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Inhibition of L-type amino acid transporter 1 has antitumor activity in lung cancer

Research Project

Project/Area Number 21790793
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionGunma University (2010)
Shizuoka Cancer Center Research Institute (2009)

Principal Investigator

KAIRA Kyoichi  Gunma University, 医学部, 医員 (40400783)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsアミノ酸トランスポーター / 肺癌 / 予後因子 / 抗腫瘍効果 / 非小細胞肺癌 / 化学療法 / LAT1 / LAT1阻害剤 / mTOR / FAMT-PET / gefitinib / 治療 / 予後
Research Abstract

L-type amino acid transporter 1 (LAT1) is highly expressed in various neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC). Expression of LAT1 mRNA in 54 lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395 cell. LAT1 expression was examined in correlation with clinical features and outcome in 120 NSCLC patients. Inhibition of LAT1 by BCH reduced cell viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH reduced the viability of the cells more than either agent alone. Inhibition of LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein expression was closely associated with wild type EGFR, and was an independent significant factor to predict a poor prognosis. Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (35 results)

All 2011 2010 2009 Other

All Journal Article (29 results) (of which Peer Reviewed: 29 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Biologic correlates of ^<18>F-FDG uptake on PET in pulmonary pleomorphic carcinoma.2011

    • Author(s)
      Kaira K, Endo M, Nakagawa K, et al.
    • Journal Title

      Lung Cancer 71

      Pages: 144-150

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Excision Repair Cross-Complementation Group 1, Breast Cancer Susceptibility 1, and β III-Tubulin in Thymic Epithelial Tumors.2011

    • Author(s)
      Kaira K, Serizawa M, Koh Y, et al.
    • Journal Title

      J Thorac Oncol 6

      Pages: 606-613

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Correlation Between 18F-FDG Uptake on PET and Molecular Biology in Metastatic Pulmonary Tumors.2011

    • Author(s)
      Kaira K, Okumura T, Ohde Y, et al.
    • Journal Title

      J Nucl Med 52

      Pages: 705-711

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] MUC1 expression in thymic epithelial tumors : MUC1 may be useful marker as differential diagnosis between type B3 thymoma and thymic carcinoma.2011

    • Author(s)
      Kaira K, Murakami M, Serizawa M, et al.
    • Journal Title

      Virchows Arch 458

      Pages: 615-620

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary pleomorphic carcinoma : a clinicopathological study including EGFR mutation.2010

    • Author(s)
      Kaira K, Horie Y, Ayabe E, et al.
    • Journal Title

      J Thorac Oncol 5

      Pages: 460-465

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biologic correlation of ^<18>F-FDG PET in thymic epithelial tumors.2010

    • Author(s)
      Kaira K, Endo M, Abe M, et al.
    • Journal Title

      J Clin Oncol 28

      Pages: 3746-3753

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CD98 expression is associated with the grade of malignancy in thymic epithelial tumors.2010

    • Author(s)
      Kaira K, Takahashi T, Abe M, et al.
    • Journal Title

      Oncol Rep 24

      Pages: 861-867

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] L-type amino acid transporter 1 expression predicts the response to preoperativehyperthrmo-chemoradiotherapy for advanced rectal cancer.2010

    • Author(s)
      Ebara T, Kaira K, Saito J, et al.
    • Journal Title

      Anticancer Res 30

      Pages: 4223-4227

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of L-type amino acid transporter 1 expression and L-[3-18F]-a-methyl tyrosine uptake in outcome of non-small cell lung cancer.2010

    • Author(s)
      Kaira K, Oriuchi N, Shimizu K, et al.
    • Journal Title

      Nucl Med Biol 37

      Pages: 911-916

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer.2010

    • Author(s)
      Imai H, Kaira K, Oriuchi N, et al.
    • Journal Title

      Anticancer Res 30

      Pages: 4819-4828

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pooled analysis of the reports of erlotinib after failure of gefitinib for non-small cell lung cancer.2010

    • Author(s)
      Kaira K, Naito T, Takahashi T, et al.
    • Journal Title

      Lung Cancer 68

      Pages: 99-104

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survivors of more than 5 years in advanced non-small cell lung cancer.2010

    • Author(s)
      Kaira K, Takahashi T, Murakami H, et al.
    • Journal Title

      Lung Cancer 67

      Pages: 120-123

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ratio of standardized uptake value on PET helps predict response and outcome after chemotherapy in advanced non-small celllung cancer.2010

    • Author(s)
      Kaira K, Endo M, Asakura K, et al.
    • Journal Title

      Ann Nucl Med 24

      Pages: 697-705

    • NAID

      10027659641

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of therapy response in lung cancer with 18F-α-methyl tyrosine PET.2010

    • Author(s)
      Kaira K, Oriuchi N, Yanagitani N, et al.
    • Journal Title

      AJR Am J Roentgenol 195

      Pages: 2104-2111

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer2010

    • Author(s)
      Imai H, Kaira K, et al
    • Journal Title

      Anticancer Research

      Volume: 30巻 Pages: 4819-28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of L-type amino acid transporter 1 and L-[3-18F]-a-methyl-tyrosine uptake in outcome of non-small cell lung cancer2010

    • Author(s)
      Kaira K, et al
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 37巻 Pages: 911-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biologic correlation of 2-[18F]-fluoro-2-deoxy-D-glucose uptake on positron tomography in thymic epithelial tumors2010

    • Author(s)
      Kaira K, et al
    • Journal Title

      Journal of Clinical Oncology

      Volume: 10巻 Pages: 3746-53

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2hc heavy chain (CD98) expression in stage I pulmonary adenocarcinoma.2009

    • Author(s)
      Kaira K, Oriuchi N, Imai H, et al.
    • Journal Title

      Lung Cancer 66

      Pages: 120-126

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] L-typeamino transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas.2009

    • Author(s)
      Kaira K, Oriuchi N, Imai H, et al.
    • Journal Title

      J Surg Oncol 99

      Pages: 433-438

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non-small cell lung cancer.2009

    • Author(s)
      Imai H, Kaira K, Oriuchi N, et al.
    • Journal Title

      Histopathology 54

      Pages: 804-813

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer.2009

    • Author(s)
      Kaira K, Oriuchi N, Shimizu K, et al.
    • Journal Title

      Cancer Sci 100

      Pages: 753-758

    • NAID

      10025144864

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of thoracic tumors with 18F-FMT and 18F-FDG PET-CT : a clinicopathological study.2009

    • Author(s)
      Kaira K, Oriuchi N, Shimizu K, et al.
    • Journal Title

      Int J Cancer 124

      Pages: 1152-1160

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 18F-FMT uptake seen within primary cancer on PET helps predict outcome of non-small cell lung cancer.2009

    • Author(s)
      Kaira K, Oriuchi N, Shimizu K, et al.
    • Journal Title

      J Nucl Med 50

      Pages: 1770-1776

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 18F-FMT uptake seen within primary cancer on PET helps predict outcome of non-small cell lung cancer.2009

    • Author(s)
      Kaira K, et al.
    • Journal Title

      Journal of Nuclear Medicine 50

      Pages: 1770-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD98 expression is associated with poor prognosis in resected non-small-cell lung cancer with lymph node metastases.2009

    • Author(s)
      Kaira K, et al.
    • Journal Title

      Annals of Surgical Oncology 16

      Pages: 3473-81

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] L-type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage 1 non-small cell lung cancer.2009

    • Author(s)
      Imai H, Kaira K, et al.
    • Journal Title

      Histopathology 54

      Pages: 804-13

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] L-type amino acid transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas.2009

    • Author(s)
      Kaira K, et al.
    • Journal Title

      Joumal of Surgical Oncology 99

      Pages: 433-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in stage 1 pulmonary adenocarcinoma.2009

    • Author(s)
      Kaira K, et al.
    • Journal Title

      Lung Cancer 66

      Pages: 120-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer.2009

    • Author(s)
      Kaira K, et al.
    • Journal Title

      Cancer Science 100

      Pages: 753-8

    • NAID

      10025144864

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 胸腺上皮腫瘍のFDG集積に関する臨床病理学的検討2010

    • Author(s)
      解良恭一
    • Organizer
      第50回日本核医学会学術総会
    • Place of Presentation
      大宮ソニックシティー(埼玉県)
    • Year and Date
      2010-11-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 胸腺上皮腫瘍のFDG集積に関する臨床病理学的検討2010

    • Author(s)
      解良恭一
    • Organizer
      日本核医学学会
    • Place of Presentation
      大宮(大宮ソニックシティー)
    • Year and Date
      2010-11-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胸腺上皮腫瘍のFDG集積に関する臨床病理学的検討2010

    • Author(s)
      解良恭一
    • Organizer
      第51回日本肺癌学会総会
    • Place of Presentation
      広島国際会議場(広島県)
    • Year and Date
      2010-11-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 非小細胞肺癌におけるゲフィチニブ無効後のエルロチニブ投与の文献的統合解析2009

    • Author(s)
      解良恭一
    • Organizer
      第50回日本肺癌学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-11-13
    • Related Report
      2010 Final Research Report
  • [Presentation] 肺癌におけるLAT1発現と予後解析2009

    • Author(s)
      解良恭一
    • Organizer
      日本呼吸器学会
    • Place of Presentation
      東京
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://lib.bioinfo.pl/user:123723

    • Related Report
      2010 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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