MARIA ANGELO PEPE CARNEIRO
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Artigo IPEN-doc 30791 In vivo HOXB7 gene silencing and cotreatment with tamoxifen for Luminal A breast cancer therapy2024 - VALLE, ANA B.C. dos S.; SILVA, FABIO F.A. da; CARNEIRO, MARIA A.P.; ESPUCHE, BRUNO; TAVARES, GUILHERME D.; BERNARDES, EMERSON S.; MOYA, SERGIO E.; PITTELLA, FREDERICOBackground: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo. Methods: HNP were prepared by the self-assembly of a methoxy-poly (ethylene glycol)-block-poly (L-glutamic acid) copolymer (PEG-pGlu) and the coprecipitation of CaPO4 to incorporate siRNA. The in vitro cell viability and migration were evaluated prior to in vivo experiments. Further, animals bearing early-stage and advanced Luminal A breast cancer were treated with HNP-siHOXB7, HNP-siHOXB7 + TMX, and TMX. Antitumoral activity and gene expression were evaluated following histopathological, hematological, and biochemical analysis. Results: The HNP were efficient in delivering the siRNA in vitro and in vivo, whilst HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity. Conclusions: Therefore, our findings suggest that HOXB7 can be an interesting molecular target for Luminal A breast cancer, especially associated with hormone therapy, aiming for adverse effect mitigation and higher therapeutic efficacy.Artigo IPEN-doc 29138 Selection of aptamers against the Jagged-1 protein2022 - SILVA, F.F.A. da; SANTOS, S.N. dos; PEREIRA, J.P.M.; GUSHIKEN JUNIOR, D.S.; CARNEIRO, M.A.P.; NASCIMENTO, I.C.C.; ULRICH, A.H.; BERNARDES, E.S.The breast cancer is one of the biggest public health problems in the world, being the main female type of cancer that affects the population. The Jagged-1 protein plays an important role in the biology and development of cancer, influencing angiogenesis, growth of neoplastic cells, tumor stem cells, epithelial mesenchymal transition, metastatic processes and resistance to therapies in various types of cancer. In this project, our aim was to select an aptamer for JAG1 ligand using an aptamer library that could be used as a radiopharmaceutical for PET/SPECT/CT diagnosis of tumors that express JAG1. Our work showed that MDA-MB-231-JAG1 cells overexpress more mRNA and JAG1 protein than control cells (MDA-MB-231-Control). We also selected aptamers with high affinity for MDA-MB-231-JAG1 cells that could be a useful tool for the development of new radiopharmaceuticals for the diagnosis and treatment of tumors that overexpress JAG1.Artigo IPEN-doc 28274 Selection of aptamers against Jagged-1 protein2021 - SILVA, F.F.A. da; SANTOS, S.N. dos; GUSHIKEN JUNIOR, D.S.; CARNEIRO, M.A.P.; BERNARDES, E.S.