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Selection of drucrs against ovarian cancer and trial of discovering new molecular targets using gene expression profiles

Research Project

Project/Area Number 13671690
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

YAEGASHI Nobuo  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00241597)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsovarian cancer / microarray / molecular target / chemotherapy
Research Abstract

To clarify genes that play critical roles for carcinogenesis steps and acquisition of drug resistance of ovarian cancer, we studies approximately 6,000 gene expressions using an oligonucleotide microarray system. Gene expression patterns were analyzed by clustering technique, which standardized the gene expression level in normal ovarian tissues. With written informed consent, ovarian cancer tissues from surgical specimens were frozen at-80 C and mRNA was extracted from the tissues. Clustered gene expression profiles of ovarian cancer tissues were clearly different from those of normal tissues. However. there were no significant differences among each histological subtype of cancers. The expression levels of 97 genes were commonly up-regulated in cancer tissues and those of 227 genes were down-regulated. Among these genes, cytokeratin18, Am-1=Evil, HER3, keratin19, ear-2, βtubulin, GSTπ, c-erb-B2, nm23, BRCA2, p57, IGFBP5.6, Brush-1 and TGFB1BP were thought to become a molecular target … More of developng new anti-cancer drugs. One of highly effective drugs against ovarian cancer, paclitaxel, acts as a mitotic spindle poison, i.e., paclitaxel promotes assembly of tubulins and stabilizes them, preventing depolymerization. Our results that βtsubulin was up-regulated in all cancer specimens gave a theoretical evidence to the application of paclitaxel against ovarian cancer treatment. Then, we studied gene expression profiles of human ovarian cancer cell, KF28, Drug-resistant subclones of KF2B were prepared, KFr13, which is resistant to cis-platinum and, KF28TX and KFr13TX, which are resistant to paclitaxel. The cis-platinum-resistant clone showed the high expression of genes related with depoisoning pathway through glutathione, with glycolysis/ glycogenesis, with transketolase and with polyamine synthesis enzymes. The paclitaxel-resistant clones highly expressed multiple drug resistant genes, MDR and semaphorinE, etc. Comparison of clinical factors with expression levels of genes identified in this study will help to develop new molecular target drugs and to clarify mechanism of the acquisition of drug resistance. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Ito K, Suzuki T, Akahira J, Moriya T, Kaneko C, Utsunomiya H, Yaegashi N, Okarnura K, Sasano H.: "Expression of androgen receptor and 5a-reductases in the human normal endonietrium and its disorders"International Journal of Cancer. 99. 652-657 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akahira J, Suzuki T, Ito K, Kaneko C, Darnet AD, Moriya T, Okamura K, Yaegashi N, Sasano H.: "Differential expression of progesteron receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors"Japanese Journal of Cancer Research. 93. 807-815 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokomizo R, Matsuzaki S, Uehara S, Murakami T, Yaegashi N, Okamura K.: "Erythropoietin and erythropoietin receptor expresiion in human endometrium throughout the menstrual cyst"Molecular Human Reproduction. 8. 441-446 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akahira J, Suzuki T, Ito K, Darnel AD, Moriya I, Yaegashi N, Okamura K, Sasano H.: "Expression of 5alpha-reductases in human epithelial ovarian cancer : its correlation with androqen receptor status"Japanese Journal of Cancer Research. 92. 926-932 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami T., Terada Y, Sugawara J, Yaegashi N, Okamura K.: "The current status of gynecological laparoscopic surgery in educational facilities in Japan"Tohoku Journal of Experimental Medicine. 193. 175-180 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akahira J., Suzuki T., lto K., Darnel AD., Moriya T., Yaegashi N., Okamura K., Sasano H.: "Expression of 5alpha-reductases in human epithelial ovarian cancer: its correlation with androgen receptor status."Japanese Journal of Cancer Research. 92. 926-932 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami T., Terada Y., Sugawara J., Yaegashi N., Okamura K.: "The current status of gynecological laparoscopic surgery in educational facilities in Japan."Tohoku Journal of Experimental Medicine. 193. 175-180 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito K., Suzuki T., Akahira J., Moriya T., Kaneko C., Utsunomiya H., Yaegashi N., Okamura K., Sasano H.: "Expression of androgen receptor and 5a-reductases in the human normal endometrium and its disorders."International Journal of Cancer. 99. 652-657 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akahira J., Suzuki T., Ito K., Kaneko C., Darnel AD., Moriya T., Okamura K., Yaegashi N., Sasano H.: "Differential expression of progesteron receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors."Japanese Journal of Cancer Research. 93. 807-815 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokomizo R., Matsuzaki S., Uehara S., Murakami T., Yaegashi N., Okamura K.: "Erythropoietin and erythrcpoietin receptor expression in human endometrium throughout the menstrual cyst."Molecular Human Reproduction. 8. 441-446 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito K, Suzuki T, Akahira J, Moriya T, Kaneko C, Utsunomiya H, Yaegashi N, Okamura K, Sasano H.: "Expression of androgen receptor and 5a-reductases in the human normal endometrium and its disorders"International Journal of Cancer. 99. 652-657 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akahira J, Suzuki T, Ito K, Kaneko C, Darnel AD, Moriya T, Okamura K, Yaegashi N, Sasano H.: "Differential expression of progesteron receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors"Japanese Journal of Cancer Research. 93. 807-815 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yokomizo R, Matsuzaki S, Uehara S, Murakami I, Yaegashi N, Okamura K.: "Erythropoietin and erythropoietin receptor expresiion in human endometrium throughout the menstrual cyst"Molecular Human Reproduction. 8. 441-446 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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