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Article: Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts

TitleMolecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2010
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.annalsofsurgery.com
Citation
Annals Of Surgery, 2010, v. 251 n. 6, p. 1154-1161 How to Cite?
AbstractObjective: We aimed to explore the precise molecular mechanism of early and invasive tumor growth in a small-for-size graft after liver transplantation and to identify the distinct molecular signature linked to acute-phase injury and late-phase tumor invasiveness. Summary background data: Acute phase small-for-size liver graft injury plays an important role in tumor recurrence after liver transplantation. For prevention of such recurrence, understanding of its underlying mechanism will be important in developing novel therapeutic strategies. Methods: An orthotopic rat liver transplantation model was applied using whole grafts and small-for-size (50%) grafts. The recipients were injected with hepatoma cell lines via the portal vein to mimic tumor recurrence after liver transplantation. Tumor invasive properties were compared between the tumor developed from small and whole graft. Gene signatures of acute phase graft injury (days 1 and 3) and late phase tumor recurrence (days 14 and 21) were screened using cDNA microarray analysis and further confirmed by quantitative RT-PCR. The potential gene candidate CXCL10 was singled out for further functional studies to investigate its role in tumor progression. Results: A number of genes linked to inflammatory responses and tumor invasiveness were found over-expressed in small-for-size liver grafts and/or tumors developed in small liver grafts by cDNA microarray screening. Real-time RT-PCR also confirmed that the gene CXCL10 was over-expressed not only in small-for-size graft at the early phase, but also in tumor from small-for-size graft at the late phase after liver transplantation. In vitro functional studies further confirmed that CXCL10 promoted tumor-invasion-related properties and tumor-associated macrophage activation. Conclusion: CXCL10 over-expression, the distinct gene signature of acute-phase graft injury and tumor invasiveness in small-for-size liver grafts, may contribute to early tumor recurrence after liver transplantation. CXCL10 and its downstream signals may be potential therapeutic targets in the prevention of tumor recurrence after liver transplantation using small-for-size graft. © 2010 Lippincott Williams & Wilkins.
Persistent Identifierhttp://hdl.handle.net/10722/92831
ISSN
2015 Impact Factor: 8.569
2015 SCImago Journal Rankings: 4.503
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant CouncilRGC7606/06M
HKU5/CRF/08
University of Hong Kong
Funding Information:

Supported by Research Grant Council (RGC7606/06M and HKU5/CRF/08) and Seed funding for basic research, University of Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorMan, Ken_HK
dc.contributor.authorCo Shih, Ken_HK
dc.contributor.authorNg, KTPen_HK
dc.contributor.authorXiao, JWen_HK
dc.contributor.authorGuo, DYen_HK
dc.contributor.authorSun, CKWen_HK
dc.contributor.authorLim, ZXHen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorMau Lo, Cen_HK
dc.date.accessioned2010-09-17T10:58:41Z-
dc.date.available2010-09-17T10:58:41Z-
dc.date.issued2010en_HK
dc.identifier.citationAnnals Of Surgery, 2010, v. 251 n. 6, p. 1154-1161en_HK
dc.identifier.issn0003-4932en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92831-
dc.description.abstractObjective: We aimed to explore the precise molecular mechanism of early and invasive tumor growth in a small-for-size graft after liver transplantation and to identify the distinct molecular signature linked to acute-phase injury and late-phase tumor invasiveness. Summary background data: Acute phase small-for-size liver graft injury plays an important role in tumor recurrence after liver transplantation. For prevention of such recurrence, understanding of its underlying mechanism will be important in developing novel therapeutic strategies. Methods: An orthotopic rat liver transplantation model was applied using whole grafts and small-for-size (50%) grafts. The recipients were injected with hepatoma cell lines via the portal vein to mimic tumor recurrence after liver transplantation. Tumor invasive properties were compared between the tumor developed from small and whole graft. Gene signatures of acute phase graft injury (days 1 and 3) and late phase tumor recurrence (days 14 and 21) were screened using cDNA microarray analysis and further confirmed by quantitative RT-PCR. The potential gene candidate CXCL10 was singled out for further functional studies to investigate its role in tumor progression. Results: A number of genes linked to inflammatory responses and tumor invasiveness were found over-expressed in small-for-size liver grafts and/or tumors developed in small liver grafts by cDNA microarray screening. Real-time RT-PCR also confirmed that the gene CXCL10 was over-expressed not only in small-for-size graft at the early phase, but also in tumor from small-for-size graft at the late phase after liver transplantation. In vitro functional studies further confirmed that CXCL10 promoted tumor-invasion-related properties and tumor-associated macrophage activation. Conclusion: CXCL10 over-expression, the distinct gene signature of acute-phase graft injury and tumor invasiveness in small-for-size liver grafts, may contribute to early tumor recurrence after liver transplantation. CXCL10 and its downstream signals may be potential therapeutic targets in the prevention of tumor recurrence after liver transplantation using small-for-size graft. © 2010 Lippincott Williams & Wilkins.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.annalsofsurgery.comen_HK
dc.relation.ispartofAnnals of Surgeryen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleMolecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver graftsen_HK
dc.typeArticleen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailCo Shih, K: kcshih@hku.hken_HK
dc.identifier.emailNg, KTP: ledodes@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailMau Lo, C: chungmlo@hkucc.hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityCo Shih, K=rp01374en_HK
dc.identifier.authorityNg, KTP=rp01720en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityMau Lo, C=rp00412en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/SLA.0b013e3181d96e3den_HK
dc.identifier.pmid20485145-
dc.identifier.scopuseid_2-s2.0-77953022144en_HK
dc.identifier.hkuros170730-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953022144&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume251en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1154en_HK
dc.identifier.epage1161en_HK
dc.identifier.eissn1528-1140-
dc.identifier.isiWOS:000278561700025-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridCo Shih, K=35765776400en_HK
dc.identifier.scopusauthoridNg, KTP=7403178513en_HK
dc.identifier.scopusauthoridXiao, JW=24336664800en_HK
dc.identifier.scopusauthoridGuo, DY=36171425600en_HK
dc.identifier.scopusauthoridSun, CKW=7404248685en_HK
dc.identifier.scopusauthoridLim, ZXH=25822628500en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridLiu, Y=25928027200en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridMau Lo, C=7401771672en_HK

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