title: Systemic administration of reovirus (Reolysin) inhibits growth of human sarcoma xenografts.
abstract: BACKGROUND
  Despite advancement in therapies, overall survival rates for relapsed pediatric sarcomas are dismal. Newer therapies are needed to effectively salvage these patients. Oncolytic viruses (such as reovirus) and other genetically altered viruses (such as herpes simplex viruses and adenoviruses) have shown efficacy in a variety of solid tumors including sarcomas. Reolysin is an unmodified oncolytic reovirus that selectively replicates in Ras-activated cancer cells while not causing any significant human illness in its wild form.
  
  
  METHODS
  By using a panel of pediatric sarcoma cell lines in vitro and flank xenografts in vivo, Reolysin was evaluated as a single agent and in combination with cisplatin and radiation therapy. Electron microscopy and immunohistochemistry was used to demonstrated a cytopathic effect in treated tumors.
  
  
  RESULTS
  Reolysin inhibited the proliferation and viability of sarcoma cell lines at a dose of 1 to 10 virus particles per cell. In vivo, 5 × 10(9) plaque-forming units (PFU) administered via the tail vein every other day for 3 doses every 21 days inhibited the growth of tumor xenografts with improvement in event-free survival. In the SKES1 Ewing sarcoma line, there was therapeutic enhancement when reovirus was administered in combination with radiation or cisplatin. In the RH30 line and the OS33 line, therapeutic enhancement was demonstrated with radiation and cisplatin, respectively.
  
  
  CONCLUSIONS
  These results suggest that Reolysin alone or in combination with other cytotoxic agents may be effective therapy in pediatric sarcomas.
authors.affiliation: Department of Pediatric Hematology/Oncology, Phoenix Children's Hospital, Phoenix, Arizona 85016, USA. phingorani@phoenixchildrens.com
authors.forename: Pooja
authors.initials: P
authors.lastname: Hingorani
authors.forename: Wendong
authors.initials: W
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Lin
authors.forename: Laibin
authors.initials: L
authors.lastname: Liu
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003131:Combined Modality Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods*; D012087:Reoviridae; D012509:Sarcoma / Q000188:drug therapy* / Q000517:prevention & control* / Q000532:radiotherapy*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents