Development of new molecular targeted medicine for ovarian cancer

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390512
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The Jikei University School of Medicine
• Principal Investigator: OKAMOTO Aikou The Jikei University School of Medicine, Lecturer, 医学部, 講師 (20204026)
• Co-Investigator(Kenkyū-buntansha): YAMADA Kyosuke The Jikei University School of Medicine, Lecturer, 医学部, 講師 (30230452) ; TAKAKURA Satoshi The Jikei University School of Medicine, Assistant, 医学部, 助手 (60256401) ; OCHIAI Kazunori The Jikei University School of Medicine, Professor, 医学部, 教授 (20152514) ; TANAKA Tadao The Jikei University School of Medicine, Professor, 医学部, 教授 (50110929)
• Project Period (FY): 2003 – 2005
• Keywords: IDO / Paclitaxel / ovarian cancer / cDNA microarray / cDANマイクロアレイ

Research Abstract

Purpose : We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. Experimental Design : Using 2 newly established PTX-resistant ovarian cancer cell lines from an original PTX-sensitive cell line and 4 super-sensitive and 4 refractory surgical ovarian cancer specimens from PTX-based chemotherapy, molecules associated with chemoresistance were screened with gene expression profiling arrays containing 39,000 genes. We further analyzed 44 genes that showed significantly different expressions between PTX-sensitive samples and PTX-resistant samples with permutation tests, which were common in cell lines and patients' tumors. Results : Eight of these genes showed reproducible results with the real time reverse transcriptase polymerase chain reaction, of which indoleamine 2,3-dioxygenase (IDO) gene expression was the most prominent and consistent. Moreover, by immunohistochemical analysis using a total of 24 serous type ovarian cancer surgical specimens (stage III:n=21,stage IV:n=7) excluding samples used for GeneChip analysis, the Kaplan-Meier survival curve showed a clear relationship between IDO staining patterns and overall survival (log-rank test : P=0.0001). All patients classified as negative survived without relapse. The 50% survival of patients classified as sporadic, focal and diffuse was 41,17 and 11 months, respectively. Conclusion : The IDO screened with the GeneChip was positively associated with PTX resistance and with impaired survival in patients with serous type ovarian cancer.

Research Products

• [Journal Article] Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. (2006)
  • Author(s): Yanaihira N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC.
  • Journal Title: Cancer Cell. 9 Pages: 189-198
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IGFBP1 and Follistatin-like 3 genes are significantly up-regulated in expression profiles of the IUGR placenta. (2006)
  • Author(s): Okamoto A, Endo H, Kalionis B, Shinya M, Saito M, Nikaido T, Tanaka T.
  • Journal Title: Placdenta 27 Pages: 317-321
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. (2006)
  • Author(s): Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC.
  • Journal Title: Cancer Cell. 9 Pages: 189-198
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 2, 3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. (2005)
  • Author(s): Okamoto A, Nikaido T, Ochiai K, Takakura S, Saito M, Aoki Y, Ishii N, Yanaihara N, Yamada K, Takikawa O, Kawaguchi R, Isonishi S, Tanaka T, Urashima M.
  • Journal Title: Clin Cancer Res. 11 Pages: 6,030-6,039
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Clinical significance of p21 (WAF1/CIP1) and p53 expression in serous cystadenocarcinoma of the ovary. (2005)
  • Author(s): Terauchi F, Okamoto A, Nagashima T, Kobayashi Y, Moritake T, Yamamoto Y, Takakura S, Iwaki S, Ogura H.
  • Journal Title: Oncol Rep. 14 Pages: 343-368
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms. (2005)
  • Author(s): Endo H, Okamoto A, Yamada K, Nikaido T, Tanaka T
  • Journal Title: Int J Mol Med 16 Pages: 79-84
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genes associated with the genesis of leiomyoma of the uterus in a commonly deleted chromosomal region at 7q22. (2005)
  • Author(s): Saito E, Okamoto A, Saito M, Shinozaki H, Takakura S, Ochiai K, Tanaka T.
  • Journal Title: Oncol Rep 3 Pages: 469-472
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. (2005)
  • Author(s): Okamoto A, Nikaido T, Ochiai K, Takakura S, Saito M, Aoki Y, Ishii N, Yanaihara N, Yamada K, Takikawa O, Kawaguchi R, Isonishi S, Tanaka T, Urashima M.
  • Journal Title: Clin Cancer Res. 11 Pages: 6030-6039
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without (2005)
  • Author(s): Endo H, Okamoto A, Yamada K, Nikaido T, Tanaka T.
  • Journal Title: Int J Mol Med 16 Pages: 79-84
  • Description: 「研究成果報告書概要(欧文)」より