LEANDRO DE LIMA COUTINHO
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
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- Interferon-gamma is quintessential for NOS2 and COX2 expression in ER- breast tumors that lead to poor outcome(2023) CHENG, Robert Y. S.; RIDNOUR, Lisa A.; WINK, Adelaide L.; GONZALEZ, Ana L.; FEMINO, Elise L.; RITTSCHER, Helene; SOMASUNDARAM, Veena; HEINZ, William F.; COUTINHO, Leandro; RANGEL, M. Cristina; EDMONDSON, Elijah F.; BUTCHER, Donna; KINDERS, Robert J.; LI, Xiaoxian; WONG, Stephen T. C.; MCVICAR, Daniel W.; ANDERSON, Stephen K.; PORE, Milind; HEWITT, Stephen M.; BILLIAR, Timothy R.; GLYNN, Sharon A.; CHANG, Jenny C.; LOCKETT, Stephen J.; AMBS, Stefan; WINK, David A.A strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER breast cancer has been established. However, the mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single-cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFN gamma combined with IL1 beta or TNF alpha. Given that IFN gamma is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFN gamma presents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8(+) T cells were spatially analyzed in aggressive ER-, TNBC, and HER2 + breast tumors. High expression and clustering of NOS2-expressing tumor cells occurred at the tumor/stroma interface in the presence of stroma-restricted CD8(+) T cells. High expression and clustering of COX2-expressing tumor cells extended into immune desert regions in the tumor core where CD8(+) T cell penetration was limited or absent. Moreover, high NOS2-expressing tumor cells were proximal to areas with increased satellitosis, suggestive of cell clusters with a higher metastatic potential. Further in vitro experiments revealed that IFN gamma + IL1 beta/TNF alpha increased the elongation and migration of treated tumor cells. This spatial analysis of the tumor microenvironment provides important insight into distinct neighborhoods where stroma-restricted CD8(+) T cells exist proximal to NOS2-expressing tumor niches that could have increased metastatic potential.
bookPart Células-tronco tumorais(2022) SOUZA, Isabela Cristina de; COUTINHO, Leandro; RANGEL, Maria Cristina Rodrigues; FERREIRA, Matthew Thomas- In vitro anticancer properties of anthocyanins: A systematic review(2022) NASCIMENTO, Erika de Arruda; COUTINHO, Leandro de Lima; SILVA, Cleber Jose da; LIMA, Vera Lucia Arroxelas Galva de; AGUIAR, Jaciana dos SantosAnthocyanins have been associated with beneficial effects on human health. Cancer has been one of the main public health issues due to its aggressiveness and high mortality rate. This systematic review aimed to address recent research (from January 2000 to September 2021) on the anticancer activity of anthocyanins assessed by in vitro assays. The selected studies revealed that anthocyanins have anticancer potential by inhibiting cancer cell viability and proliferation, controlling cell cycle, and promoting apoptosis.,
conferenceObject Effects of sulforaphane association to conventional therapy for treating triple-negative breast cancer(2023) COUTINHO, L. L.; CHENG, R.; RIDNOUR, L.; JUNQUEIRA, M. S.; CHAMMAS, R.; WINK, D.; TORTELLI, T. C.; RANGEL, M.- Sulforaphane: An emergent anti-cancer stem cell agent(2023) COUTINHO, Leandro de Lima; TORTELLI JUNIOR, Tharcisio Citrangulo; RANGEL, Maria CristinaCancer is a major public health concern worldwide responsible for high morbidity and mortality rates. Alternative therapies have been extensively investigated, and plant-derived compounds have caught the attention of the scientific community due to their chemopreventive and anticancer effects. Sulforaphane (SFN) is one of these naturally occurring agents, and studies have shown that it is able to target a specific cancer cell population displaying stem-like properties, known as cancer stem cells (CSCs). These cells can self-renewal and differentiate to form highly heterogeneous tumor masses. Notably, most of the conventional chemotherapeutic agents cannot target CSCs once they usually exist in a quiescent state and overall, the available cytotoxic drugs focus on highly dividing cells. This is, at least in part, one of the reasons why some oncologic patients relapse after standard therapy. In this review we bring together studies supporting not only the chemopreventive and anticancer properties of SFN, but especially the emerging anti-CSCs effects of this natural product and its potential to be used with conventional antineoplastic drugs in the clinical setting.