title: Combination of the tumor angiogenesis inhibitor bevacizumab and intratumoral oncolytic herpes virus injections as a treatment strategy for human gastric cancers.
abstract: OBJECTIVE
  Advanced gastric cancer is difficult to treat due to the frequency of liver metastases and peritoneal dissemination. A combination of two new strategies, including the anti-angiogenesis inhibitor bevacizumab and an oncolytic herpes virus is a promising treatment for advanced cancer.
  
  
  METHODS
  The effects of bevacizumab on oncolytic herpes virus replication and viral cytotoxicity were examined at varying bevacizumab concentrations and viral titers. In addition, the ability of these two new promising anticancer agents to inhibit tumor growth was studied. Histological examinations of CD31 and LacZ were used to assess angiogenesis and virus distribution within the tumor, respectively.
  
  
  RESULTS
  Bevacizumab did not affect viral replication or viral cytotoxicity in vitro. The combination of bevacizumab and the oncolytic herpes virus hrR3 significantly reduced tumor growth in vivo in an experimental gastric cancer model. Bevacizumab inhibited angiogenesis caused by local injection of hrR3 and induced virus spread. Bevacizumab increased the distribution of the intratumorally injected oncolytic herpes virus within the tumor.
  
  
  CONCLUSIONS
  Combination therapy consisting of bevacizumab and an oncolytic herpes virus is a promising new treatment strategy for gastric cancer.
authors.affiliation: Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Deguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Shikano
authors.forename: Hideki
authors.initials: H
authors.lastname: Kasuya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nawa
authors.forename: Sawako
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Shin
authors.initials: S
authors.lastname: Takeda
authors.forename: Tan
authors.initials: T
authors.lastname: Gewen
authors.forename: Tevfik T
authors.initials: TT
authors.lastname: Sahin
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Kanzaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Saori
authors.initials: S
authors.lastname: Fukuda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000472:pathogenicity*; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab