{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:50:11Z","timestamp":1767340211828,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T00:00:00Z","timestamp":1583107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/16776-3"],"award-info":[{"award-number":["2015\/16776-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxins12030157","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T07:50:53Z","timestamp":1583135453000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas"],"prefix":"10.3390","volume":"12","author":[{"given":"Adriana Tomoko","family":"Nishiya","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia Kazumi","family":"Nagamine","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivone Izabel Mackowiak da","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Caringi","family":"Miraldo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nayra","family":"Villar Scattone","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luiz","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8476-1306","authenticated-orcid":false,"given":"Jos\u00e9 Guilherme","family":"Xavier","sequence":"additional","affiliation":[{"name":"Rous Animal Pathology, Private Veterinary Pathology Services. Av. Lacerda Franco 127, Sao Paulo 01536-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio","family":"Santos","sequence":"additional","affiliation":[{"name":"Rous Animal Pathology, Private Veterinary Pathology Services. Av. Lacerda Franco 127, Sao Paulo 01536-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina Oliveira","family":"Massoco de Salles Gomes","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6350-8982","authenticated-orcid":false,"given":"Jerrold Michael","family":"Ward","sequence":"additional","affiliation":[{"name":"Global Vet Pathology, Montgomery Village, MD 20886, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihui","family":"Liu","sequence":"additional","affiliation":[{"name":"Aging Institute and Division of Infectious Diseases, Department of Medicine, University of Pittsburg, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen Howard","family":"Leppla","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Henrik","family":"Bugge","sequence":"additional","affiliation":[{"name":"Proteases &amp; Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lucia Zaidan","family":"Dagli","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1053\/j.ctsap.2007.03.004","article-title":"Canine Oral Melanoma","volume":"22","author":"Bergman","year":"2007","journal-title":"Clin. 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