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The molecular-biological overall analysis of tumor characteristics and host factor in primary lung cancer.

Research Project

Project/Area Number 08407039
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKanazawa University

Principal Investigator

WATANABE You  School of Medicine Department of Surgery (1) Kanazawa University Professor., 医学部, 教授 (20019897)

Co-Investigator(Kenkyū-buntansha) OHTA Yasuhiko  Kanazawa University Hospital, Department of Surgery (1), Assistant, 医学部・附属病院, 助手 (00272964)
ODA Makoto  Kanazawa University Hospital, Department of Surgery (1), Assistant, 医学部・附属病院, 助手 (50224241)
MURAKAMI Sinya  School of Medicine, Department of Surgery (1), Speaker., 医学部, 講師 (20210007)
関戸 伸明  金沢大学, 医学部・附属病院, 助手 (10293359)
林 義信  金沢大学, 医学部・附属病院, 助手 (00251950)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1996: ¥10,600,000 (Direct Cost: ¥10,600,000)
KeywordsLung cancer / VEGF / Micrometastasis / PAI-2 / Angiogenesis / cytokeratin / bcl-2 / P53 / PAI-2 / p53 / bcl-2 / MT-MMP-1
Research Abstract

1.) As a result of immunohistochemical study, the bcl-2 protein expression in epidermoid carcinoma was higher than that in adenocarcinoma. In epidermoid carcinoma, a bcl-2 protein expressing group showed a better survival rate than a non-expressing group. A p53 protein positive group showed a poorer survival rate than a negative group. The bcl-2 expression in epidermoid carcinoma patients is a potentially valuable prognostic factor. And p53 protein might be a valuable prognostic indicator in non-small cell lung cancer, particularly in adenocarcinoma.
2) The expression of u-PA, u-PAR, and PAT-1 was detected in approximately 80% of lung cancers. A diminished expression level of PAI-2 was significantly correlated with lymph node metastasis and a poor prognosis. The expression of PAI-2 may be useful as a marker for evaluating the prognosis of lung cancer.
3) Using monoclonal antibodies against cytokeratin (CK) and a novel immunohistochemical method for the detection of CK positive tumor cells, we examined disseminated tumor cells in the bone marrow and lymph nodes of primary lung cancer patients. Lymphatic micrometastases and bone marrow micrometastases were detected in 27.3% and 23.5% of lung cancer patients, respectively. After revised staging based on the sites of nodal micrometastases, patients with stage II or stage IIIA disease showed significantly poorer survival rates than those with stage I disease. A significant correlation was found between the reduced E-cadherin expression in primary sites and nodal micrometastases.
4) In lung cancer tissue samples, the expression of VEGF mRNA was found at a high rate independent of histological subtypes. Among the four splicing variants, VEGF121 and 165 were the dominant types. As a marker of tumor angiogenesis, the VEGF expression level may be a significant prognostic indicator of lung cancers in early stages.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] 疋島一徳: "肺癌手術の術前化学療法におけるFas抗原発現とアポトーンス発現に関する免疫組織化学的研究" 金沢大学十全医学会雑誌. 105. 551-568 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大竹由美子: "原発性非小細胞肺癌におけるBcl-2蛋白およびp5.3蛋白発現の予後因子としての意義について" 金沢大学十全医学会雑誌. 106. 96-104 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 徳楽正人: "肺癌における膜型マトリックスメタブロテアーゼ(MT-MMP)の発現とゼラチナーゼA(MMP-2)活性化に際しての意義" 金沢大学十全医学会雑誌. 106. 320-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino H.外: "Significance of plasminogen activator inhibitor 2 as a Prognostic marker in Primary lung cancer : association of decreased plasminogen ……" Br J Cancer. 78. 833-839 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsunezuka Y.外: "Expression of membrane-oype matrix metalloproteinase i(MTI-MMP) in tumor cells enhances Pulmonary metastasis in an experimental ……" Cancer Res. 56. 5678-5683 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 春原哲之: "原発性・転移性肺腫瘍における接着分子CD44発現に関する研究-p53蛋白発現とK-ras点突然変異との関連-" 金沢大学十全医学会雑誌. 106. 214-235 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y 外: "Signiticance of vascular endothelial growth factor messenger RNA expression in primary long Cancer." Clin Cancer Res. 2. 1411-1416 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y.外: "Vascular endothelial growth factor.-121 mRNA expression and microvessel density in Primary long cancer." Oncology Rep. 3. 713-717 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y.外: "Vescular endcthelial growth factor and lymph node metastasis in Primary long Cancer." Br J Cancer. 76. 1041-1045 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y.外: "Inhibition of lymph node metastisis by an anti-angiogenic agent,TNP-470" Br J Cancer. 75. 512-515 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 太田安彦: "パネルディスカッションII 胸部悪性疾患に対する分子生物学的診断,治療の現状と展望-肺癌におけるYEGF121の発現と血管新生-" 日胸外会誌. 45. 396-398 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高畠一郎: "原発性非小細胞肺癌における所属リンパ節、原発巣の臨床病理学的研究" 金沢大学十全医学会雑誌. 105. 406-419 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 吉羽秀磨: "原発性非小細胞肺癌におけるトロンボスポンジン1発現の意義について" 金沢大学十全医学会雑誌. 107. 420-433 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 野沢寛: "I期原発性非小細胞肺癌における微小リンパ節転移検出の意義" 金沢大学十全医学会雑誌. 107. 293-302 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe Y 外: "Frequency of lymph node occult micrometastasis or bone-marrow micrometastasis verified in stage 1NSCLC surgical patients." 2ND International Congress of Thorax Surgery. June. 24-26 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 亀水忠: "原発性非小細胞肺癌患者における骨髄中癌細胸の検出とその臨床的意義" 金沢大学十全医学会雑誌. 108. 137-147 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 渡辺洋宇 外: "肺癌微小転移巣の検出とその意義" 日本医事新報. 3900. 43-49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hikishima K.: "Immunohistochemical study on fas antigen expression and manifestation of apotosis after preoperative chemotherapy for lung cancer-analysis by CAS 200-" J Juzen Med Soc. 105. 551-568 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohtake Y.: "Bcl-2 and p53 protein expression in non-small cell lung cancers : correlation with survival time" J Juzen Med Soc. 106. 96-104 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokuraku M.: "Expression of membrane-type matrix metalloproteinase (MT-MMP) in lung carcibnomas, and its signification for activation of of gelatinase A (MMP-2)" J Juzen med soc. 103. 320-326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino H,et al.: "Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancer : association of decreased plasminogen activator inhibitor 2 with lymph node metastasis" Br J Cancer. 78. 833-839 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsunezuka Y, et al.: "Expression of membrane-type matrix metalloproteinase 1 (MTl-MMP) in tumor cells enhances plumonary metastasis in an experimental metastasis assay." Cancer Res. 56. 5678-5683 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sunohara T.: "Expression of cell adhesion molecule CD44 in primary and metastatic lung tumors-correlation with p53 protein expression and K-ras point mutation-" J Juzen Med Soc. 106. 214-235 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y,et al.: "Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer" Clin Cancer Res. 2. 1411-1416 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y,et al.: "Vascular endothelial growth factor-121 mRNA expression and neomicrovessel density in primary lung cancer." Oncology Rep. 3. 713-717 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y, et al.: "Vascular endothelial growth factor and lymph node metastasis in primary lung cancer" Br J Cancer. 76. 1041-1045 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta Y,et al.: "Inhibition of lymph node metastasis by an anti-angiogenic agent, TNP-470" Br J Cancer. 75. 512-515 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takabatake I.: "Clinicopathological regional lymph node and tumor parameters in patients with non-small cell lung cancer." J Juzen Med Soc. 105. 406-419 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshiba H.: "Thrombospondin-1 expression in primary non-small cell lung cencers." J Juzen Med Soc. 107. 420-433 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozawa H.: "Detection of lymphatic micrometastases in patients with stage I non-small cell lung cancer" J Juzen Med Soc. 107. 293-302 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe Y,et la.: "Frequency of lymph node occult micrometastasis or bone-marrow micrometastasis verified in stage I NSCLC surgical patients" 2Nd International Congress of Thorax Surgery. 55-59 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamesui T.: "Detection of disseminated tumor cells in bone marrow of patients with non-small cell lung cancer-correlation with the expression of E-cadherin, alpha-catenin beta-catenin proteins." J Juzen Med Soc. 108. 137-147 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino H: "Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancar:association desreased plasminogen activator...." Br J Cancer. 78. 833-839 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉羽秀麿: "原発性非小細胞肺癌におけるトロンボスジン1発現の意義について" 金沢大学十全医学会雑誌. 107. 420-433 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 野沢 寛: "I期原発性非小細胞肺癌における微小リンパ節転移検出の意義" 金沢大学十全医学会雑誌. 107. 293-302 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe Y.: "Frequency of lymph node occolt micrometastasis of bone-marrow micrometastasis verified in stage 1 NSCLC surgical patients." 2ND International Congress of Thorex Surgery.June. 24-26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasuhiko Ohta: "Relationship between microlymphatic vessel density within tumors and lymphnode metastasis" Oncology Reports. 4. 889-892 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasuhiko Ohta: "Expression of α-smooth-muscle actin antigen in thymoma and thymic cancer" Oncology Reports. 4. 893-897 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasuhiko Ohta: "Inhibition of lymphnode metastasis by an antiangiogenic agent,TNP-470" British Journal of Cancer. 75・4. 512-515 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Keiichi Muraoka: "Effects of natural antioxidantson the activation of transcription factor NF-KB and p53" Food Factors for Cancer Prevention. 468-471 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 太田 安彦: "肺癌におけるVEGF121の発現と血管新生" 日本胸部外科学会雑誌. 45・3. 396-398 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 徳楽 正人: "肺癌における膜型マトリックスメタロプロテアーゼ(MT-MMP)の発現とゼラチナーゼ(MMP-2)活性化に際しての意義" 金沢大学十全医学会雑誌. 106・3. 320-326 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大竹 由美子: "原発性非小細胞肺癌におけるBcl-2蛋白およびp53蛋白発現の予後因子としての意義について" 金沢大学十全医学会雑誌. 106・1. 96-104 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 春原 哲之: "原発性・転移性肺腫瘍における接着分子CD44発現に関する研究-p53蛋白発現とK-ras点突然変異との関係-" 106・2. 214-235 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasuhiko Ohta et al.: "Significance of Vascular Endothelial Grawth Factor Messenger RNA Expression in Primary Lung Cancer" Clinical Cancer Research. 2. 1411-1416 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuhiko Ohta et al.: "Vascular endothel growth factor-121 mRNA expression and neomicrovessel density in primary lung cancer" Oncology Reports. 3. 713-717 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshio Tsunezuka: "Expression of Membrane-type Matrix Metalloproteinase1 (MT1-MMP) in Tumor Cells Enhances Pulmanary Metastasisin an Experimcental Metastasis Assay" Cancer Research. 56. 5678-5683 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 呉哲彦: "p53遺伝子転写活性化に対するbcl-2の影響についての基礎的研究" 金沢大学十全医学会雑誌. 105(2). 249-256 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 疋島一徳: "肺癌手術の術前化学療法におけるFas抗原発現とアポトーシス発現に関する免疫組織化学的研究" 金沢大学十全医学会雑誌. 105(4). 551-568 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 常塚宣男: "膜型マトリックスメタロプロテアーゼ-1(MT-MMP-1)cDNA導入による癌細胞の転移,浸潤の促進" 金沢大学十全医学会雑誌. 105(2). 272-286 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 太田安彦: "肺癌におけるVEGF121の発現と血管新生" 日本胸部外科学会雑誌. 45(3). 75-77 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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