title: 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.
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.
authors.affiliation: Laboratório de Urogenital Carcinogênese e Imunoterapia do Departamento de Biologia Estrutural e Funcional da Universidade de Campinas (UNICAMP), Campinas, SP, Brasil.
authors.forename: Queila Cristina
authors.initials: QC
authors.lastname: Dias
authors.affiliation: FarmaBrasilis R & D, Campinas, SP, Brasil.
authors.forename: Iseu da Silva
authors.initials: ID
authors.lastname: Nunes
authors.affiliation: Laboratório de Urogenital Carcinogênese e Imunoterapia do Departamento de Biologia Estrutural e Funcional da Universidade de Campinas (UNICAMP), Campinas, SP, Brasil.
authors.forename: Patrick Vianna
authors.initials: PV
authors.lastname: Garcia
authors.affiliation: Laboratório de Urogenital Carcinogênese e Imunoterapia do Departamento de Biologia Estrutural e Funcional da Universidade de Campinas (UNICAMP), Campinas, SP, Brasil.|FarmaBrasilis R & D, Campinas, SP, Brasil.
authors.forename: Wagner Jose
authors.initials: WJ
authors.lastname: Favaro
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018450:Disease Progression; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008565:Membrane Proteins / Q000627:therapeutic use*; D023421:Models, Animal; D016328:NF-kappa B / Q000032:analysis; D051059:PTEN Phosphohydrolase / Q000032:analysis; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D002945:Cisplatin; D004317:Doxorubicin; D008565:Membrane Proteins; D016328:NF-kappa B; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; C487216:Pten protein, rat
keywords: Cisplatin; Immunotherapy; Urinary Bladder Neoplasms