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Conference Paper: Circulating endothelial progenitor cells mobilized by acute phase small-for-size graft injury promote tumor recurrence after liver transplantation

TitleCirculating endothelial progenitor cells mobilized by acute phase small-for-size graft injury promote tumor recurrence after liver transplantation
Authors
Issue Date2011
PublisherThe Transplantation Society.
Citation
The 12th TTS Basic Science Symposium and 2nd ESOT Basic Science Meeting (BSS 2011), Boston, MA., 11-14 June 2011. How to Cite?
AbstractOBJECTIVE: We aim to investigate the impact of acute-phase small-for-size graft injury on mobilization of circulating endothelial progenitor cells (EPCs) in the patients with hepatocellular carcinoma (HCC) after liver transplantation and to explore the molecular mechanism in a series of in vivo and in vitro functional studies. METHODS: In clinical study, 115 HCC recipients were included. The intragraft gene signature of the grafts greater (Group 1) and less than 60% (Group 2) of standard liver weight (SLW) were characterized by microarry analysis. Circulating EPCs (CD34+CD133+CD45-) were compared by FACS analysis. Clinical-pathological data including the incidence of tumor recurrence and metastasis were compared. In animal study, a rat orthotopic liver transplantation model using the recipient with liver cirrhosis was established with the application of whole or small-for-size (50%) graft. Circulating EPCs and intragraft mRNA levels of CXCL10/CXCR3 were compared. EPCs migration and differentiation in liver graft was further confirmed using a rat model with green fluorescence protein labeling. The direct role of CXCL10 on EPCs mobilization was further studied in a CXCL10-/- mouse model and in vitro assays. RESULTS: The patients were grouped into Group 1 (>= 60% SLW, n=37) and Group 2 (<60% SLW, n=78). The numbers of patients beyond Milan criteria [15/37(40.5%) vs 29/49(59.2%), p=0.838] or UCSF criteria [9/37(24.3%) vs 19/60(31.7%), p=1] were similar. Much more patients in Group 2 developed tumor recurrence and lung metastasis [19/78(24.4%) vs 3/37(8%), p=0.04]. Level of circulating EPCs was significantly higher in Group 2 (Day 3: 0.09% vs 0.002%, p=0.019; Week 4: 0.12% vs 0.033%, p=0.037; Week 8: 0.0585% vs 0.025%, p=0.018; Week 12: 0.055% vs 0.028%, p=0.025). Intragraft gene expression of CXCL10 was significantly high in Group 2. Over-expression of CXCL10 and more circulating EPCs was confirmed in the rat liver transplantation model using small-for-size graft. The direct role of CXCL10 on mobilization of circulating EPCs was further confirmed in CXCL10-/- mouse. CONCLUSION: A significantly higher population of postoperative circulating EPCs, which are mobilized by small-for-size graft injury through CXCL10/CXCR3 signaling, may lead to a higher incidence of tumor recurrence and metastasis after liver transplantation using small-for-size graft.
DescriptionAbstract
Persistent Identifierhttp://hdl.handle.net/10722/137908

 

DC FieldValueLanguage
dc.contributor.authorMan, Ken_US
dc.contributor.authorLing, Cen_US
dc.contributor.authorShao, Yen_US
dc.contributor.authorNg, KTPen_US
dc.contributor.authorFan, STen_US
dc.contributor.authorLo, CMen_US
dc.date.accessioned2011-08-26T14:36:43Z-
dc.date.available2011-08-26T14:36:43Z-
dc.date.issued2011en_US
dc.identifier.citationThe 12th TTS Basic Science Symposium and 2nd ESOT Basic Science Meeting (BSS 2011), Boston, MA., 11-14 June 2011.en_US
dc.identifier.urihttp://hdl.handle.net/10722/137908-
dc.descriptionAbstract-
dc.description.abstractOBJECTIVE: We aim to investigate the impact of acute-phase small-for-size graft injury on mobilization of circulating endothelial progenitor cells (EPCs) in the patients with hepatocellular carcinoma (HCC) after liver transplantation and to explore the molecular mechanism in a series of in vivo and in vitro functional studies. METHODS: In clinical study, 115 HCC recipients were included. The intragraft gene signature of the grafts greater (Group 1) and less than 60% (Group 2) of standard liver weight (SLW) were characterized by microarry analysis. Circulating EPCs (CD34+CD133+CD45-) were compared by FACS analysis. Clinical-pathological data including the incidence of tumor recurrence and metastasis were compared. In animal study, a rat orthotopic liver transplantation model using the recipient with liver cirrhosis was established with the application of whole or small-for-size (50%) graft. Circulating EPCs and intragraft mRNA levels of CXCL10/CXCR3 were compared. EPCs migration and differentiation in liver graft was further confirmed using a rat model with green fluorescence protein labeling. The direct role of CXCL10 on EPCs mobilization was further studied in a CXCL10-/- mouse model and in vitro assays. RESULTS: The patients were grouped into Group 1 (>= 60% SLW, n=37) and Group 2 (<60% SLW, n=78). The numbers of patients beyond Milan criteria [15/37(40.5%) vs 29/49(59.2%), p=0.838] or UCSF criteria [9/37(24.3%) vs 19/60(31.7%), p=1] were similar. Much more patients in Group 2 developed tumor recurrence and lung metastasis [19/78(24.4%) vs 3/37(8%), p=0.04]. Level of circulating EPCs was significantly higher in Group 2 (Day 3: 0.09% vs 0.002%, p=0.019; Week 4: 0.12% vs 0.033%, p=0.037; Week 8: 0.0585% vs 0.025%, p=0.018; Week 12: 0.055% vs 0.028%, p=0.025). Intragraft gene expression of CXCL10 was significantly high in Group 2. Over-expression of CXCL10 and more circulating EPCs was confirmed in the rat liver transplantation model using small-for-size graft. The direct role of CXCL10 on mobilization of circulating EPCs was further confirmed in CXCL10-/- mouse. CONCLUSION: A significantly higher population of postoperative circulating EPCs, which are mobilized by small-for-size graft injury through CXCL10/CXCR3 signaling, may lead to a higher incidence of tumor recurrence and metastasis after liver transplantation using small-for-size graft.-
dc.languageengen_US
dc.publisherThe Transplantation Society.-
dc.relation.ispartofTTS Basic Science Symposium and ESOT Basic Science Meeting, BSS 2011en_US
dc.titleCirculating endothelial progenitor cells mobilized by acute phase small-for-size graft injury promote tumor recurrence after liver transplantationen_US
dc.typeConference_Paperen_US
dc.identifier.emailMan, K: kwanman@hku.hken_US
dc.identifier.emailLing, C: lingcc@hku.hken_US
dc.identifier.emailShao, Y: yshao@hku.hken_US
dc.identifier.emailNg, KTP: ledodes@hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.authorityMan, K=rp00417en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.identifier.authorityLo, CM=rp00412en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros190183en_US
dc.publisher.placeCanada-
dc.description.otherThe 12th TTS Basic Science Symposium and 2nd ESOT Basic Science Meeting (BSS 2011), Boston, MA., 11-14 June 2011.-

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