title: Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.
abstract: OBJECTIVE
  With current treatment regimens, high-risk neuroblastoma (NB) remains largely incurable. Oncolytic viral therapy uses replication-competent viruses, like Sindbis virus (SINV), to kill cancers. The SINV AR339 strain is blood borne and relatively non-virulent. We evaluated the feasibility of SINV AR339 for treating human NB.
  
  
  METHODS
  The cytotoxicity and viral growth of SINV AR339 were evaluated for five human NB cell lines, SK-N-SH, IMR-32, LAN-5, GOTO, and RT-BM-1. SINV-induced apoptosis was confirmed by TUNEL assays and PARP-1 cleavage. In vivo effects of SINV on neuroblastoma cell xenografts in nude mice were assessed by intratumoral or intravenous SINV inoculation.
  
  
  RESULTS
  In five human NB cell lines, SINV infections induced remarkable cytotoxicity. The mRNA expressions of anti-apoptotic genes, Bcl-2 and Bcl-xL, in LAN-5 and RT-BM-1, which were less sensitive to SINV infection, increased in response to SINV infection, while the other NB cell lines sensitive to SINV infection failed to respond. In nude mice, intratumoral and intravenous SINV inoculations caused significant regression of NB xenograft tumors.
  
  
  CONCLUSIONS
  Our results suggested that SINV AR339 was significantly oncolytic against human NB. Thus, SINV showed promise as a novel therapy for treating NB.
authors: Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.|Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Ayako
authors: A
authors: Takenouchi
authors: Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Kengo
authors: K
authors: Saito
authors: Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.|Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Eriko
authors: E
authors: Saito
authors: Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Takeshi
authors: T
authors: Saito
authors: Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Tomoro
authors: T
authors: Hishiki
authors: Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Tadashi
authors: T
authors: Matsunaga
authors: Laboratory Animal Center, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Naohisa
authors: N
authors: Isegawa
authors: Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Hideo
authors: H
authors: Yoshida
authors: Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
authors: Naomi
authors: N
authors: Ohnuma
authors: Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan. sirasawa@faculty.chiba-u.jp.
authors: Hiroshi
authors: H
authors: Shirasawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D012845:Sindbis Virus
keywords: Neuroblastoma; Oncolytic viral therapy; Sindbis virus