DANIELLE RIBEIRO SANTOS
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conferenceObject IMPAIRED HDL-MEDIATED CELL CHOLESTEROL REMOVAL IN ADVANCED BREAST CANCER(2023) SAWADA, M. I.; SANTANA, M.; REIS, M.; ASSIS, S. De; PEREIRA, L.; SANTOS, D.; NUNES, V.; CORREA-GIANNELLA, M. L.; GEBRIM, L. H.; PASSARELLI, M.- The Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in Macrophages(2024) ASSIS, Sayonara Ivana Santos de; AMENDOLA, Leonardo Szalo; OKAMOTO, Maristela Mitiko; FERREIRA, Guilherme da Silva; IBORRA, Rodrigo Tallada; SANTOS, Danielle Ribeiro; SANTANA, Monique de Fatima Mello; SANTANA, Kelly Gomes; CORREA-GIANNELLA, Maria Lucia; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; MACHADO, Ubiratan Fabres; PASSARELLI, MarisaAdvanced glycation end products (AGEs) prime macrophages for lipopolysaccharide (LPS)-induced inflammation. We investigated the persistence of cellular AGE-sensitization to LPS, considering the nuclear content of p50 and p65 nuclear factor kappa B (NFKB) subunits and the expression of inflammatory genes. Macrophages treated with control (C) or AGE-albumin were rested for varying intervals in medium alone before being incubated with LPS. Comparisons were made using one-way ANOVA or Student t-test (n = 6). AGE-albumin primed macrophages for increased responsiveness to LPS, resulting in elevated levels of TNF, IL-6, and IL-1beta (1.5%, 9.4%, and 5.6%, respectively), compared to C-albumin. TNF, IL-6, and IL-1 beta secretion persisted for up to 24 h even after the removal of AGE-albumin (area under the curve greater by 1.6, 16, and 5.2 times, respectively). The expressions of Il6 and RelA were higher 8 h after albumin removal, and Il6 and Abca1 were higher 24 h after albumin removal. The nuclear content of p50 remained similar, but p65 showed a sustained increase (2.9 times) for up to 24 h in AGE-albumin-treated cells. The prolonged activation of the p65 subunit of NFKB contributes to the persistent effect of AGEs on macrophage inflammatory priming, which could be targeted for therapies to prevent complications based on the AGE-RAGE-NFKB axis.
- Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors(2023) SAWADA, Maria Isabela Bloise Alves Caldas; SANTANA, Monique de Fatima Mello; REIS, Mozania; ASSIS, Sayonara Ivana Santos de; PEREIRA, Lucas Alves; SANTOS, Danielle Ribeiro; NUNES, Valeria Sutti; CORREA-GIANNELLA, Maria Lucia Cardillo; GEBRIM, Luiz Henrique; PASSARELLI, MarisaThe association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naive BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and C-14-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.