Significance of RCAS1 as targeted molecular therapy in fibrosis and the canceration of the endometriosis

• Project/Area Number: 23592469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fukuoka University
• Principal Investigator: SHIROTA Kyoko 福岡大学, 医学部, 講師 (70441756)
• Co-Investigator(Kenkyū-buntansha): MIYAMOTO Shingo 福岡大学, 医学部, 教授 (40209945)
• Co-Investigator(Renkei-kenkyūsha): SAITO Tamio 独立行政法人理化学研究所, ケミカルバイオロジー研究基盤施設, 支援促進チームチームヘッド (40260228) ; SONODA Kenzo 九州大学, 大学病院, 講師 (30294929)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 子宮内膜症 / RCAS1 / 国際情報交換

Research Abstract

Endometriosis can affect a woman's whole life, in terms of pelvic pain, infertility, abnormal pregnancy and ovarian cancer. The aim of this study is to provide a clue to elucidate the molecular mechanisms underling the endometriosis related pain and canceration. We have investigated RCAS1 receptor-binding cancer antigen expressed on SiSo cells) as a beneficial target molecule for the treatment of endometriosis in the future. High level of RCAS1 concentration in ascites was revealed in the case of rAFS (Revised American Fertility Society) classification stage IV. In the collagen gel contraction assay, RCAS1 clearly caused significantly decrease the areas of gel surface. Although its putative mechanisms remain undefined, this research suggested a possibility that RCAS1 is involved in endometriosis-associated fibrosis. Further exploration of RCAS1 biological function will facilitate development of novel therapeutic strategies for endometriosis that does not depend on estrogen.

Research Products

• [Journal Article] Production of Sry knockout mouse using TALEN via oocyte injection (2013)
  • Author(s): Kato T, Miyata K, Sonobe M, Yamashita S, Tamano M, Miura K, Kanai Y, Miyamoto S, Sakuma T, Yamamoto T, Inui M, Kikusui T, Asahara H, Takada S
  • Journal Title: Scientific Reports Volume: 3 Pages: 3136-3136
  • Peer Reviewed
• [Journal Article] Molecular hierarchy of heparin-binding EGF-like growth factor-regulated angiogenesis in triple-negative breast cancer (2013)
  • Author(s): Yotsumoto F, Tokunaga E, Oki E, Maehara Y, Yamada H, Nakajima K, Nam SO, Miyata K, Koyanagi M, Doi K, Shirasawa S, Kuroki M, Miyamoto S
  • Journal Title: Mol Cancer Res Volume: 11 Pages: 506-17
  • Peer Reviewed
• [Journal Article] Clinical significance of cell-free and concentrated ascites re-infusion therapy for advanced and recurrent gynecological cancer (2012)
  • Author(s): Ueda T, Maehara M, Takahashi Y, Nakayama N, Kondo H, Shirota K, Yoshizato T, Miyamoto S
  • Journal Title: Anticancer Res Volume: 32 Pages: 2353-7
  • Peer Reviewed
• [Journal Article] Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors (2012)
  • Author(s): Fukuoka M, Hamasaki M, Koga K, Hayashi H, Aoki M, Kawarabayashi T, Miyamoto S, Nabeshima K
  • Journal Title: Virchows Arch Volume: 461 Pages: 457-66
  • Peer Reviewed
• [Journal Article] Clinical significance of amphiregulin and epidermal growth factor in colostrum (2012)
  • Author(s): Nojiri T, Yoshizato T, Fukami T, Obama H, Yagi H, Yotsumoto F, Miyamoto S
  • Journal Title: Arch Gynecol Obstet Volume: 286 Pages: 643-7
  • Peer Reviewed
• [Journal Article] Inhibition of phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model (2012)
  • Author(s): Tsunoda T, Ota T, Fujimoto T, Doi K, Tanaka Y, Yoshida Y, Ogawa M, Matsuzaki H, Hamabashiri M, Tyson DR, Kuroki M, Miyamoto S, Shirasawa S
  • Journal Title: Mol Cancer Volume: 11 Pages: 46-46
  • Peer Reviewed
• [Journal Article] Regulatory mechanisms of the HB-EGF autocrine loop in inflammation, homeostasis, development and cancer (2012)
  • Author(s): Miyata K, Yotsumoto F, Nam SO, Kuroki M, Miyamoto S
  • Journal Title: Anticancer Res Volume: 32 Pages: 2347-52
  • Peer Reviewed
• [Journal Article] up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells (2012)
  • Author(s): Ota T, Doi K, Fujimoto T, Tanaka Y, Ogawa M, Matsuzaki H, Kuroki M, Miyamoto S, Shirasawa S, Tsunoda T. KRAS
  • Journal Title: Anticancer Res Volume: 32 Pages: 2271-5
  • Peer Reviewed
• [Journal Article] Soluble heparin-binding EGF-like growth factor (HB-EGF) detected by newly developed immuno-PCR method is a clear-cut serological biomarker for ovarian cancer (2012)
  • Author(s): Kasai N, Kobayashi K, Shioya S, Yoshikawa Y, Yotsumoto F, Miyamoto S, Mekada E, Enokizono J
  • Journal Title: Am J Transl Res Volume: 4 Pages: 415-21
  • Peer Reviewed
• [Journal Article] Assessment of HB-EGF levels in peritoneal fluid and serum of ovarian cancer patients using ELISA (2011)
  • Author(s): Hikita S, Yotsumoto F, Fukami T, Horiuchi S, Sanui A, Miyata K, Nam SO, Tsujioka H, Ueda T, Shirota K, Yoshizato T, Maeda K, Ishikawa T, Okuno Y, Kuroki M, Mekada E, Miyamoto S
  • Journal Title: Anticancer Res Volume: 31 Pages: 2553-9
  • Peer Reviewed
• [Journal Article] Uterine inversion due to a leiomyoma on postpartum day 41: a case report (2011)
  • Author(s): Shirota K, Ota T, Tsujioka H, Miyamoto S
  • Journal Title: J Obstet Gynaecol Res Volume: 37 Pages: 897-900
  • Peer Reviewed
• [Journal Article] Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts (2011)
  • Author(s): Naganuma Y, Choijamts B, Shirota K, Nakajima K, Ogata S, Miyamoto S, Kawarabayashi T, Emoto M
  • Journal Title: Cancer Sci Volume: 102 Pages: 1545-52
  • NAID: 10030242351
  • Peer Reviewed
• [Journal Article] Involvement of anticentromere antibody in interference with oocyte meiosis and embryo cleavage (2011)
  • Author(s): Shirota K, Nagata Y, Honjou K, Tsujioka H, Yoshizato T, Miyamoto S
  • Journal Title: Fertil Steril Volume: 95 Pages: 2729-31
  • Peer Reviewed
• [Journal Article] A novel anti-human HB-EGF monoclonal antibody with multiple antitumor mechanisms against ovarian cancer cells (2011)
  • Author(s): Miyamoto S, Iwamoto R, Furuya A, Takahashi K, Sasaki Y, Ando H, Yotsumoto F, Yoneda T, Hamaoka M, Yagi H, Murakami T, Hori S, Shitara K, Mekada E
  • Journal Title: Clin Cancer Res Volume: 17 Issue: 21 Pages: 6733-41
  • DOI: 10.1158/1078-0432.ccr-11-1029
  • Peer Reviewed
• [Journal Article] A possible clinical adaptation of CRM197 in combination with conventional chemotherapeutic agents for ovarian cancer (2011)
  • Author(s): Tsujioka H, Fukami T, Yotsumoto F, Ueda T, Hikita S, Takahashi Y, Kondo H, Kuroki M, Miyamoto S
  • Journal Title: Anticancer Res Volume: 31 Pages: 2461-5
  • Peer Reviewed
• [Journal Article] Clinical usefulness of contrast-enhanced color Doppler ultrasonography in invasive and noninvasive gestational trophoblastic diseases : a preliminary study (2011)
  • Author(s): Emoto M, Sadamori R, Hachisuga T, Kawarabayashi T, Miyamoto S
  • Journal Title: J Reprod Med Volume: 56 Pages: 224-34
  • Peer Reviewed
• [Journal Article] Metronomic irinotecan chemotherapy combined with ultrasound irradiation for a human uterine sarcoma xenograft (2011)
  • Author(s): Choijamts B, Naganuma Y, Nakajima K, Kawarabayashi T, Miyamoto S, Tachibana K, Emoto M
  • Journal Title: Cancer Sci Volume: 102 Pages: 452-9
  • NAID: 10029290476
  • Peer Reviewed
• [Journal Article] Targeting the heparin-binding epidermal growth factor-like growth factor in ovarian cancer therapy (2011)
  • Author(s): Tsujioka H, Yotsumoto F, Hikita S, Ueda T, Kuroki M, Miyamoto S
  • Journal Title: Curr Opin Obstet Gynecol Volume: 23 Pages: 24-30
  • Peer Reviewed
• [Journal Article] Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells (2011)
  • Author(s): Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, Miyamoto S, Mekada E, Seiki M
  • Journal Title: Cancer Sci Volume: 102 Pages: 111-6
  • NAID: 10029288679
  • Peer Reviewed
• [Journal Article] A case of cystic biliary atresia with an antenatally detected cyst : the possibility of changing from a correctable type with a cystic lesion (I cyst) to an uncorrectable one (IIId) (2011)
  • Author(s): Masumoto K, Kai H, Oka Y, Otake R, Yoshizato T, Miyamoto S, Hirose S, Hamasaki M, Nabeshima K, Iwasaki A
  • Journal Title: Pediatr Surg Int Volume: 27 Pages: 99-102
  • Peer Reviewed
• [Presentation] 医療イノベーションを目指したがん治療の創薬開発 (2013)
  • Author(s): 宮本新吾
  • Organizer: 東京大学医科学研究所特別講演会
  • Place of Presentation: 東京
  • Year and Date: 2013-02-04
• [Presentation] 子宮内膜症におけるRCAS1の発現と瘢痕化に対する作用 (2013)
  • Author(s): 城田京子, 中山直美, 津野晃寿, 奈須家栄, 楢原久司, 園田顕三, 宮本新吾
  • Organizer: 第64回日本産科婦人科学会
  • Place of Presentation: 神戸
• [Presentation] シンポジウム卵巣癌を対象とした分子標的治療薬BK?UMの臨床開発 (2012)
  • Author(s): 宮本新吾
  • Organizer: 2012年日台癌のトランスレーショナル研究シンポジウム
  • Year and Date: 2012-11-21
• [Presentation] 医療イノベーションを目指したがん治療の創薬開発?HB-EGFを標的とした新規卵巣癌治療薬? (2012)
  • Author(s): 宮本新
  • Organizer: 北関東婦人科がん講演会
  • Place of Presentation: 埼玉県
  • Year and Date: 2012-05-25
• [Presentation] Dienogest (DNG) treatment enhances the follicular amount of human chorionic gonadotrophin (hCG) in patients with severe endometriosis (2012)
  • Author(s): Shirota K, Honjou K, Toman H, Nakayama N, Ito H, Nagata Y, Miyamoto S
  • Organizer: 2ND ASIAN CONFERENCE ON ENDOMETRIOSIS
  • Place of Presentation: Istanbul, Turkey
• [Presentation] 子宮内膜症におけるRCAS1の発現と瘢痕化に対する作用 (2012)
  • Author(s): 城田京子、中山直美、津野晃寿、奈須家栄、楢原久司、園田顕三、宮本新吾
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 兵庫県
• [Presentation] Heparin-binding epidermal growth factor-like growth factor as a novel targeting molecule for ovarian cancer therapy HSUM (2011)
  • Author(s): Miyamoto S
  • Organizer: International conference on Medical Molecular Biology Mongolia
  • Year and Date: 2011-07-08
• [Presentation] Involvement of anti-centromere antibody in interference with oocyte meiosis and embryo cleavage HSUM (2011)
  • Author(s): Shirota K
  • Organizer: International conference on Medical Molecular Biology Mongolia
  • Year and Date: 2011-07-08
• [Presentation] 当科における子宮内膜症治療の現状 (2011)
  • Author(s): 城田京子、中山直美、宮本新吾
  • Organizer: 第68回日本生殖医学会九州支部会
  • Place of Presentation: 福岡県
  • Year and Date: 2011-04-24
• [Presentation] Changes in the treatment of endometriosis in the last 6 years in our department (2011)
  • Author(s): Shirota K
  • Organizer: 6th AAGL International Congress on Minimally Invasive Gynecology
  • Place of Presentation: Osaka
• [Presentation] 当科における過去6年間の子宮内膜症治療の変遷 (2011)
  • Author(s): 城田京子
  • Organizer: 第24回日本内視鏡外科学会
  • Place of Presentation: 大阪府