A new strategy for gynecologic malignancy using drug delivery system based on nanomicelles

• Project/Area Number: 22591848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Teikyo University (2011-2012); The University of Tokyo (2010)
• Principal Investigator: NAKAGAWA Shunsuke 帝京大学, 医学部, 講師 (70270874)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮頸癌 / プロテアソーム阻害剤 / ドラッグデリバリーシステム / ヒトパピローマウイスル / ドラッグデリバリー / 子宮頸がん / HPV / siRNA / ユビキチンプロテアソーム / HPV癌蛋白E6 / 高分子ナノミセル / 分子標的治療

Research Abstract

Human Papillomavirus (HPV) has a crucial role in development of cervical cancer. HPV E6 oncoprotein inactivates tumor suppressors through ubiquitin-mediated degradation. Proteasome inhibitor suppresses degradation of target protein. We designed and created proteasome inhibitor MG132 containing nanomicelle.MG132 containing nanomicelle inhibited growth of xenograft tumor from HPV-positive cervical cancer cell lines. These data underscore the possibility that proteasome inhibitor MG132 containing nanomicelle might be an attractive new strategy for cervical cancer treatment based on drug delivery system.

Research Products

• [Journal Article] Retreatment with nedaplatin in patients with recurrent gynecological cancer after the development of hypersensitivity reaction to carboplatin (2013)
  • Author(s): Arimoto T, Oda K, Nakagawa S, Kawana K, Tsukazaki T, Adachi K, Matsumoto Y, Yano T, Kozuma S, Taketani Y
  • Journal Title: J Obstet Gynaecol Res Volume: 39(1) Pages: 336-40
• [Journal Article] Sequential effects of the proteasome inhibitor bortezomib and chemotherapeutic agents in uterine cervical cancer cell lines (2013)
  • Author(s): Miyamoto Y, Nakagawa S, Wada-Hiraike O, Seiki T, Tanikawa M, Hiraike H, Sone K, Nagasaka K, Oda K, Kawana K, Nakagawa K, Fujii T, Yano T, Kozuma S, Taketani Y.
  • Journal Title: Oncol Rep. Volume: 29 Issue: 1 Pages: 51
  • DOI: 10.3892/or.2012.2072
  • Peer Reviewed
• [Journal Article] Regulation of SIRT1 determines initial step of endometrial receptivity by controlling E-cadherin expression (2012)
  • Author(s): Shirane A, Wada-Hiraike O, Tanikawa M, Seiki T, Hiraike H, Miyamoto Y, Sone K, Hirano M, Oishi H, Oda K, Kawana K, Nakagawa S, Osuga Y, Fujii T, Yano T, Kozuma S, Taketani Y
  • Journal Title: Biochem Biophys Res Commun Volume: 424(3) Pages: 604-10
• [Journal Article] Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas (2012)
  • Author(s): Shoji K, Oda K, Kashiyama T, Ikeda Y, Nakagawa S, Sone K, Miyamoto Y, Hiraike H, Tanikawa M, Miyasaka A, Koso T, Matsumoto Y, Wada-Hiraike O, Kawana K, Kuramoto H, McCormick F, Aburatani H, Yano T, Kozuma S, Taketani Y
  • Journal Title: PLoS One Volume: 7(5)
• [Journal Article] Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer (2012)
  • Author(s): Ikeda Y, Oda K, Nakagawa S, Murayama-Hosokawa S, Yamamoto S, Ishikawa S, Wang L, Takazawa Y, Maeda D, Wada-Hiraike O, Kawana K, Fukayama M, Aburatani H, Yano T, Kozuma S, Taketani Y
  • Journal Title: Int J Gynecol Cancer Volume: 22(5) Pages: 725-31
• [Journal Article] Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary (2012)
  • Author(s): Morita Y, Wada-Hiraike O, Yano T, Shirane A, Hirano M, Hiraike H, Koyama S, Oishi H, Yoshino O, Miyamoto Y, Sone K, Oda K, Nakagawa S, Tsutsui K, Taketani Y
  • Journal Title: Reprod Biol Endocrinol Volume: 10 Pages: 14-14
• [Journal Article] Interstitial pneumonitis induced by pegylated liposomal doxorubicin in a patient with recurrent ovarian cancer (2012)
  • Author(s): Inaba K, Arimoto T, Hoya M, Kawana K,Nakagawa S, Kozuma S, Taketani Y
  • Journal Title: Med Oncol Volume: 29(2) Pages: 1255-7
• [Journal Article] Second-line chemotherapy with docetaxel and carboplatin in paclitaxel and platinum-pretreated ovarian, fallopian tube, and peritoneal cancer (2012)
  • Author(s): Arimoto T, Nakagawa S, Oda K, Kawana K, Yasugi T, Taketani Y
  • Journal Title: Med Oncol Volume: 29(2) Pages: 1253-4
• [Journal Article] Genotype-dependent efficacy of a Dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas (2012)
  • Author(s): Shoji K, Oda K, Nakagawa S,-Hiraike O, McCormick F, Aburatani H, Yano T, Kozuma S, Taketani Y.
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e37431-e37431
  • DOI: 10.1371/journal.pone.0037431
  • Peer Reviewed
• [Journal Article] Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer. (2012)
  • Author(s): Ikeda Y, Oda K, Nakagawa S
  • Journal Title: Int J Gynecol Cancer Volume: 22(5） Issue: 5 Pages: 725-31
  • DOI: 10.1097/igc.0b013e31824c6ea6
  • Peer Reviewed
• [Journal Article] Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: An implicative role of SIRT1 in the ovary (2012)
  • Author(s): Y.Morita, K.Tsutsui, et al
  • Journal Title: Reprod.Biol.Endocrinbl. Volume: 10 Issue: 1 Pages: 14-24
  • DOI: 10.1186/1477-7827-10-14
  • Peer Reviewed
• [Journal Article] Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells : an implicative role of SIRT1 in the ovary (2012)
  • Author(s): Morita Y, Nakagawa S
  • Journal Title: Reprod Biol Endocrinol Volume: 10 Pages: 14-14
  • Peer Reviewed
• [Journal Article] β-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors (2011)
  • Author(s): Maeda D, Shibahara J, Sakuma T, Isobe M, Teshima S, Mori M, Oda K, Nakagawa S, Taketani Y, Ishikawa S, Fukayama M
  • Journal Title: Am J Surg Pathol Volume: 35(10) Pages: 1429-40
• [Journal Article] Multifunctional transcription factor TFII-I is an activator of BRCA1 function (2011)
  • Author(s): Tanikawa M, Wada-Hiraike O, Nakagawa S, Shirane A, Hiraike H, Koyama S, Miyamoto Y, Sone K, Tsuruga T, Nagasaka K, Matsumoto Y, Ikeda Y, Shoji K, Oda K, Fukuhara H, Nakagawa K, Kato S, Yano T, Taketani Y
  • Journal Title: Br J Cancer Volume: 104(8) Pages: 1349-55
• [Journal Article] Rsf-1 (HBXAP) expression is associated with advanced stage and lymph node metastasis in ovarian clear cell carcinoma (2011)
  • Author(s): Maeda D, Chen X, Guan B, Nakagawa S, Yano T, Taketani Y, Fukayama M, Wang TL, Shih IeM
  • Journal Title: Int J Gynecol Pathol Volume: 30(1) Pages: 30-5
• [Journal Article] Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report (2011)
  • Author(s): Shoji K, Oda K, Nakagawa S, Kawana K, Yasugi T, Ikeda Y, Takazawa Y, Kozuma S, Taketani Y
  • Journal Title: Med Oncol Volume: 28(3) Pages: 771-4
• [Journal Article] The mechanism and implications of hScrib regulation of ERK (2010)
  • Author(s): Nagasaka K, Massimi P, Pim D, Subbaiah VK, Kranjec C, Nakagawa S, Yano T, Taketani Y, Banks L
  • Journal Title: Small GTPases Volume: 1(2) Pages: 108-112
• [Journal Article] Mucosal carcinoma of the fallopian tube coexists with ovarian cancer of serous subtype only: a study of Japanese cases (2010)
  • Author(s): Maeda D, Ota S, Takazawa Y, Ohashi K, Mori M, Imamura T, Nakagawa S, Yano T, Taketani Y, Fukayama M
  • Journal Title: Virchows Arch Volume: 457(5) Pages: 597-608
• [Journal Article] The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction (2010)
  • Author(s): Nagasaka K, Pim D, Massimi P, Thomas M, Tomaic V, Subbaiah VK, Kranjec C, Nakagawa S, Yano T, Taketani Y, Myers M, Banks L
  • Journal Title: Oncogene Volume: 29(38) Pages: 5311-21
• [Journal Article] Bilateral microscopic adenocarcinoma of the fallopian tubes detected by an endometrial cytologic smear (2010)
  • Author(s): Maeda D, Takazawa Y, Ota S, Takeuchi Y, Seta A, Nakagawa S, Yano T, Taketani Y, Fukayama M
  • Journal Title: Int J Gynecol Pathol Volume: 29(3) Pages: 273-7
• [Journal Article] Identification of DBC1 as a transcriptional repressor for BRCA1 (2010)
  • Author(s): Hiraike H, Wada-Hiraike O, Nakagawa S, Koyama S, Miyamoto Y, Sone K, Tanikawa M, Tsuruga T, Nagasaka K, Matsumoto Y, Oda K, Shoji K, Fukuhara H, Saji S, Nakagawa K, Kato S, Yano T, Taketani Y
  • Journal Title: Br J Cancer Volume: 102(6) Pages: 1061-7
• [Journal Article] Repression of estrogen receptor beta function by putative tumor suppressor DBC1 (2010)
  • Author(s): Koyama S, Wada-Hiraike O, Nakagawa S, Tanikawa M, Hiraike H, Miyamoto Y, Sone K, Oda K, Fukuhara H, Nakagawa K, Kato S, Yano T, Taketani Y
  • Journal Title: Biochem Biophys Res Commun Volume: 392(3) Pages: 357-62
• [Journal Article] Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway (2010)
  • Author(s): Murayama-Hosokawa S, Oda K, Nakagawa S, Ishikawa S, Yamamoto S, Shoji K, Ikeda Y, Uehara Y, Fukayama M, McCormick F, Yano T, Taketani Y, Aburatani H
  • Journal Title: Oncogene Volume: 29(13) Pages: 1897-908
• [Journal Article] Clinicopathological Significance of Loss of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma (2010)
  • Author(s): Maeda D, Mao TL, Fukayama M, Nakagawa S, Yano T, Taketani Y, Shih IeM
  • Journal Title: Int J Mol Sci Volume: 11(12) Pages: 5120-8
  • NAID: 120007089060
• [Journal Article] Identification of DBC1 as a transcriptional repressor for BRCA1. (2010)
  • Author(s): Hiraike H, Wada-Hiraike O, Nakagawa S
  • Journal Title: Br J Cancer Volume: 102 Pages: 1061-7
  • Peer Reviewed
• [Journal Article] Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway. (2010)
  • Author(s): Murayama-Hosokawa S, Oda K, Nakagawa S
  • Journal Title: Oncogene Volume: 29 Pages: 1897-908
  • Peer Reviewed
• [Presentation] 臓器別シンポジウム:子宮頸癌 (2011)
  • Author(s): 中川俊介
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2011-10-05
• [Presentation] プルテアソーム阻害剤をもちいた新規子宮頸癌の治療戦略 (2011)
  • Author(s): 中川俊介
  • Organizer: 日本癌学会 臓器別シンポジューム
• [Presentation] Deleted in breast cancer-1 is targeted for the ubiquitin-mediated degradation by human papillomavirus E6 oncoprotein. (2010)
  • Author(s): Takayuki Seiki, Shunsuke Nakagawa
  • Organizer: 69^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2010-09-22
• [Presentation] FIGO 2012 Rome ItalyGenome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer
  • Author(s): Ikeda Y, Oda K, Nakagawa S
• [Patent(Industrial Property Rights)] プロテアソームインヒビター内包高分子ミセル (2010)
  • Inventor(s): 片岡一則、中川俊介他
  • Industrial Property Rights Holder: 片岡一則、中川俊介他
  • Filing Date: 2010-02-19