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)

AIE-75 has been known as a 75-kDa autoantigen detected in the serum of autoimmune enteropathy (AIE) and as a colon cancer-related antigen, and now designated as a gene causative of Usher syndrome type 1C hereditary syndromic hearing loss. It binds to a novel putative tumor suppressor MCC2 that is homologous to MCC (mutated in colon cancer) through a PSD-95/Dlg/ZO-1 (PDZ) domain. To clarify the functional role in colon cancer cells, we transfected AIE-75 gene into SW480 colon cancer cells which do not express AIE-75. Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage, resulting in emergence of hyperploid giant-nucleated or multi-nucleated cells. Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75. Since PP2AC is known to regulate G2/M checkpoint, we suggest that AIE-75 interacts with PP2AC and prevent cells to transit mitotic phase.
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PMID:Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells. 1521 44

Radiation therapy for abdominal recurrence of colon cancer is rarely an option due to subsequent bowel injury. Our case is a woman who underwent resection for a large retroperitoneal recurrence of caecal cancer. Tumour deposits encasing the iliac vessels had to be left behind. A silicone breast prosthesis for displacement of the abdominal content was implanted, allowing postoperative irradiation with 50 Gy. The prosthesis was removed once radiotherapy was accomplished; tumour regression was then complete. Complications are described, so are indications for surgical management of local recurrences of colonic origin as well as technical aspects of abdominal implantation of displacing prostheses. At follow-up after eighteen months the patient has no signs of enteropathy, she enjoys a good quality of life, and she is free of disease. Still, her prognosis is considered uncertain.
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PMID:[Protective silicone prosthesis prior to radiotherapy of recurrent colonic cancer]. 1647 82

The aim of this study was to evaluate the expression pattern of Toll-like receptors (TLRs) in the pouch mucosa of ulcerative colitis patients in comparison with that in the ileum mucosa of noninflammatory bowel disease patients. Pouch mucosal biopsy specimens were collected from postoperative patients who had undergone surgery for ulcerative colitis. Normal ileum specimens were collected from colon cancer patients. The specimens were assessed by immunofluorescence histochemistry using TLR2, TLR3, TLR4, and TLR5 polyclonal antibodies. The normal ileal mucosa constitutively expressed TLR3 and TLR5, whereas TLR2 and TLR4 were barely detectable. In the mucosa of active pouchitis, TLR2 and TLR4 was strongly upregulated, and TLR4 was upregulated even in a noninflamed pouch. No TLR3 or TLR5 expression was detectable. These data suggest that pouchitis may be associated with distinctive changes in selective TLR expression in the pouch mucosa, and that TLR4 alterations in the innate response system may contribute to the pathogenesis of these disorders in particular.
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PMID:The expression patterns of Toll-like receptors in the ileal pouch mucosa of postoperative ulcerative colitis patients. 1649 44

The term "Western diseases" refers to those conditions that are rare or absent in underdeveloped areas of the Third World and increase in frequency with adoptions of Western customs. In adults, they include such common conditions as coronary artery disease, essential hypertension, appendicitis, cholesterol gall stones, and colon cancer. The best examples of Western diseases in the pediatric population are asthma, allergies, appendicitis, and inflammatory bowel disease. Limited data from sub-Saharan Africa suggest other pediatric surgical conditions may fall into this category, including hypertrophic pyloric stenosis, gastroesophageal reflux, perirectal abscess, anal fissure, gastroschesis, and neuroblastoma. Existing theories for the origins of Western diseases have postulated a role for decreased dietary fiber, improved hygiene, fetal programming, and a protective effect of tropical enteropathy. How these factors might relate to the rise of appendicitis, inflammatory bowel disease, and possibly other common pediatric surgical diseases in industrialized societies remains poorly understood. Further research is needed to better define geographical differences in common pediatric surgical conditions and to investigate how genetic and environmental factors interact to modify risk of disease. Understanding the molecular mechanisms that give rise to Western diseases could lead to new therapeutic and prevention strategies for some of the most common pediatric surgical conditions in industrialized countries.
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PMID:Western diseases: current concepts and implications for pediatric surgery research and practice. 1808 4

Although the absolute risk of enteropathy-associated malignancies in celiac disease is generally very small due to low prevalence/incidence rates, the relative risk may be considerable so that prevention strategies based on appropriate data seem clinically desirable. The great majority of the case-control and cohort studies which have been published in the last years point to a significantly elevated risk for tumors in the gastrointestinal (GI) tract in terms of hazard/odds ratios, observed/expected ratios, and/or standardized incidence/morbidity ratios in the magnitude>5.0, whereas the risk for tumor outside the GI tract seems to be much lower (PubMed December 2007). Chronic inflammation with persistent symptoms/complaints and especially chronic refractory disease type II are considered to be particular individual risk factors. In addition, genetic factors and/or certain gene combinations may unfavorably influence the course of the disease. In the absence of controlled and prospective trials and corresponding evidence-based guidelines as they have been published for colon cancer, the strategies of prevention in patients with celiac disease differ from center to center according to their own experience/ expertise. Besides regular clinical, serologic/immunologic and endoscopic/histologic assessment a careful history taking with special regard to the disease course and a detailed ultrasound examination of the entire abdomen in patients at risk may play an important role in the long-term follow-up.
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PMID:[Celiac sprue and malignancies: analysis of risks and prevention strategies]. 1880 30

After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a multifunctional compound which exhibits some general as well as some specific effects, depending on the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer.
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PMID:Thirty four years since the discovery of gastrointestinal melatonin. 1881 27

Aspirin was commercialized more than a 100 years ago. Today, this compound is still widely prescribed, and new mechanisms of action and indications are being tested. Inhibition of cyclooxygenase (COX)-1 and COX-2 by aspirin or its related compounds, nonsteroidal antiinflammatory drugs (NSAIDs), has been associated with both adverse and beneficial effects in the gastrointestinal (GI) tract. Inhibition of COX-1 has been linked to GI adverse effects. Adverse effects of NSAIDs and aspirin in the upper GI tract include esophagitis, peptic ulcer, peptic ulcer complications, and death. Effective preventive therapies are available that have been associated with a progressive decline in the rate of hospitalization due to upper GI complications. NSAIDs and aspirin can also damage the small bowel and the colon. NSAID enteropathy is frequent and in most cases subclinical (increased mucosal permeability, inflammation, erosion, ulcer). However, more serious clinical outcomes such as anemia, bleeding, perforation, obstruction, diverticulitis, and deaths have also been described. Prevention therapy of NSAID damage to the lower GI tract is not well defined. Inhibition of COX-2 by NSAIDs, coxibs, or aspirin seems to provide beneficial effects to the GI tract. Observational studies show that these compounds reduce the risk of both upper and lower GI cancers. Randomized controlled trials have shown that aspirin and coxibs reduce the recurrence rate of colonic polyps, and long-term cohort studies have shown that aspirin reduces the risk of colon cancer time and dose dependently. New studies will have to define the appropriate population that may benefit with these therapies.
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PMID:Nonsteroidal antiinflammatory drugs and cyclooxygenase inhibition in the gastrointestinal tract: a trip from peptic ulcer to colon cancer. 1968 14

Step-up therapy in Crohn's disease refers to the classic therapeutic approach resulting in progressive increase of therapies with the increasing severity of the disease. This approach has been recently challenged by the top-down strategy, where biologicals together with thiopurines were used as first-line therapy. Several arguments exist against the top-down therapy. The current ECCO recommendation is in favor of the step-up therapy. ECCO recommended budesonide 9 mg daily as the preferred treatment in mild to moderate Crohn's disease patients. The benefit of mesalazine in small bowel disease is limited and should be considered clinically no more effective than placebo. Antibiotics cannot be recommended unless septic complications are suspected. No treatment is an option for some patients with mild symptoms. Budesonide is preferred to prednisone for mild active Crohn's disease because it is associated with fewer side effects. Active mild colonic disease may be treated with sulfasalazine and when needed with systemic corticosteroids as well. Topical treatment should be considered for distal disease. The national cooperative Crohn's disease study and the European co-operative Crohn's disease study established corticosteroids as an effective therapy for inducing remission in Crohn's disease. Remission is achieved in 60-83% of the patients. A Cochrane review of the efficacy of azathioprine and 6-mercaptopurine for inducing remission in active Crohn's disease showed a benefit for thiopurine therapy compared with placebo. Methotrexate is another effective medication that has been confirmed in a systematic review. Once remission has been achieved with systemic corticosteroids, maintenance with azathioprine should be considered. For patients with extensive colitis, long-term treatment with mesalazine is an option as this may reduce the risk of colon cancer, although this is still unproved in Crohn's disease. In conclusion, the natural course of most patients with Crohn's disease is relatively mild and there is a room for step-up therapy. The efficacy of most medications is similar to the efficacy of infliximab but with less adverse effects. Infliximab should be reserved only for patients where other therapies failed.
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PMID:Mild to moderate Crohn's disease: still room for step-up therapies? 1978 63

Collagenous sprue has traditionally been defined as a small intestinal mucosal disorder characterized by persistent diarrhea, severe malabsorption with multiple nutrient deficiencies and progressive weight loss. Pathologically, a severe to variably severe "flattened" mucosal biopsy lesion with distinctive sub-epithelial deposits in the lamina propria region is detected. Histochemical stains and ultrastructural studies have confirmed that these deposits contain collagens. Often, an initial diagnosis of celiac disease is considered but no continued response to treatment with a gluten-free diet occurs. Recent reports indicate an intimate relationship between collagenous sprue and celiac disease, sometimes with concomitant T-cell enteropathy. In addition, permanent disappearance of these deposits after resection of a localized colon cancer suggested that this disorder could actually represent a paraneoplastic morphologic marker of an occult malignancy. Studies showing either gastric or colonic involvement (or both) with this unusual collagenous inflammatory mucosal process may also reflect a far more extensive and heterogeneous process than previously appreciated.
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PMID:Update on collagenous sprue. 2008 73

Adult celiac disease is a chronic intestinal disorder that has been estimated to affect up to 1-2% of the population in some nations. Awareness of the disease has increased, but still it remains markedly underdiagnosed. Celiac disease is a pathologically defined condition with several characteristic clinical scenarios that should lead the clinician to suspect its presence. Critical to diagnosis is a documented responsiveness to a gluten-free diet. After diagnosis and treatment, symptoms and biopsy-proven changes may recur and appear refractory to a gluten-free diet. Recurrent symptoms are most often due to poor diet compliance, a ubiquitous and unrecognized gluten source, an initially incorrect diagnosis, or an associated disease or complication of celiac disease. Some patients with persistent symptoms and biopsy-proven changes may not have celiac disease at all, instead suffering from a sprue-like intestinal disease, so-called unclassified sprue, which is a specific entity that does not appear to respond to a gluten-free diet. Some of these patients eventually prove to have an underlying malignant cause, particularly lymphoma. The risk of developing lymphoma and other malignancies is increased in celiac disease, especially if initially diagnosed in the elderly, or late in the clinical course of the disease. However, recent studies suggest that the risk of gastric and colon cancer is low. This has led to the hypothesis that untreated celiac disease may be protective, possibly due to impaired absorption and more rapid excretion of fat or fat-soluble agents, including hydrocarbons and other putative cocarcinogens, which are implicated in the pathogenesis of colorectal cancer.
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PMID:Adult celiac disease and its malignant complications. 2043 55


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