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Article: The significance of acute phase small-for-size graft injury on tumor growth and invasiveness after liver transplantation

TitleThe significance of acute phase small-for-size graft injury on tumor growth and invasiveness after liver transplantation
Authors
Issue Date2008
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.annalsofsurgery.com
Citation
Annals Of Surgery, 2008, v. 247 n. 6, p. 1049-1057 How to Cite?
AbstractOBJECTIVE: To test the hypothesis that acute phase small-for-size graft injury may promote late phase tumor recurrence after liver transplantation. SUMMARY BACKGROUND DATA: Living donor liver transplantation may provide the substantial intention-to-treat survival advantage for liver cancer patients. However, liver grafts from live donors are almost always small for size for adult recipients. Besides, tumor recurrence and metastasis after living donor liver transplantation have been reported. METHOD: An orthotopic Buffalo rat liver transplantation model using whole (100%, group W) and small-for-size grafts (50%, group S) was applied. Hepatoma cells were injected into the grafts after reperfusion. Comparison was made as regards acute phase graft injury and tumor growth together with cell proliferation (Ki67), angiogenesis (vascular endothelial growth factor), stellate cell activation (α-smooth muscle actin), and cell signaling pathway related to migration and invasion (Rac, rho-associated, coiled-coil containing protein kinase, and proline-rich tyrosine kinase 2). Invasiveness of the tumors developed was further assessed after their direct implantation into livers of nude mice. RESULTS: Liver tumors developed earlier and faster in group S with significantly greater tumor burden [hepatic replacement area: 61%; range, 47%-72%; vs. 18%; 12%-27%; P = 0.001] and tumor cell proliferation (92% vs. 59%; P = 0.0021) in a more invasive growth pattern with a higher incidence of venous invasion (91.7% vs. 25%; P = 0.003) and more frequent hepatic stellate cell activation. There was upregulation of protein expression of Rac/rho-associated, coiled-coil containing protein kinase/proline-rich tyrosine kinase 2/vascular endothelial growth factor signaling in group S. When implanted into livers of nude mice, tumors from group S had a higher incidence of local (70% vs. 0%; P = 0.003) and lung metastasis (50% vs. 0%; P = 0.033). This phenotype was consistent with their ultrastructural features linking to angiogenesis and invasiveness. CONCLUSION: Significant activation of cell signaling pathways leading to tumor invasion and migration in small-for-size liver grafts promotes tumor growth and metastasis after liver transplantation. © 2008 Lippincott Williams & Wilkins, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/88620
ISSN
2015 Impact Factor: 8.569
2015 SCImago Journal Rankings: 4.503
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMan, Ken_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorXiao, JWen_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorSun, BSen_HK
dc.contributor.authorNg, IOen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorSun, CKen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T09:45:46Z-
dc.date.available2010-09-06T09:45:46Z-
dc.date.issued2008en_HK
dc.identifier.citationAnnals Of Surgery, 2008, v. 247 n. 6, p. 1049-1057en_HK
dc.identifier.issn0003-4932en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88620-
dc.description.abstractOBJECTIVE: To test the hypothesis that acute phase small-for-size graft injury may promote late phase tumor recurrence after liver transplantation. SUMMARY BACKGROUND DATA: Living donor liver transplantation may provide the substantial intention-to-treat survival advantage for liver cancer patients. However, liver grafts from live donors are almost always small for size for adult recipients. Besides, tumor recurrence and metastasis after living donor liver transplantation have been reported. METHOD: An orthotopic Buffalo rat liver transplantation model using whole (100%, group W) and small-for-size grafts (50%, group S) was applied. Hepatoma cells were injected into the grafts after reperfusion. Comparison was made as regards acute phase graft injury and tumor growth together with cell proliferation (Ki67), angiogenesis (vascular endothelial growth factor), stellate cell activation (α-smooth muscle actin), and cell signaling pathway related to migration and invasion (Rac, rho-associated, coiled-coil containing protein kinase, and proline-rich tyrosine kinase 2). Invasiveness of the tumors developed was further assessed after their direct implantation into livers of nude mice. RESULTS: Liver tumors developed earlier and faster in group S with significantly greater tumor burden [hepatic replacement area: 61%; range, 47%-72%; vs. 18%; 12%-27%; P = 0.001] and tumor cell proliferation (92% vs. 59%; P = 0.0021) in a more invasive growth pattern with a higher incidence of venous invasion (91.7% vs. 25%; P = 0.003) and more frequent hepatic stellate cell activation. There was upregulation of protein expression of Rac/rho-associated, coiled-coil containing protein kinase/proline-rich tyrosine kinase 2/vascular endothelial growth factor signaling in group S. When implanted into livers of nude mice, tumors from group S had a higher incidence of local (70% vs. 0%; P = 0.003) and lung metastasis (50% vs. 0%; P = 0.033). This phenotype was consistent with their ultrastructural features linking to angiogenesis and invasiveness. CONCLUSION: Significant activation of cell signaling pathways leading to tumor invasion and migration in small-for-size liver grafts promotes tumor growth and metastasis after liver transplantation. © 2008 Lippincott Williams & Wilkins, Inc.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.subject.meshAcute-Phase Reaction - metabolism - pathology-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshGraft Survival-
dc.subject.meshLiver Neoplasms - pathology - surgery-
dc.subject.meshLiver Transplantation-
dc.titleThe significance of acute phase small-for-size graft injury on tumor growth and invasiveness after liver transplantationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0003-4932&volume=247&issue=6&spage=1049&epage=1057&date=2008&atitle=The+significance+of+acute+phase+small-for-size+graft+injury+on+tumor+growth+and+invasiveness+after+liver+transplantationen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailNg, IO: iolng@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityNg, IO=rp00335en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/SLA.0b013e31816ffab6XXXen_HK
dc.identifier.pmid18520234-
dc.identifier.scopuseid_2-s2.0-44449132236en_HK
dc.identifier.hkuros144257en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44449132236&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume247en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1049en_HK
dc.identifier.epage1057en_HK
dc.identifier.eissn1528-1140-
dc.identifier.isiWOS:000256262500020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridXiao, JW=24336664800en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridSun, BS=23101636500en_HK
dc.identifier.scopusauthoridNg, IO=7102753722en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridSun, CK=7404248685en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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