THAUANY MARTINS TAVONI

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  • article 1 Citação(ões) na Scopus
  • article 0 Citação(ões) na Scopus
    Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)
    (2023) ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; GUIDO, Maria Carolina; CARVALHO, Priscila Oliveira; TAVONI, Thauany Martins; LOPES, Natalia Menezes; SILVA, Bruna Miranda de Oliveira; JENSEN, Leonardo; STOLF, Noedir Antonio Groppo; MARANHA, Raul Cavalcante
    Atherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
  • conferenceObject
    LIPID CORE NANOPARTICLES AS VEHICLE FOR DOCETAXEL REDUCES ATHEROSCLEROTIC LESION, INFLAMMATION, CELL DEATH AND PROLIFERATION IN AN ATHEROSCLEROSIS RABBIT MODEL
    (2018) MENEGHINI, Bianca C.; TAVARES, Elaine R.; GUIDO, Maria C.; TAVONI, Tauany M.; KALLIL FILHO, Roberto; MARANHAO, Raul C.
  • article 0 Citação(ões) na Scopus
    Lipid transfer to HDL, CETP and HDL composition in coronary artery disease patients with or without type 2 diabetes mellitus
    (2020) TAVONI, Thauany M.; SPRANDEL, Marilia C. O.; LAVERDY, Oscar G.; STRUNZ, Celia M. C.; RAMIRES, Jose A. F.; KALIL-FILHO, Roberto; HUEB, Whady A.; MARANHAO, Raul C.
  • conferenceObject
    Effect of exercise training on HDL subclasses and cholesterol transfers to HDL in elderly individuals
    (2022) BRAGA, P. G. Senger; TAVONI, T. M.; BARONI, R. V.; ALDIN, M. N.; ALVES, M. J. N. N.; ROCHA, G. A.; BACHI, A. L. L.; NEGRAO, C. E.; VAISBERG, M. W.; FREITAS, F. R.; FIGUEIREDO NETO, A. M.; DAMASCENO, N. R. T.; MARANHAO, R. C.
  • article 2 Citação(ões) na Scopus
    Treatment With Methotrexate Associated With Lipid Core Nanoparticles Prevents Aortic Dilation in a Murine Model of Marfan Syndrome
    (2022) GUIDO, Maria Carolina; LOPES, Natalia de Menezes; ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; JENSEN, Leonardo; CARVALHO, Priscila de Oliveira; TAVONI, Thauany Martins; DIAS, Ricardo Ribeiro; PEREIRA, Lygia da Veiga; LAURINDO, Francisco Rafael Martins; MARANHAO, Raul Cavalcante
    In Marfan syndrome (MFS), dilation, dissection, and rupture of the aorta occur. Inflammation can be involved in the pathogenicity of aortic defects and can thus be a therapeutic target for MFS. Previously, we showed that the formulation of methotrexate (MTX) associated with lipid nanoparticles (LDE) has potent anti-inflammatory effects without toxicity. To investigate whether LDEMTX treatment can prevent the development of aortic lesions in the MFS murine model. Mg Delta loxPneo MFS (n = 40) and wild-type (WT, n = 60) mice were allocated to 6 groups weekly injected with IP solutions of: (1) only LDE; (2) commercial MTX; (3) LDEMTX (dose = 1mg/kg) between 3rd and 6th months of life. After 12 weeks of treatments, animals were examined by echocardiography and euthanatized for morphometric and molecular studies. MFS mice treated with LDEMTX showed narrower lumens in the aortic arch, as well as in the ascending and descending aorta. LDEMTX reduced fibrosis and the number of dissections in MFS but not the number of elastic fiber disruptions. In MFS mice, LDEMTX treatment lowered protein expression of pro-inflammatory factors macrophages (CD68), T-lymphocytes (CD3), tumor necrosis factor-alpha (TNF-alpha), apoptotic factor cleaved-caspase 3, and type 1 collagen and lowered the protein expression of the transforming growth factor-beta (TGF-beta), extracellular signal-regulated kinases 1/2 (ERK1/2), and SMAD3. Protein expression of CD68 and CD3 had a positive correlation with an area of aortic lumen (r(2) = 0.36; p < 0.001), suggesting the importance of inflammation in the causative mechanisms of aortic dilation. Enhanced adenosine availability by LDEMTX was suggested by higher aortic expression of an anti-adenosine A2a receptor (A2a) and lower adenosine deaminase expression. Commercial MTX had negligible effects. LDEMTX prevented the development of MFS-associated aortic defects and can thus be a candidate for testing in clinical studies.
  • conferenceObject
    Effect of caloric restriction and statins on the process of cholesterol transfer to HDL in women with premature CAD
    (2020) LEAL, D. P.; TAVONI, T. M.; KAWABARA, K. L.; FARIA, N. F. O.; NASCIMENTO, J. R. O.; CESAR, L. A. M.; STRUNZ, C. M. C.; MANSUR, A. D. P.
  • article 0 Citação(ões) na Scopus
    Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study
    (2024) MARINHO, Lucas Lage; RACHED, Fabiana Hanna; MORIKAWA, Aleksandra Tiemi; TAVONI, Thauany Martins; CARDOSO, Ana Paula Toniello; TORRES, Roberto Vitor Almeida; JR, Antonildes Nascimento Assuncao; JR, Carlos Vicente Serrano; NOMURA, Cesar Higa; MARANHAO, Raul Cavalcante
    Introduction Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.Methods We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment.Results Forty patients aged 65.6 +/- 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed.Conclusion In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers.Clinical Trial Registration https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
  • article 3 Citação(ões) na Scopus
    Novel Approach for Bone Marrow Transplantation Conditioning in Acute Myelogenous Leukemia not Responding to the Induction Therapy Using Etoposide Carried in Lipid Core Nanoparticles: A Pilot Clinical Study
    (2020) ROHR, Sandra S.; MARANHAO, Raul C.; TAVONI, Thauany M.; MORIKAWA, Aleksandra T.; ARECO, Kelsy; DEUS, Debora F.; OLIVEIRA, Jose S. R.
    Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 +/- 5 days and 16 +/- 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD. This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials. (C) 2020 American Society for Transplantation and Cellular Therapy.
  • article 22 Citação(ões) na Scopus
    Effects of Short-Term Hypothyroidism on the Lipid Transfer to High-Density Lipoprotein and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer
    (2019) SIGAL, Gilbert A.; TAVONI, Thauany M.; SILVA, Bruna M. O.; KALIL FILHO, Roberto; BRANDAO, Lenine G.; MARANHAO, Raul C.
    Background: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. Methods: Eighteen women (age 44 +/- 11 years; body mass index 27.9 +/- 5.2 kg/m(2)) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. Results: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 +/- 35 vs. 167 +/- 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 +/- 8 vs. 46 +/- 10 mg/dL; p = 0.0025), non-HDL-C (149 +/- 38 vs. 201 +/- 46 mg/dL; p < 0.0001), unesterified cholesterol (53 +/- 10 vs. 70 +/- 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 +/- 0.19 vs. 1.44 +/- 0.22 g/L; p < 0.04), and apo B (0.97 +/- 0.25 vs. 1.31 +/- 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 +/- 0.03 vs. 0.11 +/- 0.02; p < 0.0001), triglycerides (0.11 +/- 0.02 vs. 0.09 +/- 0.02; p < 0.0001), phospholipids (0.44 +/- 0.09 vs. 0.40 +/- 0.07; p = 0.0205), and esterified cholesterol (0.14 +/- 0.03 vs. 0.13 +/- 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. Conclusions: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.