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1998 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1996 – 1998
KeywordsLung cancer / VEGF / Micrometastasis / PAI-2 / Angiogenesis / cytokeratin / bcl-2 / P53
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.

  • Research Products

    (32 results)

All Other

All Publications (32 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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