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Toxins (Basel) ; 12(3)2020 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-32121654

RESUMEN

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.


Asunto(s)
Antígenos Bacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Toxinas Bacterianas/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Animales , Antígenos Bacterianos/genética , Antígenos Bacterianos/farmacología , Antineoplásicos/farmacología , Toxinas Bacterianas/genética , Toxinas Bacterianas/farmacología , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Perros , Femenino , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Melanoma/metabolismo , Melanoma/patología , Melanoma/veterinaria , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/veterinaria , Ingeniería de Proteínas , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
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