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CLINICAL AND EXPERIMENTAL STUDY OF APOPTOSIS IN GASTRIC AND ESOPHAGEAL CARCINOMAS

Research Project

Project/Area Number 06671255
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

AIZAWA Kikuo  NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,UNIVERSITY HOSPITAL,ASSISTANT, 医学部・附属病院, 助手 (10222449)

Co-Investigator(Kenkyū-buntansha) SUZUKI Tsutomu  NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESOR, 医学部, 助教授 (40183420)
NISHIMAKI Tadashi  NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,UNIVERSITY HOSPITAL,LECTURER, 医学部・附属病院, 講師 (70242427)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsapoptosis / bcl-2 / p53 / proliferative activity / gastric carcinoma / prognostic factors / ecophageal carcinoma / cisplatin-resistance / p53 / PCNA / TUNEL法 / 抗癌剤 / 抗癌剤耐性 / 耐性克服剤 / DNA断片化 / C-myc
Research Abstract

Summary 1. Apoptosis and Bcl-2 expression in gastric carcinomas
Two-hundred and twenty one advanced gastric carcinomas were investigated using Gavrieli's method for detection of apoptotic cells and immunohistochemistry for Bcl-2, p53 and proliferating cell nuclear antigen (PCNA). The apoptotic index (AI) was associated with differentiated type tumors, positive lymphatic vessel invasion and a high PCNA-labeling index. Bcl-2 expression was detected in 72 of 221 cases (32.6%) and found to be inversely correlated with depth of tumor invasion, blood vessel invasion and lymph node metastasis. Moreover, it was correlated with a low AI.p53 expression was detected in 64 cases (29.0%) and neither correlated with AI nor Bcl-2 expression. Bcl-2 expression was associated with a better prognosis. These results indicate that apoptosis is associated with cell proliferation and Bcl-2 expression in gastric carcinomas. Bcl-2 may be expressed in the early phase of gastric carcinogenesis.
Summary 2. Induction of apoptosis in cisplatin-resistant human esophageal cancer cells
We have attempted to determine whether buthionine sulfoximine (BSO) and cyclosporin A (CsA) enhance cisplatin-induced apoptosis in cisplatin-resistant human esophageal cancer cells. The human esophageal cancer cell line TE2 and its 2.4-fold cisplatin-resistant derivative TE2R were used in this study. Cisplatin induced DNA fragmentation corresponding to the nucleosome ladders characteristics of apoptosis in TE2 but not in TE2R.BSO enhanced cisplatin sensitivity of both cell lines but affected neither cisplatin resistance nor induction of apoptosis, although CsA showed a resistance-modifying activity in TE2R.This effect was associated with induction of apoptosis at a relatively low concentration of cisplatin, when tested alone did not induce apoptosis. Our data indicate that CsA may overcome cisplatin resistance by enhancing the susceptibility to cisplatin-induced apoptosis in human esophageal cancer cells.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kikuo Aizawa: "Expression of P53 protein and proliferating cell nuclecr antign(PCNA)in aduanced gastric carcinoma" International Gastric Camen Congress Nishi M,Sugano M and Takahashi T(eds).739-743 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Norio Tanaka: "Modulation of cisplatin sensitivity and resistance by buthionire salfoximine and cyclosporin A in human esophageal cancer cells" Internationl Joural of Oncology. 9. 934-940 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kikuo Aizawa, Tadashi Nishimaki, Tsutomu Suzuki, Katsuyoshi Hatakeyama, Jun Soga and Terukazu Muto: "Expression of p53 protein and proliferating cell unclear antigen (PCNA) in advanced gastric carcinoma : clinicopathological correlation and prognostic significance. In : Nishi M,Sugano H and Takahashi T (eds)." International Gastric Cancer Congress. Monduzzi Editore, Bologna.739-743 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Norio Tanaka, Kikuo Aizawa, Norio Katayanagi, Hiroshi Yabusaki, Tsutomu Suzuki and Otsuo Tanaka: "Modulation of cisplatin sensitivity and resistance by buthionine sulfoximine and cyclosporin A in human esophageal cancer cells." International Journal of Oncology. 9. 934-940 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Norio Tanaka: "Modulation of cisplacin sensitivity and resistance by buthionine sulfoximine and cyclosporin A in human esophageal cancer cells" Int On col. 9. 935-940 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kikuo Aizawa: "Chemotherapy of human α-fetoprotein-producing gastric carcinomas grown in nude mice" Oncology Reports. 4. 397-400 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tadashi Nishimaki: "Intramural metastases from thoraeic esophageal cancer : local indicators of advanced disease" World J Surg. 20. 32-37 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jun Soga: "Carcinomas involving the esophagogastric junction (EGJ-Ca),a reavaluation of the criteria" Int Surg. 81. 149-151 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kikuo Aizawa: "Expression of p53 protein and proliferating cell nuclear antigen (PCNA)in advanced gastric carcinoma: clinicopathological correlation and prognostic sighifican" 1st International Gastric Cancer Congress. Nishi M,Sugano H and Takahashi T(eds)Monduzzi Editore,Balogna,Itoly. 739-743 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kikuo Aizawa: "Chemotherapy of human small-cell gastrointestinal carcinoma xenograts in nude mice." Surgical Oncology. 4. 139-145 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Yabusaki: "Inhibition of tamor-cell invasion and gelatinase production in metastatic human gastric carcinoma cells by retinoic acid and bestatin." International J. of Oncology. 7. 841-846 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsutomu Suzuki: "Carcinoma of the lower esophagus and gustic cardia." 1st International Gastric Caner Congress. Nishi M, Sugano Hand Takahashi T(eds)Monduzzi Editore,Bologna,Itoly. 459-463 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Jun Soga: "An evaluation of composite pattevns observed in two gastric carcinoids." J. Experimental and Clinical Cancer Research. 14. 349-361 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 本山 俤一: "実験消化管癌-ヒト胃癌培養細胞とヌードマウス移植腫瘍-" 日本消化器病学会雑誌. 92. 735-741 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] KiKuo Aizawa: "Augmentation of 5-fluorouracil cytotoxicity by epidermal growth fwtor in a newly established huinan signetcarcinome of the Stomach in culture" Jpn.J.Surg,(Surgery Today). 24. 420-428 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] KiKuo Aizawa: "Different characteristics of hepatoid and hon-hepatoid α-feteorctein producing gaifric carcinomas:an experimental studyhsing xenogcfted funcors" Int.J.Cancer. 58. 430-435 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ichiro Muto: "Expression of placental alkaline phosphatase isoengymc in human gastrointestinal carcinomas as iden tified using monoclonal antibcdies" Acta Med.et Biol. 42. 171-178 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinsuke Tanaka: "Flow cytometric analysis of early stepsin development of adnamycin resistantc in a human gastric cancer cell line" Jpn.J.Cancer.Res. 85. 86-92 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kikuo Aizawa: "Chenotherapy of human smaii-cell gastrointestind curcinoma xenografts in nude mice" Surg.Oncol. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kikuo Aizawa: "Expression of p53 profein and proliferating cell nuclecr untigen(RNA) in advanced gastnc curcinomo:clinicoputhological correlation and prognostic significarce" 1st International Gastric Cancer Congress.M.Nishi,T.Takahashi,H.Sugano.cds.Monduzzi,Bologha.Italy. (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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