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Analysis of Cell Cycle Related Gene and Cell Culture in Esophageal Cancer. (Carcinogenesis, Tumor Progression and Prognostic Factor)

Research Project

Project/Area Number 07671386
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIMADA Yutaka  Kyoto University, Graduate School of Medicine, Department of Surgery & Surgical Basic Science, Assistent Professor, 医学研究科, 講師 (30216072)

Co-Investigator(Kenkyū-buntansha) IMAMURA Masayuki  Kyoto University, Graduate School of Medicine, Department of Surgery & Surgical, 医学研究科, 教授 (00108995)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsEsophageal cancer / Esophageal cancer cell lines / Cell Cycle related gene / Prognostic factor / CDDP chemosensitivity / p53 mutation / p16 / CyclinD1 / p53 / p16 / Cyclin D_1 / MDM2 / 化学療法感受性 / 悪性度評価 / 細胞周期 / CDK4 / Cyclin D1 / HPV
Research Abstract

Of the 30 esophageal squamous cell carcinoma (ESC) cell lines, 28 (93.3%) showed aberration of the p16 gene : Of the 15 primary esophageal tumors, aberrations of the p16 gene were detected in 7 (41%), while all cell lines derived from these tumors showed aberrations. We detected homozygous deletions in 9 cell lines which were established from tumors without them, and all of these deletions were observed even in cultures at early passage. These results suggest a possibility that cells exhibiting homozygous deletions in tumors expanded through the establishment of cell lines.
With regard to p53 mutation, of the 29 cell lines 22 (75.9%) showed p53 mutation. Compared with the results in these fresh tumor materials, the mutation incidence in cell lines was significantly high and the mutation spectrum was also different. In 7 cell lines established from mutation-free tumors, newly acquired mutations were detected in 5, which suggests that mutations might occur during the process of establishi … More ng cell lines.
The prognosis for patients with loss of APC locus, p53 mutation, CyclinD1 amplification and MDM2 amplification was significantly lower than that of patients without gene abnormality. Best predictability was obtained by a combined analysis of p53 mutation and MDM2 amplification. Loss of Rb gene revealed to be significant on the prognosis for patients, when a combined analysis of Rb and CyclinD1 gene was made.
Finaly, we checked the relation of gene abnormalities and histological effect of esophaegal cancer patients. Histological effect (grade>0) were noted in 62.5% (15/24) of the patients without p53 mutation, whereas, 6 out of 19 patients (31.6%) with p53 mutation had histological effect. The positive cases of immunohistochemical p53 staining in resected specimens and pre-treatment biopsy sample also tended to resist cisplatin. p53 mutation and its regulating genes may be a marker of chemosensitivity in esophageal SCC patients and chemotherapy may be selected according to the findings of p53 mutation and p53 regulating genes. Less

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Shimada Y et al: "Genetic Alterations in Esophageal Cancer Patients with short and I cng term Survival Rates stter curative Esophagectomy" Ann Surg. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisahi Tanaka, Yutaka Shinada et al: "Multiple types of aberrations in the p16(INK 4a) and p15 (INK 4b) genes in 30 esophageal squamous cell carcinoma cell lines" Int. J. Cancer. 70. 437-442 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y et al: "Pregnostic value to monolayer cultwe patterming in primary cell cuture in oesophageal cancer." Br. J. Surg.83. 1148-1151 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisashi Tanaka, Ichio Shibagaki Yutaka Sbinada: "Charaterization of p53 gene mutations in esophageal squamous cell carinama cell linesi lncrea ed frequncy and difterent spectre of mutations from prinary tumors." Int J Cancer. 65. 372-376 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ichio Shibagaki, Hisashi Tanaka Yutaka Shimada: "p53 Mutation, MDM2 anplification and HPV infection are Frequently in volved but not associated with each other esonhageal squamons cell carcinema" Climical Cancer Research. 1. 769-773 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y et al: "Recent Advances in Gastroenterological Carcinogene -sts 1" Monduzzi Editore, 1232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y et al: "Recent Advances in Diseases at the Esophagus" Monduzzi Editore, 1133 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yutaka Shimada, Masayuki Imamura.Ichio Shibagaki, Hisashi Tanaka, Tokiharu Miyahara Masayuki Kato and Kanji Ishizaki.: "Genetic Alterations in Esophageal Cancer Patients with Short and Long Term Survival Rates after Curative Esophagectomy." Ann Surg. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisashi Tanaka, Yutaka Shimada, Masayuki Imamura, Ichio Shibagaki, Kanji Ishizaki.: "Multiple types of aberrations in the p16 (INK4a) and p15 (INK4b) genes in 30 esophageal squamous cell carcinoma cell lines." Int J Cancer. 70. 437-442 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y,Kanda Y,Shibagaki I,Kato M,Watanabe G,Tanaka H,Kano M,Imamura M: "Prognostic value of monolayr culture patterning in primary cell culture in oesophageal cancer." Br J Surg. 83. 1148-1151 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisashi Tanaka, Ichio Shibagaki, Yutaka Shimada, Takashi Wagata, Masayuki Imamura, Kanji Ishizaki: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors." Int J Cancer. 65. 372-376 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ichio Shibagaki, Hisashi Tanaka, Yutaka Shimada, Takashi Wagata, Mitsuo Ikenaga, Masayuki Imamura, and Kanji Ishizaki: "p53 Mutation, MDM2 amplification and HPV infection are Frequently involved but not associated with each other esophageal squamous cell carcinoma." Clinical Cancer Research. 1. 769-773 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y and Imamura M: A berration of p16/INK4a, and p15/INK4b and p53 genes in esophageal cancer. Recent Advances in Gastroenterological Carcinogenesis 1 Edt.by E.Tahara, K.Sugimachi, T.Oohara Monduzzi Editore 57-63, 1232 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y,Tanaka H,Shibagaki I,Kato M,Miyahara T,Watanabe G,Kano M,Furutani M,Yamazaki S,Sugie T,Okino T,Imamura M: Characterization of newly established esophageal cancer cell lines (KYSE-series).Recent Advances in Diseases of the Esophagus/A.Peracchia et al (eds.), Monduzzi Editore, 109-114, 1133 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimada Y et al: "Genetic Alterations in Esophageal Cancer Patients with Short and Long Term Survival Rates after Curative Esophagectomy" ANNALS OF SURGERY. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka H.Shimada Y.et al: "Multiple types of aberrations in the p16 (INK 4a) and p15 (Ink 4b) genes in 30 rsophageal squamans cell earcinoma cell lines." Int J Cancer. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimada Y et al: "The predictive value of mamologer culture patterning in primary cell culture in oesophayeal cancer" Br J Surg. 83. 1148-1151 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,H.Shibagaki I.Shimada Y.et al: "Clxiracterization of p53 gene matations in esophayeal squamous cell carinoma cell lines Increased ftequtncy and different spectrunot mutations from prlmary tumcis." Int J Cancer. 65. 372-376 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Zhou X.Suzuki H.Shimada Y.et al: "Genomic DNA and Messenger RNA cxpression Alterations of the CDKN2B and CDKIV2 Genes in esophagenl Squamous Carcinoma cell lines" Genes,Chromosomes & Cancer. 13. 285-290 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shibazaki I.Tanaka H.Simada Y.et al: "p53 Mutation MDM2 Amplifi cation and HPV infection are Frequently involved but not associated with each other esophegeal squamaus cell carcinoma" Clinical Cancer Research. 1. 769-773 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 嶋田 裕: "新外科学大系追補1-消化管の外科" 中山書店, 12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shibagaki I, et al: "p53 mutation, MDM2 amplification and HPV infection are frequently involved but not associated with each other in esophageal squamous cell carcinoma" Clinical Cancer Research. 1. 769-773 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 嶋田裕 他: "食道癌の分子生物学と治療 1)癌遺伝子" 外科. 57. 1054-1061 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Xiaoling Zhou, et al.: "Genomic DNA and Messenger RNA expression alterations of the CDKN2B and CDKN2 genes in esophageal squamous carcinoma cell lines." Genes Chromosomes & Cancer. 13. 285-290 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Jian Li, et al.: "Multiple tumor supresson 1 gene and esophageal carcinoma." International Journal of oncology. 7. 257-260 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimada Y. et al: "The predictive value of monolayer culture patterning in primary cell culture in oesophageal cancer." Br J Surg. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka H. et al.: "High frequency of p53 gene alteration in esophageal squamous cell carcinoma cell 7 lnes caused by acqulred mutation after establishment in culture." Int J Cancer. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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

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