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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-1-23
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pubmed:abstractText |
Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1600-6135
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
347-55
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17229077-Amides,
pubmed-meshheading:17229077-Animals,
pubmed-meshheading:17229077-Carcinoma, Hepatocellular,
pubmed-meshheading:17229077-Cell Line, Tumor,
pubmed-meshheading:17229077-Cell Movement,
pubmed-meshheading:17229077-Cell Proliferation,
pubmed-meshheading:17229077-Disease Models, Animal,
pubmed-meshheading:17229077-Enzyme Inhibitors,
pubmed-meshheading:17229077-Immunosuppressive Agents,
pubmed-meshheading:17229077-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17229077-Liver Neoplasms, Experimental,
pubmed-meshheading:17229077-Liver Transplantation,
pubmed-meshheading:17229077-Male,
pubmed-meshheading:17229077-Neoplasm Invasiveness,
pubmed-meshheading:17229077-Neoplasm Recurrence, Local,
pubmed-meshheading:17229077-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17229077-Pyridines,
pubmed-meshheading:17229077-Rats,
pubmed-meshheading:17229077-Rats, Inbred BUF,
pubmed-meshheading:17229077-Signal Transduction,
pubmed-meshheading:17229077-Tacrolimus,
pubmed-meshheading:17229077-rho-Associated Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model.
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pubmed:affiliation |
Second Department of Surgery, Faculty of Medicine, Hirashima University, Hiroshima, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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