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p53-based gene therapy of ovarian cancer with chemo-resistance

Research Project

Project/Area Number 07671785
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTottori University, Faculty of Medicine

Principal Investigator

KIGAWA Junzo  Tottori Univ.・Dept.Obstet.Gynecol., Assistant Professor, 医学部, 講師 (00177784)

Co-Investigator(Kenkyū-buntansha) MINAGAWA Yukihisa  Tottori Univ.・Dept.Obstet.Gynecol., Assistant Professor, 医学部附属病院, 講師 (70190692)
TERAKAWA Naoki  Tottori Univ.・Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Keywordsovarian cancer / chemoresistance / p53 gene / gene therapy / p53 / 遺伝子変異
Research Abstract

The aim of this study was to know the role of p53-gene therapy for patients with chemoresistant ovarian cancer. To examine the role of p53 gene in the chemoresistance of epithelial ovarian cancer, we investigated p53 gene and its protein in tumors before and after chemotherapy in the same patients. Mutation of p53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation of the gene was observed in 5 patients who were all the nonresponders. By Western blot analysis, p53 protein was detected in 10 patients (3 responders and 7 nonresponders) before chemotherapy. After chemotherapy, expression of p53protein increased in these nonresponders and became to be positive in another 2 nonresponders. These results suggest for the first time that p53 gene and expression of p53 protein in tumors are altered by chemotherapy and the alteration of p53 status may be involved in the mechanisms of chemoresistance in epithelial ovarian cancer. … More Additionally, expression of GST-l and concentration of glutathione in tumors before and after chemotherapy were examined. Then we found that increased levels of GST-l and GSH expression after chemotherapy were linked to drug-resistance in patients with epithelial ovarian cancer. Next, We developed wt-p53 expression vector as following. Recombinant adenovirus was grown and propagated in 293 cells, a human embryonic kidney cell line transformed by Ad5 E1A and E1B genes. Recombinant adenoviruses purified on the method of sequential centrifugation in CsCl step gradients. To construct the Adex p53, a 1.95-kb BamH l-EcoR l fragment containing the full-length complementary DNA (cDNA) for human wild-type p53 (wt-p53) was isolated from pProSp53. The p53 coding sequence was inserted into pAdex1CAwt adenovirus gene transfer cosmid cassette. The cosmid was cotransfected the EcoT22 l-digested Ad5-dlx by the calcium phosphate method to 293 cells. Then tranfect experimental study showed that tumor suppression in even tumor with wt- p53, although the relation between p53 gene therapy status and chemosenseitivity. The present study suggests that p53 gene therapy will be useful approach for ovarian cancer. Less

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kigawa J.: "Platinum concentrations in uterus and serum after internal iliac arterial infusion of platinum conpounds in rabbits." Obstet Gynecol. 86・2. 265-268 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morishita K.: "Growth inhibition of uterine cervical cancer cells by a sequential administration of anticancer drugs and irradiation." Gynecol Obstet Invest. 40・1. 57-60 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kigawa J.: "The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer." Am J Clin Oncol. 19・3. 255-259 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itamochi H.: "Antitumor effects by internal iliac arterial infusion of platinum compounds in a rabbit cervical cancer model." Obstet Gynecol. 89・2. 286-290 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cheng X.: "Glutathione-transferase-π and glutathione concentration in ovarian carcinoma before and after chemotherapy." Cancer. 79・3. 521-527 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Terakawa N.: "Hormone-dependent cancer" Marcel Dekker, Inc (New York), 22 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kigawa J.: "Obstet Gynecol" Platinum concentrations in uterus and serum after internal iliac arterial infusion of platinum compounds in rabbits.86-2. 265-8 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morishita K.: "Gynecol and Obstet Invest" Growth inhibition of uterine cervical cancer cells by a sequential administration of anticancer drugs and irradiation. 40-1. 57-60 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kigawa J.: "Am J Clin Oncol" The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer. 19-3. 255-259 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itamochi H.: "Obstet Gynecol" Antitumor effects by internal iliac arterial infusion of platinum compounds in a rabbit cervical cancer model.89-2. 286-290 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cheng X.: "Cancer" Glutathione s-transferase-l and glutathione concentration in ovarian carcinoma before and after chemotherapy.79-3. 521-527 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Terakawa N.: Hormone-dependent cancer. Marcel Dekker, Inc (New York), (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kigawa J.: "Platinum concentrations in uterus and serum after internal iliac arterial infusion of platinum compounds in rabbits." Obstet Gynecol. 86・2. 265-268 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morishita K.: "Growth inhibition of uterine cervical cancer cells by a sequential administration of anticancer drugs and irradiation." Gynecol Obstet Invest. 40・1. 57-60 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kigawa J.: "The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer." Am J Clin Oncol. 19・3. 255-259 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itamochi H.: "Antitumor effects by internal iliac arterial infusion of platinum compounds in a rabbit cervical cancer model." Obstet Gynecol. 89・2. 286-290 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cheng X.: "Glutathione s-transferase-π and glutathione concentration in ovarian carcinoma before and after chemotherapy." Cancer. 79・3. 521-527 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Terakawa N.: "Hormone-dependent cancer" Marcel Dekker,Inc(New York), 22 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Junzo Kigawa: "Platinum concentrations in uterus and serum after interal iliac arterial infusion of platinum compounds in rabbits" Obstetrics and Gynocology. 86. 265-268 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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