LUCIANA NOGUEIRA DE SOUSA ANDRADE
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
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma(2012) FERREIRA, D. S.; ANNONI, R.; SILVA, L. F. F.; BUTTIGNOL, M.; SANTOS, A. B. G.; MEDEIROS, M. C. R.; ANDRADE, L. N. S.; YICK, C. Y.; STERK, P. J.; SAMPAIO, J. L. M.; DOLHNIKOFF, M.; WENZEL, S. E.; MAUAD, T.Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics both large and small airways has not been investigated. Objective To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non-smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real-time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non-smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.
- Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors(2023) SANTOS, Nathalia L.; BUSTOS, Silvina O.; REIS, Patricia P.; CHAMMAS, Roger; ANDRADE, Luciana N. S.Management of advanced melanoma remains challenging, with most BRAF (B-Raf proto-oncogene, serine/threonine kinase)-mutated metastatic patients relapsing within a few months upon MAPK inhibitors treatment. Modulation of tumor-derived extracellular vesicle (EVs) cargo with enrichment of antitumoral molecules is a promising strategy to impair tumor progression and increase treatment response. Herein, we report that restored expression of miR-195-5p, down-regulated in melanoma favoring drug resistance, increases the release of EVs enriched in the tumor suppressor miRNAs, miR-195-5p, miR-152-3p, and miR-202-3p. Incorporating these EVs by bystander tumor cells resulted in decreased proliferation and viability, accompanied by a reduction in CCND1 and YAP1 mRNA levels. Upon treatment with MAPK inhibitors, miR-195 EVs significantly decreased BCL2-L1 protein levels and increased cell death ratio and treatment efficacy. Additionally, EVs exogenously loaded with miR-195-5p by electroporation reduced tumor volume in vivo and impaired engraftment and growth of xenografts implanted with melanoma cells exposed to MAPK inhibitors. Our study shows that miR-195-5p antitumoral activity can be spread to bystander cells through EVs, improving melanoma response to targeted therapy and revealing a promising EV-based strategy to increase clinical response in patients harboring BRAF mutations.
conferenceObject 7-Ketocholesterol loaded-phosphatidylserine liposome induces cell death, autophagy, and growth inhibition of melanoma and breast adenocarcinoma.(2018) FAVERO, Giovani Marino; TORTELLI JR., Tharcisio Citrangulo; FERNANDES, Daniel; PRESTES, Ana Paula; KMETIUK, Louise N. B.; OTAKE, Andreia Hanada; ANDRADE, Luciana N. S.; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; MARQUES, Fabio L. N.; CHAMMAS, RogerconferenceObject MicroRNA-195 acts as a tumor suppressor miRNA in human melanoma cells by targeting Prohibitin 1.(2018) CIRILO, Priscila D. R.; CORREA, Bruna R. S.; QIAO, Mei; ANDRADE, Luciana N. S.; CHAMMAS, Roger; PENALVA, Luiz O. F.article 12 Citação(ões) na Scopus Oncogenic effects of PAFR ligands produced in tumours upon chemotherapy and radiotherapy(2017) CHAMMAS, Roger; ANDRADE, Luciana Nogueira de Sousa; JANCAR, SoniabookPart Introdução ao microambiente tumoral(2015) MARTINS NETO, Adalberto Alves; CARDIM, Sílvia Guedes Braga; MOTHé, Cíntia Maria Alves; ANDRADE, Luciana Nogueira de SousabookPart Células-tronco tumorais(2015) CARDOSO, Ana Carolina Ferreira; ANDRADE, Luciana Nogueira de SousabookPart Introdução à comunicação celular(2022) SALLAS, Mayara Luciana; NUNES, Rafaella Almeida Lima; ANDRADE, Luciana Nogueira de Sousa- NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients(2019) JANDREY, Elisa H. F.; MOURA, Ricardo P.; ANDRADE, Luciana N. S.; MACHADO, Camila L.; CAMPESATO, Luiz Felipe; LEITE, Katia Ramos M.; INOUE, Lilian T.; ASPRINO, Paula F.; SILVA, Ana Paula M. da; BARROS, Alfredo Carlos S. D. de; CARVALHO, Andre; LIMA, Vladmir C. de; CARRARO, Dirce M.; BRENTANI, Helena P.; CUNHA, Isabela W. da; SOARES, Fernando A.; PARMIGIANI, Raphael B.; CHAMMAS, Roger; CAMARGO, Anamaria A.; COSTA, Erico T.The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20-30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response. Here, we present N-Myc downstream-regulated gene 4 (NDRG4) epigenetic silencing as a mechanistic biomarker of metastasis in ductal invasive breast tumors. While aberrant NDRG4 DNA hypermethylation is significantly associated with the development of metastatic disease, downregulation of NDRG4 transcription and protein expression is functionally associated with enhanced lymph node adhesion and cell mobility. Here, we show that epigenetic silencing of NDRG4 modulates integrin signaling by assembling beta 1-integrins into large punctate clusters at the leading edge of tumor cells to promote an ""adhesive switch,"" decreasing cell adhesion to fibronectin and increasing cell adhesion and migration towards vitronectin, an important component of human lymph nodes. Taken together, our functional and clinical observations suggest that NDRG4 is a potential mechanistic biomarker in breast cancer that is functionally associated with metastatic disease.
- Simultaneous silencing of lysophosphatidylcholine acyltransferases 1-4 by nucleic acid nanoparticles (NANPs) improves radiation response of melanoma cells(2021) SAITO, Renata F.; RANGEL, Maria Cristina; HALMAN, Justin R.; CHANDLER, Morgan; ANDRADE, Luciana Nogueira de Sousa; ODETE-BUSTOS, Silvina; FURUYA, Tatiane Katsue; CARRASCO, Alexis German Murillo; CHAVES-FILHO, Adriano B.; YOSHINAGA, Marcos Y.; MIYAMOTO, Sayuri; AFONIN, Kirill A.; CHAMMAS, RogerRadiation induces the generation of platelet-activating factor receptor (PAF-R) ligands, including PAF and oxidized phospholipids. Alternatively, PAF is also synthesized by the biosynthetic enzymes lysophosphatidylcholine acyltransferases (LPCATs) which are expressed by tumor cells including melanoma. The activation of PAF-R by PAF and oxidized lipids triggers a survival response protecting tumor cells from radiation-induced cell death, suggesting the involvement of the PAF/PAF-R axis in radioresistance. Here, we investigated the role of LPCATs in the melanoma cell radiotherapy response. LPCAT is a family of four enzymes, LPCAT1-4, and modular nucleic acid nanoparticles (NANPs) allowed for the simultaneous silencing of all four LPCATs. We found that the in vitro simultaneous silencing of all four LPCAT transcripts by NANPs enhanced the therapeutic effects of radiation in melanoma cells by increasing cell death, reducing long-term cell survival, and activating apoptosis. Thus, we propose that NANPs are an effective strategy for improving radiotherapy efficacy in melanomas.