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Relationship Between the Alteration of Apoptosis Related Genes and Sensitivity for Radiotherapy and Chemotherapy in Human Cancer

Research Project

Project/Area Number 07671368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionUniversity of Tokyo

Principal Investigator

TOMINAGA Osamu  University of Tokyo, Department of Surgery, Assistant, 医学部・附属病院, 助手 (10261976)

Co-Investigator(Kenkyū-buntansha) OSADA Takuya  University of Tokyo, Department of Sugery, Assistant, 医学部・附属病院, 助手 (90272559)
ISHIMARU Gosei  University of Tokyo, Department of Sugery, Assistant, 医学部・附属病院, 助手 (70272557)
SETO Yasuyuki  University of Tokyo, Department of Surgery, Assistant, 医学部・附属病院, 助手 (00260498)
NAGAWA Hirokazu  University of Tokyo, Department of Surgery, Assistant Proffesor, 医学部・附属病院, 助教授 (80228064)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsApoptosis / Radiotherapy / Chemotherapy / Cancer / Bcl-2 / p53 / 食道癌 / 大腸癌 / bcl-2
Research Abstract

P53, p21^<WAF1/CIP1>, Bcl-2 and Bax were analyzed in esophageal and colorectal cancer cell lines. p53 and p21^<WAF1/CIP1> were expressed in about 70% and 40% of the cell lines respectively. Bcl-2 was expressed in the majority of the esophageal cancer cell lines and a few colorectal cancer cell lines. Bax was detected in most of the cell lines studied. To search for the determinant factors of radiosensitivity in rectal carcinoma, p53, p21 and Bcl-2 were selected for possible predictive factors for rediosensitivity. Expressions of p53, p21 and Bcl-2were studied in 49 rectal carcinomas by immunohistochemistry before (biopsy specimen) and after (resected specimen) radiatiion and their relations with pathologic effect of rediotherapy. The total dose of rediation was =0Gy in all patients, by 2.5Gy each time, 5 times a week. p53, p21/WAF1 and Bcl-2 expressions were 53.1%, 30.6% and 71.4%, respectively. There was a significant inverse correlation between the expression of p53 and p21. Moderate to marked pathologic effect of radiation was found in 36.7% of the tumors, while others showed little effect. Of the p53 positive tumors, 88.5% were radioresistant, while 65.2% of the p53 negative tumors were radiosensitive. Of the p21 positive tumors, 80,0% were radiosensitive, while 82.4% of the p21 negative tumors were radioresistant. The combinations of p53 (+) and p21 (-) , as a predictor of radioresistance, and p53 (-) and p21 (+), as a predictor of radiosensitivity, enhanced sensitivity (90.0%), specificity (95.4%) and accuracy (93.8%). The expression of Bcl-2 showed no correlation with radiosensitivity. Immunochemically detected p53 and p21 expression can be used as independent predictors for radiosensitivity of redctal carcinoma. The combination of these two factors can make the selection for radiosensitive tumor more sensitive, specific and accurate.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Nita M.E.: "Alterations of cell cycle and apoptosis regulators in esophageal and colorectal cancer cell lines." Recent Advances in Gastroenterological Carcinogenesis. I. 439-443 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga, O.: "Expressions of cell cycle regulators in human colorectal cancer cell lines." Japanese Journal of Cancer Research. 88. 855-860 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fu C.G.: "Role of p53、p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients." Disease of Colon Rectum. 41. 68-74 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga, O.: "Screening for APC mutations based on the detection of truncated APC proteins." Digestive Diseases and Sciences. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nita M.E.: "Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer." Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nita M.E., Tominiga O., Nagawa H., Kaizaki, S., Fujii S., Yuan X., Tsuno N., Fu C.G., & Muto T: "Alterations of cell cycle and apoptosis regulators in esophageal and colorectal cancer cell lines" Recent Advances in Gastroenterological Carcinogenesis Monduzzi Editore, Bologna. I. 439-433 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga O., Nita M.E., Nagawa H., Fujii S., Tsuruo T.& Muto T.: "Expressions of cell cycle regulators in human colorectal cancer cell lines" Jpn.J.Cancer Res.88. 855-860 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fu C.G., Tominaga O., Nagawa H., Nita M.E., Higuchi Y., Tsuruo T.& Muto T.: "Role of p53, p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients." Dis.Colon Rectum. 41. 68-74 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tominaga O., Nita M.E., Nagawa H., & Muto T.: "Screening for APC mutations based on the detection of truncated APC proteins" Digestive Diseases and Sciences. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nita M.E., Tominaga O., Nagawa H., Tsuruo T.& Muto T.: "Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nita M.E.: "Alterations of cell cycle and apoptosis regulators in esophageal and colorectal cancer cell lines." Recent Advances in Gastroenterological Carcinogenesis. I. 439-443 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tominaga O.: "Expressions of cell cycle regulators in human colorectal cancer cell lines." Japanese Journal of Cancer Research. 88. 855-860 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fu C.G.: "Role of p53,p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients." Disease of Colon Rectum. 41. 68-74 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tominaga O.: "Screening for APC mutations based on the detection of truncated APC proteins." Digestive Diseases and Sciences. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Nita M.E.: "Dihydropyrimidine dehydrogenase but not thymidylate synthase expression is associated with resistance to 5-fluorouracil in colorectal cancer." Hepato-Gastroenterology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Nita M.E.et al.: "Alterations of cell cycle and apoptosis regulators in esophageal and colorectal cancer cell lines." Recent Advances in Gastroenterological Carcinogenesis. 1. 439-443 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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