Novel cancer therapeutic strategies to target RCAS1

• Project/Area Number: 21592134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyushu University
• Principal Investigator: SONODA Kenzo 九州大学, 大学病院, 講師 (30294929)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: RCAS1 / リンパ球アポトーシス / 腫瘍間質組織 / 血管新生 / ectodomain shedding / 悪性腫瘍 / 治療標的分子 / RNA干渉 / 腫瘍間質組 / ビメンチン

Research Abstract

RCAS1 can induce apoptosis in immune cells including peripheral lymphocytes and natural killer cells after converted to a secreted type by ectodomain shedding. Because RCAS1 not only helps tumor cells to evade immune surveillance but also induces cancer stromal tissue remodeling, RCAS1 is believed to exaggerate aggressive characteristics of human malignancies. Clinically, RCAS1 expression correlates with several pathological variables including tumor size, stage, invasion depth, and lymph node metastasis and is a negative predictor of overall survival in 15 different kinds of cancer. Novel therapeutic strategies against cancer are now under development by targeting an intriguing biomarker RCAS1.

Research Products

• [Journal Article] RCAS1 is a promising therapeutic target against cancer : its multifunctional bioactivities and clinical significance (2012)
  • Author(s): Kenzo Sonoda
  • Journal Title: Expert Review of Obstetrics and Gynecology Volume: 7(3) Pages: 123-129
  • Peer Reviewed
• [Journal Article] RCAS1分子を標的とした婦人科がん治療法の開発 (2012)
  • Author(s): 園田顕三
  • Journal Title: 産婦人科の実際「特集:婦人科悪性腫瘍の治療開発とそのシーズ」 Volume: 61(2) Pages: 229-234
• [Journal Article] RCAS1分子を標的とした婦人科がん治療法の開発 (2012)
  • Author(s): 園田顕三
  • Journal Title: 産婦人科の実際 Volume: 61 Pages: 229-234
• [Journal Article] Novel therapeutic strategies to target RCAS1, which induces apoptosis via ectodomain shedding (2011)
  • Author(s): Kenzo Sonoda
  • Journal Title: Histology Histopathology Volume: 26 Pages: 1475-1486
  • NAID: 120005133051
  • Peer Reviewed
• [Journal Article] 婦人科がんとMolecular Biology-Overview (2011)
  • Author(s): 園田顕三、和氣徳夫
  • Journal Title: 産科と婦人科「特集:婦人科がんのMolecular Biology」 Volume: 78(1) Pages: 21-26
• [Journal Article] 婦人科がんとMolecular Biology-Overview (2011)
  • Author(s): 園田顕三、和氣徳夫
  • Journal Title: 産科と婦人科 Volume: 78 Pages: 21-26
• [Journal Article] Takafumi Inoue, Shinichiro Yamaguchi, Tomoko Yoneda, Norio Wake (2010)
  • Author(s): Tatsuhiro Ohgami, Kiyoko Kato, Hiroaki Kobayashi, Kenzo Sonoda
  • Journal Title: Low-dose mithramycin exerts its anti-cancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers Cancer Science Volume: 101 Pages: 1387-1395
  • Peer Reviewed
• [Journal Article] Koichiro Abe, Shingo Baba, Masayuki Sasaki, Tsunehisa Kaku, Norio Wake (2010)
  • Author(s): Shinji Ogawa, Hiroaki Kobayashi, Satoshi Amada, Hideaki Yahata, Kenzo Sonoda
  • Journal Title: Sentinel node detection with 99mTc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy. International Journal of Clinical Oncology. Volume: 15 Pages: 52-58
  • Peer Reviewed
• [Journal Article] Expression of activated signal transducer and activator of transcription-3(Stat3) as a predictor of poor prognosis in cervical cancer (2010)
  • Author(s): Kenzo Sonoda
  • Journal Title: Expert Review of Obstetrics and Gynecology Volume: 5(2) Pages: 161-164
  • Peer Reviewed
• [Journal Article] Shingo Miyamoto, Manabu Nakashima, Norio Wake. Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding (2010)
  • Author(s): Kenzo Sonoda
  • Journal Title: Experimental Cell Research Volume: 316 Pages: 1795-1803
  • Peer Reviewed
• [Journal Article] Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding (2010)
  • Author(s): Sonoda K, et al.
  • Journal Title: Exp Cell Res Volume: 316 Pages: 1795-1803
  • NAID: 120005227172
  • Peer Reviewed
• [Journal Article] Expression of activated signal transducer and activator of transcription-3 (Stat3) as a predictor of poor prognosis in cervical cancer (2010)
  • Author(s): Sonoda K.
  • Journal Title: Expert Rev Obstet Gynecol Volume: 5 Pages: 161-164
  • Peer Reviewed
• [Journal Article] Sentinel node detection with ^<99m>Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (2010)
  • Author(s): Ogawa S, Sonoda K, et al.
  • Journal Title: Int J Clin Oncol Volume: 15 Pages: 52-58
  • NAID: 10027201656
  • Peer Reviewed
• [Journal Article] Low-dose mithramycin exerts its anti-cancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers (2010)
  • Author(s): Ohgami T, Sonoda K, et al.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1387-1395
  • Peer Reviewed
• [Journal Article] Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain sheddine (2010)
  • Author(s): Sonoda K, et al.
  • Journal Title: Exp Cell Res (in press)
  • Peer Reviewed
• [Journal Article] Expression of activated signal transducer and activator of transcription-3(Stat3)as a predictor of poor prognosis in cervical cancer (2010)
  • Author(s): Sonoda K.
  • Journal Title: Expert Rev Obstet Gynecol 5 Pages: 161-164
  • Peer Reviewed
• [Journal Article] Sentinel node detection with ^<99m>Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (2010)
  • Author(s): Ogawa S, Sonoda K, et al.
  • Journal Title: Int J Clin Oncol 15 Pages: 52-58
  • NAID: 10027201656
  • Peer Reviewed
• [Journal Article] Low-dose mithramycin exerts its anti-cancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers (2010)
  • Author(s): Ohgami T, Sonoda K, et al.
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Journal Article] Carcinoma of the uterine cervix : Counter point (2010)
  • Author(s): Sonoda K, et al.
  • Journal Title: Patient surveillance after cancer treatment (in press)
  • Peer Reviewed
• [Journal Article] Shingo Miyamoto, Hiroaki Kobayashi, Shinji Ogawa, Kaoru Okugawa, Shuichi Taniguchi, and Norio Wake (2009)
  • Author(s): Kenzo Sonoda
  • Journal Title: The level of RCAS1 expression is inversely correlated with the number of vimentin-positive stromal cells in epithelial ovarian cancer. International Journal of Gynecological Cancer Volume: 19(5) Pages: 838-843
  • Peer Reviewed
• [Journal Article] Masahide Kuroki, Eisuke Mekada, Shingo Miyamoto. Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer (2009)
  • Author(s): Hiroshi Yagi, Fusanori Yotsumoto, Kenzo Sonoda
  • Journal Title: International Journal of Cancer Volume: 124 Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer (2009)
  • Author(s): Yagi H, Sonoda K, et al.
  • Journal Title: Int J Cancer 124 Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] The level of RCAS1 expression is inversely correlated with the number of vimentin-positive stromal cells in epithelial ovarian cancer (2009)
  • Author(s): Sonoda K, et al.
  • Journal Title: Int J Gynecol Cancer 19 Pages: 838-843
  • Peer Reviewed
• [Presentation] RCAS1による細胞死誘導機構の解析 (2010)
  • Author(s): 西中川拓也、遠城寺宗近、園田顕三、中島学
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] Analysis of apoptotic cell death induced by RCAS1 (2010)
  • Author(s): 西中川拓也、園田顕三, 他
  • Organizer: 第69回 日本癌学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] New therapeutic modalities by targeting RCAS1 which induces apoptosis via ectodomain shedding mediated by ADAM9 (2009)
  • Author(s): Kenzo Sonoda
  • Organizer: Molecular targets and cancer therapeutics
  • Place of Presentation: 米国ボストン市
  • Year and Date: 2009-11-18
• [Presentation] New therapeutic modalities by targeting RCAS1 which induces apoptosis via ectodomain shedding mediated by ADAM9 (2009)
  • Author(s): 園田顕三
  • Organizer: Molecular targets and cancer therapeutics
  • Place of Presentation: 米国、ボストン市
  • Year and Date: 2009-11-18
• [Presentation] RCAS1による細胞死誘導機構の解析 (2009)
  • Author(s): 西中川拓也、遠城寺宗近、園田顕三、中島学
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-01
• [Presentation] Analysis of apoptotic cell death induced by RCAS1 (2009)
  • Author(s): 西中川拓也, 園田顕三, 他
  • Organizer: 第68回 日本癌学会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-01
• [Presentation] Shingo Miyamoto, Manabu Nakashima, Hiroaki Kobayashi, Eisuke Mekada, Norio Wake (2009)
  • Author(s): Kenzo Sonoda
  • Organizer: RCAS1 induces apoptosis in cells expressing its putative receptor via ectodomain shedding mediated by ADAM9 100th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: 米国デンバー市
  • Year and Date: 2009-04-19
• [Presentation] RCAS1 induces apoptosis in cells expressing its putative receptor via ectodomain shedding mediated by ADAMS (2009)
  • Author(s): 園田顕三, et al.
  • Organizer: 100th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: 米国、デンバー市
  • Year and Date: 2009-04-19
• [Presentation] RCAS1のshedding分泌機構におけるkey protease同定解析 (2009)
  • Author(s): 園田顕三、宮本新吾、小林裕明、和氣徳夫
  • Organizer: 第61回日本産科婦人科学会
  • Place of Presentation: 京都市
  • Year and Date: 2009-04-05
• [Presentation] RCAS1の shedding 分泌機構における key protease 同定解析 (2009)
  • Author(s): 園田顕三, 他
  • Organizer: 第61回 日本産科婦人科学会
  • Place of Presentation: 京都市
  • Year and Date: 2009-04-05
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/gynob/index.html