Source:http://linkedlifedata.com/resource/pubmed/id/19465904
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2009-7-31
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pubmed:abstractText |
Systemic analysis for chromosomal instability and inactivation of cell cycle checkpoints are scarce during hepatocarcinogenesis. We studied 24 patients with chronic B viral cirrhosis including 30 cirrhotic regenerative nodules, 35 low-grade dysplastic nodules, 15 high-grade dysplastic nodules, 7 dysplastic nodules with hepatocellular carcinoma foci, and 18 hepatocellular carcinomas. Eight normal livers were studied as the control group. Telomere length and micronuclei were detected by Southern blot and Feulgen-fast green dyeing technique, respectively, and p21(WAF1/CIP1) expression was studied by immunohistochemistry. Micronuclei >1 per 3000 hepatocytes were found in 17% of low-grade dysplastic nodules, 87% of high-grade dysplastic nodules, and 100% of high-grade dysplastic nodules with hepatocellular carcinoma foci and hepatocellular carcinomas in contrast to those of all normal livers, and 90% of cirrhosis showed no micronuclei. The micronuclei index showed a gradual increase during hepatocarcinogenesis and there was a significant increase between cirrhosis and low-grade dysplastic nodules, low-grade dysplastic nodules and high-grade dysplastic nodules, and high-grade dysplastic nodules and hepatocellular carcinomas. Telomere length showed a gradual shortening during hepatocarcinogenesis and a significant reduction was found in high-grade dysplastic nodules (P=0.024) and hepatocellular carcinomas (P=0.031) compared with normal and cirrhotic livers. The micronuclei index was correlated with telomere shortening (P=0.016). The p21(WAF1/CIP1) labeling index was significantly higher in cirrhosis than in normal livers (P=0.024) and markedly decreased in low-grade dysplastic nodules, high-grade dysplastic nodules, and hepatocellular carcinomas compared with cirrhosis (P<0.05). The p21(WAF1/CIP1) labeling index was associated with telomere length (P<0.001) but not micronuclei index. This study shows that telomere shortening, chromosomal instability, and inactivation of p21(WAF1/CIP1) checkpoint function occur in low-grade dysplastic nodules as well as in high-grade dysplastic nodules, and their cooperation is considered to be critical for malignant transformation during hepatitis B virus associated-multistep hepatocarcinogenesis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1530-0285
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1121-31
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pubmed:meshHeading |
pubmed-meshheading:19465904-Adult,
pubmed-meshheading:19465904-Blotting, Southern,
pubmed-meshheading:19465904-Carcinoma, Hepatocellular,
pubmed-meshheading:19465904-Cell Transformation, Neoplastic,
pubmed-meshheading:19465904-Chromosomal Instability,
pubmed-meshheading:19465904-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:19465904-Female,
pubmed-meshheading:19465904-Gene Expression,
pubmed-meshheading:19465904-Gene Expression Profiling,
pubmed-meshheading:19465904-Gene Silencing,
pubmed-meshheading:19465904-Hepatitis B, Chronic,
pubmed-meshheading:19465904-Humans,
pubmed-meshheading:19465904-Immunohistochemistry,
pubmed-meshheading:19465904-Liver Neoplasms,
pubmed-meshheading:19465904-Male,
pubmed-meshheading:19465904-Micronuclei, Chromosome-Defective,
pubmed-meshheading:19465904-Middle Aged,
pubmed-meshheading:19465904-Precancerous Conditions,
pubmed-meshheading:19465904-Telomere
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pubmed:year |
2009
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pubmed:articleTitle |
Chromosomal instability, telomere shortening, and inactivation of p21(WAF1/CIP1) in dysplastic nodules of hepatitis B virus-associated multistep hepatocarcinogenesis.
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pubmed:affiliation |
Department of Pathology, Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Center for Chronic Metabolic Disease, Yonsei University College of Medicine, Seoul, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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