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)

A variety of premalignant lesions, including Barrett's esophagus, colonic polyps, ulcerative colitis, primary sclerosing cholangitis, intraductal mucin secreting papillomatosis are now well recognized and accessible to direct endoscopic assessment and biopsy or brushing. This review emphasizes the potential usefulness of genetic markers, in particular Ki-ras oncogene and p53 tumor suppressor gene mutations, in the endoscopic surveillance of these premalignant conditions. The adjunction of Ki-ras and p53 assays in material collected during endoscopic procedures may help the clinician detect earlier and with a higher accuracy neoplastic progression.
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PMID:Use of genetic markers during endoscopic screening and follow-up of gastrointestinal precancerous lesions. 757 78

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

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.
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PMID:Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm. 1158 58

In the therapy of hilar cholangiocarcinoma, the most favorable survival rates over the long-term are achieved by a surgical concept involving a no-touch-technique, en-bloc-resection and wide tumor-free margins. Currently, these goals can be best achieved by our strategy to combine extended right hepatic resections and principle portal vein resection. In spite of extending resectability to patients with locally advanced tumors, formally curative resections could be performed in 80% of the patients. The 5-year survival rate in these patients is 61%. Liver transplantation had been abandoned by most centers in the 1980s due to poor overall results. Recently, a neoadjuvant strategy involving radiochemotherapy has been reported to result in excellent survival figures at least in a subset of patients suffering from cholangiocellular carcinoma arising in a primary sclerosing cholangitis (PSC). This protocol has been mainly proposed by the Mayo Clinic group and reached 5-year survival rates of 80% in those patients in whom it had been applicable. A substantial drop out rate from this neoadjuvant regimen due to tumor progression or treatment related complications is still a problem.
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PMID:Radical surgery for hilar cholangiocarcinoma. 1804 97

Perihilar cholangiocarcinoma is a complex and devastating disease. Its complexity in part arises from the difficulty of establishing a diagnosis, especially in primary sclerosing cholangitis (PSC) patients. We have found fluorescent in situ hybridization (FISH) of cytologic specimens to be helpful in establishing a diagnosis of cholangiocarcinoma. In particular, FISH polysomy is useful in establishing a diagnosis of this malignancy. Endoscopic ultrasound with fine needle aspirates of regional lymph nodes has high utility in identifying patients who have advanced disease with lymph node metastases. Patients who are resectable by conventional surgical techniques are referred for surgery. However, patients who are not resectable or who have PSC and meet highly selective criteria become eligible for liver transplantation. The protocol employs external beam radiation therapy followed by brachytherapy, and then capecitabine until a staging laparotomy is performed. There is a high dropout rate while patients await liver transplantation of approximately 30% at 12 months, due to tumor progression. Overall, survival rates are approximately 65-70% at 5 years. The disease recurrence rate is 20%. Patients who have masses greater than 3 cm or who do not meet the criteria identified above have worse outcomes. These survival rates are better than those following surgical resection. Vascular complications occur frequently after liver transplantation. Portal venous anastomotic strictures are very common and can be managed by stent placement. In summary, neoadjuvant chemoradiation plus liver transplantation achieves excellent survival for patients with early-stage perihilar cholangiocarcinoma.
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PMID:Liver transplantation for perihilar cholangiocarcinoma. 2379 34

The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions, including differentiation, proliferation, survival, and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from complete. Current knowledge suggests a role for epidermal growth factor receptor (EGFR) in cholangiocyte specification and proliferation, and in hepatocyte transdifferentiation into cholangiocytes during liver regeneration to restore biliary epithelium integrity. High expression and activation of EGFR and/or ErbB2 were recently demonstrated in biliary lithiasis and primary sclerosing cholangitis, two cholangiopathies regarded as risk factors for CCA. In CCA, ErbB receptors are frequently overexpressed, leading to tumor progression and low prognosis. Anti-ErbB therapies were efficient only in preclinical trials and have suggested the existence of resistance mechanisms with the need to identify predictive factors of therapy response. This review aims to compile the current knowledge on the functions of ErbB receptors in physiology and physiopathology of the biliary epithelium. (Hepatology 2018;67:762-773).
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PMID:Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology. 2867 39