Treatment of hepatocellular carcinoma after liver transplantation by graft versus tumor effcect using bone marrow co-transplantation

• Project/Area Number: 16591254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: DONO Keizo Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (60283769)
• Co-Investigator(Kenkyū-buntansha): NAGANO Hiroaki Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10294050) ; MARUBASHI Shigeru Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20362725) ; MONDEN Morito Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00127309)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Liver transplantation / Hepatocellular carcinoma / Bone marrow transplantation / Graft versus tumor effect / Micro metastasis / 肝細胞癌 / graft versus leukemia effect

Research Abstract

Liver transplantation has been established as an effective treatment for hepatocellular carcinoma with complete resection of tumors and restoration of liver function. However advanced cancer patients may already have extra hepatic lesions at the time of transplantation, which lead to recurrence of tumor after transplantation. Several adjuvant attempts has been made to reduce tumor recurrent rate after transplantation, but failed to confirm effectiveness.
In this study, we tried to show that liver transplantation together with bone marrow transplantation from the same donor can prevent recipients from recurrence by graft versus tumor effect of inoculated bone marrow derived immune cells.
In animal model, establishment of stable bone marrow chimera was difficult in cancer baring mice. Unfortunately we could not show direct anti cancer effect of co-transplanted marrow cells, the concept of graft versus tumor effect against residual solid tumor is attractive and further trial should be made in the future.

Research Products

• [Journal Article] J Surg Res (2005)
  • Author(s): Hayashi S., et al.
  • Journal Title: New measurement of hepatic blood flow by xenon CT system : an animal study with PGE1. 129.1 Pages: 24-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Arch Histol Cytol. (2005)
  • Author(s): Lu Z., et al.
  • Journal Title: Participation of autophagy in the degeneration process of rat hepatocytes after transplantation following prolonged cold preservation. 68.1 Pages: 71-80
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transplantation (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: Steroid-free living-donor liver transplantation in adults. 80.5 Pages: 704-706
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transplantation. (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: Living-donor liver transplantation with renoportal anastomosis for patients with large spontaneous splenorenal shunts. 80.12 Pages: 1671-1675
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] J Gastrointest Surg. (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: Portal venous reconstruction in a living liver donor with an anomalous hepatic arterial and portal venous anatomy. 9.3 Pages: 365-368
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] New measurement of hepatic blood flow by xenon CT system : an animal study with PGE1. (2005)
  • Author(s): Hayashi S., et al.
  • Journal Title: J Surg Res. 129(1) Pages: 24-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Participation of autophagy in the degeneration process of rat hepatocytes after transplantation following prolonged cold preservation. (2005)
  • Author(s): Lu Z., et al.
  • Journal Title: Arch Histol Cytol. 68(1) Pages: 71-80
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Steroid-free living-donor liver transplantation in adults. (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: Transplantation 80(5) Pages: 704-706
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Living-donor liver transplantation with renoportal anastomosis for patients with large spontaneous splenorenal shunts. (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: Transplantation 80(12) Pages: 1671-1675
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Portal venous reconstruction in a living liver donor with an anomalous hepatic arterial and portal venous anatomy. (2005)
  • Author(s): Marubashi S., et al.
  • Journal Title: J Gastrointest Surg. 9(3) Pages: 365-368
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] J Hepatol. (2004)
  • Author(s): Kobayashi S., et al.
  • Journal Title: In vivo real-time microangiography of the liver in mice using synchrotron radiation. 40.3 Pages: 405-408
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Surgery, (2004)
  • Author(s): Marubashi, M., et al.
  • Journal Title: Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model. 136.5 Pages: 1028-1037
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vivo real-time microangiography of the liver in mice using synchrotron radiation. (2004)
  • Author(s): Kobayashi S., et al.
  • Journal Title: J Hepatol. 40(3) Pages: 405-408
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] EFFECT OF PORTAL HEMODYNAMICS ON LIVER REGENERATION STUDIED IN A NOVEL PORTOHEPATIC SHUNT RAT MODEL. (2004)
  • Author(s): Marubashi S., Dono K., et al.
  • Journal Title: Surgery 136(5) Pages: 1028-1037
• [Journal Article] In vivo real-time microangiography of the liver in mice using synchrotron radiation. (2004)
  • Author(s): Kobayashi S., Dono K., et al.
  • Journal Title: Journal of Hepatology 40 Pages: 405-408
• [Journal Article] Clinical value of alterations in p73 gene, related to p53 at 1p36,in human hepatocellular carcinoma. (2004)
  • Author(s): Aoki T., Dono K., et al.
  • Journal Title: International journal of oncology 24 Pages: 441-446
• [Journal Article] Akt2 expression correlates with prognosis of human hepatocellular carcinoma. (2004)
  • Author(s): Xu Xundi., Dono K., et al.
  • Journal Title: Oncology Reports 11 Pages: 25-32
• [Journal Article] Partial Contribution of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand(TRAIL)/TRAIL Receptor Pathway to Antitumor Effects of Interferon-α/5-Fluorouracil against Hepatocellular Carcinoma. (2004)
  • Author(s): Yamamoto T., Dono K., et al.
  • Journal Title: Clinical Cancer Res 10 Pages: 7884-7895
• [Journal Article] PCR-array Gene Expression Profiling of Hepatocellular Carcinoma. (2004)
  • Author(s): Kurokawa Y., Dono K., et al.
  • Journal Title: J.Exp.Clin.Cancer Res 23(1) Pages: 135-141
• [Journal Article] Molecular-based prediction of early recurrence in hepatosellular carsinoma. (2004)
  • Author(s): Kurokawa Y., Dono K., et al.
  • Journal Title: Journal of Hepatology 41 Pages: 284-291
• [Journal Article] Molresular Prediction of Response to 5-Fluorouracil and Interferon-α Combination Chemotherapy on Advanced Hepatocellular Carcinoma. (2004)
  • Author(s): Kurokawa Y., Dono K., et al.
  • Journal Title: Clinical Cancer Research 10 Pages: 6029-6038
• [Journal Article] Interstitial pneumonia induced by combined intraarteria1 5-flourouracil and subcutaneous interferon-α therapy for advanced hepatocellular carcinoma. (2004)
  • Author(s): Yamamoto S., Dono K., et al.
  • Journal Title: Journal of Gastroenterology 39 Pages: 793-797
• [Journal Article] Xenon-inhalation computed tomography for noninvasive quantitative measurement of tissue blood flow in hepatocellular carcinoma. (2004)
  • Author(s): Murakami T., Dono K., et al.
  • Journal Title: Investigative Radiology 39(4) Pages: 211-215
• [Journal Article] Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model.
  • Author(s): Marubashi, M., et al.
  • Journal Title: Surgery Volume 136, Issue 5 Pages: 1028-1037
  • Description: 「研究成果報告書概要(欧文)」より