Development of therapy for endometriosis.

2013 Fiscal Year Final Research Report

• 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
• Keywords: 創薬

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] 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] 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 Pages: 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
• [Remarks]
  • 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
  • Industrial Property Number: US Provisional No.61833519
  • Filing Date: 2013-06-11
  • Overseas