Article: FTY720: A promising agent for treatment of metastatic hepatocellular carcinoma

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TitleFTY720: A promising agent for treatment of metastatic hepatocellular carcinoma
AuthorsLee, TK1 2
Man, K1 2
Ho, JW1 2
Wang, XH1
Poon, RTP1 2
Xu, Y3
Ng, KT1 2
Chu, AC1 2
Sun, CK1 2
Ng, IO1 2
Sun, HC3
Tang, ZY3
Xu, R1 2
Fan, ST1 2
Issue Date2005
PublisherAmerican Association for Cancer Research.
CitationClinical Cancer Research, 2005, v. 11 n. 23, p. 8458-8466 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-05-0447
AbstractPurpose: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential). Experimental Design: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases. Results: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner. Conclusion: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis. © 2005 American Association for Cancer Research.
ISSN1078-0432
2011 Impact Factor: 7.742
2011 SCImago Journal Rankings: 1.066
DOIhttp://dx.doi.org/10.1158/1078-0432.CCR-05-0447
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLee, TK
dc.contributor.authorMan, K
dc.contributor.authorHo, JW
dc.contributor.authorWang, XH
dc.contributor.authorPoon, RTP
dc.contributor.authorXu, Y
dc.contributor.authorNg, KT
dc.contributor.authorChu, AC
dc.contributor.authorSun, CK
dc.contributor.authorNg, IO
dc.contributor.authorSun, HC
dc.contributor.authorTang, ZY
dc.contributor.authorXu, R
dc.contributor.authorFan, ST
dc.date.accessioned2010-09-06T09:43:19Z
dc.date.available2010-09-06T09:43:19Z
dc.date.issued2005
dc.description.abstractPurpose: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential). Experimental Design: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases. Results: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner. Conclusion: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis. © 2005 American Association for Cancer Research.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationClinical Cancer Research, 2005, v. 11 n. 23, p. 8458-8466 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-05-0447
dc.identifier.doihttp://dx.doi.org/10.1158/1078-0432.CCR-05-0447
dc.identifier.epage8466
dc.identifier.hkuros116899
dc.identifier.isiWOS:000233701300033
dc.identifier.issn1078-0432
2011 Impact Factor: 7.742
2011 SCImago Journal Rankings: 1.066
dc.identifier.issue23
dc.identifier.openurl
dc.identifier.pmid16322309
dc.identifier.scopuseid_2-s2.0-28544451354
dc.identifier.spage8458
dc.identifier.urihttp://hdl.handle.net/10722/88434
dc.identifier.volume11
dc.languageeng
dc.publisherAmerican Association for Cancer Research.
dc.publisher.placeUnited States
dc.relation.ispartofClinical Cancer Research
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshAntigens, CD34 - metabolism
dc.subject.meshCarcinoma, Hepatocellular - drug therapy - metabolism - secondary
dc.subject.meshDisease Models, Animal
dc.subject.meshDown-Regulation
dc.subject.meshHumans
dc.subject.meshImmunosuppressive Agents - therapeutic use
dc.subject.meshLiver Neoplasms, Experimental - drug therapy - metabolism - pathology
dc.subject.meshMice
dc.subject.meshMice, Nude
dc.subject.meshMicrocirculation
dc.subject.meshNeovascularization, Pathologic - prevention & control
dc.subject.meshPropylene Glycols - therapeutic use
dc.subject.meshSphingosine - analogs & derivatives
dc.subject.meshTumor Cells, Cultured
dc.subject.meshVascular Endothelial Growth Factor A - metabolism
dc.subject.meshWound Healing
dc.subject.meshrac GTP-Binding Proteins - chemistry - metabolism
dc.titleFTY720: A promising agent for treatment of metastatic hepatocellular carcinoma
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Centre for the Study of Liver Disease
  3. Fudan University