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モノクロトール抗体,遺伝子を用いた耐性癌の基礎的な診断と治療にする研究

Research Project

Project/Area Number 04151030
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionMie University

Principal Investigator

白川 茂  三重大学, 医学部, 教授 (20026850)

Co-Investigator(Kenkyū-buntansha) 曽根 三郎  徳島大学, 医学部附属病院, 講師 (40145024)
玉置 憲一  東海大学, 医学部, 教授 (50055860)
上田 龍三  愛知県がんセンター研究所, 化学療法部, 部長 (20142169)
下山 正徳  国公がんセンター中央病院, 副院長 (50110002)
鶴尾 隆  東京大学, 応用微生物研究所, 教授 (00012667)
Project Period (FY) 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1992: ¥17,000,000 (Direct Cost: ¥17,000,000)
Keywords多剤耐性(MDR)腫瘍 / P糖蛋白(P-glycoprotain;P-gp) / 抗P-gp抗体(MRK16,C219,U1C) / 多剤耐性遺伝子(MDR1) / MDR1mRNA発現 / ヒト・マウスキメラ抗体 / 免疫磁気ビーズ(MACS)法 / rhodamino123effluxtest
Research Abstract

(1)MRK-16によるP糖蛋白(P-gp)検出感度増強に免疫磁気ビーズ(MACS)法を用い,これとFACS法の組み合せで,臨床試料の耐性度診断に有用と考えられた(鶴尾)。(2)レーザー顕微鏡を用い,P-gpにより細胞内外の薬剤移動が規定された蛍光物質(adriamycin,rhadamine)と細胞を孵置し,細胞内蛍光強度や分布から多剤耐性(MDR)細胞の検出を試み,CyA誘導体PSC833の添加にて判定がより容易になった(下山)。(3)固型腫瘍のMDR1遺伝子/P-gp発現をRT-PCRと免疫染色で検討し,P-gp同定には後者が有用であるが感度が劣り,抗P-gp抗体の種類(C219,MRK16)で感度,細胞内局在に差があり,gliomoではMDR1遺伝子発現,P-gp産生は毛細血管に限局していた(玉置)。(4)正常及び悪性リンパ腫のリンパ筋につき抗P-gp抗体U1C2による免疫染色とRT-PCRによるMDR1mRNAの検討を行い,P-gp及びMDR1遺伝子発現はいずれのリンパ組識にも認められたが,P-gp陽性細胞はT-201ehistiocyteで腫瘍細胞ではなかった(白川)。(5)初診時急性白血病細胞(AML50例,ALL25例)につきP-gp/MDR1発現をRT-PCRを中心に検索し,免疫表現型と対比した。MDR1mRNAの発現はM1に高く,CD34(+)AML,CD7(+)AMLで有意に高く,幹細胞白血病に近縁なCD7(+)SCD3(-)CDU(-)CD8(-)ALLは8例中6例(75%)に発現され,予後不良であった(白川)。(6)3種類のamplimerを用いたRT-PCRでMDR1発現を検索し,いずれのamplimerでもMDR化したAML,ALL,CML-BCで33〜67%陽性,乳癌,卵巣癌とも原発巣より転移巣系で高値であった(向山)。また未分化甲状腺癌は予後最悪で,細胞株8株全例P-gp/MDR1の発現がみられた(菅原)。(7)P-gp抗体(MRK16,MRK17)を介したADCCの誘導に,NK細胞はMRK16のみ,単球は両抗体を介して如き,ヒト・マウスキメラ抗体はNK細胞をeffectorとしたADCC反応を増強させた。M-CSF遺伝子をMDR卵巣癌細胞に移入し,種々のM-CSF産生株を得,治療実験への応用を考えている(曽根,鶴尾)。(8)MDR克服にPSC833が有望であり(下山),MDR1発現の高いCD7(+)AMLでrhadamineeffluxtestが検討された(白川)。

Report

(1 results)
  • 1992 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Nakase K,et al: "Diagnostic and climical importance of interleubin-2 veceptor algha chain expression on non-T-coll acute loukemda cells." Br J Idaemaeol. 80. 317-326 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishikawa M,ed al: "The expression and possible rolos of protein C in haematopoiatic cells." Leukemin and Lymphome. 8. 201-211 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miwa H,et al: "Structural altorations of the p 53 gene in" Leukemia Rasearch. 16. 1105-1112 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ishii S,et al: "Expression of 85-kDa protein of adriamycin-resistant tunon cells during hematopoietic diffenntiation of THP-1 and MEL cells." Jpn J Cancer Res. 83. 107-112 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Heike Y,et al: "Augmentation by bispecific F(ab')_2 reactive with P-glycprotain and CD3 of cytotoyiaty of human effecgor cells on P-glycoprotein positive human renal cancer cells." Jpn J Cancer Res. 83. 366-372 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Niehans GA,et al: "Immunohistochemical identification of P-glyeoprotein in previoucly untreated,diffnse large cell and immunoblastic lymphomas." Cancer Res. 52. 3768-3775 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 下山 正徳: "抗癌剤の多剤耐性とその克服" 日由会誌. 81. 1065-1069 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 島田 安博,下山 正徳: "MDR遺伝子と薬剤耐性の克服" 最新医学. 48. 243-249 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mukaiyama T,et al: "Efficacy of combinad awtotrancplant of bone marrow and periphral blood stem cells on hcmatological recovery following high-dose chemotherapy." Int J Cell Cloning. 10. 168-170 (1992)

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      1992 Annual Research Report
  • [Publications] 向山 義人: "臨床におけるP-糖タンパクの発現と多剤耐性克服の試み" BIO medica. 6. 22-27 (1991)

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      1992 Annual Research Report
  • [Publications] 山口 裕子,他: "invivoにおける多剤耐性獲得機構の解明" 第51回日本癌学会総会記事. 419 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 里 悌子,他: "抗P糖蛋白モノクロートル抗体MRK16とC219の免疫組織化学的特性の比較検討" 第51回日本癌学会総会記事. 418 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishioka Y,et al: "Effector cell analysis of human multidug-resistant cell killing by morse-gumon chimoric antlboby against P-glyooprotoin." Jpn J Cancer Ras. 83. 644-649 (1992)

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      1992 Annual Research Report
  • [Publications] Sekido Y,et al: "Preferential expression of c-kit protooncogene transcripts in small cell lung cancer." Cancer Res. 51. 2416-2419 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suzuki H,et al: "p53 mutctions in non-small cell lnng cancer in Japan:Association between mutations and smoking" Cancer Res. 52. 734-736 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi T,et al: "Wild-type but not mutant p53 suppresses the growth of human lung cancer cells mnltiple ganetic lesions ." Cancer Ros. 52. 2340-2343 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsukamoto T,et al: "Molacular analysis of the protoin tyrosine phasphatase γ gone in human lung cancer cell line." Cancer Res. 52. 3506-3509 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Setom,et al: "Gene reairangement and overexpressin of PRAD1 in lymphoid malignancy with t(11;14)(g13;g32)translocation" Oncogane. 7. 1401-1406

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamauchi M,et al: "Prediction of doxorubiein resistance in gastrointestinal cancer by P-glycoprotein staining." Eur J Cancer. 28. 1422-1427 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sone S,et al: "Interlankin-4 as apotent down-regulator for human alveolar maurophages capable of producing tumor necresis factor-d and imerlankin-f" Eur Rosp J. 5. 174-181 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Orino E,et al: "1L-4 up-regulates 1L-1 receptor angagonist gone oxpressin and its production in humar blood monocytes." T Immunol. 149. 925-931 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Bhaskaran G,et al: "Differantial effoets of interleukin-4 of superaxide onion prodution by human alucolax macrophages stimulatad with lipo-polysaccharide and imerforon-γ." J Loukooyte Biol. 52. 218-223 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakamura A,et al: "Augmentation by transferrin of 1L-2-inducible killor activity and perfonin production in CD8^+T cells." Clin exp Immunol. (1993)

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      1992 Annual Research Report
  • [Publications] Heike Y,et al: "Human M-CSF gene transduction in multidrug yesistant cancer cells to engance anti-P-glycoprotoin awibody-depandont macmphage-mediated cytotoxicity." Int J Cancer. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中 佳,他: "腦腫瘍(astrocytictumor)の抗癌剤耐性機序の解析" 第51回日本癌学会総会記事. 419 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsuda H,et al: "Differential paltern of chromosomal allele loss in mulriple hepafocellulpr careinamas as evidence of their mulrifocal origin." Cancer Res. 52. 1504-1509 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kihana T,et al: "High incidence of p53 gene mutation in human oranan cancer and its association with muclear accumulation of p53 protein" Jon J Cancer Res. 83. 974-984 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oda T,et al: "Mutarion pattern of the p53 gone as a diagnostc marker for multiple hepanocellular carcinomr." Cancer Res. 52. 3674-3678 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Oda T,et al: "p53 gone mutation spectrum in hopatocellular carcinoma." Cancer Res. 52. 6358-6364 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sygawara I,et al: "Proparation and charactnization of a murine mono-clonal antibody (MDR3M) reactive with maru gene product." Jpn J Cancer Res. 83. 795-797 (1992)

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      1992 Annual Research Report
  • [Publications] Tashiro H,et al: "C-myc Overexpression in humer primary ovarian cancer:its relevance to tumor progression." Int J Cancer. 50. 828-833 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi JA,et al: "Correlation of basic fibroblast grcwth factor lovols with the dograe of matignancy and vascularity in human gliomas." J Neurosurg. 76. 792-798 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nio Y,et al: "Antitumor activity of 5'-dooxy-5-fluoro-uridine in human digestive organ cancer xonogzafts and pyrimidine nuclaotide phosphorylese activity in normal and neoplastic tissues from human digeotive organs." Andicancer Res. 12. 1141-1146 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Adachi M,et al: "Protain-tyrosine phosphatase expression in pre-B cell NALM-6" Cancer Res. 52. 737-740 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyachi H,et al: "Differential alterations of dihydro folate reductase gene in human laudemia coll lines made rictant to various folate analognes." Jpn J Cancer Res. 84. 9-12 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyachi H,et al: "MDR1 (multidrug rosistance) gone expression in adult acnte leukema;corrdations with blast phonotype." Int J Hematol. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishii K,et al: "P-glycoprotain expression in human lymph node in “The Mechnism and New A pproach on Drug-Resistance of Cancer Cells"ed.Miyazaki T" Elsevier Scilrce Publishers, (1993)

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      1992 Annual Research Report
  • [Publications] Miwa H,et al: "Expresson of MDR1 gene in CD 7(+) acute lymph oblastic leukemia cells.in“The Mechanism and New Approach on Drug-Resishcru of Cancer Cells"ed.Miyazaki T" Elsevier Scionce Publishers, (1993)

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      1992 Annual Research Report
  • [Publications] Shimoyama M: "Treatmont of patients with adult T-cell loukomia-lymphona;Anoverview.in “Ganri Moriograph on Cancer Research No.39"ed Takatsuki K" Japan Scientific Societies Press,Tokyo and CRC Press Baca Raron Ann Arbor London Tokyo, 43-56 (1992)

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      1992 Annual Research Report
  • [Publications] 島田 安博,下山 正徳: "MDRとその臨床的意義in“AnmualReview血液1993"高久史磨他編" 中外医学社, 120-126 (1993)

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      1992 Annual Research Report
  • [Publications] Tsuruo T: "Mulridrug resistance;Basic approaches for reversal.in “Drug Resistance as a Biochemical Target in Cancer Chemochorapy"" ed.Tsuruo・T,Ogawa・M Academic Press,Inc., 99-115 (1992)

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      1992 Annual Research Report
  • [Publications] Shimoyama M: "Desection of multidrug-resistant human cancer calls by mono-clonal antibodies.in “Drug Resistance as a Biochemical Target in Cancer Chemothocapy"" ed.Tsurno T,Ogawa M Academic Press,Inc., 193-209 (1992)

    • Related Report
      1992 Annual Research Report

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

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