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)

Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to be a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4+ CD45RB(hi) (T(E)) cells to induce inflammatory bowel disease (IBD) in mice, to investigate roles of inflammation on carcinogenesis in the Apc(Min/+) mouse model of intestinal polyposis. We find that transfer of T(E) cells significantly increases adenoma multiplicity and features of malignancy in recipient Apc(Min/+) mice. Surprisingly, we find that female Apc(Min/+) recipients of T(E) cells also rapidly develop mammary tumors. Both intestinal polyposis and mammary adenocarcinoma are abolished by cotransfer of anti-inflammatory CD4+ CD45RB(lo) regulatory lymphocytes or by neutralization of key proinflammatory cytokine tumor necrosis factor-alpha. Lastly, down-regulation of cyclooxygenase-2 and c-Myc expression is observed coincident with tumor regression. These findings define a novel mouse model of inflammation-driven mammary carcinoma and suggest that epithelial carcinogenesis can be mitigated by anti-inflammatory cells and cytokines known to regulate IBD in humans and mice.
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PMID:Proinflammatory CD4+ CD45RB(hi) lymphocytes promote mammary and intestinal carcinogenesis in Apc(Min/+) mice. 1639 16

Intraepithelial bacteria were isolated by the gentamicin protection assay (GPA) from biopsy samples obtained at colonoscopy (colon cancer, n = 10 patients; colonic adenoma, n = 20; control group, n = 20; cancer patients without gastrointestinal tract GIT malignancy, n = 10). After a three-month administration of E. faecium M-74 to patients with positive GPA biopsies, 172 biopsy specimens from 60 patients were examined with the GPA. The number of biopsies with intracellular bacteria was significantly higher in adenoma and carcinoma group than in control group (26 vs. 10%; p = 0.004); in cancer patients without GIT malignancy the difference was nonsignificant. E. faecium M-74 was also administered to 5 patients with colonic adenoma; according to a control colonoscopy the number of biopsies with intracellular bacteria was significantly lower after probiotic administration (48 vs. 16%; p = 0.03). A striking prevalence of intraepithelial bacteria was also showed in patients with large bowel adenoma and carcinoma. The administration of probiotic strain M-74 can thus be considered to be an effective and promising method for elimination of pathogenic bacteria in the case of inflammatory bowel disease and colon cancer.
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PMID:Intramucosal bacteria in colon cancer and their elimination by probiotic strain Enterococcus faecium M-74 with organic selenium. 1647 5

There has been a major improvement in our understanding in the area of the genetics of CRC in the last decade. Reason for this is partly that CRC has a strong hereditary trait and premalignant lesions are frequent and easily accessible. In the 1990-ies the mutations responsible for the adenoma-carcinoma sequence were discovered on after the other. In the second part of the review the authors discuss the genetic background of sporadic and IBD associated colorectal cancers as well as the role of genetics in the diagnosis, prognosis and prediction of therapy. Chromosomal instability (85%) and microsatellite instability with or without change in DNA methylation (15%) are the main mechanisms involved in the pathogenesis of sporadic colorectal cancers. It became evident that no ultimate mutations exist. Most of neoplasms are genetically heterogeneous, independent pathways and simultaneous tumorigenesis may exist within the same organ, also in the colon. Gene expression profile, clinical phenotype and prognosis may also vary according to the location. Similar genetic mutations may be found in IBD associated colorectal cancers, however, the typical sequence and importance of mutations is different. In future, fecal DNA testing may be an important screening tool for colorectal cancer; however, its routine use is still limited by its low sensitivity. Similarly, genetic investigation may play an increasing role in the prediction of prognosis, therapy and complication of chemotherapy. A more distant goal may be the individualization of the therapy.
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PMID:[Current concepts in the genetics of hereditary and sporadic colorectal cancer and the role of genetics in clinical practice: sporadic and IBD-associated colorectal tumors, significance of genetic tests in diagnosis, prognosis and assessment of chemotherapy outcome]. 1657 74

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.
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PMID:Chemoprevention for colon cancer: new opportunities, fact or fiction? 1678 36

Gastrointestinal malignancies account for about 20% of all cancers worldwide. It is widely accepted that cancer evolves through several stepwise morphological stages such as the adenoma-carcinoma and hyperplastic polyp-serrated adenoma-carcinoma sequences in colorectal cancers, and the metaplasia-dysplasia-carcinoma sequences in esophageal and gastric cancers. The morphological progression is associated with the accumulation of multiple genetic and epigenetic events. It is now recognized that epigenetic silencing of gene expression by CpG island methylation is an important alternative mechanism of inactivating tumor suppressor genes. Inflammatory conditions of the gastrointestinal and pancreaticobiliary tracts and liver such as Barrett esophagus, Helicobacter pylori gastritis, inflammatory bowel disease and viral hepatitis, are associated with increased frequency of malignancies and CpG methylation. In addition, CpG methylation is present in aberrant crypt foci and pancreatic intraepithelial neoplasia that are considered putative precursors of colon and pancreatic carcinomas, respectively. Understanding of these early genetic and epigenetic changes allows for the discoveries of potential screening, monitoring and therapeutic strategies. Targeting of the epigenetic changes that occur before the development of frank malignancy offers a potential chemopreventive strategy.
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PMID:CpG island methylation in precursors of gastrointestinal malignancies. 1690 Jun 63

The purpose of this review is to highlight new developments during the past year regarding diagnosis and clinical features of inflammatory bowel disease. Endoscopy remains the cornerstone for diagnosis and evaluation of ileocolonic inflammatory bowel disease. In ulcerative colitis, recent studies have challenged the concept of a continuous and homogeneous inflammatory process with constant rectal involvement: patchy inflammation and rectal sparing were reported in treated ulcerative colitis, and frequent cecum and appendiceal orifice skip lesions were confirmed. Cross-sectional imaging techniques usefully complement endoscopy by assessing whole-bowel thickness and detecting abscesses and fistulae. Furthermore, echo Doppler ultrasound is able to measure mesenteric blood flow, which is increased in active inflammatory bowel disease and seems to parallel inflammatory disease activity. Osteopenia, which affects approximately half of patients with inflammatory bowel disease, can be detected by dual-energy x-ray absorptiometry and prevented. Hyperhomocysteinemia, a predisposing factor for thrombosis, seems to be more frequent in inflammatory bowel disease, and can be corrected by folate supplementation. The concept of an aggressive, penetrating form of Crohn disease with early postoperative recurrence as opposed to a more indolent, nonpenetrating form of the disease, with later recurrence, was recently challenged. The most significant predictor of the risk of malignancy in inflammatory bowel disease remains the presence of dysplasia in colonic biopsy specimens. A dysplastic polypoid lesion or mass is a strong predictor of cancer but should be distinguished from the dysplasia inherent in a coincident sporadic adenoma.
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PMID:Clinical features of inflammatory bowel disease. 1703 Oct 97

Dysplasia surveillance remains the standard approach to minimize colorectal cancer (CRC) risk and morbidity in inflammatory bowel disease. Approaches to treatment in Crohn's disease are generally similar to those for ulcerative colitis. Recently the addition of dye spraying onto the colon to facilitate targeted biopsy has become increasingly associated with enhanced dysplasia surveillance; however, random biopsies are mostly still undertaken, even by those endoscopists who use chromoendoscopy. The prevailing literature continues to support colectomy for any degree of dysplasia. However, for those with adenoma-like masses, ongoing surveillance after polypectomy could still be considered appropriate. Certain endoscopic features are associated with increased incidence of neoplasia. These include not only strictures but also pseudopolyps. Past corticosteroid use and more than one screening colonoscopy were associated in two large case-control studies with reduced incidence of CRC. Although great interest has been expressed in the possible effectiveness of 5-aminosalicylic acid, it has not been proved to be an effective chemopreventive agent.
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PMID:Neoplasia in inflammatory bowel disease: surveillance and management strategies. 1710 91

We sought to assess the significance of an incidental finding of colorectal wall thickening (CRWT) on computed tomography (CT) scan in African-American and Hispanic patients. We retrospectively reviewed charts of African-American and Hispanic patients from January 1994 to December 2005. Those patients were included in whom the colonoscopy was performed due to incidental CRWT on CT scan. Patients with a history or a family history of colorectal malignancy, inflammatory bowel disease, or colorectal surgery, with an incomplete colonoscopic examination, or <18 years of age were excluded. Endoscopic and pathological findings were abstracted. Thirty-two patients met the criteria. Endoscopic examination was abnormal in 21 (65.6%). The positive predictive value of CRWT for abnormal endoscopic examination was 65.6%. Abnormal endoscopic examination revealed diverticulosis in 9 (43%), erythematous mucosa in 8 (38%), polyps in 6 (29%), mass in 2 (9%), thickened folds in 1 (5%), and diverticulitis in 1 (5%). Histopathological findings revealed colitis in 7 (33%), adenoma in 4 (19%), hyperplastic polyps in 4 (19%), adenocarcinoma in 2 (9%), lymphoid aggregates in 2 (9%), melanosis coli in 1 (5%), and normal in 1 (5%) in the abnormal examination group. Abnormal endoscopic examination was found in 65.6% of patients. The prevalence of colitis, adenomas, and malignancy was high, therefore abnormal CRWT warrants further endoscopic evaluation.
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PMID:Clinical significance of incidental colorectal wall thickening on computed tomography scan in African-American and Hispanic patients. 1740 51

Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy each have clinical potential in identifying human gastrointestinal (GI) pathologies, yet their diagnostic capability in mouse models is unknown. In this study, we combined the 2 modalities to survey the GI tract of a variety of mouse strains and ages and to sample dysplasias and inflammatory bowel disease (IBD) of the intestines. Segments (length, 2.5 cm) of duodenum and lower colon and the entire esophagus were imaged ex-vivo with combined OCT and LIE We evaluated 30 normal mice (A/J and 10- and 21-wk-old and retired breeder C57BL/6J) and 10 mice each of 2 strains modeling colon cancer and IBD (Apc(Min) and IL2-deficient mice, respectively). Histology was used to classify tissue regions as normal, Peyer patch, dysplasia, adenoma, or IBD. Features in corresponding OCT images were analyzed. Spectra from each category were averaged and compared via Student t tests. OCT provided structural information that led to identification of the imaging characteristics of healthy mouse GI. With histology as the 'gold standard,' we developed preliminary image criteria for early disease in the form of adenomas, dysplasias, and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin. In the IBD sample, LIF emission spectra displayed potentially diagnostic peaks at 635 and 670 nm, which we attributed to increased porphyrin production by bacteria associated with IBD. OCT and LIF appear to be useful and complementary modalities for ex vivo imaging of mouse GI tissues.
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PMID:Ex vivo optical coherence tomography and laser-induced fluorescence spectroscopy imaging of murine gastrointestinal tract. 1753 18

Patients with longstanding ulcerative colitis (UC) and Crohn's disease (CD) have an increased risk of colorectal cancer (CRC). CRC accounts for approximately 15% of all deaths in patients with inflammatory bowel disease (IBD). The molecular pathway leading to CRC in IBD appears to differ from the well-known adenoma-to-CRC sequence, given the fact that these cancers appear to arise from either flat dysplastic tissue or dysplasia-associated lesions or masses. The risk of CRC for patients with IBD increases by 0.5-1% yearly, 8-10 years after diagnosis. Patients with a young age at disease onset, more extensive colitis, greater inflammatory burden, concomitant primary sclerosing cholangitis, and a family history of CRC are at greatest risk. Most cancers arise in pancolitis and there is little or no increased risk associated with proctitis while left-sided colitis carries an intermediate cancer risk. The CRC risk in patients with colonic CD is similar to that of UC. Colonic dysplasia is a precursor to CRC in IBD. There is no clear evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis. Newer endoscopic and molecular techniques are being assessed for their effectiveness in augmenting conventional surveillance.
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PMID:Carcinogenesis in inflammatory bowel disease. 1782 53


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