Resumo:A neoplasia mamária canina (NMC) é o tipo de neoplasia que mais comumente afeta cadelas não castradas. A terapia para a NMC é um desafio já que não são descritos tratamentos efetivos para neoplasias de alto grau histológico. Uma possibilidade terapêutica que age diminuindo a angiogênese tumoral é a quimioterapia metronômica (QM). Tem sido proposta a quantificação da angiogênese tumoral através da mensuração do fator de crescimento endotelial vascular (VEGF) e da densidade microvascular (DMV). Desta forma, neste estudo, foi avaliada a resposta de carcinomas mamários caninos à QM por mensuração da DMV e detecção do VEGF tecidual, índice apoptótico (IA) e índice de proliferação celular (IP). Foram utilizadas 28 cadelas com carcinomas mamários, distribuídas igualmente em um grupo controle (GC) tratadas com mastectomia e um grupo tratado (GT) com QM (ciclofosfamida 15mg/m2 e piroxicam 0,3mg/kg) ambos por via oral e diariamente durante 28 dias seguido de mastectomia. As neoplasias mamárias foram classificadas e graduadas histologicamente. DMV, grau do VEGF tecidual, IA e IP de todas as neoplasias foram obtidas por imunomarcação. A análise estatística mostrou diferença entre os grupos na DMV e IA (p<0.05), evidenciando redução quantitativa na microvasculatura tumoral e aumento na apoptose de células neoplásicas. Com base neste resultado, é possível afirmar que a QM possui efeitos antiangiogênicos e pró-apoptóticos em carcinomas mamários de cadelas e pode ser utilizada como uma nova opção terapêutica / Abstract:The canine mammary tumor (CMT) is the neoplasia that most commonly affects not spayed bitches. Therapy for CMT is a challenge since there are not described effective treatments for high-grade tumors. A therapeutic option that slows down tumor angiogenesis is metronomic chemotherapy (MC). Quantification of tumor angiogenesis has been proposed by measuring the vascular endothelial growth factor (VEGF) and microvessel density (MVD). Thus, in this study, the response of canine mammary carcinomas by the MC was evaluated by the measurement of MVD and tissue VEGF detection, apoptotic index (AI) and cell proliferation index (PI). Twenty-eight dogs with malignant CMT, equally distributed into a control group (CG) treated with mastectomy and a treated group (TG) treated with MC (cyclophosphamide 15mg/m2 and piroxicam 0.3 mg/kg) both orally and daily for 28 days followed by mastectomy. Mammary tumors were classified and graded histologically. MVD, tissue VEGF, AI and PI of all malignancies were obtained by immunostaining. The analysis showed statistical difference between groups in MVD and AI (p <0.05), showing quantitative reduction in tumor microvasculature and increase in tumor cells apoptosis. Based on this result, we can affirm that MC has antiangiogenic and proapoptotic effects in mammary carcinomas of bitches and can be used as a new therapeutic option / Orientador:Alexandre Lima de Andrade / Banca:Sabryna Gouveia Calazans / Banca:Maria Cecilia Rui Luvizotto / Mestre

Made available in DSpace on 2015-10-06T13:03:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-15. Added 1 bitstream(s) on 2015-10-06T13:18:49Z : No. of bitstreams: 1 000848999.pdf: 1544826 bytes, checksum: 3fb73afedffc7650ac4620d6a79c29e9 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / The canine mammary tumor (CMT) is the neoplasia that most commonly affects not spayed bitches. Therapy for CMT is a challenge since there are not described effective treatments for high-grade tumors. A therapeutic option that slows down tumor angiogenesis is metronomic chemotherapy (MC). Quantification of tumor angiogenesis has been proposed by measuring the vascular endothelial growth factor (VEGF) and microvessel density (MVD). Thus, in this study, the response of canine mammary carcinomas by the MC was evaluated by the measurement of MVD and tissue VEGF detection, apoptotic index (AI) and cell proliferation index (PI). Twenty-eight dogs with malignant CMT, equally distributed into a control group (CG) treated with mastectomy and a treated group (TG) treated with MC (cyclophosphamide 15mg/m2 and piroxicam 0.3 mg/kg) both orally and daily for 28 days followed by mastectomy. Mammary tumors were classified and graded histologically. MVD, tissue VEGF, AI and PI of all malignancies were obtained by immunostaining. The analysis showed statistical difference between groups in MVD and AI (p <0.05), showing quantitative reduction in tumor microvasculature and increase in tumor cells apoptosis. Based on this result, we can affirm that MC has antiangiogenic and proapoptotic effects in mammary carcinomas of bitches and can be used as a new therapeutic option