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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
Dias, Queila Cristina; Nunes, Iseu da Silva; Garcia, Patrick Vianna; Fávaro, Wagner José.
  • Dias, Queila Cristina; Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia. Campinas. BR
  • Nunes, Iseu da Silva; Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia. Campinas. BR
  • Garcia, Patrick Vianna; Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia. Campinas. BR
  • Fávaro, Wagner José; Universidade de Campinas. Departamento de Biologia Estrutural e Funcional. Laboratório de Urogenital Carcinogênese e Imunoterapia. Campinas. BR
Int. braz. j. urol ; 42(5): 942-954, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: lil-796874
ABSTRACT
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.
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Full text: Available Index: LILACS (Americas) Main subject: Urinary Bladder Neoplasms / Carcinoma / Doxorubicin / Cisplatin / Immunotherapy / Membrane Proteins / Antineoplastic Agents Type of study: Evaluation studies / Prognostic study / Risk factors Limits: Animals Language: English Journal: Int. braz. j. urol Journal subject: Urology Year: 2016 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de Campinas/BR

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Full text: Available Index: LILACS (Americas) Main subject: Urinary Bladder Neoplasms / Carcinoma / Doxorubicin / Cisplatin / Immunotherapy / Membrane Proteins / Antineoplastic Agents Type of study: Evaluation studies / Prognostic study / Risk factors Limits: Animals Language: English Journal: Int. braz. j. urol Journal subject: Urology Year: 2016 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade de Campinas/BR