Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer represents the major cause for excess morbidity and mortality by malignant disease in ulcerative colitis as well as in Crohn's disease. The risk for ulcerative colitis associated colorectal cancer is increased at least 2-fold compared to the normal population and colorectal cancer is observed in 5.5-13.5% of all patients with ulcerative colitis and 0.4-0.8% of patients with Crohn's disease. Established risk factors include long duration of the disease, large extent of the disease, low activity of the disease, young age at onset, presence of complicating primary sclerosing cholangitis or stenotic disease and possibly lack of adequate surveillance, inadequate pharmacological therapy, folate deficiency and non-smoking. Crohn's disease is associated with an increased risk of colorectal carcinoma in patients with long-standing disease, strictures and fistulae under the condition that the colon is involved, tumors of the small intestine may occur occasionally. Extracolonic malignancies are rare, with the exception of biliary tract cancer. Ulcerative colitis associated colorectal cancer typically can occur in the entire colon, is often multifocal and of undifferentiated histology. Stage distribution and prognosis of ulcerative colitis associated colorectal cancer appears to be similar to that of sporadic colorectal cancer with an overall survival of about 40% (15-65%) after 5 years with tumor stage at diagnosis being the most important predictive parameter for survival. Tumor markers helpful for the diagnosis of sporadic colorectal cancer fail to differentiate between inflammatory response and malignant transformation. In contrast the histologic evidence of dysplasia was shown to be a strong indicator of underlying carcinoma or developing malignant transformation. The presence of a surface projection termed dysplasia associated lesion or mass is highly indicative of underlying or associated cancer. While the routinely performed search for dysplasia is hampered by high interobserver variation the demonstration of DNA-aneuploidy or genetic changes which may confirm the ongoing malignant transformation has not yet become clinical routine. The genetic alterations found in ulcerative colitis associated colorectal cancer involve many of the same targets found in sporadic colorectal tumors and include multiple sites of allelic deletion, microsatellite instabilities, and mutations of APC, p53, Ki-ras as well as MSH2 and other genes. The progression of dysplasia to carcinoma is generally accompanied by an accumulation of these mutations and the similarities in the biology of colorectal cancer associated with ulcerative colitis and sporadic colorectal cancer appear to outweigh their difference. In regard to the management of dysplasia and cancer, the role of surveillance programs for the early detection of ulcerative colitis associated colorectal cancer at a curable stage is still under debate. Although these programs failed at tumor prevention and lethal carcinomas are still found inadvertently in patients under surveillance, the majority of surveillance programs could reduce mortality by detecting more cancers at a still curable stage. Current recommendations for surveillance include, therefore, biennial colonoscopy with extensive biopsies after 8-10 years of total colitis or after 15-20 years of left-sided colitis. In the presence of cancer or unequivocal high-grade dysplasia and/or dysplasia associated lesion or mass proctocolectomy is considered adequate. The evidence of low-grade dysplasia should be confirmed before proctocolectomy is considered.
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PMID:Chronic inflammatory bowel disease and cancer. 1069 May 86

Like sporadic colorectal cancers, ulcerative colitis (UC)-related cancers are thought to evolve through a multistep progression pathway. The genomic alterations important in sporadic colorectal carcinogenesis are well characterized, with loss of APC function being a frequent and early event. However, the genomic alterations in UC-related carcinogenesis are yet unclear and the role of APC is controversial. In this study genomic alterations in UC-related cancers, dysplasias and nondysplasias were assessed by comparative genomic hybridization (CGH). Alterations of the APC/beta-catenin pathway were evaluated by immunohistochemistry. 32 cases of UC-related cancers (14 with synchronous dysplasias and nondysplasias) and 42 sporadic cancers were matched by UICC stage. CGH was performed using DOP-PCR amplification after microdissection. Expression of beta-catenin, E-cadherin and APC were detected by immunohistochemistry in paraffin sections. Chromosomal alterations were present in 90% of the sporadic and 94% of the UC-related cancers. 86% of the UC-related dysplasias and 36% of the nondysplasias showed changes by CGH. Chromosome 5q was lost in 56% of UC-related cancers and 36% of the dysplasias but in only 26% of the sporadic cancers. Other frequent alterations in both cancer groups were loss of 18q, 8p, 17p, and gain of 8q and 20q. Immunohistochemistry showed a decrease of membranous and an increase of cytoplasmic expression of E-cadherin and beta-catenin in UC-related and sporadic cancers. APC expression was significantly decreased in both tumor types. Clonal chromosomal alterations occur early in UC-related tumor progression. UC-related and sporadic cancers share a set of common clonal abnormalities. The frequent loss of 5q and the altered expression of APC, beta-catenin, and E-cadherin proteins in UC-related cancers indicate a critical role of the APC/beta-catenin pathway in UC-related carcinogenesis.
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PMID:[Molecular carcinogenesis in ulcerative colitis-associated and sporadic colorectal carcinoma--differences and similarities]. 1071 3

We herein summarize the reports on genetic changes in precancerous lesions in the gastrointestinal tract. It has been reported that with esophageal lesions such as dysplasia and Barrett's esophagus there is a high frequency of p53 mutations. Among gastric lesions, some cases of chronic atrophic gastritis have been shown to harbor K-ras mutations. p53 and APC mutations in intestinal metaplasia have also been demonstrated, as have APC mutations in flat adenomas. With colorectal lesions, it has been reported that K-ras, DCC, p53 mutations commonly occur while APC mutations are also seen in cases of adenoma-carcinoma. p53 and K-ras mutations have been demonstrated with serrated adenoma, and K-ras mutations with hyperplastic polyps APC mutations in familial polyposis coli, LKB1 mutations in Peutz-Jeghers syndrome, and SMAD4/DPC4 mutations in juvenile polyposis syndrome have been found. Besides these genes, other genetic changes likely occur in carcinogenesis among those with hereditary diseases. K-ras mutations in aberrant crypt foci and hMSH2 mutations in ulcerative colitis have been found. Research into the genetic changes associated with cancerous lesions should lead to the development of early diagnosis and treatment methods for gastrointestinal cancer as well as the improved comprehension of carcinogenesis.
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PMID:[Genome analyses for precancerous lesions in the gastrointestinal tract]. 1074 Jun 25

Patients with long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer (CRC) compared to the general population. For investigation of the mechanisms and prevention of UC and UC-related CRC, establishment of a promising animal model for such disease is important. 1-hydroxyanthraquinone (1-HAQ) present in certain medicinal plants such as Rubia tinctorum L. is a genotoxic and rodent colon carcinogen. Long-term feeding of 1-HAQ induced hyper-cell proliferation in rat colonic crypts with ulcerative changes, crypt abscess, severe inflammation and erosion before the occurrence of tumors, which are similar to those found in human UC. In addition, 1-HAQ has a synergistic effect with methylazoxymethaol (MAM) acetate on colon carcinogenesis. The polymerase chain reaction-single strand conformation polymorphism analysis revealed no mutations in Ki-ras and p53 in colonic neoplasms induced by MAM acetate + 1-HAQ, MAM acetate alone or 1-HAQ alone. Also, no mutations of APC were found in these tumors. These findings are similar to those found in human ulcerative colitis-associated colon cancer in contrast with sporadic colon cancers. A previous study revealed that induced colonic tumors had beta-catenin mutation with high frequency, suggesting tumor development by activation of the beta-catenin-Tcf signaling pathway. Increased expression in TNF-alpha and IL-1alpha was found in these induced colonic neoplasms, and the expression was more remarkable in colonic mucosa of rats exposed to MAM acetate + 1-HAQ, MAM acetate or 1-HAQ when compared with that in untreated rats. Thus, these cytokines may act as growth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ and the synergistic effect of 1-HAQ with MAM acetate might be related to the biological effects of the cytokines expressed in the inflammatory conditions induced by 1-HAQ.
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PMID:Colitis-related rat colon carcinogenesis induced by 1-hydroxy-anthraquinone and methylazoxymethanol acetate (Review). 1076 59

The cotton-top tamarin (CTT) (Sagiunus oedipus) has been used as an animal model to investigate the etiology and pathophysiology of several human diseases, including ulcerative colitis and its associated colorectal carcinoma (CRC). Little is known, however, about genetic synteny between CTT and humans, and about chromosome aberrations in CTT CRC. To address these issues, we have analyzed CTT lymphoblastoid and CRC cell lines using cytogenetics, fluorescence in situ hybridization (Zoo-FISH), and direct sequencing. The CTT lymphocytes had pseudodiploid chromosomes of 46. The CTT CRC cells showed near-diploid chromosomes of 45. Several clonal structural aberrations were observed, including der(1), a marker chromosome, and double minutes. Zoo-FISH using human chromosome 2, 3, 5, 6, 9, 11, 13, 15, 16, 17, 19, 22, and X paints identified homologous chromosomes and subchromosomal regions in the CTT genome. Fluorescence in situ hybridization with human telomeric probe also detected a homologous sequence in CTT genome. Direct sequencing of CTT genomic DNA using primers amplifying exons 4 and 15 of the human APC gene identified DNA sequences in CTT genome with 99% and 95% homology, respectively. These results provide a basis for further comparative studies of CTT and human genome.
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PMID:Molecular and cytogenetic analysis of lymphoblastoid and colon cancer cell lines from cotton-top tamarin (Sagiunus oedipus). 1091 70

Recent molecular studies have shown that there are differences in the prevalence and timing of certain molecular events between chronic ulcerative colitis (CUC)-associated dysplastic lesions and non-CUC-related sporadic adenomas. However, little is known regarding the molecular features of a specific subtype of CUC-related dysplasia-associated lesion or mass (DALM) that clinically, endoscopically, and pathologically resemble sporadic adenomas, and whether these lesions can be separated from non-CUC-related sporadic adenomas on the basis of their molecular genotype. Therefore, the purpose of this study was to evaluate loss of heterozygosity (LOH) of 3p, APC, and p16 in a specific group of CUC-associated "adenoma-like" DALMs and to compare the results of this tumor with those in a well-defined group of CUC-associated non-adenoma-like DALMs and non-CUC-associated sporadic adenomas. Polypectomy or resection specimens from 21 CUC patients with an adenoma-like DALM, 8 CUC patients with at least one nonadenoma-like DALM (12 lesions in total), and 23 non-CUC patients with a sporadic adenoma were evaluated for LOH of 3p, APC, and p16 by PCR analysis. The results were compared among the three different study groups and correlated with the clinical features of the patients and the pathology of their tumors. Chronic ulcerative colitis-associated adenoma-like DALMs showed LOH of 3p in five of 18 (28%) cases. This value was not significantly different from the 5% of non-CUC sporadic adenomas (p = 0.14) that were positive. However, 50% of CUC-associated non-adenoma-like DALMs were positive for LOH of 3p, and this value was significantly higher (p = 0.01) than the other groups. The frequency of LOH of APC did not differ significantly between the three patient groups (33%, 33%, and 43% in the three groups, respectively). Similar to the 3p results, CUC-associated adenoma-like DALMs and non-CUC-associated sporadic adenomas showed a similar low frequency of positivity for LOH of p16 (5% and 4%, respectively) in comparison to 56% of CUC-associated non-adenoma-like DALMs (p = 0.003). For all markers, no significant differences were detected in the CUC-associated adenoma-like DALM group between lesions that occurred within colitis compared with those that occurred in areas not involved by colitis. Chronic ulcerative colitis-associated non-adenoma-like DALMs have a different molecular genotype than CUC-related adenoma-like DALMs and non-CUC sporadic adenomas. Our data also suggests that the latter two groups of neoplasms may in fact represent a similar, if not identical, pathogenetic entity.
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PMID:Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas. 1097 94

Detailed structure activity relationships (SARs) for a series of dibasic human tryptase inhibitors are presented. The structural requirements for potent inhibitory activity are remarkably broad with a range of core template modifications being well tolerated. Optimized inhibitors demonstrate potent anti-asthmatic activity in a sheep model of allergic asthma. APC-2059, a dibasic tryptase inhibitor with subnanomolar activity, has been advanced to phase II clinical trials for the treatment of both psoriasis and ulcerative colitis.
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PMID:Dibasic inhibitors of human mast cell tryptase. Part 2: structure-activity relationships and requirements for potent activity. 1105 56

We present a patient with membranous glomerulonephritis, several clinical complications of the antiphospholipid syndrome and ulcerative colitis, but without lupus anticoagulant and antiphospholipid/cofactor antibodies. Immunological studies--other antibodies--were negative and failed to show enough criteria for any autoimmune diseases. Evaluation of her laboratory tests for hereditary thrombophilia revealed a heterozygous form of the Leiden mutation that might be associated with widespread vasculopathy. An interesting possibility is that the inherited activated protein C resistance could be an additional risk factor for vaso-occlusive manifestations appearing as a clinical sign of cardiovascular diseases and nephropathy.
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PMID:Membranous glomerulonephritis in a patient with inherited activated protein C resistance. 1130 13

Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.
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PMID:Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin. 1135 31

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.
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PMID:Platelets and anticoagulant capacity in patients with inflammatory bowel disease. 1221 55


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