title: Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.
abstract: Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (P<0.001) and decreased tumor growth (P<0.001). Pulmonary macrometastasis and Ki67 labeling were reduced with low-dose aurothiomalate (P=0.033 and 0.005, respectively), and tumor emboli and pulmonary micrometastases were decreased with high-dose aurothiomalate (P=0.010 and 0.011, respectively). There was no difference in survival, tumor development, ulceration, mitotic indices, tumor necrosis, nonpulmonary metastases, and caspase-3 labeling. Aurothiomalate treatment inhibited osteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.
authors.affiliation: Departments of aSmall Animal Clinical Sciences bInfectious Diseases and Pathology, College of Veterinary Medicine cDepartment of Radiation Oncology, College of Medicine, University of Florida, Gainesville, Florida dVCA Animal Care Center of Sonoma County, Rohnert Park, California eDepartment of Pathobiology and Diagnostic Investigation, Michigan State University, Lansing, Michigan, USA.
authors.forename: Valery F
authors.initials: VF
authors.lastname: Scharf
authors.forename: James P
authors.initials: JP
authors.lastname: Farese
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Abbott
authors.forename: Matti
authors.initials: M
authors.lastname: Kiupel
authors.forename: Marc E
authors.initials: ME
authors.lastname: Salute
authors.forename: Rowan J
authors.initials: RJ
authors.lastname: Milner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D006052:Gold Sodium Thiomalate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D006052:Gold Sodium Thiomalate; D053148:Caspase 3