Molecular mechanism for the regulation of HB-EGF transcription in ovarian cancer

• Project/Area Number: 19591947
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fukuoka University
• Principal Investigator: MIYAMOTO Shingo Fukuoka University, 医学部, 准教授 (40209945)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 婦人科腫瘍学 / 卵巣癌 / HB-EGF / 酸化LDL / CD36 / EMT / Snail / 腹膜播種 / CRM197 / 標的治療 / シグナル伝達 / EGFR

Research Abstract

本研究によって、卵巣癌標的分子であるHB-EGFは動脈硬化をきたすアテローム形成に重要な酸化LDLとその受容体であるCD36を介した経路や上皮性悪性腫瘍が間葉系細胞に形態学的に変化することにより転移・浸潤能を獲得する現象である。EMTに伴って発現亢進することが明らかとなり、これらの分子群は卵巣癌における新たな評点分子となり得ることが示唆された。

Research Products

• [Journal Article] Validation of HB-EGF and amphiregulin as targets for human cancer therapy (2008)
  • Author(s): Yotsumoto F, Yagi H, Suzuki SO, Oki E, Tsujioka H, Hachisuga T, Sonoda K, Kawarabayashi T, Mekada E, Miyamoto S.
  • Journal Title: Biochemical and Biophysical Research Communications 365(3) Pages: 555-561
  • Peer Reviewed
• [Journal Article] HB-EGF promotes transcoelomic metastasis in ovarian cancer through epithelial mesenchymal transition (2008)
  • Author(s): Yagi H, Yoshimoto F, Miyamoto S.
  • Journal Title: Molecular Cancer Therapeutics 7(10) Pages: 3441-34511
  • Peer Reviewed
• [Journal Article] Heparin-binding epidermal growth factor-like growth factor as a new target molecule for cancer therapy (2008)
  • Author(s): Miyamoto S, Yagi H, Yotsumoto F, Kawarabayashi T, Mekada E.
  • Journal Title: Advance Experimental Medical Biology 622 Pages: 281-295
• [Journal Article] 細胞増殖因子HB-EGFを分子標的とした卵巣癌治療薬の開発 (2008)
  • Author(s): 四元房典、宮本新吾、目加田英輔
  • Journal Title: BIO Clinica 23(7) Pages: 586-592
• [Journal Article] Validation of HB-EGF and amphiregulin as targets for human cancer therapy (2008)
  • Author(s): Yotsumoto F
  • Journal Title: Biochemical and Biophysical Research Communications 365 Pages: 555-561
  • Peer Reviewed
• [Journal Article] HB-EGF Promotes Transcoelomic Metastasis in Ovarian Cancer Through Epithelial Mesenchymal Transition (2008)
  • Author(s): Yagi H
  • Journal Title: Molecular Cancer Therapeutics 7 Pages: 3441-3451
  • Peer Reviewed
• [Journal Article] Heparin-binding epidermal growth factor-like growth factor as a new target molecule for cancer therapy (2008)
  • Author(s): Miyamoto S
  • Journal Title: Advance Experimental Medical Biology 622 Pages: 281-295
• [Journal Article] 細胞増殖因子HB-EGFを分子標的とした卵巣癌治療薬の開発 (2008)
  • Author(s): 四元房典
  • Journal Title: BIO Clinica 23 Pages: 586-592
• [Journal Article] Amphiregulin is much more abundantly expressed than transforming growthfactor-alpha and epidermal growth factor in human follicular fluid obtained frompatients undergoing in vitro fertilization-embryo transfer (2008)
  • Author(s): Miyamoto S, Inoue Y, et. al.
  • Journal Title: Fertil Steril
  • Peer Reviewed
• [Journal Article] Validation of HB-EGF and amphiregulin as targets for human cancer therapy (2008)
  • Author(s): Yotsumoto F, Yagi H, Suzuki SO, Oki E, Tsujioka H, Hachisuga T, Sonoda K, Kawarabayashi T, Mekada E, Miyamoto S.
  • Journal Title: Biochem Biophys Res Commun 365 Pages: 555-561
  • Peer Reviewed
• [Journal Article] The biological role of the unique molecule RCAS1:a bioactive marker that inducesconnective tissue remodeling and lymphocyte apoptosis (2008)
  • Author(s): Sonoda K, Miyamoto S, et. al.
  • Journal Title: Front Biosci 13 Pages: 1106-1116
  • Peer Reviewed
• [Journal Article] Clinical significance of RCAS1 as a biomarker of ovarian cancer (2007)
  • Author(s): Sonoda K, Miyamoto S, Yotsumoto F, Yagi H, Nakashima M, Watanabe T, Nakano H.
  • Journal Title: Oncology Reports 17(3) Pages: 623-628
  • Peer Reviewed
• [Journal Article] Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer (2007)
  • Author(s): Sonoda K, Miyamoto S, Yamazaki A, Kobayashi H, Nakashima M, Mekada E, Wake N.
  • Journal Title: Cancer 110(9) Pages: 1979-1990
  • Peer Reviewed
• [Journal Article] Diphtheria toxin mutant CRM197 possesses weak EF2-ADP-ribosyl activity that potentiates its anti-tumorigenic activity (2007)
  • Author(s): Kageyama T, Ohishi M, Miyamoto S, Mizushima H, Iwamoto R, Mekada E.
  • Journal Title: Journal of Chemistry 142(1) Pages: 95-104
  • NAID: 10020098014
  • Peer Reviewed
• [Journal Article] New approach to cancer therapy : heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule (2007)
  • Author(s): Miyamoto S, Yagi H, Yotsumoto F, Horiuchi S, Yoshizato T, Kawarabayashi T, Kuroki M, Mekada E.
  • Journal Title: Anticancer Research 27(6A) Pages: 3713-3721
  • Peer Reviewed
• [Journal Article] HB-EGFを標的とした癌標的治療 (2007)
  • Author(s): 四元房典、八木裕史、深見達弥、目加田英輔、宮本新吾
  • Journal Title: 細胞 39(7) Pages: 292-295
• [Journal Article] New approach to cancer therapy:heparin binding-epidermal growth factor-likegrowth factor as a novel targeting molecule (2007)
  • Author(s): Miyamoto S, et. al.
  • Journal Title: Anticancer Res 27 Pages: 3713-3721
  • Peer Reviewed
• [Journal Article] Biologic significance of receptor-binding cancer antigen expressed on SiSo cells(RCAS1)as a pivotal regulator of tumor growth through angiogenesis in humanuterille cancer (2007)
  • Author(s): Sonoda K, Miyamoto S, et. al.
  • Journal Title: Cancer 110 Pages: 1979-1990
  • Peer Reviewed
• [Journal Article] Diphtheria toxin mutant CRM197 possesses weak EF2-ADP-ribosyl activity thatpotentiates its anti-tumorigenic activity (2007)
  • Author(s): Kageyama T, Ohishi M, Miyamoto S, et. al.
  • Journal Title: J Biochem 142 Pages: 95-104
  • NAID: 10020098014
  • Peer Reviewed
• [Journal Article] Clinical significance of RCAS1 as a biomarker of ovarian cancer (2007)
  • Author(s): Sonoda K, Miyamoto S, et. al.
  • Journal Title: Oncol Rep 17 Pages: 623-628
  • Peer Reviewed
• [Journal Article] HB-EGFを標的とした癌治療 (2007)
  • Author(s): 四元 房典、八木 裕史、深見 達弥、目加田 英輔、宮本 新吾.
  • Journal Title: 細胞 39 Pages: 292-295
• [Presentation] Heparin-binding epidermal growth factor-like growth factor (HB)特異的抑制剤CRM197(CRM)を用いた乳癌標的治療 (2008)
  • Author(s): 四元房典
  • Organizer: 第12回バイオ治療法研究会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-12-06
• [Presentation] Heparin-binding epidermal growth factor-like growth factor (HB)特異的抑制剤CRM197 (CRM)を用いた乳癌標的治療 (2008)
  • Author(s): 四元房典
  • Organizer: 第12回バイオ治療法研究会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-12-06
• [Presentation] RCAS1 induces apoptosis in putative receptor expressing cells via ectodomain shedding mediated by ADAM9 (2008)
  • Author(s): 園田顕三
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] The validation of molecularly targeted therapy against amphiregulin in pancreatic cancer (2008)
  • Author(s): 深見達弥
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] The validation of CRM197, a specific inhibitor for HB-EGF, for molecularly targeted therapy in breast cancer patients (2008)
  • Author(s): 四元房典
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] HB-EGFとAmphiregulinを標的とした癌治療 (2008)
  • Author(s): 四元房典
  • Organizer: 第28回日本分子腫瘍マーカー研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-27
• [Presentation] The inhibition of amphiregulin blocks AKT as well as ERK activation in pancreatic cancer (2008)
  • Author(s): Fukami T
  • Organizer: 36^<th> Congress of the International Society of Oncology and BioMarkers
  • Place of Presentation: 東京
  • Year and Date: 2008-10-07
• [Presentation] Efficacy of cross-reacting material 197 (CRM197), a specific inhibitor for heparin-binding epidermal growth factor-like growth factor (HB), in breast cancer patients (2008)
  • Author(s): Yotsumoto F
  • Organizer: 36^<th> Congress of the International Society of Oncology and BioMarkers
  • Place of Presentation: 東京
  • Year and Date: 2008-10-07
• [Presentation] Phase I study of BK-UM (CRM197) in patients with ovarian cancer (2008)
  • Author(s): Miyamoto S
  • Organizer: 36^<th> Cogress of the International Society of Oncology and BioMarkers
  • Place of Presentation: 東京
  • Year and Date: 2008-10-06
• [Presentation] Phase I study of BK-UM (CRM197) in patients with ovarian cancer (2008)
  • Author(s): Miyamoto S
  • Organizer: 36^<th> Congress of the International Society of Oncology and BioMarkers
  • Place of Presentation: 東京
  • Year and Date: 2008-10-06
• [Presentation] 再発卵巣癌を対象としたHB-EGF特異的抑制剤BK-UMの第I相臨床試験 (2008)
  • Author(s): 宮本新吾
  • Organizer: 第7回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-07-18
• [Presentation] Synergisitc anti-tumor effects in combination of Gemcitabine with inhibitors for amphiregulin (2008)
  • Author(s): Fukami T
  • Organizer: American Association for Cancer Research 99^<th> Annual Meeting
  • Place of Presentation: San Diego, CA
  • Year and Date: 2008-04-16
• [Presentation] Heparin-Binding Epidermal Growth Factor-Like Growth Factor (HB) regulates mammary tumorigenesis through EGFR as well as Her2 signal (2008)
  • Author(s): Yotsumoto F
  • Organizer: American Association for Cancer Research 99^<th> Annual Meeting
  • Place of Presentation: San Diego, CA
  • Year and Date: 2008-04-16
• [Presentation] ヒト膵臓癌標的分子amphiregulinの妥当性とamphiregulin抑制剤の治療への応用性の可能性 (2007)
  • Author(s): 深見達弥
  • Organizer: 第11回バイオ治療法研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-12-01
• [Presentation] HB-EGFを標的とした卵巣癌分子標的治療の臨床治験 (2007)
  • Author(s): 宮本 新吾
  • Organizer: 第一回FUKUOKA Conference for Academic Surgeons
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-19
• [Presentation] ADAM9 plays a pivotal role in ectodomain shedding of RCAS1, which induces apoptosis in peripheral lymphocytes (2007)
  • Author(s): 園田顕三
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Amphiregulin enhances drug resistance for pancreatic and colon cancers (2007)
  • Author(s): 深見達弥
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] HB-EGF or amphiregulin is a promising target for human cancer therapy (2007)
  • Author(s): 四元房典
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Synergistic anti-tumor effects of CRM197 and paclitaxel in patientswith advanced gastric cancer (2007)
  • Author(s): 宮本新吾
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Synergistic anti-tumor effects of CRM197 and paclitaxel in patients with advanced gastric cancer (2007)
  • Author(s): Miyamoto S, et. al.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] HB-EGFを標的とした新たな卵巣癌分子標的治療の確立 (2007)
  • Author(s): 宮本 新吾
  • Organizer: 第11回癌免疫研究会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-10
• [Presentation] HB-EGF(HB)を標的とした卵巣癌治療の医師主導型治験 (2007)
  • Author(s): 宮本新吾
  • Organizer: 第6回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2007-07-21
• [Presentation] 卵巣癌におけるHB-EGFとタキソールとの関連 (2007)
  • Author(s): 深見達弥
  • Organizer: 第6回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2007-07-21
• [Presentation] 卵巣癌腹膜におけるHeparin binding ipidermal growth factor-like growth factor (HB)の役割 (2007)
  • Author(s): 八木裕史
  • Organizer: 第6回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2007-07-21
• [Presentation] Heparin-Binding Factor (HB)とamphiregulin (AR)を標的とした癌治療 (2007)
  • Author(s): 四元房典
  • Organizer: 第6回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2007-07-21
• [Presentation] Heparin binding epidermal growth factor-like growth factor (HB)に対する特異的抑制剤CRM197の卵巣癌腹膜播種に対する効果 (2007)
  • Author(s): 八木裕史
  • Organizer: 第59回日本産科婦人科学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2007-04-16
• [Presentation] 酸化LDLとCD36による卵巣癌標的分子Heparin Binding Epidermal Growth Factor Like Growth Factor (HB)発現制御機構 (2007)
  • Author(s): 四元房典
  • Organizer: 第59回日本産科婦人科学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2007-04-16
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/biochem1/MaK-bunken/kenkyugaiyo.html
• [Patent(Industrial Property Rights)] 抗癌剤の効果増強剤 (2008)
  • Inventor(s): 宮本新吾、目加田英輔
  • Industrial Property Rights Holder: 阪大微生物病研究会
  • Filing Date: 2008-01-21
• [Patent(Industrial Property Rights)] 抗癌剤の効果増強剤 (2008)
  • Inventor(s): 宮本 新吾, 目加田 英輔
  • Industrial Property Rights Holder: 阪大微生物研究会
  • Industrial Property Number: 2007-011939
  • Filing Date: 2008-01-21
  • Overseas
• [Patent(Industrial Property Rights)] ヘパリン結合上皮細胞増殖因子様増殖因子に結合するモノクローナル抗体 (2007)
  • Inventor(s): 宮本新吾、目加田英輔、協和発酵(株)
  • Industrial Property Rights Holder: 宮本新吾、目加田英輔、協和発酵(株)
  • Filing Date: 2007-12-05
• [Patent(Industrial Property Rights)] Gefinitib感受性及び抵抗性肺癌に対する制癌効果 (2007)
  • Inventor(s): 宮本新吾、目加田英輔
  • Industrial Property Rights Holder: 宮本新吾、目加田英輔
  • Filing Date: 2007-06-26
• [Patent(Industrial Property Rights)] アンフィレギュリンを用いた腸管上皮細胞増殖方法 (2007)
  • Inventor(s): 宮本新吾
  • Industrial Property Rights Holder: 宮本新吾
  • Filing Date: 2007-04-24
• [Patent(Industrial Property Rights)] amphiregulin阻害剤と抗癌剤の併用療法 (2007)
  • Inventor(s): 宮本新吾
  • Industrial Property Rights Holder: 宮本新吾
  • Filing Date: 2007-01-22
• [Patent(Industrial Property Rights)] アンフィレギュリンを用いた腸管上皮細胞増殖方法 (2007)
  • Inventor(s): 宮本 新吾, 吉里 俊幸
  • Industrial Property Rights Holder: 宮本 新吾, 吉里 俊幸
  • Filing Date: 2007-04-24
• [Patent(Industrial Property Rights)] Gefitinib感受性及び抵抗性肺癌に対する制癌効果 (2007)
  • Inventor(s): 宮本 新吾, 目加田 英輔
  • Industrial Property Rights Holder: 宮本 新吾, 目加田 英輔
  • Filing Date: 2007-06-26
• [Patent(Industrial Property Rights)] 連続投与されたCRM197による抗腫瘍効果 (2007)
  • Inventor(s): 宮本 新吾, 目加田 英輔
  • Industrial Property Rights Holder: 宮本 新吾, 目加田 英輔
  • Filing Date: 2007-08-03
• [Patent(Industrial Property Rights)] ヘパリン結合上皮細胞増殖因子様増殖因子に結合するモノクローナル抗体 (2007)
  • Inventor(s): 宮本 新吾, 目加田 英輔, 協和発酵工業
  • Industrial Property Rights Holder: 協和発酵工業
  • Industrial Property Number: 2007-315068
  • Filing Date: 2007-12-05
  • Overseas