Identification of "oncogenic kinase" in ovarian cancer

• Project/Area Number: 23592449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kobe University
• Principal Investigator: SUDO Tamotsu 神戸大学, 医学(系)研究科(研究院), 医学研究員 (50397824)
• Co-Investigator(Kenkyū-buntansha): IGUCHI Taisen 大学共同利用機関法人自然科学研究機構(共通施設), 岡崎統合バイオサイエンスセンター, 教授 (90128588)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 卵巣癌 / リン酸化酵素 / 三次元培養

Research Abstract

We clarified that PTK6, protein-tyrosine kinase-6, is over-expressed in ovarian cancers through demethylation of PTK6 gene. Ovarian cancer patients with over expression of PTK6 tend to have poor prognoses.
We developed a novel 3D cell culture system named Cell-able.The spheroids derived from ovarian cancer tissues could be grown on Cell-able.The incorporation of EdU and staining with Caspase 3/7 were useful for evaluating the sensitivity for chemotherapeutic agents and molecular targeting agents.

Research Products

• [Journal Article] Unique roles of estrogen-dependent Pten control in epithelial cell homeostasis of mouse vagina (2014)
  • Author(s): Miyagawa S, Sato M, Sudo T, Yamada G, Iguchi T
  • Journal Title: Oncogene
  • Peer Reviewed
• [Journal Article] Alpha-fetoprotein-producing ovarian clear cell adenocarcinoma simulating fetal gut in a postmenopausal woman (2014)
  • Author(s): Akemi Morimoto, Tamotsu Sudo, Toshiko Sakuma, Masanori Yasuda, Kiyoshi Fujiwara
  • Journal Title: Gynecologic Oncology Reports Volume: 8 Pages: 24-26
  • Peer Reviewed
• [Journal Article] Boron neutron capture therapy as new treatment for clear cell sarcoma: Trial on different animal model (2014)
  • Author(s): Andoh T, Fujimoto T, Sudo T, Suzuki M, Sakurai Y, Sakuma T, Moritake H, Sugimoto T, Takeuchi T, Sonobe H, Epstein AL, Fukumori Y, Ono K, Ichikawa H
  • Journal Title: Appl Radiat Isot Volume: 88 Pages: 59-63
  • Peer Reviewed
• [Journal Article] Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery (2013)
  • Author(s): Muraji M, Sudo T, Iwasaki S, Ueno S, Wakahashi S, Yamaguchi S, Fujiwara K, Nishimura R
  • Journal Title: Gynecol Oncol Volume: 131(3) Pages: 531-4
  • Peer Reviewed
• [Journal Article] VAV1 represses E-cadherin expression through the transactivation of Snail and Slug: a potential mechanism for aberrant epithelial to mesenchymal transition in human epithelial ovarian cancer (2013)
  • Author(s): Wakahashi S, Sudo T, Oka N, Ueno S, Yamaguchi S, Fujiwara K, Ohbayashi C, Nishimura R
  • Journal Title: Transl Res Volume: 162(3) Pages: 181-90
  • Peer Reviewed
• [Journal Article] Absence of human papillomavirus infection and activation of PI3K-AKT pathway in cervical clear cell carcinoma (2013)
  • Author(s): Ueno S, Sudo T, Oka N, Wakahashi S, Yamaguchi S, Fujiwara K, Mikami Y, Nishimura R
  • Journal Title: Int J Gynecol Cancer Volume: 23(6) Pages: 1084-91
  • Peer Reviewed
• [Journal Article] Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model (2013)
  • Author(s): Fujimoto T, Andoh T,Sudo T, Fujita I, Moritake H, Sugimoto T, Sakuma T, Akisue T, Kawabata S, Kirihata M, Suzuki M, Sakurai Y, Ono K, Fukumori Y, Kurosaka M, Ichikawa H
  • Journal Title: Appl Radiat Isot Volume: 73 Pages: 96-100
  • Peer Reviewed
• [Journal Article] Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases (2013)
  • Author(s): Shin-ichi Iwasaki, Tamotsu Sudo, Maiko Miwa,Masayo Ukita, Akemi Morimoto, Masaru Tamada, Sayaka Ueno, Senn Wakahash, Satoshi Yamaguchi, Kiyoshi Fujiwara, Yoshiko Sakuma, Yoshiki Mikami, Ryuichiro Nishimura
  • Journal Title: Arch Gynecol Obstet Volume: 288(2) Pages: 385-91
  • Peer Reviewed
• [Journal Article] L1 gene methylation in high-risk human papillomaviruses for the prognosis of cervical intraepithelial neoplasia (2013)
  • Author(s): Oka N, Kajita M, Nishimura R, Ohbayashi C and Sudo T
  • Journal Title: Int J Gynecol Cancer Volume: 23(2) Pages: 235-43
  • Peer Reviewed
• [Journal Article] 9. L1 gene methylation in high-risk human papillomaviruses for the prognosis of cervical intraepithelial neoplasia (2013)
  • Author(s): Oka N, Kajita M, Nishimura R, Ohbayashi C and Sudo T
  • Journal Title: Int J Gynecol Cancer Volume: 23 Issue: 2 Pages: 235-243
  • DOI: 10.1097/igc.0b013e31827da1f6
  • Peer Reviewed
• [Journal Article] 8. Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases (2013)
  • Author(s): Shin-ichi Iwasaki, Tamotsu Sudo, Maiko Miwa,Masayo Ukita, Akemi Morimoto, Masaru Tamada, Sayaka Ueno, Senn Wakahash, Satoshi Yamaguchi, Kiyoshi Fujiwara, Yoshiko Sakuma, Yoshiki Mikami, Ryuichiro Nishimura
  • Journal Title: Arch Gynecol Obstet. Volume: 288 Issue: 2 Pages: 385-391
  • DOI: 10.1007/s00404-013-2766-3
  • Peer Reviewed
• [Journal Article] VAV1 represses E-cadherin expression through the transactivation of Snail and Slug: a potential mechanism for aberrant epithelial to mesenchymal transition in human epithelial ovarian cancer (2013)
  • Author(s): Wakahashi S, Sudo T, Oka N, Ueno S, Yamaguchi S, Fujiwara K, Ohbayashi C, Nishimura R.
  • Journal Title: Transl Res Volume: 162 Issue: 3 Pages: 181-190
  • DOI: 10.1016/j.trsl.2013.06.005
  • Peer Reviewed
• [Journal Article] Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery (2013)
  • Author(s): Muraji M, Sudo T, Iwasaki S, Ueno S, Wakahashi S, Yamaguchi S, Fujiwara K, Nishimura R.
  • Journal Title: Gynecol Oncol Volume: 131 Issue: 3 Pages: 531-534
  • DOI: 10.1016/j.ygyno.2013.09.030
  • Peer Reviewed
• [Journal Article] Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model. (2013)
  • Author(s): Fujimoto T, Andoh T, Sudo T, Fujita I, Moritake H, Sugimoto T, Sakuma T, Akisue T, Kawabata S, Kirihata M, Suzuki M, Sakurai Y, Ono K, Fukumori Y, Kurosaka M, Ichikawa H
  • Journal Title: Appl Radiat Isot Volume: 73 Pages: 96-100
  • Peer Reviewed
• [Journal Article] Molecular-targeted therapies for ovarian cancer: prospects for the future (2012)
  • Author(s): Sudo T
  • Journal Title: Int J Clin Oncol Volume: 17(5) Pages: 424-9
  • NAID: 10031144328
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: morphological significance of calponin h1 (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Sudo T, Nishimura R, Ishiko O, Shiozawa T, Kanai Y, Yaegashi N, Aburatani H, Konishi I
  • Journal Title: FEBS Lett Volume: 586(13) Pages: 1824-31
  • NAID: 120007110569
  • Peer Reviewed
• [Journal Article] High-risk ovarian cancer based on 126-gene expression signature is uniquely characterized by down regulation of antigen presentation pathway (2012)
  • Author(s): Yoshihara K, Tsunoda T, Shigemizu D, Fujiwara H, Hatae M, Fujiwara H, Masuzaki H, Katabuchi H, Kawakami Y, Okamoto A, Nogawa T, Matsumura N, Udagawa Y, Saito T, Itamochi H, Takano M, Miyagi E, Sudo T, Ushijima K, Iwase H, Seki H, Terao Y, Enomoto T, Mikami M, Akazawa K, Tsuda H, Moriya T, Tajima A, Inoue I, Tanaka K
  • Journal Title: Clin Cancer Res Volume: 18(5) Pages: 1374-85
  • Peer Reviewed
• [Journal Article] The effect of abdominal radical trachelectomy on ovarian reserve: serial changes in serum anti-mullerian hormone levels (2012)
  • Author(s): Muraji M, Sudo T, Iwasaki S, Ueno S, Wakahashi S, Yamaguchi S, Fujiwara K, Nishimura R
  • Journal Title: Journal of Cancer Volume: 3 Pages: 191-5
  • Peer Reviewed
• [Journal Article] Endometrioid adenocarcinoma with high-grade transformation with serous and choriocarcinomatous differentiation - a case report (2012)
  • Author(s): Senn Wakahashi, Tamotsu Sudo, Chiho Ohbayashi
  • Journal Title: Journal of Cancer Volume: 3 Pages: 14-8
  • Peer Reviewed
• [Journal Article] Type II versus Type III fertility-sparing abdominal radical trachelectomy for early stage cervical cancer: a comparison of feasibility of surgical outcomes (2012)
  • Author(s): Miho MURAJI, Tamotsu SUDO, Ryuichiro NISHIMURA
  • Journal Title: Int J Gynecol Cancer Volume: 22(3) Pages: 479-83
  • Peer Reviewed
• [Journal Article] Molecular-targeted therapies for ovarian cancer: prospects for the future. (2012)
  • Author(s): Sudo T
  • Journal Title: Int J Clin Oncol Volume: 17(5) Issue: 5 Pages: 424-9
  • DOI: 10.1007/s10147-012-0461-1
  • NAID: 10031144328
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: morphological significance of calponin h1 (2012)
  • Author(s): Hayashi T,Horiuchi A,Sano K,Hiraoka N,Kasai M,Ichimura T,Sudo T,Nishimura R,Ishiko O,Shiozawa T,Kanai Y,Yaegashi N,Aburatani H,Konishi I.
  • Journal Title: FEBS Lett Volume: 586 Issue: 13 Pages: 1824-31
  • DOI: 10.1016/j.febslet.2012.05.029
  • NAID: 120007110569
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy (2011)
  • Author(s): Takuma Hayashi, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Mari Kasai, Tomoyuki Ichimura, Tamotsu Sudo, Nobuo Yaegashi , Hiroyuki Aburatani, Tanri Shiozawa
  • Journal Title: Ikuo Konishi Scientific Reports Volume: 1 Pages: 180-180
  • NAID: 120007110570
  • Peer Reviewed
• [Journal Article] Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-l-phenylalanine in CCS-bearing animal models (2011)
  • Author(s): Andoh T, Fujimoto T, Sudo T, Fujita I, Imabori M, Moritake H, Sugimoto T, Sakuma Y, Takeuchi T, Kawabata S, Kirihata M, Akisue T, Yayama K, Kurosaka M, Miyatake S, Fukumori Y, Ichikawa H
  • Journal Title: Appl Radiat Isot Volume: 69(12) Pages: 1721-4
  • Peer Reviewed
• [Journal Article] Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies (2011)
  • Author(s): Fujimoto T, Andoh T, Sudo T, Fujita I, Imbabura M, Moritake H, Sugimoto T, Sakuma Y, Takeuchi T, Sonobe H, Epstein AL, Akisue T, Kirihata M, Kurosaka M, Fukumori Y, Ichikawa H
  • Journal Title: 2011 Appl Radiat Isot Volume: 69(12) Pages: 1713-6
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy (2011)
  • Author(s): akuma Hayashi, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Mari Kasai, Tomoyuki Ichimura, Tamotsu Sudo , Nobuo Yaegashi , Hiroyuki Aburatani , Tanri Shiozawa , Ikuo Konishi
  • Journal Title: Nature Scientific Reports Volume: 1 Pages: 180-188
  • NAID: 120007110570
  • Peer Reviewed
• [Journal Article] The direct PAK1 inhibitor, TAT-PAK18, blocks preferentially the growth of human ovarian cancer cell lines in which PAK1 is abnormally activated by autophosphorylation at Thr 423 (2010)
  • Author(s): Hashimoto H, Sudo T, Maruta H, Nishimura R.
  • Journal Title: Drug Discov Ther Volume: 4(1) Pages: 1-4
  • Peer Reviewed
• [Journal Article] Absence of high-risk human papillomavirus (HPV) detection in endocervical adenocarcinoma with gastric morphology and phenotype (2010)
  • Author(s): Kusanagi Y, Kojima A, Mikami Y, Kiyokawa T, Sudo T, Yamaguchi S, Nishimura R
  • Journal Title: Am J Pathol Volume: 177(5) Pages: 2169-75
  • Peer Reviewed
• [Journal Article] Relationship between ABCF2 expression and response to chemotherapy or prognosis in clear cell adenocarcinoma of the ovary (2010)
  • Author(s): Tsuda H, Ito K, Yaegashi N, Hirasawa A, Sudo T, Kita T, Terai Y, Kigawa J, Sugiyama T, Aoki D
  • Journal Title: Int J Gynecol Cancer Volume: 20(5) Pages: 794-7
  • Peer Reviewed
• [Journal Article] Estrogen Receptor ESR1 Is Indispensable for the Induction of Persistent Vaginal Change by Neonatal 5alpha-Dihydrotestosterone Exposure in Mice (2010)
  • Author(s): Shinichi Miyagawa, Yoshinao Katsu, Yasuhiko Ohta, Tamotsu Sudo, Dennis B. Lubahn and Taisen Iguchi
  • Journal Title: Biology of Reproduction Volume: 82(3) Pages: 497-503
  • Peer Reviewed
• [Presentation] ﾊｲﾘｽｸHPV L1遺伝子のメチル化状態を指標とした子宮頚部上皮内病変の進展予測 (2013)
  • Author(s): 須藤保・岡智子・三輪真唯子・森本明美・玉田将・浮田真沙世・岩﨑真一・植野さやか・若橋宣・山口聡・藤原潔・西村隆一郎
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] Activation of EGFR-PI3K-Akt pathway in cervical clear cell carcinoma (2012)
  • Author(s): Ueno S, Sudo T, Miwa M, Morimoto A, Ukita M, Iwasaki S, Wakahashi S, Yamaguchi S, Fujiwara K ,Nishimura N and Mikami Y
  • Organizer: 14th Biennial Meeting of the International Gynecologic Cancer Society (IGCS)
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2012-10-13
• [Presentation] Vav1はE3 ligase であるHAKAI を介してE-cadherin を抑制し上皮性卵巣癌の上皮間葉移行に関与する (2012)
  • Author(s): 若橋宣・植野さやか・連美穂・須藤保
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
  • Year and Date: 2012-09-20
• [Presentation] Germ cell differentiation を伴うAFP 産生卵巣癌の一例 (2012)
  • Author(s): 森本明美・岩﨑真一・植野さやか・若橋宣・須藤保・山口聡・藤原潔・西村隆一郎・佐久間淑子・伊丹弘恵・安田政実
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京都
  • Year and Date: 2012-07-21
• [Presentation] 卵巣癌に対する術前化学療法の組織学的効果判定基準は予後規定因子となりえるか (2012)
  • Author(s): 連美穂・森本明美・植野さやか・岩﨑真一・若橋宣・須藤保・山口聡・藤原潔・西村隆一郎
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京都
  • Year and Date: 2012-07-20
• [Presentation] 漿液性腺癌前駆病変の一つとされる卵管上皮内癌(STIC)は浸潤能の高い細胞集団である (2012)
  • Author(s): 連美穂・植野さやか・岩﨑真一・若橋宣・山中薫・須藤保・山口聡・藤原潔・西村隆一郎
  • Organizer: 第64回日本産科婦人科学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-13
• [Presentation] 悪性卵巣腫瘍合併妊娠の全国調査 (2012)
  • Author(s): 川崎薫・池田智明・西村隆一郎・須藤保
  • Organizer: 第64回日本産科婦人科学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-13
• [Presentation] Sensitivities of anti-cancer drugs to cancer spheroid growth in the cell array three-dimensional culture system Cell-ableTM Oncology (2012)
  • Author(s): Koichi Yokota, Tomoko Jomura, Emiko Ozeki and Takashi Ikeya
  • Organizer: 第27回日本薬物動態学会
  • Place of Presentation: 千葉
• [Presentation] Activation of EGFR-PI3K-Akt pathway in cervical clear cell carcinoma (2012)
  • Author(s): Sayaka Ueno, Miho Muraji, Senn Wakahashi, Tamotsu Sudo
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
• [Presentation] VAV1 contributes to epithelial-mesenchymal transition in epithelial ovarian cancer through the suppression of E-cadherin. (2012)
  • Author(s): Senn Wakahashi,Sayaka Ueno, Miho Muraji, Tamotsu Sudo
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
• [Presentation] Prognostic factors of advanced ovarian cancer patients treated with neoadjuvant chemotherapy (2011)
  • Author(s): Muraji M・Wakahashi S・Sudo T
  • Organizer: 2nd Biennial Meeting og Asian Society of Gynecologic Oncology
  • Place of Presentation: 韓国
  • Year and Date: 2011-11-03
• [Presentation] VAV1 はE-cadherin を制御することで上皮性卵巣癌の上皮間葉移行に関与する (2011)
  • Author(s): 若橋宣・連美穂・須藤保
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 術前化学療法を施行した上皮性卵巣癌症例での予後規定因子 (2011)
  • Author(s): 連美穂・若橋宣・須藤保
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 卵巣癌におけるVAV1-Racl-PAK1 シグナル経路の活性化 (2011)
  • Author(s): 若橋宣・中村幸司・岩崎真一・植野さやか・連美穂・山中薫・須藤保・山口聡・藤原潔・西村隆一郎
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-30
• [Presentation] 上皮性卵巣癌再発症例における予後不良因子の検討 (2011)
  • Author(s): 連美穂・中村幸司・岩崎真一・植野さやか・若橋宣・山中薫・須藤保・山口聡・藤原潔・西村隆一郎
  • Organizer: 第63回日本産科婦人科学会学術講演
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-30
• [Book] 卵巣癌におけるPTEN/PI3K/AKT/mTOR シグナル 医学のあゆみ Vol.248 No.2 (2014)
  • Author(s): 須藤保
  • Publisher: 医歯薬出版株式会社