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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2005-5-3
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pubmed:abstractText |
Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis of hepatocellular carcinoma. Inhibition of VEGF receptors could theoretically reduce angiogenesis and tumor growth in hepatocellular carcinoma, but this remains to be proven with an experimental study. This study examined the angiogenesis-dependent and angiogenesis-independent activities of PTK787/ZK222584 (PTK787), a tyrosine kinase inhibitor of VEGF receptors, in nude mice bearing human hepatocellular carcinoma xenografts. The in vitro effects of PTK787 on proliferation, apoptosis, and cell cycle distribution in human hepatocellular carcinoma cell lines were also studied. Oral administration of PTK787 resulted in a significant reduction in tumor volume and microvessel formation of hepatocellular carcinoma xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis both in vivo and in vitro. The proapoptotic response was associated with down-regulation of Bcl-2 and Bcl-x(L) expression and induction of cleavage of caspase-3. In addition, PTK787 induced growth arrest in hepatocellular carcinoma cells, which was associated with G1 arrest and partial G2-M block. This effect correlated with an increase in p21(WAF1/ CIP1) (p21) and p27KIP1 (p27) protein expression. In conclusion, this study showed that PTK787 is a potent inhibitor of tumor growth in hepatocellular carcinoma by both antiangiogenic effect and direct effects on tumor cell proliferation and apoptosis. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human hepatocellular carcinoma.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Nonmuscle Myosin Type IIB,
http://linkedlifedata.com/resource/pubmed/chemical/Phthalazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/nonmuscle myosin type IIB heavy...,
http://linkedlifedata.com/resource/pubmed/chemical/vatalanib
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3691-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15867364-Angiogenesis Inhibitors,
pubmed-meshheading:15867364-Animals,
pubmed-meshheading:15867364-Apoptosis,
pubmed-meshheading:15867364-Carcinoma, Hepatocellular,
pubmed-meshheading:15867364-Carrier Proteins,
pubmed-meshheading:15867364-Caspase 3,
pubmed-meshheading:15867364-Caspases,
pubmed-meshheading:15867364-Cell Cycle Proteins,
pubmed-meshheading:15867364-Cell Growth Processes,
pubmed-meshheading:15867364-Cell Line, Tumor,
pubmed-meshheading:15867364-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15867364-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:15867364-Extracellular Matrix Proteins,
pubmed-meshheading:15867364-Humans,
pubmed-meshheading:15867364-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15867364-Liver Neoplasms,
pubmed-meshheading:15867364-Male,
pubmed-meshheading:15867364-Mice,
pubmed-meshheading:15867364-Mice, Inbred BALB C,
pubmed-meshheading:15867364-Mice, Nude,
pubmed-meshheading:15867364-Myosin Heavy Chains,
pubmed-meshheading:15867364-Neovascularization, Pathologic,
pubmed-meshheading:15867364-Nonmuscle Myosin Type IIB,
pubmed-meshheading:15867364-Phthalazines,
pubmed-meshheading:15867364-Protein Kinase Inhibitors,
pubmed-meshheading:15867364-Proteins,
pubmed-meshheading:15867364-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15867364-Pyridines,
pubmed-meshheading:15867364-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:15867364-Vascular Endothelial Growth Factor Receptor-2,
pubmed-meshheading:15867364-Xenograft Model Antitumor Assays,
pubmed-meshheading:15867364-bcl-X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Both antiangiogenesis- and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584.
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pubmed:affiliation |
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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