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Clinical and experimental studies of monoclonal antibody to liver metastasis

Research Project

Project/Area Number 04670758
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionChiba Uni.,

Principal Investigator

MATSUBARA Hiromasa (1994)  Dep.of 2nd Surg., Chiba Uni., Sch.of Med., Assistant, 医学部・附属病院, 助手 (10261926)

奥山 和明 (1992-1993)  千葉大学, 医学部, 講師 (00152439)

Co-Investigator(Kenkyū-buntansha) ISONO Kaichi  Dep.of 2nd Surg., Chiba Uni., Sch.of Med.Professor, 医学部, 教授 (70009489)
MATSUBARA Hisahiro  Dep.of 2nd Surg., Chiba Uni., Sch.of Med.Fellow, 医学部・附属病院, 医員
粟野 友太  千葉大学, 医学部, 助手 (00241951)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsliver metastasis / intraarterial infusion system / catheter for intraarterial infusion system / monoclonal antibody
Research Abstract

It is studied the efficacy of intraarterial infusion therapy with an anti-cancer agent or monoclonal antibody for liver metastasis to prevent a frequent recurrence after resection of liver metastasis.
1. Experimental study : A human monoclonal antibody 4G12, which was developed by fusion of regional lymph node cells of lung cancer patient and non-secreting myeloma cell line of mouse, was studied for the efficacy. Immunohistochemical studies were performed with 98 human tissue sections. 4G12 highly reacted to esophageal squamous cell carcinoma (55/58,94.8%) and also to several adenocarcinomas of the stomach and colon. However none of normal esophageal tissue was stained. The study of cell-binding assay also confirmed reactivity of 4G12 to human squamous cell carcinoma cell line. In vivo, organ distribution and radiommunoscintigraphy were studied in nude mice bearing human esophageal cancer xenograft. Following i.v.administration of 1.7 MBq/body^<125>I-4G12, tumor/blood ratio reached a ma … More ximum of 4.24<plus-minus>0.19 at day 5. Radioimmunoscinti graphy showed the accumulation of radiolabeled 4G12 in the region of xenografted esophageal cancer, whereas radiolabeled non-specific human lgM was not accumulated in the cancer regions. The human monoclonal antibody 4G12 might become one of the useful tools for intraarterial infusion therapy.
2. Clinical study : At first, a system of informed consent had settled. In the choice of hepatic resection for colorectal cancer patients with liver metastases, it is specifically effective for thecases with synchronous H1 solitary liver metastasis, and post-operative intraarterial infusion therapy of MMC and ADM was recommended for metachronous liver metastasis. Complications and its management in the intraarterial infusion therapy were investigated. The complications of catheter thrombosis were most frequently observed in the patients with no knots of catheter tip. However, few complication was confirmed by inserting and locating catheter with tip knots.
3. Prospective study : In Japan, the trial of gene therapy has started, and we have already taken an approach to examine the feasibility of gene therapy. It is expected an application of monoclonal antibody for development of drug delivary system, and expected an efficacy of intraarterial infusion system for channel of gene therapy. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] 奥山和明: "大腸癌肝転移例に対する肝切除の有効性" 日本大腸肛門病学会雑誌. 46. 116-122 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kazuaki Okuyama: "Evaluation of PH-Operutive inlraavterial infusion chemotherapy for colorectal cancer with liver metastasis in hishlogical finchings" Reg.cancer Treat.1-2. 48-52 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 奥山 和明: "動注療法の合併症とその対策" 癌と化学療法. 19. 1007-1013 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 奥山 和明: "大腸癌肝転移例に対する術前・術後動注療法の意義" 癌と化学療法. 19. 1511-1514 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 奥山 和明: "癌転移の機序と臨床対策" Medicament News. 1378. 12-13 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松原 宏昌: "ヒト型モノクローナル抗体4G12(Human IgM)の食道癌に対する反応特異性と生体内分布" 日本外科学会雑誌. 94. 199-199 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松原 宏昌: "Proliferating cell nuclear antigenを用いた4型びまん浸潤型大腸癌の増殖活性の免疫組織化学的評価" 日本消化器外科学会雑誌. 26. 967-967 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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