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Molecular analysis of acquired multidurg resistance in non-small cell lung cancer

Research Project

Project/Area Number 06670206
Research Category

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

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionTokai University

Principal Investigator

NAKAMURA Masato  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (00164335)

Co-Investigator(Kenkyū-buntansha) YAMAZAKI Hitoshi  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (20191273)
TAMAOKI Norikazu  Tokai University, School of Medicine, Professor, 医学部, 教授 (50055860)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsmultidrug resistance / non-small cell lung cancer / acquired resistance / MDR1 gene / MRP gene / molecular pathology / 非小細胞性肺癌 / 膜P糖蛋白質 / 肺癌Xenograft / RT-PCR
Research Abstract

We examined whether the increased expression of P-glycoprotein (P-Gp) encoded by the human multidrug resistance gene MDR1 is related to acquired multidrug resistance of lung cancer in vivo. The lung cancer xenografts (LC-6, adenocarcinoma and Lu-24, small cell carcinoma) were initially sensitive to both vincristine (VCR,1.6 mg/kg : LC-6,45% ; Lu-24,39%) and doxorubicin (DOX,12mg/kg : LC-6,29% ; Lu-24,26%) by in vivo-chemosensitivity test. Resistant variants (LC-6R,66% and Lu-24R,68%) selected with VCR (0.4mg/kg, x 9) acquired cross-resistance to DOX (51%, and 55%, respectively) . The acquired resistance to VCR/DOX in LC-6R was circumvented by coadministration of cyclosporin A (CysA,35%/14%) . Reverse transcriptasepolymerase chain reaction assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels after 4 passages without VCR.P-Gp expression levels were elevated, and P-Gp positve tumor cells increased in both LC-6R and Lu-24R.These results su … More ggest that P-Gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.
We examined the levels of expression of the multidrug resistance-associated protein (MRP) gene quantified by Northern blot analysis in comparison with those of the MDR1 gene determined by RT-PCR in 104 non-small cell lung (NSCLC) specimens (59 adenocarcinoma, Ad ; 40 squamous cell carcinoma, Sq ; 4 large cell carcinoma, La ; and 1 adenosquamous carcinoma, AdSq) . Thirty-three (31.7%) of the 104 NSCLC expressed the MRP gene at various levels. The NSCLC showing high levels of MRP gene expression (++, 19 of 33,57.6%) were predominantly squamous cell carcinomas (Ad 5, Sq 13, La 1) (p<0.05) . Six of the 8 NSCLC expressing high levels of MRP mRNA and no MDR1 (MRP++, MDR1-) were squamous cell carcinomas. Sixty-one of the 104 NSCLC patients received chemotherapy with MRP-related anticancer drugs (vindesine, VDS and etoposide, VP-16) . Twenty-three patients (37.7%) with tumor expressing high or moderate levels of MRP showed significantly worse prognoses than those with non or low-MRP-expressing tumours (p<0.05) . These results suggest that the level of MRP gene expression is related to the histopathology and prognosis of NSCLC. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoshiyuki Abe,Masato Nakamura,et al.,: "Expression of the multidrug resistance gene (MDR1) in non-small cell lung cancer" Japanese Journal of Cancer Research. 85. 536-541 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashi Imanishi,Masato Nakamura,et al.,: "Expression of the multidrug resistance gene (MDR1) and prognostic correlation in human osteogenic sarcoma" Tokai Journal of Experimental and Clinical Medicine. 19. 39-46 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshimi Tanaka,Masato Nakamura,et al.,: "Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas" Virchows Archiv. 425. 133-138 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshiyuki Abe,Masato Nakamura,et al.,: "Multidrug resistance gene (MDR1) expression in human tumor xenografts" International Journal of Oncology. 5. 1285-1292 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroshi Kijima,Masato Nakamura,et al.,: "Stability of ras oncogene mutation in the human tumor xenografts through serial passages" Anticancer Research. 14. 2583-2588 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Eiichiro Ota,Masato Nakamura,et al.,: "Expression of the multidrug resistance-associated protein (MRP) gene in non-small cell lung cancer" British Journal of Cancer. 72. 550-554 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshiyuki Abe, Massato Nakamura, Eiichiro Ota, Yuichi Ozeki, Seiichi Tamai, Hiroshi Inoue, Yoshito Ueyama, Toshiro Ogata, Norikazu Tamaoki: "Expression of the multidrug resistance gene (MDR1) in non-small cell lung cancer" Jpn.J.Cancer Res.85. 536-541 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashi Imanishi, Yoshiyuki Abe, Ryuji Suto, Shozo Higaki, Yoshito Ueyama, Masato Nakamura, Norikazu Tamaoki, Hiroaki Fukuda, Nozomu Imai: "Expression of the human multidrug resistance gene (MDR1) and prognostic correlation in human osteogenic sarcoma" Tokai J.Exp.Clin.Med.19. 39-46 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshimi Tanaka, Yoshiyuki Abe, Atsushi Tsugu, Yukihito Takamiya, Akira Akatsuka, Takashi Tsuruo, Hitoshi Yamazaki, Yoshito Ueyama, Osamu Sato, Norikazu Tamaoki, Masato Nakamura: "Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human glionas" Virchows Archiv. 425. 133-138 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshiyuki Abe, Masato Nakamura, Yasuyuki Ohnishi, Makoto Inaba, Yoshito Ueyama, Norikazu Tamaoki: "Multidrug resistance gene (MDR1) expression in human tumor xenografts" Int.Natl.J.Oncol.5. 1285-1292 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroshi Kijima, Yoshiyuki Abe, Hitoshi Yamazaki, Yasuyuki Ohnishi, Yoshito Ueyama, Norikazu Tamaoki, Masato Makamura: "Stability of ras oncogene mutation in the human tumor xenografts through serial passages" Anticancer Res.14. 2583-2588 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Eiichiro Ota, Yoshiyuki Abe, Yoshiro Oshika, Yuichi Ozeki, Masayuki Iwasaki, Hiroshi Inoue, Hitoshi Yamazaki, Seiichi Tamai, Yoshito Ueyama, K.Takagi, Toshiro Ogata, Norikazu Tamaoki, Massato Nakamura: "Expression of the multidrug resistance-associated protein (MRP) gene in non-small cell lung cancer" Britich J.Cancer. 72. 550-554 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshiyuki Abe, Massato Nakamura, et al.: ""Expression of the multidrug resistance gene (MDR1) in non-small cell lung cancer"" Jpnanese Journal of Cancer Research. 85. 536-541 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takashi Imanish, Masato Nakamura, et al.: ""Expression of the human multidrug resistance gene (MDR1) and prognostic correlation in human osteogenic sarcoma"" Tokai Journal of Experimental Clin. ical Medicine. 19. 39-46 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshimi Tanaka, Masato Nakamura, et al.: ""Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas"" Virchowa Archiv. 425. 133-138 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshiyuki Abe, Masato Nakamura, et al.: ""Multidrug resistance gene(MDR1) Expresseion in human tumor xenofragts"" International Journal of Oncology. 5. 1285-1292 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Kijima, Masato Nakamura, et al.: ""Stability of ras oncogene mutation in the human tumor xenografts through serial passages"" Anticancer Research. 14. 2583-2588 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Eiichiro Ota, Yoshiyuki Abe. Massato Nakamura, et al.: ""Expression of the multidrug resistance-associated protein (MRP) gene in non-small cell lung cancer"" British Journal of Cancer. 72. 550-554 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshiyuki Abe,Masato Nakamura,et al.: "“Expression of the multidrug resistance gene(MDR1)in non-small cell lung cancer"" Jpn.J.Cancer Res. 85. 536-541 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshimi Tanaka,Masato Nakamura,et al.,: "“Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas"" Virchows Archiv. 425. 133-138 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshiyuki Abe,Masato Nakamura,et al.: "“Multidrug resistance gene(MDR1)expression in human tumor xenografts."" Int.Natl.J.Oncol.5. 1285-1292 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiroshi Kijima,Masato Nakamura,et al.: "“Stability of ras oncogene mutation in the human tumor xenografts through serial passages"" Anticancer Res.15(in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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