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.

• Grant number: 15/16776-3
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2016
• End date: November 30, 2018
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Maria Lucia Zaidan Dagli
• Grantee: Maria Lucia Zaidan Dagli
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanomas are malignancies often diagnosed in the oral cavity of dogs. In Brazil, a study of cancer in dogs , at the University of São Paulo from 1993 to 2002, found that 3% (n = 58) of 1813 cases were melanocytic tumors. In another study of 130 cases of cancer of the oral cavity, 33.07% were melanomas, SCC 9.23% and 2.31% fibrosarcomas; Similar results were observed in 200 cases of oral tumors in a private dental service, with 26.5% of oral melanomas, 10.5% and 5.5% SCC fibrosarcomas. A common behavior to oral melanomas (OM) is the focal infiltration, recurrence and metastases to regional lymph nodes and lungs. This biological behavior resembles that of human melanoma. The aggressive nature of oral mucosal melanoma in dogs and humans, combined with short survival time after surgery, underscore the importance of developing effective new therapies for the treatment of OM. The aim of this study is to evaluate the therapeutic potential of reengeneered toxin of Bacillus anthracis, activated by urokinase (uPA) and matrix metalloproteinase (MMP) called PA-U2-R200A + PA-L1-I210A + LF in clinical and preclinical trials phase I spontaneous OM in dogs. Therefore, spontaneous OM samples of dogs will be obtained from the Veterinary Hospital Surgery Service of the University Anhembi Morumbi. The reengeneered and purified toxin from Bacillus anthracis, consisting of 3 parts - PA-U2-R200A, PA-L1 and I210A LF, will be courtesy of Parasitic Diseases Laboratory at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA for a study in partnership with Prof. Dr. Shihui Liu. Athymic mice will be transplanted with melanoma cell lines canine CML and CML-2-13 to be treated with reengenheirada toxin. In addition, dogs with spontaneous MO will be used for the phase 1 clinical trial with reengenheirada toxin, whether in vitro and in laboratory animals are positive. Since the positive, or inhibitory for the dog melanoma, we will also test the use of this toxin reengenheirada other canine tumors such as osteosarcoma and mammary tumors. We hope in this way to get new therapy for the canine OM, enabling increased patient survival. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NISHIYA, ADRIANA TOMOKO; NAGAMINE, MARCIA KAZUMI; MACKOWIAK DA FONSECA, IVONE IZABEL; MIRALDO, ANDREA CARINGI; SCATTONE, NAYRA VILLAR; GUERRA, JOSE LUIZ; XAVIER, JOSE GUILHERME; SANTOS, MARIO; MASSOCO DE SALLES GOMES, CRISTINA OLIVEIRA; WARD, JERROLD MICHAEL; et al. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas. TOXINS, v. 12, n. 3, MAR 2020. (16/20479-7, 15/25158-1, 15/16776-3, 17/12855-1)

DA FONSECA, JONATHAN MACKOWIAK; MACKOWIAK DA FONSECA, IVONE IZABEL; NAGAMINE, MARCIA KAZUMI; MASSOCO, CRISTINA DE OLIVEIRA; NISHIYA, ADRIANA TOMOKO; WARD, JERROLD MICHAEL; LIU, SHIHUI; LEPPLA, STEPHEN HOWARD; BUGGE, THOMAS HENRIK; ZAIDAN DAGLI, MARIA LUCIA. Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells. TOXINS, v. 12, n. 10, OCT 2020. (16/20479-7, 17/12855-1, 15/16776-3)

DE CARVALHO, JOYCE PIRES; CARRILHO, MARCELLA COLLANERI; DOS ANJOS, DENNER SANTOS; HERNANDEZ, CAROLINA DAGLI; SICHERO, LAURA; ZAIDAN DAGLI, MARIA LUCIA. Unraveling the Risk Factors and Etiology of the Canine Oral Mucosal Melanoma: Results of an Epidemiological Questionnaire, Oral Microbiome Analysis and Investigation of Papillomavirus Infection. CANCERS, v. 14, n. 14, p. 15-pg., 2022-07-01. (15/16776-3)