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Research Article

Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia

NAOKO KUNAMI, FUSANORI YOTSUMOTO, KENJI ISHITSUKA, TATSUYA FUKAMI, TAKASHI ODAWARA, SADAO MANABE, TOYOKAZU ISHIKAWA, KAZUO TAMURA, MASAHIDE KUROKI and SHINGO MIYAMOTO
Anticancer Research July 2011, 31 (7) 2483-2488;
NAOKO KUNAMI
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FUSANORI YOTSUMOTO
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KENJI ISHITSUKA
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  • For correspondence: kenjiishitsuka@fukuoka-u.ac.jp
TATSUYA FUKAMI
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TAKASHI ODAWARA
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SADAO MANABE
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TOYOKAZU ISHIKAWA
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KAZUO TAMURA
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MASAHIDE KUROKI
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SHINGO MIYAMOTO
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Abstract

The therapeutic outcome for T-cell acute lymphoblastic leukemia (T-ALL) remains poor; thus, novel, targeted therapies are urgently needed. Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment of various types of cancer. The aim of the present study was to investigate whether HB-EGF is a therapeutic target for T-ALL, and to further elucidate the antitumor effects of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect of CRM197 on these cells alone or in combination with anticancer agent. The expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay. HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB-EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic target for T-ALL.

  • HB-EGF
  • CRM197
  • doxorubicin
  • T-ALL
  • Received April 7, 2011.
  • Revision received June 7, 2011.
  • Accepted June 8, 2011.
  • Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 31 (7)
Anticancer Research
Vol. 31, Issue 7
July 2011
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Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia
NAOKO KUNAMI, FUSANORI YOTSUMOTO, KENJI ISHITSUKA, TATSUYA FUKAMI, TAKASHI ODAWARA, SADAO MANABE, TOYOKAZU ISHIKAWA, KAZUO TAMURA, MASAHIDE KUROKI, SHINGO MIYAMOTO
Anticancer Research Jul 2011, 31 (7) 2483-2488;

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Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia
NAOKO KUNAMI, FUSANORI YOTSUMOTO, KENJI ISHITSUKA, TATSUYA FUKAMI, TAKASHI ODAWARA, SADAO MANABE, TOYOKAZU ISHIKAWA, KAZUO TAMURA, MASAHIDE KUROKI, SHINGO MIYAMOTO
Anticancer Research Jul 2011, 31 (7) 2483-2488;
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