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In vivo Invasion Assay and Enhancement of Differentiation of Low Passage Cultured Cells Derived from Human Non-Small Cell lung Carcinoma Using De-epithelialized Rat Tracheas Transplanted into Nude Mice.

Research Project

Project/Area Number 01570777
Research Category

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

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionChiba University

Principal Investigator

SHIBA Mitsutoshi (1990)  Institute of Pulmonary Cancer Research, School of Medicine, Chiba University Surgery (Instructor), 医学部・肺癌研究施設第一臨床研究部門, 助手 (20162620)

山川 久美 (1989)  千葉大学, 医学部, 助手 (80191211)

Co-Investigator(Kenkyū-buntansha) YAMAKAWA Hisami  Institute of Pulmonary Cancer Research, School of Medicine, Chiba University Sur, 医学部肺癌研究施設第一臨床研究部門, 非常勤講師 (80191211)
BABA Masayuki  Institute of Pulmonary Cancer Research, School of Medicine, Chiba University Sur, 医学部肺癌研究施設第一臨床研究部門, 助手 (00143305)
FUJISAWA Takehiko  Institute of Pulmonary Cancer Research, School of Medicine, Chiba University Sur, 医学部肺癌研究施設第一臨床研究部門, 助教授 (80110328)
YAMAGUCHI Yutaka  Institute of Pulmonary Cancer Research, School of Medicine, Chiba University Su, 医学部肺癌研究施設第一臨床研究部門, 教授 (80009448)
柴 光年  千葉大学, 医学部, 助手 (20162620)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsin vivo invasion assay / in vivo differentiation assay / primary lung carcinoma / xenotransplantation / nude mouse / deepithelialized rat trachea / deepithelialized rat trachea / 肺癌培養細胞 / 浸潤能 / 分化能 / in vivo
Research Abstract

The investigation of human tumors using nude mouse xenograft is capable of taking into account the host reactions, whereas this is impossible in in vitro system. Nude mice offer an invasion environment similar to that of humans; however, s.c. injection procedures for conventional xenotransplantation into nude mice have encountered problems with regard to long latency periods low tumor take rates. In this project, human lung tumor-derived cell lines with low passage generation were transplanted into nude mice to determine their growth behavior and invasive potential. Six cell lines were inoculated into deepithelialized rat tracheas (5 x 10^5 cells/trachea). After cell inoculation, the tracheas were sealed and transplanted into the subcutis of nude mice. In a parallel experiment, these cell lines (1 x 10^6 cells) were injected s.c. In the subcutis, the tumor take rate was only 13% with a long latency period of 18 weeks, and 3 cell lines did not show any invasive growth to the surrounding … More tissue. In rat tracheas, all cell lines proliferated within 3 weeks, and 4 of them showed invasive growth to the tracheal wall within 1-2 weeks. Cells growing in the tracheal wall showed higher (^3H) thymidine labeling indexes and greater atypia, such as larger nuclei and prominent nucleoli, than those in the tracheal lumen. The s.c. tumor take rate correlated with the incidence of invasive growth to the tracheal wall. The survival of the patients originally bearing the six tumors also correlated closely with the invasive potential of this system. In tracheal transplants, all cell lines showed comparable or higher degree of differentiation than in the primary lesion. While most cell lines showed lower degree of differentiation in the mouse subcutis. The surfaces of tracheal transplants repopulated with the cells derived form squamous cell carcinomas were initially lined by a layer of flattened cells 2 to 3 cells thick. While those repopulated with the cells from 3 cases of adenocarcinoma were initially lined by simple epithelia consisted of cuboidal-, round-, and columnar-shaped cells, respectively. Thereafter, those cell lines revealed pseudostratified pattern, papillary growth pattern, and cribriform pattern, respectively. Ultrastructurally, they showed structures resembling ciliated bronchial epithelial cells, non-ciliated bronchiolar epithelial cells, and bronchial goblet cells, respectively.
These results indicate that the system using low passage cell lines can evaluate the invasive potential shortly after the inoculation; of a relatively small number of cells and can be used as a clinically reliable biological invasion assay. And, histological examination of cultured cells using this system was considered to be advantageous for evaluation of differentiation because it provided unique proliferation patterns unobserved in primary tumors or tumors formed after subcutaneous direct cell injections. Less

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Hisami Yamakawa,Masayuki Baba,and Yutaka Yamaguchi: "In vivo Invasion Assay of Low Passage Cultured Cells Derived from Human Lung Cancer Using Deepithelialized Rat Tracheas Xenotrasplanted into Nude Mice." Cancer Research. 50(22). 7358-7363 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisami Yamakawa,Masayusi Baba,Mitsutoshi Shiba,and Yutaka Yamaguchi: "Enhancement of Differentiation of Low Passage Cultured Cells Derived from Human NonーSmall Cell Lung Carcinoma Using Deepithelized Rat Tracheas Transplanted into Nude Mice." Differentiation.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisami Yamakawa, Masayuki Baba, and Yutaka Yamaguchi: "In vivo Invasion Assay of Low Passage Cultured Cells Derived from Human Lung Cancer Using Deepithelialized Rat Tracheas Xenotransplanted into Nude Mice." Cancer Research. 50(22). 7358-7369 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisami Yamakawa, Masayuki Baba, Mitutoshi Shiba, Yutaka Hayashi, and Yutaka Yamaguchi: "Enhancement of Differentiation of Low Passage Cultured Cells Derived from Human Non-Small Cell Lung Carcinoma Using Deepithelialized Rat Tracheas Transplanted into Nude Mice." Differentiation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisami Yamakawa,Masayuki Baba,and Yutaka Yamaguchi: "In vivo Invasion Assay of Low Passage Cultured Cells Derived from Human Lung Cancer Using Deepithelialized Rat Tracheas Xenotrasplanted into Nude Mice." Cancer Research. 50(22). 7358-7363 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hisami Yamakawa,Masayuki Baba,Mitsutoshi Shiba,and Yutaka Yamaguchi: "Enhancement of Differentiation of Low Passage Cultured Cells Derived from Human NonーSmall Cell Lung Carcinoma Using Deepithelized Rat Tracheas Transplanted into Nude Mice." Differentiation.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hisami Yamakawa: "Invasion Assay in vivo of Low Passage Cultured Cells Derived from Human Lung Cancer Using Deepithelialized Rat Tracheas Xenctransplanted into Nude Mice" Cancer Research.

    • Related Report
      1989 Annual Research Report
  • [Publications] Hisami Yamakawa: "Modulation of Differentiation of Low Passage Cultured Cells Derived from Human Non-Small Cell Lung Cancers in Denuded Rat Tracheas Transplanted into Nude Mice." American Journal of Pathology.

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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