RENATA DE FREITAS SAITO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells(2022) SAITO, Renata de Freitas; ANDRADE, Luciana Nogueira de Sousa; BUSTOS, Silvina Odete; CHAMMAS, RogerTo become resistant, cancer cells need to activate and maintain molecular defense mechanisms that depend on an energy trade-off between resistance and essential functions. Metabolic reprogramming has been shown to fuel cell growth and contribute to cancer drug resistance. Recently, changes in lipid metabolism have emerged as an important driver of resistance to anticancer agents. In this review, we highlight the role of choline metabolism with a focus on the phosphatidylcholine cycle in the regulation of resistance to therapy. We analyze the contribution of phosphatidylcholine and its metabolites to intracellular processes of cancer cells, both as the major cell membrane constituents and source of energy. We further extended our discussion about the role of phosphatidylcholine-derived lipid mediators in cellular communication between cancer and immune cells within the tumor microenvironment, as well as their pivotal role in the immune regulation of therapeutic failure. Changes in phosphatidylcholine metabolism are part of an adaptive program activated in response to stress conditions that contribute to cancer therapy resistance and open therapeutic opportunities for treating drug-resistant cancers.
bookPart Morte celular(2022) CONCEIçãO, Mércia Patrícia Ferreira; SAITO, Renata de Freitas; BUSTOS, Silvina Odete- Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure(2022) MORAIS, Jymenez de; VELOSA, Ana Paula P.; ANDRADE, Priscila C.; FREDIANI, Denise; CARRASCO, Solange; QUEIROZ, Zelita A. de Jesus; MARTIN, Patricia; SAITO, Renata F.; ELIAS, Vitoria; GOLDENSTEIN-SCHAINBERG, Claudia; CHAMMAS, Roger; SAMPAIO-BARROS, Percival D.; CAPELOZZI, Vera L.; TEODORO, Walcy R.Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of alpha 1(V) and alpha 2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naive patients with SSc-related fibrosis and four healthy controls. Our data showed increased alpha 1(V) and alpha 2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the alpha 1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 +/- 1.34 vs. 66.84 +/- 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the alpha 1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the alpha 2(V) chain was overexpressed in the small vessels (63.18 +/- 3.56 vs. 12.16 +/- 0.81; p < 0.0001) and capillaries (60.88 +/- 5.82 vs. 15.11 +/- 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased alpha 1(V) chain expression. These results highlight an intense decrease in the alpha 1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the alpha 1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.
- Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo(2022) KE, W.; CHANDLER, M.; CEDRONE, E.; SAITO, R. F.; RANGEL, M. C.; JUNQUEIRA, M. De Souza; WANG, J.; SHI, D.; TRUONG, N.; RICHARDSON, M.; ROLBAND, L. A.; DRéAU, D.; BEDOCS, P.; CHAMMAS, R.; DOKHOLYAN, N. V.; DOBROVOLSKAIA, M. A.; AFONIN, K. A.The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.