title: A possible clinical adaptation of CRM197 in combination with conventional chemotherapeutic agents for ovarian cancer.
abstract: OBJECTIVE
  Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for cancer therapy. We have already started a phase I study of CRM197, a specific HB-EGF inhibitor, for advanced ovarian cancer. In this study, we evaluated possible clinical adaptations of CRM197 in combination with conventional chemotherapeutic agents.
  
  
  METHODS
  CRM197, bevacizumab, and paclitaxel were intraperitoneally administered either alone or in combination with mice xenografted with ES2 human ovarian cancer cells. The tumor volumes and microvessel densities (MVD) were determined.
  
  
  RESULTS
  Enhanced antitumor effects were observed when paclitaxel was used in combination with bevacizumab or CRM197. The antitumor effect of paclitaxel/CRM197 was significantly higher than that of paclitaxel/bevacizumab. The tumor MVD of mice treated with paclitaxel/CRM197 was significantly lower than that of mice treated with paclitaxel/bevacizumab.
  
  
  CONCLUSIONS
  CRM197 in combination with paclitaxel significantly blocked tumor formation and angiogenesis. These results suggest that paclitaxel is a suitable candidate for CRM197 combination therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Fukuoka University, Faculty of Medicine, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. tsujioka@fukuoka-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsujioka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukami
authors.forename: Fusanori
authors.initials: F
authors.lastname: Yotsumoto
authors.forename: Taeko
authors.initials: T
authors.lastname: Ueda
authors.forename: Shoko
authors.initials: S
authors.lastname: Hikita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D000068258:Bevacizumab; D045744:Cell Line, Tumor / Q000637:transplantation; D004167:Diphtheria Toxin / Q000037:antagonists & inhibitors; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D001426:Bacterial Proteins; D004167:Diphtheria Toxin; D006131:Growth Inhibitors; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; C028581:CRM197 (non-toxic variant of diphtheria toxin); D000068258:Bevacizumab; D017239:Paclitaxel