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)

The sample population in this initial case control study of the adenosine diphosphate ribosyl transferase (ADPRT) response of inflammatory bowel disease patients included: 23 patients with ulcerative colitis (UC)-active and inactive, 13 patients with Crohn's disease (CD)-active and inactive, 14 first degree relatives of UC and CD patients, and 19 age-matched controls. Adenosine diphosphate ribosyl transferase activity was determined after one hour incubation with 1% plasma (the constitutive value) or with 1% plasma and 100 microM H2O2 (the activated value) with the resulting difference designated as the induced value. Statistically significant decrease in ADPRT activity was found for the constitutive, activated and induced values in human mononuclear leucocytes of UC and CD patients, compared with controls. The values in the first degree relatives of UC and CD patients were not significantly different from either the control or disease populations, indicating an intermediate ADPRT response. These results may be related to the nature of the immunological response of IBD patients and comparable with similar findings in other diseases with known DNA repair deficiencies--for example, colon cancer.
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PMID:Hydrogen peroxide induced adenosine diphosphate ribosyl transferase (ADPRT) response in patients with inflammatory bowel disease. 314 30

Approximately 60% of sera from ulcerative colitis (UC) patients contains Igs reactive with neutrophil components, raising the question of the origin of these anti-neutrophil cytoplasmic Abs (ANCA). Our assertion that ANCA is a marker for a mucosal disease-related immune response predicts the existence of ANCA producing B cell clones in the lamina propria lymphocyte (LPL) fraction of UC patients. This hypothesis was tested by examining 12-day culture supernatants of LPL ANCA expression. LPL were isolated from surgically removed mucosa from patients with UC, Crohn's disease (CD), and diverticulitis. Normal mucosa was obtained from accident victims or normal margins of colon cancer resections. Supernatants were assayed by a fixed neutrophil ELISA. The ANCA staining pattern of supernatants expressing ANCA, as determined by ELISA, was assessed by indirect immunofluorescent staining of alcohol-fixed neutrophils. ANCA was found in 70% of culture supernatants from UC LPL fractions. In contrast, only approximately 11% of supernatants from CD and diverticulitis/normal (noninflammatory bowel disease (IBD)) LPL displayed ANCA binding. A perinuclear (pANCA) staining pattern was obtained with 70% of ANCA-expressing UC LPL supernatants, whereas ANCA-expressing CD and non-IBD LPL supernatants displayed a cytoplasmic reaction. PBL and mesenteric lymph node lymphocytes lacked spontaneous pANCA production, and pANCA production from PBL was not inducible. These findings indicate the existence of pANCA-producing B cell clones in mucosal lesions of UC patients and support our hypothesis that pANCA production is a consequence of a mucosal immune response specific to UC.
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PMID:Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients. 767 39

A high-fat and low-fiber diet is regarded as a major risk factor for colon cancer by increasing luminal contents of secondary bile acids. Calcium, on the other hand, has been implicated as a possible preventive agent in colon tumor development. In in vitro studies with human colonic epithelium, incubation with the secondary bile acid deoxycholic acid (DCA) induced hyperproliferation of colonic crypt cells which is regarded as a sign of preneoplastic transformation. In the present study the effects of calcium chloride (CaCl2) on DCA-induced hyperproliferation were tested at different stages of DCA-induced cell injury. Colonic biopsies from 36 patients (no tumors, polyps or IBD) were incubated with CaCl2 (1 and 10 mM) and 5 microM DCA which was added to the incubation medium either together with (experiment A), after (experiment B), or before CaCl2 (experiment C). Coincubation of the biopsies with DCA and 10 mM CaCl2 at the same time (experiment A) resulted in a significant reduction of whole crypt labeling index by 12% (p < 0.05), whereas in the other incubation experiments no significant growth-inhibitory effects could be demonstrated for CaCl2. These findings may best be explained by the formation of calcium-bound bile acid salts which lost most of their toxicity for the colonic cells.
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PMID:Effects of calcium and deoxycholic acid on human colonic cell proliferation in vitro. 942 94

PSC is the most common of the clinically significant hepatobiliary diseases seen in association with IBD, with an incidence that varies from 2.5% to 7.5%. Conversely, 50% to 75% of patients with PSC have IBD. This high degree of association suggests a common pathogenetic mechanism; however, no causal relationship has been established. The etiopathogenesis of PSC remains poorly understood, despite a large number of studies looking at differing hypotheses. The diagnosis is usually established by cholangiography. Liver biopsy can sometimes be helpful in diagnosing pericholangitis. There is a significant overlap of the histology with chronic hepatitis. Serum markers have been studied for diagnosing PSC, particularly for early diagnosis of cholangiocarcinoma, but none have shown the high sensitivity and specificity needed to use them clinically. PSC usually progresses insidiously and eventually leads to cirrhosis. Despite progress in early recognition, optimal management of patients with PSC remains a challenge requiring a multidisciplinary approach among hepatologists, endoscopists, surgeons, and interventional radiologists. Colectomy for ulcerative colitis does not alter the natural history of PSC. There is a high (10% to 15%) incidence of cholangiocarcinoma in patients with PSC. This incidence along with the risk of colon cancer in patients with ulcerative colitis makes it necessary to follow these patients closely. A number of pharmacologic therapies have been evaluated, but none has proven successful in slowing the progression of PSC or prolonging survival. Endoscopic therapy has a proven utility in treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopy has not been shown to improve survival or decrease the need for liver transplantation. Liver transplantation is life-saving for patients with advanced PSC. Pericholangitis, gallstones, and chronic hepatitis are additional disorders noted in association with IBD, but they are much less common and easier to manage than PSC.
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PMID:Hepatobiliary manifestations of inflammatory bowel disease. 1037 79

Ulcerative colitis and colonic Crohn's disease (together known as inflammatory bowel disease or IBD) are both associated with increased risk for colorectal cancer. Although it is customary to emphasize differences in the biology of IBD-associated and sporadic colon cancer, we believe these are far outweighed by the similarities. These similarities suggest that they might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to speculate that both IBD-associated and sporadic colon cancer might be the consequence of bacteria-induced inflammation.
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PMID:Inflammation and colorectal cancer: IBD-associated and sporadic cancer compared. 1179 61

Ulcerative colitis and Crohn's disease (together known as Inflammatory Bowel Disease or IBD) are both associated with increased risk for colorectal cancer. Although it is conventional to emphasise differences between IBD-associated and sporadic colon cancer, such as a lower rate of Adenomatosis Polyposis Coli mutations and earlier p53 mutations, IBD-associated cancer has a similar dysplasia-cancer sequence to sporadic colon cancer, similar frequencies of major chromosomal abnormalities and of microsatellite instability and similar glycosylation changes. This suggests that IBD-associated colon cancer and sporadic colon cancer might have similar pathogenic mechanisms. Because the normal colon is arguably in a continual state of low-grade inflammation in response to its microbial flora, it is reasonable to suggest that both IBD-associated and sporadic colon cancer may be the consequence of bacteria-induced inflammation. We have speculated that the glycosylation changes might result in recruitment to the mucosa of bacterial and dietary lectins that might otherwise pass harmlessly though the gut lumen. These could then lead to increased inflammation and/or proliferation and thence to ulceration or cancer. The glycosylation changes include increased expression of onco-fetal carbohydrates, such as the galactose-terminated Thomsen-Friedenreich antigen (Gal beta1,3GalNAc alpha-), increased sialylation of terminal structures and reduced sulphation. These changes cannot readily be explained by alterations in glycosyltransferase activity but similar changes can be induced in vitro by alkalinisation of the Golgi lumen. Consequences of these changes may be relevant not only for cell-surface glycoconjugates but also for intracellular glycoconjugates.
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PMID:Altered glycosylation in inflammatory bowel disease: a possible role in cancer development. 1282 Jul 18

Colorectal cancer is the most common malignant complication in patients who have IBD. The disease is difficult to diagnose because there is an overlap in symptoms in patients who have colon cancer and those who have IBD. Much has been learned about the incidence of colorectal cancer in patients who have IBD and its correlation with disease activity, duration, and anatomic location; however, almost no data are available regarding specific therapeutic considerations during adjuvant or palliative chemotherapy for these patients with respect to their underlying disease. Patients who have IBD who develop colorectal cancer are at higher risk for developing severe diarrhea during chemotherapy that may be due to the toxic effects of cytotoxic drugs or a flare of the IBD. Continuous infusional 5-FU alone, in combination with leucovorin, or in combination with oxaliplatin (FOLFOX) seems to be tolerated best. Bolus infusions of 5-FU (Roswell Park or Mayo regimens) and combination therapy of irinotecan with 5-FU should be avoided because of severe diarrhea and the possibility of sepsis. When diarrhea develops or worsens, empiric aminosalicylates may be given. Although it is theoretically possible that anti-EGFR therapies could affect IBD activity adversely, clinical experience with cetuximab in patients who have colorectal cancer has not shown any significant gastrointestinal side effects. Therefore, it seems reasonable to use it in patients who have colorectal cancer and IBD. The administration of bevacizumab has been associated with rare episodes of intestinal perforation; it should be used with great care in patients who have IBD. More studies and an integrative, multidisciplinary approach from oncologists and gastroenterologists are needed to provide optimal care for patients who have IBD during chemotherapy for colorectal cancer
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PMID:Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease. 1695 47

The colonic epithelium is lined along its apical membrane with approximately 10(14) bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.
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PMID:TLR4 signalling in the intestine in health and disease. 1803 Dec 48

The role of vasculitis in the pathogenesis of IBD remains unclear. The aim of this study was to evaluate the detection rate of vasculitis in patients with IBD, its location in the intestinal wall layers and whether it occurs dependent of the degree of inflammation. Immunohistological staining with the endothelial cell marker CD31 and the pan-T cell marker CD3 was performed in 56 colonic specimens of Crohn's disease, in 43 of ulcerative colitis, and in 5 of colon cancer. Quantification of the degree of inflammation was done using a histological colitis score. There was no sign of vasculitis in the healthy intestinal wall layers. In Crohn's disease, specimens with minor inflammatory activity (score 0-2) disclosed no vasculitis. Vasculitis was observed in 82% of the specimens with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis was detected in all intestinal wall layers altered by inflammation. A direct association between vasculitis and granulomas was observed in only 5% of the specimens with an inflammatory degree of 4. All ulcerative colitis specimens evidenced an inflammatory degree between 2 and 4. No vasculitis was found in specimens with an inflammatory degree of 2, but in 57% with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis is only detectable in the mucous membrane changed by inflammation. Thus, the vasculitis in IBD is exclusively observed in the intestinal wall layers altered by inflammation. The extent of vasculitis depends on the degree of inflammation. An association between vasculitis and granuloma in Crohn's disease is seen in 5% of the cases.
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PMID:The vasculitis in IBD is associated with the degree of inflammation. 1926 97

Colonoscopy, the preferred procedure for colon cancer screening, has well-documented limitations. To improve colonoscopy's effectiveness, augmented endoscopy techniques, such as chromoendoscopy and narrow band imaging (NBI) have been evaluated. Both techniques are inexpensive, safe, and relatively easy to perform. Chromoendoscopy has an increasingly important role in surveillance of IBD, but significant work is needed to determine the optimal staining techniques and mucosal surface pattern analysis before this technique can be incorporated into routine clinical practice. NBI is a much newer technology with far less data. Well-designed prospective randomized controlled trials have failed to identify a benefit of NBI in screening colonoscopy, in surveillance for high-risk populations or as an adjunct for therapeutic procedures.
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PMID:Current status of chromoendoscopy and narrow band imaging in colonoscopy. 2128 87


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