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1997 年度 実績報告書

分子標的治療の臨床応用へのアプローチ

研究課題

研究課題/領域番号 09255104
研究種目

重点領域研究

研究機関名古屋市立大学

研究代表者

上田 龍三  名古屋市立大学, 医学部, 教授 (20142169)

研究分担者 大野 竜三  浜松医科大学, 教授 (70093002)
花井 陳雄  協和醗酵工業株式会社, 主任研究員
真弓 忠範  大阪大学, 薬学部, 教授 (00098485)
遠藤 啓吾  群馬大学, 医学部, 教授 (10115800)
山口 俊晴  京都府立医科大学, 助教授 (90111327)
キーワード癌組織血管内皮細胞 / モノクローナル抗体 / ミサイル療法 / キメラ抗体 / 微少残存腫瘍(MRD) / 分化誘導療法 / 分子標的 / ADF / チオレドキシン
研究概要

1.抗体療法に関しては、
1)癌組織血管内皮細胞(TEC)に対するモノクローナル抗体TES-23の作成に成功。がん組織血管を標的としたミサイル療法の有用性が示唆された(真弓)。2)ガングリオシドGM2を認識するマウスモノクローナル抗体の遺伝子を単離し、コンピューターモデリングを利用してヒト化抗体を作成(花井)。3)キメラ抗体とネオカルチノスタチン複合体chA7-NCSの投与例における免疫反応を解析(山口)。4)Ph陽性急性リンパ性白血病のBMT後の再発に微少残存腫瘍(MRD)の持続的増加の関与が示された。悪性リンパ腫に対するCD34陽性造血幹細移植療法を検討した(上田)。5)I-131標識CD20抗体のin vitroならびに動物モデルの検討から、本治療法の有用性が示唆された(遠藤)。
2.分化誘導療法に関しては、
1)ホメオボックスB6、B9遺伝子の顆粒球系分化を明らかとした(大野)。2)白血病細胞の分化において、異なる二種類の分化誘導剤の併用により相乗効果をもたらすことを明らかにした(本間)。
3.化学療法剤の新規分子標的として、
1)ADF/チオレドキシン系の抗癌剤耐性への関与、アポトーシスに関係するCaspaseやp53の活性がレドックス制御をうけることを明らかとした(淀井)。2)MAPキナーゼ(MAPK)アンチセンス核酸投与による肺癌細胞の増殖抑制およびパクリタキセルの抗腫瘍作用増強効果をえた(西條)。

  • 研究成果

    (53件)

すべて その他

すべて 文献書誌 (53件)

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  • [文献書誌] Hanamura,I.: "Idiopathic CD4^+ T-lymphocytopenia in a non-Hodgkin's lymphoma patient Internal Medicine" Int.Medicine. 36.9. 643-646 (1997)

  • [文献書誌] Joh.T.: "Chimeric MLL products with a ras binding cytoplasmic protein AF6 involved in t(6;11)(q27;q23) leukemia localize in the nucleus" Oncogene. 15. 1681-1687 (1997)

  • [文献書誌] Nishi,H.: "Reduced blood accumulation of biotinylated monoclonal antibody A7 after,the subsequent administration of avid in." Cancer Letters. 120. 127-134 (1997)

  • [文献書誌] Kitamura,K.: "Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients." J.Clin,Oncol.15. 3471-3480 (1997)

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  • [文献書誌] Kitamura,K.: "Early gastric cancer mimicfling advanced gastric cancer" Brit.J.Cancer. 75. 1769-1773 (1997)

  • [文献書誌] Otsuji,E.: "End results of simultaneous pancreatectomy,splenectomy and total gastrectomy for patients with gastric carcinoma" Brit.J.Cancer. 75. 1219-1223 (1997)

  • [文献書誌] Stabin,M.G.: "Radiation dosimetry for indium-111-pentetreotide." J.Nucl.Med.38. 1919-1920 (1997)

  • [文献書誌] Hirano,T.: "Differentiating histologic malignancy of primary brain tumors:Pentavalent technetium-99r" J.Nucl.Med.38. 20-26 (1997)

  • [文献書誌] Sakahara,H.: "Anti-murine anitibody response to mouse monoclonal antibodies in cancer patients." Jpn.J.Cancer Res.88. 895-899 (1997)

  • [文献書誌] Ohizumi,I.: "Antibody-based therapy targeting tumor vascular endothelial cells suppresses solid tumor growth in rats." Biochem.Biophys.Res.Commun.232. 493-496 (1997)

  • [文献書誌] Okada,N.: "Cytomedical therapy for IgG1 plasmacytosis in human interleukin-6 transgenic mice using hybridoma cells microencapsulated in alginate-poly(L) lysine-alginate membrane" Biochem.Biophys Res.Commun.1360. 53-63 (1997)

  • [文献書誌] Tsutsumi,Y.: "PEGylation of interleukin-6 effectively increases its thrombopoietic potency" Thromb.Haemostas.77. 168-173 (1997)

  • [文献書誌] Okada,N.: "Medical application of microencapsulating hybridoma cells in agarose microbeads "Cytomedicine",Therapeutic effect on IgG1 plasmacytosis and mesangioproliferative glomerrulonephritis in the interleukin-6 transgenic mouse." J.Control.Release. 44. 195-200 (1997)

  • [文献書誌] Muzuguchi,H.: "Cytoplasmic gene expression system enhances the efficiency of cationic liposome-mediated in vivo gene transfer into mouse brain" Biochem.Biophys.Res.Commun.234. 15-18 (1997)

  • [文献書誌] Igarashi,R.: "Lecithinaization of IL-6 enhances its thrombopoietic activity" J.Pharm.Pharmacol. 49. 113-118 (1997)

  • [文献書誌] Teramoto,T.: "A novel type of calcium channel sensitive to w-agatoxin-TK in cultured rat cerebral cortical neurons" Brain Res.756. 225-230 (1997)

  • [文献書誌] Okada,N.: "Immunological studies of SK2 hybridoma cells microencapsulated with alginate-poly(lysine-alginate(APA) membrane following allogeneic transplantation" Biochem.Biophys.Res.Commun.230. 524-527 (1997)

  • [文献書誌] Tobita,T.: "Treatment with a new synthetic retinoid,Am80,of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid." Blood. 90.3. 967-973 (1997)

  • [文献書誌] Asou,N.: "All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia." Cancer Chemother Pharmacol. 40. S30-S35 (1997)

  • [文献書誌] Kitamura,K.: "Mutant AF-2 domain of PML-RAR α in retinoic acid-resistant NB4 cells:differentiation induced by RA is triggered directly through PML-RAR α and its down-regulation in acute promyelocytic leukemia." Leukemia. 11. 1950-1956 (1997)

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  • [文献書誌] Miyoshi,H.: "Glucocorticoids induce apoptosis in acute myeloid leukemaia cell lines with at (8;21)chromosome translocation" Leukemia Res.21. 45-50 (1997)

  • [文献書誌] Kasukabe,T.: "An anticancer derivative of butyric acid(pivalyloxymethy1 butyrate)and daunorubicin cooperatively prolongs surrival of of mice inoculated with monocytic leukemia cells" Brit.J.Cancer. 75. 850-854 (1997)

  • [文献書誌] Kasukabe,T.: "Tra-1,a novel mRNA highly expressed in leukemogenic mouse mouse monocytic sublines but not in nonleukemogenis sublines" Blood. 89. 2975-2985 (1997)

  • [文献書誌] Niitsu,N.: "Neplanocin A,a potent inhibitor of S-adenosylhomocysteine hydrolase,potentiates granulocytic differentiation of acute promyelocytic leukemia cells induced by all-trans retinoic acid" Exp.Hematol.25. 1296-1303 (1997)

  • [文献書誌] Niitsu,N.: "AML1a,but not AML1b,inhibits erythroid defferentiation induced by sodium butyrate and enhances megakaryocytic differentiation of K562 leukemia cells" Cell Growth Differen.8. 319-326 (1997)

  • [文献書誌] Hirota,K.: "AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1." Proc.Natl.Acad.Sci.USA. 94. 3633-3638 (1997)

  • [文献書誌] Iwata,S.: "ATL-Derived Factor(ADF)/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion. Possible involvement of Thiol-mediated redox regulation in apoptosis caused by pro-oxidant state." J.Immunol.158. 3108-3117 (1997)

  • [文献書誌] Nakamura,H.: "Redox regulation of cellular activation" Annu.Rev.Immunol.15. 351-369 (1997)

  • [文献書誌] Furuke,K.: "Role of intracellular redox status in apoptosis induction of HTLV-infected lymphocytes by retinoic acid." Cancer Res.57. 4916-4923 (1997)

  • [文献書誌] Yamamoto,M.: "Induction of human thioredoxin in cultured human retinal pigment epithelial cells though cyclic AMP-dependent pathway:involvement in the cytoprotective activity of prostaglandin EI" Exp.Eye Res.65. 645-652 (1997)

  • [文献書誌] Akamatsu,Y.: "Redox regulation of the DNA binding activity in transcription factor PEBP2:The roles of two concerved cysteine residues" J.Biol.Chemotherapy. 272. 14497-14500 (1997)

  • [文献書誌] Ishida,T.: "Circumvention of glutathione-mediated mitomycin C-resistance by a mitomycin C analogue(KW-2149)." Int.J.Cancer. 72. 865-870 (1997)

  • [文献書誌] Fukuoka,K.: "p16INK4 expression is associated with the increased sensitivity of human non-small cell lung cancer cells to DNA topoisomerase Winhibitors" Jpn.J.Cancer Res.88. 1009-1016 (1997)

  • [文献書誌] Kurokawa,H.: "Effect of glutathione depletion on cisplatin resistance in cancer cells transfected with the & gamma;-glutamylcysteine synthetase gene" Jpn.J.Cancer Res.88. 108-110 (1997)

  • [文献書誌] Kanzawa,F.: "Evaluation of synergism by a novel three-dimensional model for the combined action of cisplatin and etoposide on the growth of a human small-cell lung-cancer cell line,SBC-" Int.J.Cancer. 71. 311-319 (1997)

  • [文献書誌] Kanzawa,F.: "In vitro interaction between gemcitabine and other anticancer drug suing a novel three-dimensional model" Semin.Oncol.24. S7-8-S7-16 (1997)

  • [文献書誌] Arioka,H.: "In vitro and in vivo modulation by rhizoxin of non-p-glycoprotein-mediated vindesine resistance" J.Cancer Res.Clin.Oncol.123. 195-200 (1997)

  • [文献書誌] Ogasawara,H.: "In vitro enhancement of a water-soluble duocarmycin-derivative,KW-2189 antitumor activity by caffeine-meiated DNA-repair inhibition in a human lung cancer cells" Jpn.J.Cancer Res.88. 1033-1037 (1997)

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公開日: 1999-03-15   更新日: 2016-04-21  

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