Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

Autor(es)

Queila Cristina Dias ^[1] ; Iseu da Silva Nunes ^[2] ; Patrick Vianna Garcia ^[3] ; Wagner José Fávaro

Afiliação do(s) autor(es)

^[1] Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia - Brasil

^[2] FarmaBrasilis R & D - Brasil

^[3] Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL BRAZ J UROL; v. 42, n. 5, p. 942-954, 2016-10-00.

Resumo

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy. (AU)

• Processo FAPESP: 14/12047-4 - Mecanismos e efeitos do imunomodulador P-MAPA no tratamento dos cânceres de próstata e não-músculo invasivo da bexiga urinária: interfaces entre metabolismo energético, balanço oxidativo, angiogênese e via de sinalização dos receptores toll-like
• Beneficiário: Wagner José Fávaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular