Dissecting the genetic susceptibility for cholangiocarcinoma in primary sclerosing cholangitis

Lazaridis, Konstantinos N.

doi:10.1002/hep.22100

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…The diagnosis of CCA can be challenging because its cholangiographic characteristics can imitate the stricturing lesions of PSC (115). The development of CCA is not reliably heralded by symptomatic or biochemical changes.…”

Section: Ccamentioning

confidence: 99%

Primary sclerosing cholangitis

Silveira

Lindor

2008

Canadian Journal of Gastroenterology

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Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a 'beaded' appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.

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Section: Ccamentioning

confidence: 99%

Primary sclerosing cholangitis

Silveira

Lindor

2008

Canadian Journal of Gastroenterology

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“…Chronic cholestatic disease in adults and children and in animal models is associated with an increased risk for development of hepatocellular carcinoma (HCC) (61, 92,[153][154][155][156][157][158][159][160][161][162]. Nuclear receptors and their respective ligands regulate transcriptional activity of target genes involved in tumor development and suppression.…”

Section: Cancermentioning

confidence: 99%

Nuclear receptor ligands in therapy of cholestatic liver disease

Sturm

Wagner²,

Trauner³

2009

Front Biosci

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Cholestasis is a clinical syndrome resulting from disturbed bile formation. The etiology includes different diseases ranging from genetic defects in hepatocellular bile formation to inflammatory diseases of the bile ducts. Many cholestatic diseases are progressive and ultimately fatal. Whatever the cause, cholestasis results in intrahepatic accumulation of cytotoxic bile acids which lead to liver injury reflected by disruption of hepatocellular integrity, inflammation, fibrosis, cirrhosis and increased risk for development of cancer. Determinants of bile secretion undergo an adaptive response during cholestasis aiming to minimize hepatic injury. This adaptation occurs by modification of transport and metabolism of bile acids and other organic solutes in liver, kidney and intestine. The underlying molecular mechanisms are mediated mainly at a transcriptional level by a complex network involving ligand-activated nuclear receptors. However, the adaptive response to accumulation of bile acids cannot fully prevent or repair liver injury in cholestasis. Therefore, novel therapeutic strategies have to be developed involving nuclear receptor ligands which may intensify the protection of the hepatobiliary system in cholestatic disease.

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“…The development of cancer is a complex biological process, and other yet unknown polymorphisms are likely to be associated with CC risk. Combining NKG2D SNPs with other polymorphisms in a panel of markers may be useful in creating a test to assess CC risk [29] .…”

Section: Nkg2dmentioning

confidence: 99%

Molecular mechanisms of cholangiocarcinoma

Fava

2010

WJGP

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Cholangiocarcinoma (CC), the malignant tumor of the epithelial cells lining the biliary ducts, has undergone a worldwide increase in incidence and mortality. The malignant transformation of the biliary cells originates from a multistep process evolving through chronic inflammation of the biliary tract to CC. In the last few years several advances have been towards understanding and clarifying the molecular mechanisms implicated in the cholangiocarcinogenesis process. However, many pathophysiologic aspects governing the growth of CC are still undefined. The poor prognosis of this tumor underlines the urgent need to codify the underlying molecular mechanisms involved in the growth and progression of CC in order to design effective preventive measures and valid treatment regimens. This review reports on progresses made in the last few years in clarifying the molecular pathways involved in the process of cholangiocarcinogenesis.

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Dissecting the genetic susceptibility for cholangiocarcinoma in primary sclerosing cholangitis

Cited by 8 publications

References 16 publications

Primary sclerosing cholangitis

Primary sclerosing cholangitis

Nuclear receptor ligands in therapy of cholestatic liver disease

Molecular mechanisms of cholangiocarcinoma

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