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Research Article

HB-EGF Inhibition in Combination with Various Anticancer Agents Enhances its Antitumor Effects in Gastric Cancer

AYAKO SANUI, FUSANORI YOTSUMOTO, HIROSHI TSUJIOKA, TATSUYA FUKAMI, SHINJI HORIUCHI, KYOKO SHIROTA, TOSHIYUKI YOSHIZATO, TATSUHIKO KAWARABAYASHI, MASAHIDE KUROKI and SHINGO MIYAMOTO
Anticancer Research August 2010, 30 (8) 3143-3149;
AYAKO SANUI
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FUSANORI YOTSUMOTO
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HIROSHI TSUJIOKA
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TATSUYA FUKAMI
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SHINJI HORIUCHI
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KYOKO SHIROTA
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TOSHIYUKI YOSHIZATO
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TATSUHIKO KAWARABAYASHI
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MASAHIDE KUROKI
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SHINGO MIYAMOTO
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  • For correspondence: smiya@cis.fukuoka-u.ac.jp
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Abstract

Advanced gastric cancer (GC) is one of the most lethal malignancies. Although many anticancer agents exist for the treatment of GC, its prognosis remains extremely poor. Therefore, further development of targeted therapies is required for patients with GC. To assess the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) as a target for GC therapy, the expression of EGF receptor ligands in GC cell lines, and the antitumor effects of an HB-EGF inhibitor (CRM197) as a single agent and in combination with other anticancer agents was assessed in GC cells. HB-EGF was the predominantly expressed ligand among EGF receptor ligands in all the cells. CRM197 induced significant cell apoptosis. Anticancer agents augmented the secretion of HB-EGF into the medium and simultaneously induced cell apoptosis. Combination of CRM197 with other anticancer agents significantly enhanced cell apoptosis. Additionally, co-administration of CRM197 and paclitaxel resulted in synergistic antitumor effects. These results suggested that HB-EGF is a rational target for GC therapy.

  • HB-EGF
  • HER2
  • 5-FU
  • paclitaxel
  • gastric cancer
  • Received June 8, 2010.
  • Revision received July 14, 2010.
  • Accepted July 16, 2010.
  • Copyright© 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 30 (8)
Anticancer Research
Vol. 30, Issue 8
August 2010
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HB-EGF Inhibition in Combination with Various Anticancer Agents Enhances its Antitumor Effects in Gastric Cancer
AYAKO SANUI, FUSANORI YOTSUMOTO, HIROSHI TSUJIOKA, TATSUYA FUKAMI, SHINJI HORIUCHI, KYOKO SHIROTA, TOSHIYUKI YOSHIZATO, TATSUHIKO KAWARABAYASHI, MASAHIDE KUROKI, SHINGO MIYAMOTO
Anticancer Research Aug 2010, 30 (8) 3143-3149;

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HB-EGF Inhibition in Combination with Various Anticancer Agents Enhances its Antitumor Effects in Gastric Cancer
AYAKO SANUI, FUSANORI YOTSUMOTO, HIROSHI TSUJIOKA, TATSUYA FUKAMI, SHINJI HORIUCHI, KYOKO SHIROTA, TOSHIYUKI YOSHIZATO, TATSUHIKO KAWARABAYASHI, MASAHIDE KUROKI, SHINGO MIYAMOTO
Anticancer Research Aug 2010, 30 (8) 3143-3149;
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