Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis.
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PMID:The adenoma-carcinoma sequence in the colorectum--early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential. 141 17

Molecular genetic studies of tumor-specific allele loss, originally associated primarily with research regarding childhood hereditary cancers such as retinoblastoma and Wilms' tumors, only lately have been recognized as a relatively fast and fruitful way of locating cancer genes on human chromosomes. To date, over 25 different cancers have been tied to a gene (or genes) on a specific chromosome when this method has been used. During the past year alone, this approach has permitted detection of three genes involved in either hereditary or sporadic colorectal cancers. These three genes, located on chromosomes 5q, 17p, and 18q, are believed to belong to the newly described tumor suppressor (or growth suppressor) gene class, whose effects are opposite those of activated cellular oncogenes, which promote uncontrolled cell growth. Present studies, however, have not shown losses of any of these tumor suppressor genes to be correlated with the presence of activated ras genes in colorectal adenomas or carcinomas. During progression from adenoma to carcinoma, ras gene mutations and 5q allelic deletions are likely to be earlier events, whereas allelic losses from chromosomes 18q and 17p seem to occur more often in advanced tumors. Involvement of the genes on 5q (FAP) and 18q (Lynch syndrome II) in hereditary colon cancer syndromes is supported by linkage studies, but their respective roles (as well as that of the gene on 17p) in familial and sporadic colorectal cancer remain to be precisely defined. Probable isolation of these three genes by molecular cloning within the next few years will help elucidate their specific biologic functions. It will also permit early detection, and thus prevention, of some familial colon cancers (such as FAP), and possibly allow DNA marker-based separation of different colon cancer subtypes of similar histologic appearance.
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PMID:Molecular genetic studies of colon cancer. 264 66

Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although it is usually not familial, there is a rare dominantly inherited susceptibility to colon cancer, familial adenomatous polyposis (FAP; also often previously called familial polyposis coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These are sufficiently likely to give rise to adenocarcinomas to make prophylactic removal of the colon usual in diagnosed FAP individuals. Adenomas may occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. Adenomata have been suggested to be precancerous states for most colorectal tumours. Knudson has suggested that the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumour cells, and that the same gene may be involved in both familial and non-familial cases of a given tumour. Following up a case report of an interstitial deletion of chromosome 5 in a mentally retarded individual with multiple developmental abnormalities and FAP, we have now shown that the FAP gene is on chromosome 5, most probably near bands 5q21-q22.
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PMID:Localization of the gene for familial adenomatous polyposis on chromosome 5. 303 73

Sulindac is useful in regression of adenomatous polyps. In addition to orally administered sulindac, rectal preparations also appear to be efficacious [32]. However, further studies are necessary to determine whether regression of adenomas, the precursor of colorectal cancer, will cause decrease in colorectal cancer risk in both FAP and non FAP patients. Moreover, clinical studies are needed to test the application of this potential chemopreventative drug in several other patient populations. Several interesting observations have been made concerning the use of sulindac. Indomethacin, a related NSAID to sulindac, did not cause polyp regression. Also, upper gastrointestinal tract polyps in the stomach and duodenum appear not to be affected by sulindac therapy. These observations might be explained by the metabolism of sulindac in which the pharmacologically active sulfide metabolite is generated and distributed in the large intestine. Also, investigators noted that after discontinuation of sulindac adenomas recurred. Sulindac treatment was well tolerated at the usual clinical doses. Although some investigators have speculated on the effect of prostaglandin inhibition sulindac on cAMP-dependent mechanisms which control cellular proliferation [33], the cause of adenoma regression is unknown. There is evidence that colorectal endogenous prostaglandin levels decrease with sulindac. Evaluation of colorectal mucosal cellular proliferation in patients treated with sulindac has revealed a decrease in labelling index by bromodeoxyuridine labeling in one study [28] but no change in labelling index by [3H]thymidine incorporation in another investigation [34]. Also, ki 67 labelling index, another measure of cellular proliferation, was not affected in the colorectal mucosa of patients taking sulindac.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sulindac and polyp regression. 771 90

A case of familial adenomatous polyposis is reported in a 39 year old patient who underwent a Whipple's resection for adenoma of the duodenum. He subsequently developed a pancreatic glucagonoma. Endocrine neoplasia other than papillary carcinoma of thyroid has seldom been reported in association with FAP. The true incidence of islet cell tumours in FAP may be underestimated.
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PMID:Pancreatic islet cell tumour in a patient with familial adenomatous polyposis. 796 61

A concise review of the literature that evaluates the risk of colorectal cancer among NSAID users has been presented. Animal studies document a protective effect of NSAIDs in preventing colorectal cancers in carcinogen-induced (AOM) models and in Min mice. NSAIDs are protective in the animal model, even if given 14 weeks after administration of the carcinogen, indicating that these agents must be acting early in the adenoma-to-carcinoma sequence. Treatment of FAP patients with NSAIDs causes regression of adenomas that were already present before initiation of therapy. Many epidemiologic studies have examined the relationship between aspirin use and colorectal cancer. Most show a marked decrease in the relative risk (40% to 50%) of this tumor among continuous aspirin users. The appropriate dose and duration of aspirin treatment needed for optimal results are still unknown. Future work, directed at the molecular basis for the chemoprotective effects of NSAIDs in humans, may reveal strategies for the development of better chemopreventive agents. One effect shared by all NSAIDs is inhibition of cyclooxygenase. Presently, whether inhibition of COX-1 or COX-2 is required for the protective effect of aspirin and other NSAIDs is unclear. The authors and others have demonstrated that COX-2 is up-regulated from 2 to 50 fold in 85% to 90% of colorectal adenocarcinomas, making the COX-2 enzyme a more likely target. The authors have also reported a dramatic increase in COX-2 expression in colon tumors that develop in rats after AOM treatment. Drugs are currently being developed that preferentially inhibit either COX-1 or COX-2. If COX-2 is found to be a relevant target in the prevention of colorectal cancer, these newly developed, selective NSAIDs may play a role in future chemoprevention strategies.
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PMID:Nonsteroidal anti-inflammatory drugs, eicosanoids, and colorectal cancer prevention. 896 Aug 92

The authors have presented a concise review of the studies which evaluate the risk of colorectal cancer among NSAID users. Animals studies have clearly documented a protective effect of NSAIDs in preventing colon cancers in a carcinogen-induced (AOM) model. NSAIDs are protective in the animal model, even if given 14 weeks after administration of the carcinogen, indicating that they must be playing a role very early in the adenoma-to-carcinoma sequence of events. Several studies have indicated that treatment of FAP patients with NSAIDs causes a regression of adenomas that were already present prior to initiation of NSAID therapy. Many epidemiological studies have examined the relationship between aspirin use and colorectal cancer. Most of these studies have shown a marked decrease in the relative risk (40-50%) of colorectal cancer among continuous aspirin users. The appropriate dose and duration of aspirin treatment for optimal effects are still unknown. Future work, directed at the molecular basis for the chemoprotective effects of NSAIDs in humans, may reveal strategies for the development of better chemopreventive agents. One effect shared by all NSAIDs is their ability to inhibit cyclooxygenase. Presently, it is not clear whether inhibition of cyclooxygenase-1 or -2 effects on other signaling pathways are required for the protective effect of aspirin and other NSAIDs. The authors and others have demonstrated that COX-2 is upregulated from 2- to 50-fold in 85-90% of colorectal adenocarcinomas, which makes the COX-2 enzyme a possible target. Drugs are currently under development at several pharmaceutical companies that preferentially inhibit either COX-2 or COX-2. If COX-2 is found to be a relevant target in the prevention of colorectal cancer, then these newly developed, more selective NSAIDs may play a role in future chemoprevention strategies.
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PMID:Colorectal cancer and nonsteroidal anti-inflammatory drugs. 916 Jan 11

Recent advancement of molecular biology disclose responsible genes of FAP(familial adenomatous polyposis) and HNPCC(hereditary non polyposis colorectal cancer). Gardner Syndrome is now categorized as subtype of FAP. Turcot Syndrome is now known as a heterogeneous disease. Turcot Syndrome caused by APC gene develops medulloblastoma and Turcot Syndrome caused by mismatch repair gene develops glioblastoma. Because of the discovery of APC gene, the presymptomatic diagnosis of asymptomatic gene carriers are now available and preventive surgery can be planned. FAP patients with mutated APC gene between codon 1250 and 1464 shows severe phenotype. It is known that FAP patient whose APC gene mutation locates at codon 1309 develops cancer 10 years earlier in comparison to the rest of the cases. Consequently risky rectal mucosa should be removed in this group of patients. As for HNPCC, presymptomatic diagnosis is still not possible because the penetrance rate has not been estimated yet and some additional responsible genes are expected to be discovered. Replication error, mutator phenotype of mismatch repair gene is useful indicator to predict second primary cancers. When the patient in a HNPCC family develops adenoma with microsatellite mistability, preventive colectomy might be one of the surgical option with the informed consent of the patient.
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PMID:[Molecular biological background of FAP and HNPCC, and treatment strategies of both diseases depend upon genetic information]. 969 69

Patients with FAP (familial adenomatous polyposis) are known to be at high risk for duodenal cancer. Although the adenoma-carcinoma sequence is thought to exist in the duodenum, clinical observation of the development of duodenal adenoma to cancer has rarely been reported. We outline a 44-yr-old postcolectomy man with FAP who underwent regular gastroduodenoscopy annually or biannually and was found to be harboring duodenal ampullary cancer 5 yr after colectomy. Endoscopic and pathological examination of the ampullary lesion during these 5 yr revealed progression of pathology from adenoma to carcinoma. Pathology of the surgical specimen confirmed ampullary cancer. This in vivo demonstration of the adenoma-carcinoma sequence highlights the current limitations of duodenal surveillance in FAP.
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PMID:Malignant change in a duodenal adenoma in familial adenomatous polyposis: report of a case. 973 48

The most studied mechanism of malignant transformation has been cell proliferation. The relationship between programmed cell death (apoptosis), cell proliferation, and apoptosis regulatory genes (p53 and bcl-2), was studied in normal colonic epithelium, 26 sporadic adenomas both early and late, 25 FAP adenomas, and 34 carcinomas. We showed a decrease in programmed cell death and an increase in cell proliferation during the transition from adenoma to carcinoma. The increase of expression of p53 from early (10%) to late adenomas (87%) contrasted with the decrease of bcl-2 staining. Sixty-two per cent and 23% of carcinomas were reactive for p53 and bcl-2 respectively. Abnormal early activation of the bcl-2 gene, rather than late p53 gene mutation appears to be responsible for inhibition of apoptosis in colorectal carcinogenesis. bcl-2 was higher in FAP adenomas than in sporadic cases, and in carcinomas favouring the accumulation of long-living cells, which are more subject to mutation and thus cancerization.
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PMID:Programmed cell death in colorectal carcinogenesis. 1065 86


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