title: Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug.
abstract: Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.|Department of Surgery, University of California, San Diego, California, USA.|Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kiyuna
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Pathology, University of California Los Angeles, California, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Nelson
authors.affiliation: Department of Pathology, University of California Los Angeles, California, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Dry
authors.affiliation: Department of Pathology, University of California Los Angeles, California, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Yanagawa
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Russell
authors.affiliation: Department of Pediatrics and Department of Orthopaedics, David Geffen School of Medicine, Mattel Children's Hospital, UCLA's Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
authors.affiliation: Division of Hematology-Oncology, University of California, Los Angeles, California, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California, USA.
authors.forename: Irmina
authors.initials: I
authors.lastname: Elliott
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Ryusei
authors.initials: R
authors.lastname: Matsuyama
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, California, USA.
authors.forename: Fritz C
authors.initials: FC
authors.lastname: Eilber
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.|Department of Surgery, University of California, San Diego, California, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001691:Biological Therapy / Q000379:methods*; D001859:Bone Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009336:Necrosis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D012516:Osteosarcoma / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D000077157:Sorafenib; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Salmonella typhimurium A1-R; nude mouse; osteosarcoma; patient-derived xenograft; tumor-targeting