Development of therapy for endometriosis.

• Project/Area Number: 23390388
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUGIHARA KAZUHIRO 浜松医科大学, 医学部, 准教授 (00265878)
• Co-Investigator(Kenkyū-buntansha): KANAYAMA Naohiro 浜松医科大学, 医学部, 教授 (70204550) ; ITOH Hiroaki 浜松医科大学, 医学部附属病院, 准教授 (70263085) ; TAMURA Naoaki 浜松医科大学, 医学部附属病院, 助教 (90402370)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 創薬 / 産婦人科学 / 子宮内膜症 / DDS型分子標的治療薬

Research Abstract

Endometriosis is a common gynecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with NSAIDs or surgery to remove lesions, all of which provide a temporary but not complete cure. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. We identify an endometriosis-targeting peptide internalized by cells, designated z13. Proteomics analysis revealed the z13 receptor as the CNGB3. We then linked z13 with an apoptosis inducing peptide and with an endosome-escaping peptide. When these peptides were coadministered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighboring organs. This study reports a potential therapeutic capable of eliminating endometriosis from the human peritoneum.

Research Products

• [Journal Article] C1 esterase inhibitor activity in amniotic fluid embolism (2014)
  • Author(s): Tamura N. Kimura S, Farhana M, Uchida T, Suzuki K, Sugihara K, Itoh H, Ikeda T, Kanayama N
  • Journal Title: Critical Care Medicine
• [Journal Article] A Comparison between Placental Gene Expression of 11βHydroxysteroid Dehydrogenases and Infantile Growth during at Ten Months (2014)
  • Author(s): Muramatsu-Kato K, Itoh, H, Kohmura Y, Murakami H, Uchida T, Suzuki K, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re Volume: 40(2) Pages: 465-472
• [Journal Article] A Comparison between Placental Gene Expression of 11βHydroxysteroid Dehydrogenases and Infantile Growth during at Ten Months. (2014)
  • Author(s): Muramatsu-Kato K, Itoh, H, Kohmura Y, Murakami H, Uchida T, Suzuki K, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re. Volume: - Issue: 2 Pages: 465-472
  • DOI: 10.1111/jog.12200
  • Peer Reviewed
• [Journal Article] C1 esterase inhibitor activity in amniotic fluid embolism. (2014)
  • Author(s): Tamura N. Kimura S, Farhana M, Uchida T, Suzuki K, Sugihara K, Itoh H, Ikeda T, Kanayama N
  • Journal Title: Critical Care Medicine. Volume: -
  • Peer Reviewed
• [Journal Article] Regulation of human sperm motility by polylactosamines derived from seminal fluid (2013)
  • Author(s): Sugihara K, Shibata TK, Takata K, Kimura T, Kanayama N, Williams R, Hatakeyama S, Akama TO, Kuo CW, Khoo KH, Fukuda MN
  • Journal Title: FEBS Lett Volume: 587 Pages: 3195-3201
• [Journal Article] Changes of maternal dietary intake, body weight and fetal growth through pregnancy in pregnant Japanese women (2013)
  • Author(s): Kubota K, Itoh H, Tasaka M, Naito H, Fukuoka Y, Muramatsu K, Kohmura KY, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re Volume: 39(9) Pages: 1383-1390
• [Journal Article] In vivo regulation of steroid hormones by the Chst10 sufotransferase in mouse (2013)
  • Author(s): Suzuki-Anekoji M, Suzuki A, Wu SW, Angata K, Murai KK, Sugihara K, Akama TO, Khoo KH, Nakayama J, Fukuda MN, Fukuda M
  • Journal Title: J Biol Chem Volume: 288(7) Pages: 5007-5016
• [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero (2013)
  • Author(s): Kohmura YK, Kanayama N, Muramatsu K, Tamura N, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Aoe S, Sasaki T, Suganami T, Ogawa Y, Itoh H
  • Journal Title: Reprod Sci Volume: 20(7) Pages: 813-27
• [Journal Article] Cerebral oxygen saturation evaluated by near-infrared timeresolved spectroscopy (TRS) in pregnant women duringcesarean section -A promising new method of maternal monitoring (2013)
  • Author(s): Yamazaki K, Suzuki K, Itoh H, Muaramatsu K, Nagahashi K, Tamura N, Uchida T, Sugihara K, Maeda H, Kanayama N
  • Journal Title: Clin Physiol Funct I Volume: 33(2) Pages: 109-116
• [Journal Article] Zinc Coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation (2013)
  • Author(s): Ozawa H, Asahina T, Murakami H, Yaguchi C, Kohmura Y, Kohno E, Hirano T, Horiuchi K, Tamura N, Sugihara K, Ooi H, Kanayama N
  • Journal Title: Fetal Digan Ther Volume: 33(2) Pages: 90-97
• [Journal Article] Zinc Coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation. (2013)
  • Author(s): Ozawa H, Asahina T, Murakami H, Yaguchi C, Kohmura Y, Kohno E, Hirano T, Horiuchi K, Tamura N, Sugihara K, Ooi H, Kanayama N
  • Journal Title: Fetal Digan Ther. Volume: 33(2) Pages: 90-97
  • Peer Reviewed
• [Journal Article] Cerebral oxygen saturation evaluated by near-infrared timeresolved spectroscopy (TRS) in pregnant women duringcesarean section -A promising new method of maternal monitoring - (2013)
  • Author(s): Yamazaki K, Suzuki K, Itoh H, Muaramatsu K, Nagahashi K, Tamura N, Uchida T, Sugihara K, Maeda H, Kanayama N
  • Journal Title: Clin Physiol Funct I. Volume: 33(2) Pages: 109-116
  • Peer Reviewed
• [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero. (2013)
  • Author(s): Kohmura YK, Kanayama N, Muramatsu K, Tamura N, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Aoe S, Sasaki T, Suganami T, Ogawa Y, Itoh H
  • Journal Title: Reprod Sci. Volume: 20(7) Pages: 813-827
  • Peer Reviewed
• [Journal Article] Regulation of steroid hormones by HNK-1 Chst10 in vivo in the mouse. (2013)
  • Author(s): Suzuki-Anekoji M, Suzuki A, Wu SW, Angata K, Murai KK, Sugihara K, Akama TO, Khoo KH, Nakayama J, Fukuda MN, Fukuda M
  • Journal Title: J Biol Chem. Volume: 288(7) Pages: 5007-5016
  • Peer Reviewed
• [Journal Article] Changes of maternal dietary intake, body weight and fetal growth through pregnancy in pregnant Japanese women. (2013)
  • Author(s): Kubota K, Itoh H, Tasaka M, Naito H, Fukuoka Y, Muramatsu K, Kohmura KY, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re. Volume: 39(9) Pages: 1383-1390
  • Peer Reviewed
• [Journal Article] Tumor targeting by a carbohydrate ligand-mimicking Peptide. (2013)
  • Author(s): Hatakeyama S, Shibata TK, Tobisawa Y, Ohyama C, Sugihara K, Fukuda MN
  • Journal Title: Methods in Molecular Biology. Volume: 1022 Pages: 369-386
  • Peer Reviewed
• [Journal Article] Regulation of human sperm motility by polylactosamines derived from seminal fluid. (2013)
  • Author(s): Sugihara K, Shibata TK, Takata K, Kimura T, Kanayama N, Williams R, Hatakeyama S, Akama TO, Kuo CW, Khoo KH, Fukuda MN
  • Journal Title: FEBS Lett. Volume: 587 Pages: 3195-3201
  • Peer Reviewed
• [Journal Article] Enhancement of mouse sperm tail motility by trophinin-binding peptide (2012)
  • Author(s): Park SK, Yoon J, Wang L, Shibata TK, Motamedchaboki K, Shim KJ, Chang MS, Lee SH, Tamura N, Hatakeyama S, Nadano D, Sugihara K, Fukuda MN
  • Journal Title: Reprod Biol Endocrin Volume: 10 Issue: 1 Pages: 101-101
  • DOI: 10.1186/1477-7827-10-101
• [Journal Article] Identification of mono- and di-sulfated N-acetyl-lactosaminyl oligosaccharide structures as epitopes specifically recognized by humanized monoclonal antibody HMOCC-1 raised against ovarian cancer (2012)
  • Author(s): Shibata TK, Matsumura F, Wang P, Yu S, Chou CC, Khoo KH, Kitayama K, Akama TO, Sugihara K, Kanayama N, Kojima-Aikawa K, Seeberger PH, Fukuda M, Suzuki A, Aoki D, Fukuda MN
  • Journal Title: J Biol Chem Volume: 287(9) Pages: 6592-6602
• [Journal Article] Immunohistochemical Detection of Meconium in the Fetal Membrane, Placenta and Unbilical Cord (2012)
  • Author(s): Furuta N, Yaguchi C, Itoh H, Morishima Y, Tamura N, Kato M, Uchida T, Suzuki K, Sugihara K, Kawabata Y, Suzuki N, Sasaki T, Horiuchi K, Kanayama N
  • Journal Title: Placenta Volume: 33(1) Pages: 24-30
• [Journal Article] Transient ligation of umbilical vessels elevates placental tissue oxygen index(TOI) values measured by near-infrared spectroscopy (NIRS) in clawn miniature pig animal model (2012)
  • Author(s): Suzuki K, Itoh H, Muramatsu K, Yamazaki K, Nagahashi K, Furuta N, Tamura N, Uchida T, Sugihara K, Sumimoto K, Kanayama N
  • Journal Title: Clin Exp Obstet Gyn Volume: 39 (3) Pages: 293-298
• [Journal Article] Reduction in Levels of Maternal Complements during Delivery by Cesarean Section (2012)
  • Author(s): Kato M, Itoh H, Nagahashi K, Izima M, Yaguchi C, Uchida T, Suzuki K, Sugihara K, Kanayama N
  • Journal Title: J Obstet Gynaecol Re Volume: 38(1) Pages: 165-71
• [Journal Article] Targeted drug delivery to tumor vasculature by a carbohydrate ligand mimicry peptide (2011)
  • Author(s): Hatakeyama S, Sugihara K, Shibata TK, Nakayama J, Akama TO, Tamura N, Wong SM, Bobkov AA, Takano Y, Ohyama C, Fukuda M, Fukuda MN
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(49) Pages: 19587-19592
• [Presentation] Targeted drug delivery to brain tumor vasculature by carbohydrate mimetic peptide in mouse glioma model. (2013)
  • Author(s): Misa Suzuki‐Anekoji, Jiunn‐Chern Yeh, Motohiro Nonaka, Toshiaki K. Shibata, Jun Nakayama, Tomoya O. Akama, Kazuhiro Sugihara, Minoru Fukuda, Michiko N. Fukuda
  • Organizer: The 2013 Annual Conference of the Society for Glycobiology
  • Place of Presentation: St.Petersburg Florida, USA
  • Year and Date: 2013-11-17 – 2013-11-20
• [Presentation] Attenuation of fibroblast growth factor signaling by poly-N-acatyllactosamine type glycans implicated to human sperm motility. (2013)
  • Author(s): Sugihara K, Shibata TK, Akama TO, Kuo C-W, Khoo K-H, Fukuda MN
  • Organizer: The 2013 Annual Conference of the Society for Glycobiology
  • Place of Presentation: St.Petersburg Florida, USA
  • Year and Date: 2013-11-17 – 2013-11-20
• [Presentation] ペプチド創薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: 第5回 Japan Endometriosis Forum
  • Place of Presentation: ハイアットリージェンシー大阪、大阪
  • Year and Date: 2013-11-02
  • Invited
• [Presentation] 子宮内膜症に対するペプチド治療薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: BioJapan 2013 World Business Forum
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2013-10-09 – 2013-10-11
• [Presentation] 腫瘍血管表面特異マーカーアネキシン１を標的とするIF7を用いた抗腫瘍薬 (2013)
  • Author(s): 杉原一廣
  • Organizer: BioJapan 2013 World Business Forum
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2013-10-09 – 2013-10-11
  • Invited
• [Presentation] 糖鎖をmimicするペプチドを用い腫瘍血管内皮細胞を標的とするドラッグデリバリーシステム (2013)
  • Author(s): 杉原一廣
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台国際センター、東北大学百周年記念会館川内萩ホール、宮城
  • Year and Date: 2013-08-29 – 2013-08-31
• [Presentation] 精液へ分泌される糖鎖ポリラクトサミンによる精子運動の調節機構 (2013)
  • Author(s): 柴田俊章、杉原一廣、木村たか子、高田佳世子、中村友紀、俵史子、金山尚裕
  • Organizer: 第31回日本受精着床学会総会・学術講演会
  • Place of Presentation: 別府国際コンベンションセンター、大分
  • Year and Date: 2013-08-08 – 2013-08-09
• [Presentation] 臨床的羊水塞栓症における C1 インヒビター活性の検討 (2013)
  • Author(s): 田村直顕、木村 聡、杉原 一廣、伊東 宏晃、池田 智明、金山 尚裕
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌他、北海道
  • Year and Date: 2013-05-10 – 2013-05-12
• [Presentation] Identification of sulfated N-acetyl-lactosaminyl oligosaccharide structures as epitopes recognized by humanized monoclonal antibody HMOCC-1 raised against ovarian cancer (2013)
  • Author(s): ShibataTK, Sugihara K, Fukuda MN, Suzuki A, Kanayama N, Aoki D
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌他、北海道
  • Year and Date: 2013-05-10 – 2013-05-12
• [Book] Handbook of Glycosyltransferases and Related Genes. (2014)
  • Author(s): FukudaMN, Sugihara K, Akama TO
  • Total Pages: 10
  • Publisher: SpringerReference.
• [Book] 泌尿器外科 (2013)
  • Author(s): 畠山真吾、柴田俊章、田村直顕、飛澤悠葵、米山徹、杉原一廣、大山力、福田道子
  • Total Pages: 4
  • Publisher: 医学図書出版
• [Remarks]
  • URL: http://www.hama-med.ac.jp/uni_introduction_report_souran_07161504.html
• [Remarks] 浜松医科大学 教員総覧 杉原一廣
  • URL: http://www.hama-med.ac.jp/uni_introduction_report_souran_07161504.html
• [Patent(Industrial Property Rights)] COMPOSITIONS AND METHODS FOR TARGETED ENDOMETRIOSIS TREATMENT (2013)
  • Inventor(s): 杉原一廣, 福田道子
  • Industrial Property Rights Holder: 杉原一廣, 福田道子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-06-11
  • Overseas
• [Patent(Industrial Property Rights)] COMPOSITIONS AND METHODS FOR TARGETED ENDOMETRIOSIS TREATMENT (2013)
  • Inventor(s): 杉原一廣、福田道子
  • Industrial Property Rights Holder: 杉原一廣、福田道子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-06-11
  • Overseas