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Establishment and clinical application of sensitive gene-mutation detection system in lung cancer

Research Project

Project/Area Number 18390385
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionHyogo College of Medicine

Principal Investigator

TANAKA Fumihiro  Hyogo College of Medicine, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR (10283673)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Seiki  Hyogo College of Medicine, 医学部, PROFESSOR (10252438)
MATSUMOTO Seiji  Hyogo College of Medicine, 医学部, INSTRUCTOR (60412011)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,320,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2007: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsThoracic surgery / Lung cancer / Gene mutations / Sensitive detection / EGFR
Research Abstract

1) Primary lung cancer is a malignant tumor with a poor prognosis and the 5-year survival rate after complete resection remains 30-40%, which may be caused by frequent incidence of postoperative distant metastases. Thus, a highly-sensitive system to detect occult- or micro-metastases should be established to improve prognosis after surgery for lung cancer, and recent advance in molecular biology suggest that gene-based detection system for micro-metastases may be clinically useful. Thus, we have established a highly sensitive system to detect gene mutations which may be present in clinical samples, and we have examined clinical value of the PCR-SSCP system in the diagnosis of micro-metastases of lung cancer in the present study.
2) With the PCR-SSCP system, mutations of EGFR gene cam be detected in a variety of clinical samples such as formalin-fixed and paraffin-embedded sections and pleura effusion, and the sensitivity was 10-100 times higher than that with traditional sequencing system. However, the PCR-SSCP system failed to detect mutated gene that was originating from primary tumors and was released in peripheral blood. To improve the sensitivity, we are now trying to develop more sophisticated detection system or a novel strategy for detection of gene mutation such as mutation analysis of genes in circulating tumor cells (CTC) that were prepared form peripheral blood of lung cancer patients
3) The present study with the PCR-SSCP system revealed as follows; a) EGFR gene can be mutated in not only lung adenocarcinoma tissues but also in pre-cancerous tissues such as atypical adenomatous hyperplasia (AAH), b) multiple cancer in the lung of one patient can be exactly classified into lung metastases or into multiple lung cancer with gene-mutation analysis wit the PCR-SSCP system. These results may contribute to improvement of diagnosis and therapy of lung cancer based on individual characteristics of tumors.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (42 results)

All 2008 2007 2006 Other

All Journal Article (34 results) (of which Peer Reviewed: 15 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer(NSCLC)2008

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Ann Surg Oncol 15

      Pages: 547-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Schedule-dependent synergistic effect of pemetrexed combined with gemcitabine against malignant pleural mesothelioma and non-small cell lung cancer cell lines2008

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Chemotherapy (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer(NSCLC)2008

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Ann Surg Oncol 15(2)

      Pages: 547-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Perimembrane Aurora-A expression is a significant prognostic factor incorrelation with proliferative activity in non-small-cell lung cancer (NSCLC)2008

    • Author(s)
      Fanaka F, 他
    • Journal Title

      Ann Surg Oncol 15巻・2号

      Pages: 547-554

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Schedule-dependent synergistic effect of pemetrexed combined with gemcitabine against malignant pleural mesothelioma and non-small cell lung cancer cell lines2008

    • Author(s)
      Tallaka F, 他
    • Journal Title

      Chemotherapy

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of epidermal growth factor receptor(EGFR)gene mutations on the expression of EGFR,phosphoryl-Akt,and phosphoryl-MAPK,and on the prognosis of patients with non-small cell lung cancer2007

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Surg Oncol 95

      Pages: 63-69

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 肺がんのアジュバント治療と分子標的2007

    • Author(s)
      田中 文啓
    • Journal Title

      がん分子標的 5

      Pages: 195-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] UFT(tegafur and uracil)as postoperative adjuvant chemotherapy for solid tumors(carcinoma of the lung,stomach,colon/rectum,and breast):clinical evidence,mechanism of action,and future direction2007

    • Author(s)
      Tanaka F
    • Journal Title

      Surg Today 37

      Pages: 923-934

    • NAID

      10019804619

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of tissue inhibitor of metalloproteinase-3(TIMP-3)and its prognostic significance in resected non-small cell lung cancer2007

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Surg Oncol 95

      Pages: 250-257

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Influence of epidermal growth factor receptor(EGFR) gene mutations on the expression of EGFR, phosphoryl Akt, and phosphoryl-MAPK, and on the prognosis of patients wit non-small cell lung cancer2007

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Surg Oncol 95(1)

      Pages: 63-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] UFT(tegafur and uracil) as postoperative adjuvant chemotherapy for solid tumors(carcinoma of the lung, stomach, colon/rectum, and breast) : clinical evidence, mechanisr of action, and future direction.2007

    • Author(s)
      Tanaka F.
    • Journal Title

      Surg Today 37(11)

      Pages: 923-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of tissue inhibitor of metalloproteinase-3(TIMP-3) and its prognostic significance in resected non-small cell lung cancer2007

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Surg Oncol 95(3)

      Pages: 250-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] UFT (tegafur and uracil) as postoperative adjuvant chemotherapy for solid tumors (carcinoma of the lung,stomach,colon/rectum,and breast):clinical evidence,mechanism of action,and future direction2007

    • Author(s)
      Fanaka F
    • Journal Title

      Surg Today 37巻・11号

      Pages: 923-943

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and itsprognostic significance in resected non-small cell Iung cancer2007

    • Author(s)
      Tanaka F, 他
    • Journal Title

      J Surg Oncol 95巻・3号

      Pages: 250-257

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of epidermal growth factor recePtor (EGFR) gene mutations on the expression of EGFR,phosphoryl-Akt,and phosphoryl-MAPK,and on the prognosis of patients with non-small cell lung cancer2007

    • Author(s)
      Tanaka F, 他
    • Journal Title

      J Surg Oncol 95巻・1号

      Pages: 63-69

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肺がんのアジュバント治療と分子標的2007

    • Author(s)
      田中 文啓
    • Journal Title

      がん分子標的治療 5巻・3号

      Pages: 195-205

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Lung adenocarcinoma harboring mutations in the ERBB2 kinase domain2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Mol Biol 8

      Pages: 351-356

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Thorac Oncol 1

      Pages: 46-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer(NSCLC)2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Lung Cancer 51

      Pages: 323-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Maspin expression and its clinical significance in non-small cell lung cancer2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Ann Surg Oncol 13

      Pages: 1517-1523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MDA-7/IL-24-based cancer gene therapy:translation from the laboratory to the clinic2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Curr Gene Ther 6

      Pages: 73-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 非小細胞がんに対する化学療法の最新動向:非小細胞肺がんの術後補助化学療2006

    • Author(s)
      田中 文啓, 他
    • Journal Title

      呼吸器科 9

      Pages: 117-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lung adenocarcinoma harboring mutations in the ERBB2 kinase domain2006

    • Author(s)
      Tanaka F, et at.
    • Journal Title

      J Mol Biol 8(3)

      Pages: 351-356

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosi in non-small cell lung cancer2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      J Thorac Oncol 1(1)

      Pages: 46-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer(NSCLC)2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Lung Cancer 51(3)

      Pages: 323-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Maspin expression and its clinical significance in non-small cell lung cancer2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Ann Surg Oncol 13(11)

      Pages: 1517-23

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] MDA-7/IL-24-based cancer gene therapy : translation from the laboratory to the clinic2006

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Curr Gene Ther 6(1)

      Pages: 73-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer (NSCLC).2006

    • Author(s)
      Katakura H
    • Journal Title

      Lung Cancer 51・3

      Pages: 323-328

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lung adenocarcinoma harboring mutations in the ERBB2 kinase domain2006

    • Author(s)
      Sonobe M
    • Journal Title

      J Mol Diag 8・3

      Pages: 351-356

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MDA-7/IL-24-based cancer gene therapy : translation from the laboratory to the clinic2006

    • Author(s)
      Inoue S
    • Journal Title

      Curr Gene Ther 6・1

      Pages: 73-95

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 非小細胞肺がんの術後補助化学療法2006

    • Author(s)
      田中 文啓
    • Journal Title

      呼吸器科 9・2

      Pages: 117-123

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer2006

    • Author(s)
      Nagai S
    • Journal Title

      J Thorac Oncol 1・1

      Pages: 46-51

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Maspin expression and its clinical significance in non-small cell lung cancer2006

    • Author(s)
      Nakagawa M
    • Journal Title

      Ann Surg Oncol 13・11

      Pages: 1517-1523

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Schedule-dependent synergistic effect of pemetrexed combined with gemcitabine against malignant pleural mesothelioma and non-small cell lung cancer cell lines

    • Author(s)
      Tanaka F, et. al.
    • Journal Title

      Chemotherapy (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Surgeons'role for pathologic staging and optimal adjuvant treatment.Progress in potentially-resectable NSCLC2007

    • Author(s)
      Tanaka F, et. al.
    • Organizer
      韓国肺癌学会(KASLC)
    • Place of Presentation
      ソウル市
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Surgeons'role for pathologic staging and optimal adjuvant treatment. Progress in potentially-resectable NSCLC.2007

    • Author(s)
      Tanaka F.
    • Organizer
      The Korean Association for Study of Lung Cancer(KASLC) meeting
    • Place of Presentation
      Seoul(South Korea)
    • Year and Date
      2007-11-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ゲフィチニブの効果と安全性を考える2007

    • Author(s)
      田中 文啓
    • Organizer
      第9回日本医薬品情報学会総会
    • Place of Presentation
      京都市
    • Year and Date
      2007-07-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FDG-PET in correlation with epidermal growth factor receptor gene mutations in resected non-small cell lung cancer(NSCLC)2007

    • Author(s)
      Tanaka F, et. al.
    • Organizer
      第98回米国癌学会(AACR)
    • Place of Presentation
      ロサンゼルス市
    • Year and Date
      2007-04-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] FDG-PET in correlation with epidermal growth factor receptor gene mutations in resected non-small cell lung cancer(NSCLC)2007

    • Author(s)
      Tanaka F, et. al.
    • Organizer
      The 98th annual meeting of the American Association for Cancer Research(AACR)
    • Place of Presentation
      Los Angels(USA)
    • Year and Date
      2007-04-18
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of HuR,a mRNA-binding protein in non-small cell lung cancer(NSCLC)in correlation with COX-2,MVD and tumor progression2006

    • Author(s)
      Tanaka F, et. al.
    • Organizer
      第97回米国癌学会(AACR)
    • Place of Presentation
      ワシントンDC
    • Year and Date
      2006-04-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of HuR, a mRNA-binding protein in non-small cell lung cancer(NSCLC) in correlation with COX-2, MVD and tumo progression.2006

    • Organizer
      The 98th annual meeting of the American Association for Cancer Research(AACR)
    • Place of Presentation
      Washington DC(USA)
    • Year and Date
      2006-04-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review 呼吸器20072007

    • Author(s)
      田中 文啓
    • Total Pages
      246
    • Publisher
      中外医学社
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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