Safety, tumor reduction, and clinical impact of Zika Virus injection in dogs with advanced-stage brain tumors

Malignant brain tumors are among the most aggressive cancers with poor prognosis and no effective treatment. Recently, we reported the oncolytic potential of Zika virus infecting and destroying the human central nervous system (CNS) tumors in vitro and in immunodeficient mice model. However, translating this approach to humans requires pre-clinical trials in another immunocompetent animal model. Here, we analyzed the safety of Brazilian Zika virus (ZIKVBR) intrathecal injections in three dogs bearing spontaneous CNS tumors aiming an anti-tumoral therapy. We further assessed some aspects of the innate immune and inflammatory response that triggers the anti-tumoral response observed during the ZIKVBR administration in vivo and in vitro. For the first time, we showed that there were no negative clinical side effects following ZIKVBR CNS injections in dogs, confirming the safety of the procedure. Furthermore, the intrathecal ZIKVBR injections reduced tumor size in immunocompetent dogs bearing spontaneous intracranial tumors, improved their neurological clinical symptoms significantly, and extended their survival by inducing the destruction specifically of tumor cells, sparing normal neurons, and activating an immune response. These results open new perspectives for upcoming virotherapy using ZIKV to destroy and induce an anti-tumoral immune response in CNS tumors for which there are currently no effective treatments.

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Malignant brain tumors are among the most aggressive cancers with poor prognosis and no effective treatment. Recently, we reported the oncolytic potential of Zika virus infecting and destroying the human central nervous system (CNS) tumors in vitro and in immunodeficient mice model. However, translating this approach to humans requires pre-clinical trials in another immunocompetent animal model. Here, we analyzed the safety of Brazilian Zika virus (ZIKVBR) intrathecal injections in three dogs bearing spontaneous CNS tumors aiming an anti-tumoral therapy. We further assessed some aspects of the innate immune and inflammatory response that triggers the anti-tumoral response observed during the ZIKVBR administration in vivo and in vitro. For the first time, we showed that there were no negative clinical side effects following ZIKVBR CNS injections in dogs, confirming the safety of the procedure. Furthermore, the intrathecal ZIKVBR injections reduced tumor size in immunocompetent dogs bearing spontaneous intracranial tumors, improved their neurological clinical symptoms significantly, and extended their survival by inducing the destruction specifically of tumor cells, sparing normal neurons, and activating an immune response. These results open new perspectives for upcoming virotherapy using ZIKV to destroy and induce an anti-tumoral immune response in CNS tumors for which there are currently no effective treatments.

Estudos dos polimorfismos do sistema renina-angiotensina em afrodescendentes hipertensos tratados / Study of renin-angiotensin aldosterone system polymorphisms in treated hypertensive African descendents

A hipertensão arterial (HA) é um dos principais fatores de risco para a morbimortalidade cardiovascular. Os polimorfismos do sistema renina-angiotensina-aldosterona (SRAA) estão envolvidos na fisiopatologia da HA. Estudos mostram que afrodescendentes tendem a ser hipertensos com taxa mais alta de complicações. Este estudo teve por objetivo avaliar a prevalência dos polimorfismos do SRAA - da enzima conversora de angiotensina (ECA I/D), do antagonista do receptor da angiotensina II (AT1R A/C1166) e da aldosterona sintase (CYP11B2-344T/C) - em pacientes hipertensos afrodescendentes em tratamento. Vinte e três pacientes hipertensos afrodescendentes foram avaliados clinicamente (pressão arterial - PA e índice de massa corporal - IMC), laboratorialmente (perfil lipídico, creatinina e glicemia) e foram analisados os polimorfismos da ECA, AT1R e CYP por PCR. Os dados obtidos foram comparados com os de 21 hipertensos não afrodescendentes. Não houve diferença significativa na PA, IMC e perfil metabólico entre os grupos. Entretanto, o estudo dos polimorfismos do SRAA revelou diferenças significativas na distribuição dos genótipos (grupo I afro e II não afro): a frequência para os genes da ECA foi 47,8% DD, 43,5% DI e 8,7% I vs. 14,3% DD, 47,6% DI e 38,1% II (p=0,0017); para genes do AT1R: 100% AA, 0% AC e 0% CC no I vs. 33,3,% AA, 22,2% AC e 44,4% CC no II (p <0,0001); e, para o gene CYP11B2: 56% TT, 21,7% TC e 4,3% CC no I vs. 33% TT, 77,7% TC e 5,5% CC no II (p=0,034) entre os afrodescendentes e controles, respectivamente. Os resultados sugerem diferenças genéticas entre os pacientes hipertensos afrodescendentes no grupo estudado.