• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1991 Fiscal Year Annual Research Report

腫瘍・宿主条件の系統的解析に基づく癌化学療法の最適化設計

Research Project

Project/Area Number 03151032
Research InstitutionKyoto University

Principal Investigator

橋田 充  京都大学, 薬学部, 助教授 (20135594)

Co-Investigator(Kenkyū-buntansha) 内藤 幹彦  東京大学, 応用微生物研究所, 助手 (00198011)
谷川 允彦  福井医科大学, 医学部, 助教授 (00111956)
田代 田鶴子  (財)癌研究会, 癌化学療法センター, 研究員 (20085608)
西條 長宏  国立がんセンター研究所, 部長 (00215526)
加藤 哲郎  秋田大学, 医学部, 助教授 (40004642)
Keywords癌化学療法 / 腫瘍・宿主条件 / 薬物送達システム / ファ-マコキネティクス / 多剤耐性 / 化学塞栓療法 / モノクロ-ナル抗体 / メタロチオネイン
Research Abstract

本研究では、癌化学療法の効果を決定する腫瘍・宿主側因子として、腫瘍細胞の生化学的、生物学的感受性、腫瘍が発生あるいは転移した部位の血行動態などの環境、全身レベルでの物質代謝動態などを取り上げ、それぞれに関する基礎研究を通じて個々の段階における治療効果の増強を図ると共に、併せて癌を俯瞰的に眺める立場より癌化学療法の最適化設計指針を確立することを目的として研究を行なった。研究の第一段階として、耐性克服、転移防止、進行癌の治療、副作用の制御など癌化学療法の隘路となっている諸問題について各領域毎に問題点を取り上げ、それを克服する具体的なアプロ-チを模索した結果、全体に共通する生物学的要因に対する普遍的理解が進み、薬物送達システム(DDS)に代表される治療技術の開発が促進された。具体的には、例えば、シスプラチンに代表される抗癌剤の体内動態に関するファ-マコキネティクス解析により、至適投与法が確立され奏功率の予測が可能となった。また、モノクロ-ナル抗体を利用したタ-ゲティング療法や化学塞栓療法に関する基礎的・臨床的検討が進められ、こうした療法の適用と効果を明確にすることができた。一方、抗癌剤に対する耐性獲得現象に関しても、P糖蛋白が関与する耐性機構やシスプラチン耐性腫瘍細胞株の耐性機構について検討が行われ、耐性細胞に対しても有効性を示す新規抗癌剤の候補物質が見いだされた。さらに、抗癌剤の副作用を抑制する試みに関しても、メタロチオネイン誘導作用の強いビスマス化合物およびその投与法が見いだされ、臨床試験の段階に至った。今後の課題として、上記各項目に加えて、アンチセンスオリゴヌクレオチドを用いた遺伝子治療に対する基礎研究にも取り組んでいく予定である。

  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Akinori Noguchi: "Tumor localization and in vivo antitumor activity of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C-dextran conjugate" Japan Journal of Cancer Research. 82. 219-226 (1991)

  • [Publications] Koyo Nichida: "Hepatic disposition characteristics of electrically charged macromolecules in rat in vivo and in the perfused liver" Pharmaceutical Research. 8. 437-444 (1991)

  • [Publications] 野口 明則: "新しい合成法による抗ヒト大腸癌モノクロ-ナル抗体A7とマイトマイシンCーデキストラン結合体の複合体の合成" Drug Delivery System. 6. 171-175 (1991)

  • [Publications] Koyo Nishida: "Hepatic disposition characteristics of ^<111>In-labeled lactosaminated bovine serum albumin in rats" Pharmaceutical Research. 8. 1253-1256 (1991)

  • [Publications] Masaaki Masegi: "Permeability of macromolecules in cultured endothelial and tumor cell layers on microporous membranes" International Journal of Pharmaceutics. 78. 103-113 (1992)

  • [Publications] Makiya Nishikawa: "Demonstration of the receptor-mediated hepatic uptake of dextran in mice" Journal of Pharmacy and Pharmacology. 44. (1992)

  • [Publications] 橋田 充: "癌治療のためのDDSの開発と問題点" Drug Delivery System. 7. 5-14 (1992)

  • [Publications] Makiya Nishikawa: "Pharmacokinetics of receptor-mediated hepatic uptake of glycosilated albumin in mice" International Journal of Pharmaceutics. (1992)

  • [Publications] S.Niimi: "Resistant to anticancer drug in NTH3T3 cells transfected with c-myc and/or c-H-ras genes" British Journal of Cancer. 63. 237-241 (1991)

  • [Publications] Yasutsuna Sasaki: "Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay" Cancer Chemotherapy and Pharmacology. 27. 263-270 (1991)

  • [Publications] Yasutsuna Sasaki: "Phase I study and pharmacological analysis of cis-diammine (glycolato)platinum (254-S;NSC 375101D) administered by 5-day continuous intravenous infusion" Cancer Research. 51. 1472-1477 (1991)

  • [Publications] M.Nishiyama: "Relationship between accumilation,intracellular metabolism and DNA damage of fluoro-doxorubicin (ME2203) and its metabolite (M1) in multi-drug resistant K562 cells" Journal of Cell Pharmacology. 2. 104-111 (1991)

  • [Publications] Toshihiko Morikage: "Reversal of cisplatin resistance with amphotericin B in a non-small cell lung cancer cell line" Japanese Journal of Cancer Research. 82. 747-751 (1991)

  • [Publications] Kazuo Kasahara: "Metallothionein content correlates with the sensitivity of human cell lung cancer cell lines to cisplatin" Cancer Reserch. 51. 3237-3242 (1991)

  • [Publications] Yuichiro Takeda: "Establishment of a human leukemia subline resistant to the growth inhibitory effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) and showing non-P-glycprotein-mediated multi-drug resistance" International journal of Cancer. 48. 931-937 (1991)

  • [Publications] Jacquerline A.Goldberg: "Mitomycin C-loaded microcapsules in the treatment of colorectal liver metastases:Pharmacokinetics of regionally administered particulate chemotherapy" Cancer. 67. 952-955 (1991)

  • [Publications] Nobuhuko Tanigawa: "Significance of surgical adjuvant chemotherapy for gastric cancer" Journal of Surgical Oncology. 46. 203-207 (1991)

  • [Publications] Nobuhiko Tanigawa: "In vitro growth ability and chemosensitivity of biopsied gastric and colorectal cancer cells assessed with the human tumor clonogenic assay and the thymidine incorporation assay" European Journal of Cancer. 28. 31-34 (1992)

  • [Publications] Takumi Shimomatsuya: "Proliferative activity of human tumors:Assessment of bromodeoxyuridine and flow cytometory" Japanese Journal of Caner Research. 82. 357-362 (1991)

  • [Publications] H.Morimoto: "Significance of postoperative early chemotherapy for locoregional lymph node metastases of gastric and colorectral cancer" Oncelogy. 48. 210-214 (1991)

  • [Publications] Tazuko Tashiro: "Characterization of acquired resistance to cis-diammine-dichloro-platinum(II) in mouse leukemia cell lines" Japanese Journal of cancer Research. 83. 219-225 (1992)

  • [Publications] M.Watanabe: "Cellular pharmacology of MX2,a new morpholino anthracycline,in human pleiotropic drug-resistant cells" Cancer Research. 51. 157-161 (1991)

  • [Publications] Mikihiko Naito: "Two types of interaction between P-glycoprotein and ionophore antibiotics" Journal of Cell Pharmacology. 2. 263-267 (1991)

  • [Publications] T.Isoe: "Cisplatin inhibits ubiquitin-ATP-dependent proteolysis and ubiquitination" Anticancer Research. 11. 1905-1910 (1991)

  • [Publications] S.Ishii: "Expression of 85-kDa protein of adriamycin-resistant tumor cells during hepatopoietic differentiation of THP-4 and HEL cells" Japanese Journal of Cancer Research. 83. 107-112 (1992)

  • [Publications] M.Satoh: "Effect of preinduction of metallothionein of paraquat toxicity in mice" Archives of Toxicology. 66. 145-148 (1992)

  • [Publications] M.Satoh: "Effect of co-administration of selenite on toxicity and antitumoractivity of cis-diamminedichloroplatinum(II) administered repeatedly in mice" Cancer Chemotherapy and Pharmacology. (1992)

  • [Publications] O.Kagimoto: "Effect of the administration of bismuth mitrate on radiogenic thymoma induction in mice" Journal of Radiation Research. (1992)

  • [Publications] Kanji Takada: "Pharmacokinetics of FK-506,a novel immunosuppressant,after intravenous and oral administration to rats" Journal of Pharmacobio-Dynamics. 14. 34-42 (1991)

  • [Publications] 高後 裕: "鉄結合蛋白質トランスフェリンとその受容体" 蛋白質・核酸・酵素. 37. 26-36 (1992)

  • [Publications] Yoshinobu Takakura (Eds.V.J.Stella and W.N.A.Charman): "Lymphatic Transport after Parenteral Drug Administration,In "Lymphatic Transport of Drugs"" CRC Press(Boca Raton), 251-272 (1992)

  • [Publications] 橋田 充(片岡 一則編): "薬物送達システムによる選択的化学療法,生命工学シリ-ズIII・生命材料工学" 裳華房, 175-202 (1991)

  • [Publications] Tetsuro Kato (Eds.A.R.Alderson et al.): "Mitomycin Embolization (Chemoembolization) in the Treatment of Renal Cell Carcinoma,In "Urological Oncology:Dilemmas and Developments" pp.29-37" John Wiley & Sons (Chichesoer), (1991)

  • [Publications] 永沼 章(井村 裕夫編): "副作用軽減への新しいアプロ-チ,がんのバイオサイエンス4 pp.94ー105" 東京大学学術出版会, (1991)

  • [Publications] Yutaka Kohgo (Eds.G.Y.Wu and C.H.Wu): "Mechanism and Clinical Significance of Soluble Hepatic Cell Surface Receptors,In "Liver Disease"" Marcel Dekker Inc.(New York), 305-319 (1991)

URL: 

Published: 1993-03-16   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi