A new molecular target therapy for gastric can cer targeting nuclear translocation of the CTF of EGFR ligands

• Project/Area Number: 22790665
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: SHIMURA Takaya 名古屋市立大学, 大学院・医学研究科, 助教 (90405192)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 胃癌 / 分子標的治療 / HB-EGF / Amphiregulin / EGFR

Research Abstract

HB-EGF-CTF nuclear translocation increased motility and invasion of gastric cancer cell. The nuclear immunoreactivity of HB-EGF-CTF was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors in human gastric cancer. These results suggested that HB-EGF-CTF nuclear translocation induce gastric cancer invasion(Shimura T, et al. BMC Cancer 2012, in press).
AR nuclear translocation significantly induced chemoresistance in vitro and in vivo, and AR-nuclear staining was extracted as a significant poor prognostic factor in human gastric cancer. As these results, AR nuclear translocation reduces chemosensitivity to anti-cancer drugs and would be associated with poor prognosis in human gastric cancer(Yoshida M, Shimura T, et al. Cancer Sci 2012).

Research Products

• [Journal Article] Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion (2012)
  • Author(s): Shimura T, Yoshida M, Fukuda S, Ebi M, Hirata Y, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Higashiyama S, Joh T
  • Journal Title: BMC cancer Volume: (in press)
• [Journal Article] The relationship between antitumor effects and relative dose intensity of S-1 plus cisplatin treatment for metastatic gastric cancer (2012)
  • Author(s): Kitagawa M, Shimura T, Yamada T, Ebi M, Hirata Y, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T
  • Journal Title: Anticancer Res Volume: 32(5) Pages: 1763-8
• [Journal Article] Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer (2012)
  • Author(s): Yoshida M, Shimura T, Fukuda S, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Nakazawa T, Higashiyama S, Joh T
  • Journal Title: Cancer Sci Volume: 103(4) Pages: 708-15
• [Journal Article] The impact of cross-resistance between paclitaxel and docetaxel for metastatic gastric cancer (2012)
  • Author(s): Shimura T, Kitagawa M, Yamada T, Yoshida M, Ebi M, Hirata Y, Mizushima T, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T
  • Journal Title: Onkologie Volume: 35(4) Pages: 176-83
• [Journal Article] C-reactive protein is a potential poor prognostic factor for metastatic gastric cancer (2012)
  • Author(s): Shimura T, Kitagawa M, Yamada T, Ebi M, Mizoshita T, Tanida S, Kataoka H, Kamiya T, Joh T
  • Journal Title: Anticancer Res Volume: 32(2) Pages: 491-6
• [Journal Article] Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer (2012)
  • Author(s): Yoshida Michihiro
  • Journal Title: Cancer Science Volume: 103 Issue: 4 Pages: 708-715
  • DOI: 10.1111/j.1349-7006.2012.02204.x
  • Peer Reviewed
• [Journal Article] The impact of cross-resistance between paclitaxel and docetaxel for metastatic gastric cancer (2012)
  • Author(s): Shimura T, et al
  • Journal Title: Onkologie Volume: 35 Issue: 4 Pages: 176-183
  • DOI: 10.1159/000337400
  • Peer Reviewed
• [Journal Article] C-reactive protein is a potential poor prognostic factor for metastatic srastric cancer (2012)
  • Author(s): Shimura T, et al
  • Journal Title: Anticancer Research Volume: 32 Pages: 491-496
  • Peer Reviewed
• [Journal Article] Metastatic Colorectal Cancer with Severe Liver Dysfunction Successfully Treated Using FOLFOX Therapy (2011)
  • Author(s): Shimura T, Kataoka H, Joh T, (他8名, 1番目)
  • Journal Title: J Gastrointest Cancer Volume: 42(1) Pages: 68-72
• [Journal Article] TGFβinduces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells (2010)
  • Author(s): Ebi M, Kataoka H, Shimura T, Kubota E, Hirata Y, Mizushima T, Mizoshita T, Tanaka M, Mabuchi M, Tsukamoto H, Tanida S, Kamiya T, Higashiyama S, Joh T
  • Journal Title: Biochem Biophys Res Commun Volume: 402(3) Pages: 449-54
• [Journal Article] Clinical features of interstitial lung disease induced by standard chemotherapy(FOLFOX or FOLFIRI) for colorectal cancer (2010)
  • Author(s): Shimura T, Fuse N, Yoshino T, Minashi K, Tahara M, Doi T, Joh T, Ohtsu A
  • Journal Title: Ann Oncol Volume: 21(10) Pages: 2005-10
• [Journal Article] Intranuclear translocation signaling of HB-EGF carboxy-terminal fragment and mucosal defense through cell proliferation and migration in digestive tracts (2010)
  • Author(s): Tanida S, Kataoka H, Mizoshita T, Shimura T, Kamiya T, Joh T
  • Journal Title: Digestion Volume: 82(3) Pages: 145-9
• [Presentation] Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer (2011)
  • Author(s): 吉田道弘, 志村貴也, 他
  • Organizer: 第22回日本消化器癌発生学会総会
  • Place of Presentation: ホテルニューオータニ佐賀(佐賀県)
  • Year and Date: 2011-11-26
• [Presentation] 胃癌治療におけるパクリタキセルとドセタキセルの交差耐性の検討 (2011)
  • Author(s): 志村貴也.(1番目)北川美香, 吉田道弘, 山田智則, 海老正秀, 水島隆史, 平田慶和, 村上賢治, 片岡洋望, 城卓志
  • Organizer: 53th JDDW
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer (2011)
  • Author(s): 志村貴也
  • Organizer: 第53回JDDW
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2011-10-20
• [Presentation] HB-EGF-CTF nuclear translocation induces gastric cancer invasion (2011)
  • Author(s): Shimura T, Yoshida M, Fukuda S, Mizoshita T, Kataoka H, Higashiyama S, Joh T, .(1番目)
  • Organizer: 70^<th> Japan Cancer Association
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2011-10-05
• [Presentation] HB-EGF-CTF nuclear translocation induces gastric cancer invasion (2011)
  • Author(s): Shimura T, et al
  • Organizer: 70^<th> Japan Cancer Association Meeting
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-05
• [Presentation] Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer (2011)
  • Author(s): Yoshida M, Shimura T, Fukuda S, Mizoshita T, Kataoka H, Higashiyama S, Joh T.(2番目)
  • Organizer: 70^<th> Japan Cancer Association
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2011-10-03
• [Presentation] Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer (2011)
  • Author(s): Yoshida M, Shimura T, et al
  • Organizer: 70^<th> Japan Cancer Association Meeting
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] The impact of cross-resistance between paclitaxel and docetaxel for gastric cancer (2011)
  • Author(s): Shimura T, Kitagawa M, Tomonori Yamada, Michihiro Yoshida, Masahide Ebi, Yoshikazu Hirata, Takashi Mizushima, Tsutomu Mizoshita, Satoshi Tanida, Hiromi Kataoka, Takeshi Kamiya, Joh T.(1番目)
  • Organizer: 9^<th> JSMO
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2011-07-22
• [Presentation] The impact of cross-resistance between paclilaxel and docetaxel for gastric cancer (2011)
  • Author(s): 志村貴也
  • Organizer: 9^<th> JSMO Meeting
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-07-22
• [Presentation] 胃癌におけるamphiregulin核移行と抗癌剤耐性 (2011)
  • Author(s): 吉田道弘, 志村貴也, 他
  • Organizer: 第97回消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2011-05-15
• [Presentation] HB-EGF-CTF nuclear translocation induces gastric cancer invasion (2010)
  • Author(s): Shimura T, Yoshida M, Tanaka M, Kataoka H, Higashiyama S, Joh T, et al, (1番目)
  • Organizer: 35th ESMO
  • Place of Presentation: Milan, Italy
  • Year and Date: 2010-10-11
• [Presentation] HB-EGF-CTF nuclear translocation induces gastric cancer invasion. (2010)
  • Author(s): 志村貴也
  • Organizer: 35th ESMO
  • Place of Presentation: イタリア、ミラノ(Fieramilano city)
  • Year and Date: 2010-10-11
• [Presentation] Amphiregulin nuclear translocation might reduce chemosensitivity in gastric cancer. (2010)
  • Author(s): 吉田道弘
  • Organizer: 35th ESMO
  • Place of Presentation: イタリア、ミラノ(Fieramilano city)
  • Year and Date: 2010-10-11
• [Presentation] Amphiregulin nuclear translocation might reduce chemosensitivity in gastric cancer (2010)
  • Author(s): Yoshida M, Shimura T, Higashiyama S, Kataoka H, Joh T, et al.(2番目)
  • Organizer: 35th ESMO
  • Place of Presentation: Milan, Italy
  • Year and Date: 2010-10-08
• [Presentation] 胃癌の新規分子標的としてのHB-EGF-CTFシグナルの意義 (2010)
  • Author(s): 志村貴也.(1番目)、吉田道弘、福田信治、東山繁樹、溝下勤、久保田英嗣、谷田諭史、片岡洋望、神谷武、城卓志
  • Organizer: 第42回胃病態機能研究会
  • Place of Presentation: 札幌
  • Year and Date: 2010-08-07
• [Presentation] 胃癌の新規分子標的としてのHB-EGF-CTFシグナルの意義 (2010)
  • Author(s): 志村貴也
  • Organizer: 第42回胃病態機能研究会
  • Place of Presentation: 札幌(札幌プリンスホテル国際館パミール)
  • Year and Date: 2010-08-07
• [Presentation] 胃癌におけるamphiregulin核移行の意義の検討 (2010)
  • Author(s): 吉田道弘
  • Organizer: 第29回消化器病態生理勉強会
  • Place of Presentation: 東京(京王プラザホテル)
  • Year and Date: 2010-07-31
• [Remarks] 名古屋市立大学大学院医学研究科消化器代謝内科学ホームページ業績集
  • URL: http://www.ncu-shotai.ac/index.html