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1998 Fiscal Year Final Research Report Summary

Targeting Cancer Chemotherapy : For the Control of Metastatic Liver Cancer

Research Project

Project/Area Number 08045067
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionUniversity-to-University Cooperative Research
Research Field 応用薬理学・医療系薬学
Research InstitutionKumamoto University

Principal Investigator

MAEDA Hiroshi  Kumamoto University School of Medicine, Professor, 医学部, 教授 (90004613)

Co-Investigator(Kenkyū-buntansha) OLLIFF Simon P.  The University of Birmingham, Queen Elizabeth Hospital, Assistant Professor, クィーンエリザベスII病院, 講師
SEYMOUR Len W.  The University of Birmingham, CRC Institute for Cancer Studies, Associate Profes, がん研究センター, 助教授
KERR David J.  The University of Birmingham, CRC Institute for Cancer Studies, Director/Profess, がん研究センター, 所長/教授
KONNO Toshimitsu  Kumamoto University Hospital, Assistant Professor, 医学部附属病院, 講師 (60117348)
Project Period (FY) 1996 – 1998
KeywordsSMANCS / Lipiodol / hepatoma / EPR effect / new concept in cancer chemotherapy / arterial injection / preventive adjuvant chemotherapy / colon cancer / liver metastasis
Research Abstract

(1)To disseminate the state of the art for the treatment of primary cancer, the arterialinlection of SMANCS/Lipiodol with the hepatic or tumor feeding artery was performed at Queen Elizabeth II Hospital of the University of Birmingham, U.K.This method was new in Europe.
(2)We could confirm that this method, developed in Japan, is similarly effective inpatients in U.K.
(3)The understanding of the new concept for cancer chemotherapy is now established among oncologists in Birmingham, U.K.Namely, the amount of drug needs to result in regression of tumor should be based on the tumor size but not maximum tolerable dose as practiced in old concept. That is, dose regimen is proportional to the tumor size, which is also parallel to the response rate, but not body weight or surface area of the patients as in old concept. The rationale behinds this theory is that arterial administration of oily formulation is most selectively targeted to the tumor (> 1000-fold in tumor/blood concentration), but th … More is delivery method drug distribution was found of very little to elsewhere innormal tissues or organs. Thus, excessive amount of drug dosage is not needed in our system, which could damage normal tissues or organs.
(4)These clinical data from Queen Elizabeth II Hospital of the University of Biririgham were reported recently in two journals, and also in Joint Meeting of NCl (USA) EORTC (Europe) in June, 1998, Amsterdam.
(5)Utilizing this most effective tumor delivery system using lipiodol via tumor feeding artery, recombinant DNA of interteron-gamma (IFN-gamma)-poly L-lysine complex was injected into rabbit bearing VX-2 carcinoma in the liver. The result showed that gene was delivery to the tumor selectively, which expressing beta-galactosidase gene, but expression of IFN-gamma was very little or none. This indicates that enhanced and sustained gene expression is the key issue at this point for gene therapy, and yet premature.
(6)After obtaining a convincing result for the treatment of the primary liver cancer, we decided to approach our final goal ; that is, the control of colon cancer metastasis to the liver. The first choice of the treatment of colon cancer is surgical resection, however, about half of the patients undergo surgical removal of tumor develops liver metastasis. Our protocol is to inject SMANCS/Lipiodol (1-2 ml) into the portal vein upon surgery (laporatomy) because it is considered that colon tumor shedding or dissemination occurs during the surgical resection. Our experimental data using rabbit model showed that the incidence of cancer metastasis is reduced to less than 1 % of control without portal SMANCS treatment by SMANCS/Lipiodol via the portal vein. The collaborative study will be initiated within six months it we could find a sponsor. Less

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 前田浩、澤智裕: "21世紀に向けての癌治療のパラダイムシフト-ミサイル療法、DDS、QQL careの次にくるもの-" Drug Delivery System. 64(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jun Wu,他: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist,and a nitric oxide scavenger" Cancer Research. 58. 159-165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoichiro Noguchi,他: "Early phase tumor accumulation of macromolecures: A great difference between the tumor vs normal tissue in their clearance rate" Japanese Journal of Cancer Research. 89. 307-314 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Len W.Seymour,他: "A novel dosage approach for evaluation of SMANCS in the treatment of primary hepatocellular carcinoma" Int'l J.Oncology. 12. 1217-1223 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masami Kimura,他: "Intracavitary administration: Pharmacokinetic advantages of macromolecular anticancer agents against petioneal and pleural carcinomatoses" Anticancer Research. 18. 2547-2550 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 前田浩: "肝癌に対する高分子抗癌剤動注療法における癌組織集積性-とくにスマンクス/リピオドール療法を中心に-" 医学のあゆみ. 184. 385-391 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 前田浩: "SMANCS研究の最近のあゆみ" 癌と化学療法. 25. 1-9 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.R.Duncan, et al.: "Drug targeting in caner therapy : The magic bullet, What next?" J.Drug Targeting. 3. 317-319 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Maeda, et al.: "Bradykinin and nitric oxide in infectious disease and cancer." Immunopharmacology. 33. 222-230 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Maeda and T.Konno: "Metamorphosis of neocarzinostatin to SMANCS-Chemistry, Pharmacology and clinical effect of the first prototype anticancer polymer therapeutic." Neocarzinostatin : The Past, Present, and Future of an Anticancer Drug(eds.H.Maeda, K.Edo and N.Ishida). Springer-Verlag, Tokyo. 227-267 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Oda, et al.: "Targeted vinblastine chemotherapy with two preparations of lipiodol contrast medium." Anticancer Research. 17. 3521-3530 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Wu, et al.: "Modulation of enhance vascular permiability in tumor by a bradylinin antagonist, a cyclooxygenase inhibitor, and an NO scavenger." Cancer Research. 58. 159-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Noguchi, et al.: "Early phase tumor accumulation of macromolecules : A great difference in clearance rate between tumor and normal tissues." Jpn.J.Cancer Res.89. 307-314 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] L.W.Seymour, et al.: "A novel dosage approach for evaluation of SMANCS in the treatment of primary hepatocellular carcinorma." Int'l J.Oncology. 12. 1217-1223 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kimura, et al.: "Intracavitary administration : Pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and pleural carcinomatoses." Anticancer Research. 18. 2547-2550 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Olliff, et al.: "Evaluation of SMANCS [poly-(styrene-co-maleyl-half-n-butylate)-neocarzinostatin] in treatment of inoperable hepatocellular carcinoma." Annals of Oncology. 9, No.S2. 676 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Konno, et al.: "Targeted chemotherapy of hepatocellular carcinoma with SMANCS/Lipiodol-How to use SMANCS/Lipiodol.(in Japanese)" Gan to Kagaku Ryoho, (Jpn.J.Cancer & Chemother.). 25. 10-18 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Maeda: "Recent advances in research on SMANCS.(Review)(in Japanese)" Gan to Kagaku Ryoho, (Jpn.J.Cancer & Chemother.). 25. 1-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Kurruppu, et al.: "SMANCS-lipiodol complex arrests the growth of liver metastases from colorectal cancer in a murine model." Cancer. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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