Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

Autor(es):Mostrar menos -

Nishiya, Adriana Tomoko ^[1] ; Nagamine, Marcia Kazumi ^[1] ; Mackowiak da Fonseca, Ivone Izabel ^[1] ; Miraldo, Andrea Caringi ^[1] ; Scattone, Nayra Villar ^[1] ; Guerra, Jose Luiz ^[1] ; Xavier, Jose Guilherme ^[2] ; Santos, Mario ^[2] ; Massoco de Salles Gomes, Cristina Oliveira ^[1] ; Ward, Jerrold Michael ^[3] ; Liu, Shihui ^{[4, 5]} ; Leppla, Stephen Howard ^[6] ; Bugge, Thomas Henrik ^[7] ; Zaidan Dagli, Maria Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, BR-05508270 Sao Paulo, SP - Brazil

^[2] Private Vet Pathol Serv, Rous Anim Pathol, Av Lacerda Franco 127, BR-01536000 Sao Paulo, SP - Brazil

^[3] Global Vet Pathol, Montgomery Village, MD 20886 - USA

^[4] Univ Pittsburg, Aging Inst, Pittsburgh, PA 15261 - USA

^[5] Univ Pittsburg, Div Infect Dis, Dept Med, Pittsburgh, PA 15261 - USA

^[6] NIAID, Microbial Pathogenesis Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 - USA

^[7] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 12, n. 3 MAR 2020.
• Citações Web of Science: 0

Resumo

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM. (AU)

• Processo FAPESP: 16/20479-7 - Avaliação dos efeitos da toxina do Bacillus anthracis reengenheirada, ativada pela uroquinase (uPA) e metaloproteinases (MMPs), em Hemangiossarcoma canino: estudos in vitro e in vivo
• Beneficiário: Márcia Kazumi Nagamine
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/25158-1 - Estabelecimento de cultivo primário de células de melanoma canino visando testes de novos agentes antineoplásicos
• Beneficiário: Andreia Caringi Miraldo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/16776-3 - Avaliação dos efeitos da toxina do Bacillus anthracis reengenheirada, ativada pela urokinase (UPA) e metaloproteinases (MMPs), para o tratamento de melanomas e de outras neoplasias de cães.
• Beneficiário: Maria Lucia Zaidan Dagli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/12855-1 - Investigação da atividade do peptídeo Q-conexina carboxil-terminal (ACT1) associado ao inibidor de histonas desacetilases butirato sódico e a antineoplásicos convencionais, para o tratamento de tumores mamários caninos: ensaios in vitro.
• Beneficiário: Ivone Izabel Mackowiak da Fonseca
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado