Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solu...

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Main Authors: Perry A. Soriano, Nian Liu, Erick Castillo, Brock Foster, Avo Artinyan, Joseph Kim, Wendong Huang, Lawrence D. Wagman
Format: Article
Language:English
Published: Hindawi Limited 2011-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.4061/2011/490463
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spelling doaj-9b4fc0c3b66b4309a3a463847df0dc8b2020-11-24T23:21:10ZengHindawi LimitedInternational Journal of Hepatology2090-34482090-34562011-01-01201110.4061/2011/490463490463Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine ModelPerry A. Soriano0Nian Liu1Erick Castillo2Brock Foster3Avo Artinyan4Joseph Kim5Wendong Huang6Lawrence D. Wagman7Liver Tumor Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USACenter for Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USALiver Tumor Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USALiver Tumor Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USALiver Tumor Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USALiver Tumor Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USACenter for Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USAThe Center for Cancer Prevention and Treatment, St. Joseph Hospital, 1000 West La Veta Avenue, Orange, CA 92868, USAIntroduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. 𝑇-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, 𝑃=0.048) with no difference on D7 (𝑃=0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.http://dx.doi.org/10.4061/2011/490463
collection DOAJ
language English
format Article
sources DOAJ
author Perry A. Soriano
Nian Liu
Erick Castillo
Brock Foster
Avo Artinyan
Joseph Kim
Wendong Huang
Lawrence D. Wagman
spellingShingle Perry A. Soriano
Nian Liu
Erick Castillo
Brock Foster
Avo Artinyan
Joseph Kim
Wendong Huang
Lawrence D. Wagman
Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
International Journal of Hepatology
author_facet Perry A. Soriano
Nian Liu
Erick Castillo
Brock Foster
Avo Artinyan
Joseph Kim
Wendong Huang
Lawrence D. Wagman
author_sort Perry A. Soriano
title Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
title_short Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
title_full Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
title_fullStr Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
title_full_unstemmed Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
title_sort oxaliplatin but not irinotecan impairs posthepatectomy liver regeneration in a murine model
publisher Hindawi Limited
series International Journal of Hepatology
issn 2090-3448
2090-3456
publishDate 2011-01-01
description Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. 𝑇-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, 𝑃=0.048) with no difference on D7 (𝑃=0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.
url http://dx.doi.org/10.4061/2011/490463
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