, but were practically not detected in the adjacent normal-looking colon epithelium. Gradually increasing expression of heparanase was evident as the cells progressed from severe dysplasia through well-differentiated to poorly differentiated colon carcinoma. Deeply invading colon carcinoma cells showed the highest levels of the heparanase mRNA and protein associated with expression of both the gene and enzyme by adjacent desmoplastic stromal fibroblasts. A high expression was also found in colon carcinoma metastases to lung, liver, and lymph nodes, as well as in the accompanying stromal fibroblasts. Moreover, extracts derived from tumor tissue expressed much higher levels of the heparanase protein and activity as compared to the normal colon tissue. In all specimens, the heparanase gene and protein exhibited the same pattern of expression. These results suggest a role of heparanase in colon cancer progression and may have both prognostic and therapeutic applications.
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PMID:Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. 1102 21

The progressive accumulation of genetic changes in both oncogenes and tumor-suppressor genes parallels the clinical and histopathologic progression from normal colonic epithelium through benign adenomas to frank colon cancer. A similar progression is postulated in the transition of normal squamous epithelium to metaplastic mucosa (Barrett's esophagus) and subsequently through dysplasia to adenocarcinoma of the esophagus. A common link between colorectal cancer and Barrett's esophagus or esophageal carcinoma might be explained by either genetic predisposition or common environmental risk factors. The multistep nature of oncogenesis is most directly illustrated by molecular experimental genetic studies which demonstrate that the progression from adenoma to colon carcinoma results from the accumulation of molecular genetic alterations involving mainly 3 factors: activation of oncogenes; inactivation of tumor-suppressor genes; and abnormalities in genes involved in DNA mismatch repair. Changes in oncogenes encoding four distinct groups of proteins (peptide growth factors, protein kinases, signal transducing proteins, and nuclear transcriptional regulatory proteins) can contribute to colon carcinogenesis. In addition, various carcinogens may act at different stages of this model, affecting somatic mutations and resulting in additional genetic alterations. Other promoters, including hormones, may enhance the likelihood of these events through the stimulation of the rate of cell turnover. Diseased detoxification processes may also play a role in carcinogenesis.
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PMID:New concepts of molecular biology for colon carcinogenesis. 1110 Mar 35

Aberrant crypt foci (ACF) are putative early preneoplastic lesions of colon cancer. To date, many different ACF parameters have been measured as indicators of degree of colon cancer risk. It has been suggested that ACF producing sialomucins (SIM) may be more advanced types of ACF than those producing sulphomucins (SUM), but little data are available to support this. The objective of this experiment was to see if SIM ACF, as observed in whole mount colons, are different from other ACF and surrounding normal colonic crypts in terms of their rate of cell proliferation and degree of dysplasia. Results showed that all ACF had a higher rate of cell proliferation than normal crypts and that SIM ACF had higher cell proliferation in the top regions of the crypt, higher phih index of cell proliferation, higher degree of dysplasia, greater size and increased degree of luminal alterations than SUM ACF. We conclude that SIM ACF, as observed in whole mount colons, have more alterations and are more advanced towards tumorigenesis than SUM ACF and may be a better predictor of colon cancer risk than other measures of ACF.
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PMID:Sialomucin production in aberrant crypt foci relates to degree of dysplasia and rate of cell proliferation. 1124 14

CpG island hypermethylation is a mechanism of gene silencing that can be usurped by neoplastic cells to inactivate undesirable genes. In the colon, hypermethylation often starts in normal mucosa as a function of age and is markedly increased in cancer. To test the hypothesis that subjects at increased risk of colon cancer have higher levels of methylation in their nonneoplastic mucosa, we studied methylation patterns of five genes in the normal and dysplastic mucosa of patients with ulcerative colitis (UC), a condition associated with a marked increased risk of colon cancer. One gene (Mlh1) was unmethylated in all tissues examined. All four remaining genes had low but detectable levels of methylation in the epithelium of UC patients without evidence of dysplasia, and this methylation was not different from non-UC controls. By contrast, all four genes were highly methylated in dysplastic epithelium from high-grade dysplasia (HGD)/cancer patients with UC; methylation in HGD versus controls averaged 40.0% versus 7.4% (P = 0.00003) for ER, 44.0% versus 3.0% (P < 0.00003) for MYOD, 9.4% versus 2.4% (P = 0.03) for p16 exon 1, and 57.5% versus 30.6% (P = 0.01) for CSPG2. Importantly, three of the four genes were also highly methylated in the normal appearing (nondysplastic) epithelium from these same HGD/cancer patients, indicating that methylation precedes dysplasia and is widespread in these patients. Compared with controls, methylation averaged 20.1% versus 7.2% (P = 0.07) for ER, 18.4% versus 3.0% (P < 0.008) for MYOD, and 7.9% versus 2.4% (P = 0.007) for p16 exon 1. These results are consistent with the hypothesis that age-related methylation marks (and may lead to) the field defect that reflects acquired predisposition to colorectal neoplasia. Furthermore, the data suggest that chronic inflammation is associated with high levels of methylation, perhaps as a result of increased cell turnover, and that UC can be viewed as resulting in premature aging of colorectal epithelial cells.
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PMID:Accelerated age-related CpG island methylation in ulcerative colitis. 1132 21

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus.
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PMID:Cyclooxygenase-2 expression in Barrett's esophagus. 1133 Apr 14


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