UMLS:C0596263 - FACTA Search

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Query: UMLS:C0596263 (carcinogenesis)
64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level. The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1-) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.
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PMID:Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary mucinous carcinomas are usually microsatellite stable. 1280 58

Alterations in the expression of mucin family members play an important role as well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and progression of pancreatic cancer. We analyzed the expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic tumors. MUC1 expression was observed in almost all samples, whereas MUC2 expression was not. MUC5AC expression was observed in 73.9% of the cancerous regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in 37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression of these mucins was not observed in the hyperplastic regions and normal pancreatic duct and was observed in only two dysplastic regions. The survival of pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than that of other patients (P=0.04). In conclusion, the localization of mucin expression, especially stromal expression of MUC1 or SIMA, might be a prognostic factor for patients with pancreatic cancer.
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PMID:Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors. 1465 47

SOX2, a SRY-related HMG box protein, is thought to be an important transcription factor during organogenesis, including the stomach although the expression and function are unclear. We investigated SOX2 protein expression to clarify its roles in differentiation and carcinogenesis of the stomach. Using polyclonal SOX2 antibodies, expression of SOX2 in gastric normal mucosae, intestinal metaplasia and carcinomas from 68 gastric carcinoma patients was studied by immuohistochemistry. SOX2 was strongly and moderately expressed in the nuclei of the foveolar epithelium and intestinal metaplasia, respectively, the expression being much higher than that in carcinomas (p<0.0001). Using antibodies to MUC5AC, MUC2 and CD10, the 68 gastric carcinomas were classified into gastric type, intestinal type, mixed gastric and intestinal type, and null type. A significant difference in SOX2 expression was observed between the gastric and intestinal types (p<0.05), with a higher expression in the former than in the latter. Moreover, over-expression of SOX2 induced the mRNA expression of endogenous MUC5AC, a specific mucin marker for the gastric type, in COS-7 cells. Our findings indicate that SOX2 may play a role in differentiation of the human gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type.
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PMID:Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma. 1471

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.
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PMID:Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis. 1504 36

A current challenge is to define the biological characteristics of colon tumor cells resistant to chemotherapy. Distinct sub-populations of mucus-secreting cells were previously obtained from the colon cancer cell line HT-29 after long-term treatment with the anti-cancer drugs, 5-fluorouracil (5-FU) and methotrexate (MTX). Since mucins are increasingly implicated as playing a role in carcinogenesis, we studied the pattern of mucin expression in two HT-29 clones of mucus-secreting and two clones of enterocyte-like phenotype which differ in their capacity to resist to 5-FU and/or MTX. The expression of both transmembrane (MUC1, MUC3, MUC4) and secreted gel-forming (MUC2, MUC5AC, MUC5B, MUC6) mucins in clones was studied by northern and/or western blotting. The four HT-29 clones showed three cellular phenotypes: (1) The mucus-secreting clone HT29-5F12 consists of unpolarized cells with mucus secretions that have anti-colonic mucin immunoreactivity, and mainly expresses MUC2 and is resistant to 5-FU and sensitive to MTX; (2) The mucus-secreting clone HT29-5M21 forms a monolayer of polarized cells with strong anti-gastric mucin immunoreactivity and mainly expresses MUC5AC and MUC5B and is resistant to MTX and sensitive to 5-FU; (3) The two enterocyte-like clones, HT29-5F7 and HT29-5M12 are resistant to both MTX and 5-FU and express mainly MUC1 and MUC5B, respectively. These clones which originate from a same colorectal tumour and display different patterns of mucin expression as well as differing resistance to MTX and 5-FU will make useful in vitro models for studying the potential role of mucins or other biological markers in drug resistance pathways.
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PMID:Differential mucin expression in colon carcinoma HT-29 clones with variable resistance to 5-fluorouracil and methotrexate. 1505 Mar 69

MUCs are glycoproteins with various roles in homeostasis and carcinogenesis. Among other actions, MUC1 may inhibit cell-cell and cell-stroma interactions and function as a signal transducer, participating in cancer progression. In contrast, MUC2 is normally found only in goblet cells, where it contributes to the protective barrier function of these cells. Recently, a tumour suppressor role has been demonstrated for MUC2, and both MUC1 and MUC2 appear to have important roles in pancreatic neoplasia. MUC1 appears to be a marker of aggressive phenotype and may facilitate the vascular spread of carcinoma cells. In contrast, MUC2 is rarely detectable in aggressive pancreatic tumours, but is commonly expressed in intraductal papillary mucinous neoplasms (IPMNs), which are rare, indolent tumours, in intestinal IPMNs, and in indolent colloid carcinomas. MUC2 appears to be not only a marker of this indolent pathway, but also partly responsible for its less aggressive nature. Thus, in pancreatic neoplasia, MUC1 and MUC2 have potential diagnostic and prognostic value as markers of aggressive and indolent phenotypes, respectively, and have potential as therapeutic targets.
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PMID:MUC1 and MUC2 in pancreatic neoplasia. 1511 50

Myxoma is the most common benign neoplasm of the heart. This work is the first to present an unusual left atrium and mitral valve cardiac myxoma which cannot be completely resected. This cardiac myxoma was also associated with abundant mucopolysaccharidic matrix, including mucin. Mucin gene expression is cell- and tissue-specific, with variations during cell differentiation and inflammation, and is altered during carcinogenesis. The expression of mucin genes in cardiac myxoma has never been elucidated previously. Detailed immunohistochemical analysis of MUC1, MUC2 and MUC5AC has been performed in this left atrium and mitral valve myxoma. Notably, the expressions of mucins in cardiac myxoma must be further evaluated.
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PMID:Mucin gene expression in cardiac myxoma. 1511 1

Although general characteristics of intraductal papillary mucinous neoplasms (IPMNs) and their delineation from other pancreatic tumors have been well established, several issues regarding their biology and management remain unresolved. It has been noted briefly by us and other authors that there are different types of papillae in IPMNs; however, their frequency, biologic significance, and clinical relevance are unknown. In this study, the association of different papillary patterns with clinical, pathologic, and biologic parameters was studied in 74 IPMNs, and the expression profile of CDX2 (a specific marker and one of the key determinants of intestinal "programming," and a tumor suppressor) was determined immunohistochemically in addition to MUC1 (a marker of an "aggressive" phenotype in pancreatic neoplasia) and MUC2 ("intestinal type mucin," a marker of the "indolent" phenotype, and a tumor suppressor). The patterns of papillae identified and their association with these parameters were as follows: 1) The intestinal-type (Yonezawa's dark-cell type), similar to villous adenomas, was seen in 26 of 74 (35%) cases. The majority harbored carcinoma in situ (85%) or borderline atypia (15%). They tended to be large (mean, 5.5 cm). Most expressed CDX2 (95%) and MUC2 (92%) but not MUC1 (8%). This type was more commonly associated with colloid-type invasion (14 of 16 invasive carcinomas were of colloid type). 2) The pancreatobiliary type, characterized by arborizing papillae lined by cuboidal cells resembling papillary neoplasms of the biliary tract, was present in 22% of the cases. These were mostly graded as carcinoma in situ (94%); they rarely expressed CDX2 (6%) or MUC2 (19%) but often showed MUC1 labeling (44%). This pattern was more commonly associated with the tubular type of invasive carcinoma and had a slight tendency for a more aggressive clinical course. 3) The null type was characterized by abundant apical mucin and basally located nuclei, similar to the gastric foveolar epithelium. Thirty-one percent of IPMNs had this type of papillae, but this pattern was also present in the background of other IPMNs and in the cystic components of most cases as well. Most pure null-type IPMNs were devoid of complexity and consequently classified as adenoma (48%). They tended to be small (mean, 2.6 cm), were often negative for CDX2, MUC1, and MUC2, and were rarely associated with invasive carcinoma. 4) Some IPMNs (12%) exhibited features that were difficult to classify, and 2 cases had a mixture of pancreatobiliary and intestinal types of papillae. In conclusion, IPMNs include pathologically and biologically distinct epithelial patterns. CDX2 and MUC2 expression is relatively specific for the intestinal type papillae, confirming that these IPMNs indeed exhibit intestinal differentiation. Their close association with colloid carcinoma, which also shows consistent MUC2 and CDX2 expression, supports the existence of an intestinal pathway of carcinogenesis. This "metaplastic" pathway may reflect different genetic events in the development of these IPMNs, and the presence of intestinal differentiation may potentially be used in prognostication and stratification of patients into appropriate treatment categories.
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PMID:Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: delineation of an "intestinal" pathway of carcinogenesis in the pancreas. 1522 52

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.
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PMID:Phenotypic alterations of mucins and cytokeratins during gallbladder carcinogenesis. 1526 Aug 48

Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.
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PMID:Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. 1575 82

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