Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules participate in a broad variety of biological processes, i.e. tumor progression and inflammation, through their involvement in cell-to-cell interactions and immunoinflammatory cell migration. This review describes the basic properties of adhesion molecules with reference to inflammatory bowel disease and colorectal carcinoma. Accumulating data suggest that adhesion molecules could be pathogenetically pertinent to other gastrointestinal disorders such as celiac disease (nontropical sprue) and gastroduodenal ulcer. Future therapeutic approaches in inflammatory and malignant disorders may possibly be development of principles targeting adhesion molecules.
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PMID:Adhesion molecules in inflammatory and neoplastic intestinal diseases. 854 67

The peptides encoded by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans. Previous studies showed that up-regulation of TA1/ E16 expression was associated with rat hepatocarcinogenesis and human tumor cell lines; therefore, we analyzed several primary human tumors including a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript was detected in all but one colorectal carcinoma but not in normal colon or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size. TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus. Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue. Immunoperoxidase staining localized the protein primarily to the supranuclear region of colon carcinoma cells, whereas normal epithelial cells were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon. Up-regulation of this gene in various human cancers suggests a common role in the carcinogenic process and possible application as a tumor marker.
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PMID:Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products. 889 58

Microsatellite instability occurs in the colonic mucosa of patients with inflammatory bowel disease and may predispose the mucosa to neoplastic transformation. It is unknown whether microsatellite instability also plays a role in the neoplastic risk associated with primary sclerosing cholangitis. We examined 134 tissue samples from 21 patients with sclerosing cholangitis for microsatellite instability at eight loci. All tissues were also stained immunohistochemically using an antibody to the proliferation marker Ki-67. Microsatellite instability did not occur in any samples from the intrahepatic or extrahepatic biliary system, although one patient demonstrated instability in the colon. Ki-67 indices ranged from 0 to 2.5 in nondysplastic biliary epithelium and from 1.5 to 29.4 in areas of dysplasia. The absence of microsatellite instability in sclerosing cholangitis suggests that the genetic basis of neoplastic progression in chronic inflammatory disease of the bile ducts differs from that of intestinal cancers arising in the setting of chronic inflammatory bowel disease and may relate to differences in the microenvironment in these two sites.
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PMID:Microsatellite instability is absent in liver and biliary mucosa of patients with primary sclerosing cholangitis. 1008 Jan 56

Several matrix metalloproteinases (MMPs) have been implicated in intestinal inflammation, mucosal wound healing, and cancer progression. The purpose of this study was to examine the cellular location and putative function of MMP-19, MMP-26 (matrilysin-2), and MMP-28 (epilysin), in normal, inflammatory, and malignant conditions of the intestine. Peroperative tissue specimens from patients with ulcerative colitis (UC) (n = 16) and archival tissue samples of ischemic colitis (n = 9), Crohn's disease (n = 7), UC (n = 8), colon cancer (n = 20), and healthy intestine (n = 5) were examined using immunohistochemical analyses with polyclonal antibodies. Unlike many classical MMPs, MMP-19, MMP-26, and MMP-28 were all expressed in normal intestine. In inflammatory bowel disease (IBD), MMP- 19 was expressed in nonmigrating enterocytes and shedding epithelium. MMP-26 was detected in migrating enterocytes, unlike MMP-28. In colon carcinomas, MMP-19 and MMP-28 expression was downregulated in tumor epithelium. Staining for MMP-26 revealed a meshwork-like pattern between cancer islets, which was absent from most dedifferentiated areas. Our results suggest that MMP-19 is involved in epithelial proliferation and MMP-26 in enterocyte migration, while MMP-28 expression is not associated with inflammatory and destructive changes seen in IBD. In contrast to many previously characterized MMPs, MMP-19 and MMP-28 are downregulated during malignant transformation of the colon and may play a prominent role in tissue homeostasis.
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PMID:Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer. 1518 74

Alpha-methylacyl-CoA racemase (AMACR) catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters, and is overexpressed in a variety of neoplasms, such as prostate and colon cancer. The aim of this study was to evaluate AMACR expression in the metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus (BE), ulcerative colitis (UC), and Crohn's disease (CD) and to determine whether its expression can be used to detect dysplastic epithelium in these conditions. One hundred thirty-four routinely processed biopsy and/or resection specimens from 134 patients with BE [M/F ratio: 5.7, mean age: 67 y (36 negative (intestinal metaplasia only), 14 indefinite for dysplasia (IND), 16 low-grade dysplasia (LGD), 32 high-grade dysplasia (HGD), and 36 invasive adenocarcinoma (ACA)] and 74 specimens from 74 patients with inflammatory bowel disease (IBD) [56 with ulcerative colitis, 18 with Crohn's disease, M/F ratio: 1.8, mean age: 55 y (17 negative, 7 IND, 26 LGD, 10 HGD, and 14 ACA)] were immunostained with a monoclonal AMACR antibody (p504S). The degree of cytoplasmic staining in all cases was evaluated in a blinded fashion according to the following grading system: 0, negative (0% cells positive); 1+, 1% to 10% cells positive; 2+, 10% to 50% cells positive; or 3+, >50% cells positive. In patients with BE, AMACR was not expressed in any negative foci (0%) but was significantly increased (P<0.0001) in foci of LGD (38%), HGD (81%), and ACA (72%). Three of 14 (21%) IND foci from 3 BE patients were only focally positive (grade 1: 7%, 2: 14%). However, 1 of these 3 patients had follow-up information available and had developed ACA subsequently. Similarly, in patients with IBD, AMACR was not expressed in any foci considered negative for dysplasia, but was significantly increased (P<0.0001) in foci of LGD (96%), HGD (80%), and ACA (71%). Only 1/7 (14%) IND focus from 1 patient was focally positive (grade 1). The sensitivity for the detection of LGD and HGD in BE and IBD was 38% and 81%, and 96% and 80%, respectively, for the 2 types of disorders. The specificity was 100% for both BE and IBD. AMACR is involved in the neoplastic progression in BE and IBD. The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions.
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PMID:AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease. 1681 30

DNA hypermethylation is one of major epigenetic changes. Hypermethylation of many genes has been reported to be related with carcinogenesis and tumor progression of colorectal cancer. Some genes including estrogen receptor is associated with ageing, and changes related with ageing may be accelerated in inflammatory bowel disease. Furthermore, fecal DNA methylation will be able to be used as a marker of colorectal cancer and inflammatory bowel disease. Evaluation of hypermethylation potentially contributes diagnosis of colorectal diseases.
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PMID:DNA hypermethylation in colorectal neoplasms and inflammatory bowel disease: a mini review. 1709 3

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, developing colorectal cancer similar to human inflammatory bowel disease-associated neoplasia. TGF-beta1 is a multifunctional signaling molecule with a wide array of roles. Animal experiments suggest that TGF-beta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting a significant stimulation of tumor growth invasion and metastasis during tumor progression. We assessed association of functional polymorphisms (-1082G/A; -592C/A) and TGF-beta1 (-509C/T; +869C/T) influencing the IL-10 production to colorectal cancer risk in a case-control study of 62 patients and 124 matched controls. No significant differences were observed among cancer patients and controls for IL-10 -1082G/A; -592C/A genotype frequencies. Evaluation of odds ratios (OR) for the TGF-beta1 +869C/T genotypes showed a significant increased risk for individuals bearing +869CC genotype compared to +869CT- and +869TT-positive individuals. These results suggest that the +869C allele, responsible for a Leu-->Pro substitution in the signal peptide sequence of the TGF-beta1 protein, may have a predisposing role in the development of colorectal cancer.
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PMID:Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma. 1726 58

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal adenocarcinoma. The factors that result in IBD-associated carcinogenesis are not understood. We hypothesized that altered expression of intestinal epithelial tight junction proteins might contribute to neoplastic progression. Semiquantitative immunohistochemical staining of human biopsies was used to assess expression of the tight junction proteins claudin-1, claudin-2, claudin-4, and occludin in IBD, IBD-associated dysplasia, acute, self-limited colitis (ASLC), and sporadic adenomas. Claudin-1 and claudin-2 expression was elevated in active IBD, adenomas, and IBD-associated dysplasia, but not ASLC. In contrast, claudin-4 expression was elevated in both active IBD and ASLC. Occludin expression was similar to control in all cases. Importantly, in IBD, claudin-1 and claudin-2 expression correlated positively with inflammatory activity. To investigate mechanisms underlying altered claudin expression, beta-catenin activation was assessed as nuclear localization. Like claudin-1 and claudin-2, beta-catenin was markedly activated in IBD, sporadic dysplasia, and IBD-associated dysplasia, but was only slightly activated in ASLC. Taken together, these data suggest that beta-catenin transcriptional activity is elevated in chronic injury and that this may contribute to increased claudin-1 and claudin-2 expression. We speculate that increased claudin-1 and claudin-2 expression may be involved at early stages of transformation in IBD-associated neoplasia.
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PMID:Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. 1871 53

REG4, the latest member of the regenerating gene family, is overexpressed in inflammatory bowel diseases and gastrointestinal carcinomas. To date, its pathophysiologic role has not been well established. Using HT-29 models, we previously identified REG4 as being overexpressed in colorectal tumor cells displaying a drug-resistance phenotype; some also displayed invasive properties. Thus, we investigated the potential functions of REG4 in biological processes involved in colorectal tumor progression such as cell proliferation, migration and invasion. Colon cancer cells secreting REG4 (HT29-5M21, HT29-5F7 and HT29/REG4-8) or not (HT-29, HT29/CT1 and Caco-2/TC7) were used to analyze the autocrine and paracrine effects of REG4. REG4 was continuously secreted into the culture medium of colon cancer cells. REG4 stimulated cell growth in a paracrine manner after 24 h of treatment. Notably, REG4 promoted migration and invasion of tumor cells in both an autocrine and paracrine manner, and these effects were significantly decreased by concomitant treatment with an anti-REG4 antibody. Using pharmacological inhibitors, we showed that PI3K/Akt, PKAs, PKCs and Rho-like GTPases, but not MAPK, are involved in REG4 invasion signals. In addition, REG4 expression was found to be increased in tissues harboring proliferation and migration properties such as the developing intestine and tissues from inflammatory bowel disease, hyperplastic polyps, adenoma and colorectal cancers. In various situations, REG4 expression was not confined to proliferating cells, regenerating cells or cells of the invasive front of metastatic tumors, suggesting that extracellular REG4 may act on epithelial cells in a paracrine manner. Altogether, our results indicate that REG4 is a multifunctional secreted protein which acts on colorectal cancer cells in an autocrine and paracrine manner. According to its biological functions and tissue expression, REG4 may play an important role in the development and progression of colorectal cancer, as well as in intestinal morphogenesis and epithelium restitution.
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PMID:REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. 2012 89

Patients with ulcerative colitis and Crohn's disease are at increased risk of developing intestinal cancers via mechanisms that remain incompletely understood. However, chronic inflammation and repeated events of inflammatory relapse in inflammatory bowel disease (IBD) expose these patients to a number of signals known to have tumorigenic effects including persistent activation of the nuclear factor-kappaB and cyclooxygenase-2/prostaglandin pathways, release of proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6, and enhanced local levels of reactive oxygen and nitrogen species. These inflammatory signals can contribute to carcinogenesis via 3 major processes: 1) by increasing oxidative stress, which promotes DNA mutagenesis thus contributing to tumor initiation; 2) by activating prosurvival and antiapoptotic pathways in epithelial cells, thereby contributing to tumor promotion; and 3) by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of tumor cells, thus supporting tumor progression and metastasis. The present review integrates clinical and basic research observations in an attempt to provide a comprehensive understanding of how inflammatory processes may contribute to intestinal cancer development in IBD patients.
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PMID:Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease. 2015 48


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