VERA LUIZA CAPELOZZI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome(2022) FERNANDES, Marcos V. S.; ROCHA, Nazareth N.; FELIX, Nathane S.; RODRIGUES, Gisele C.; SILVA, Luisa H. A.; COELHO, Mariana S.; FONSECA, Ana Carolina F.; TEIXEIRA, Ana Carolina G. M.; CAPELOZZI, Vera L.; PELOSI, Paolo; SILVA, Pedro L.; MARINI, John J.; ROCCO, Patricia R. M.Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24 h, Wistar rats (n = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: 1) 3 cmH(2)O for 2 h (control); 2) 3 cmH(2)O for 1 h followed by an abrupt increase to 9 cmH(2)O for 1 h (no adaptation time); 3) 3 cmH(2)O for 30 min followed by a gradual increase to 9 cmH(2)O over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmH(2)O to 9 cmH(2)O over 1 h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared with the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared with other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (P = 0.002) and shorter adaptation time (P = 0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure. NEW & NOTEWORTHY In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.
- Sterilized human skin graft with a dose of 25 kGy provides a privileged immune and collagen microenvironment in the adhesion of Nude mice wounds(2022) MIRANDA, Jurandir Tomaz de; BRINGEL, Fabiana de Andrade; VELOSA, Ana Paula Pereira; PROTOCEVICH, Veronica; FERNEZLIAN, Sandra de Morais; SILVA, Pedro Leme; CAPELOZZI, Vera Luiza; MATHOR, Monica Beatriz; TEODORO, Walcy RosoliaThis study aimed to report the effects of different doses of ionizing radiation on inflammatory and repair stage of human skin graft adherence in Nude mice wounds. Animals were divided into transplanted with irradiated human skin grafts (IHSG) at 25 and 50 kGy (IHSG 25 kGy; IHSG 50 kGy) and non-IHSG and euthanized on the 3rd, 7th and 21st days after the surgery, by gross and microscopic changes, immunostaining for human type I collagen (Col I) and mouse Col I and Col III and inflammatory cells. We found an effectiveness of human split-thickness graft adherence in mice transplanted with IHSG 25 kGy, as well decrease in dermo-epidermal necrosis and neutrophils, lower loss of skin thickness, epithelization and neo-vascularization. Day 21 post-transplantation with IHSG 25 kGy was observed a well-preserved human skin in the border of the graft, a prominent granulation tissue in an organization by proliferated fibroblasts, Col III deposition and increased B-cells and macrophages. A complete adherence of human skin graft occurred with IHSG 25 kGy. We suggest that the ionizing radiation at 25 kGy mediates inflammation and the repair stage of human skin graft adherence in murine model, thus emerging as a potential tool in healing cutaneous wounds.
- Effects of different fluid management on lung and kidney during pressure-controlled and pressure-support ventilation in experimental acute lung injury(2022) CARVALHO, Eduardo Butturini de; FONSECA, Ana Carolina Fernandes; MAGALHAES, Raquel Ferreira; PINTO, Eliete Ferreira; SAMARY, Cynthia dos Santos; ANTUNES, Mariana Alves; BALDAVIRA, Camila Machado; SILVEIRA, Lizandre Keren Ramos da; TEODORO, Walcy Rosolia; ABREU, Marcelo Gama de; CAPELOZZI, Vera Luiza; FELIX, Nathane Santanna; PELOSI, Paolo; ROCCO, Patricia Rieken Macedo; SILVA, Pedro LemeOptimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF). A conservative fluid strategy (CF) was compared with LF during PSV and PCV on lungs and kidneys in an established model of ALI. Twenty-eight male Wistar rats received endotoxin intratracheally. After 24 h, they were treated with CF (minimum volume of Ringer's lactate to maintain normovolemia and mean arterial pressure >= 70 mmHg) or LF (similar to 4 times higher than CF) combined with PSV or PCV (VT = 6 ml/kg, PEEP = 3 cmH(2)O) for 1 h. Nonventilated animals (n = 4) were used for molecular biology analyses. CF-PSV compared with LF-PSV: (1) decreased the diffuse alveolar damage score (10 [7.8-12] vs. 25 [23-31.5], p = 0.006), mainly due to edema in axial and alveolar parenchyma; (2) increased birefringence for occludin and claudin-4 in lung tissue and expression of zonula-occludens-1 and metalloproteinase-9 in lung. LF compared with CF reduced neutrophil gelatinase-associated lipocalin and interleukin-6 expression in the kidneys in PSV and PCV. In conclusion, CF compared with LF combined with PSV yielded less lung epithelial cell damage in the current model of ALI. However, LF compared with CF resulted in less kidney injury markers, regardless of the ventilatory strategy.
- Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor(2022) MACHADO-RUGOLO, J.; BALDAVIRA, C. M.; PRIETO, T. G.; OLIVIERI, E. H. R.; FABRO, A. T.; RAINHO, C. A.; CASTELLI, E. C.; RIBOLLA, P. E. M.; AB'SABER, A. M.; TAKAGAKI, T.; NAGAI, M. A.; CAPELOZZI, V. L.The common epidermal growth factor receptor (EGFR) mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-tyrosine kinase inhibitors (EGFR-TKI). However, the clinical outcome and response to treatment for many other rarer mutations are still unclear. In this study, we report the results of Brazilian patients in stage IB-IIIA non-small cell lung cancer (NSCLC) following complete resection with minimal residual disease and EGFR mutations treated with adjuvant chemotherapy and/or EGFR-TKIs. The frequency of EGFR mutations was investigated in 70 cases of early stage NSCLC. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, as well as in exons 3, 7, 14, 16, 22, 27, and 28, and/or the presence of different mutations in a single tumor (complex mutations) are considered rare. EGFR mutations were detected in 23 tumors (32.9%). Fourteen cases carried rare mutations and were treated with platinum-based chemotherapy and two cases were treated with erlotinib. The clinical outcome is described case by case with references to the literature. Notably, we found two rare EGFR mutations and one of them with an unknown response to chemotherapy and/or EGFR-TKIs. We have provided complementary information concerning the clinical outcome and treatment of patients with early stage NSCLC for several rare EGFR mutations not previously or only rarely reported. Description of cases harboring rare mutations can support the decision-making process in this subset of patients.
- Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum(2022) CHINOCA, J.; ANDRADE, D. S.; MENDES, A.; MARCHI, P. De; PRIETO, T. G.; BALDAVIRA, C. M.; FARHAT, C.; MARTINS, J. R. M.; NADER, H. B.; CARRARO, D. M.; CAPELOZZI, V. L.; SA, V deWe evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (10) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT + IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT + IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.
conferenceObject Genomic profile of primary non-small cell lung cancer and matched mediastinal lymph nodes by next-generation sequencing: a pilot study(2022) ANTONANGELO, L.; FARIA, C. S.; TERRA, R. M.; NASCIMENTO, E. C. T. do; MELLO, E. S. de; MANGONE, F. R. R.; NAGAI, M. A.; AGATI, M. E. M.; CAPELOZZI, V. L.- COVID-19 bimodal clinical and pathological phenotypes(2022) BATAH, Sabrina S.; BENATTI, Maira N.; SIYUAN, Li; TELINI, Wagner M.; BARBOZA, Jamile O.; MENEZES, Marcelo B.; NADAI, Tales R.; SA, Keyla S. G.; VASWANI, Chirag M.; GUPTA, Sahil; ZAMBONI, Dario S.; WADA, Danilo T.; CALADO, Rodrigo T.; OLIVEIRA, Rene D. R.; LOUZADA-JUNIOR, Paulo; AUXILIADORA-MARTINS, Maria; VERAS, Flavio P.; CUNHA, Larissa D.; CUNHA, Thiago M.; LUPPINO-ASSAD, Rodrigo; BALANCIN, Marcelo L.; MORAIS, Sirlei S.; MARTINS, Ronaldo B.; ARRUDA, Eurico; CHAHUD, Fernando; SANTOS, Marcel Koenigkam; CETLIN, Andrea A.; CUNHA, Fernando Q.; SANTOS, Claudia dos; CAPELOZZI, Vera L.; FUKUOKA, Junya; ACHCAR, Rosane Duarte; FABRO, Alexandre T.
- Effects of time-controlled adaptive ventilation on cardiorespiratory parameters and inflammatory response in experimental emphysema(2022) OLIVEIRA, Milena Vasconcellos de; MAGALHAES, Raquel Ferreira de; ROCHA, Nazareth de Novaes; FERNANDES, Marcus Vinicius; ANTUNES, Mariana Alves; MORALES, Marcelo Marcos; CAPELOZZI, Vera Luiza; SATALIN, Joshua; ANDREWS, Penny; HABASHI, Nader M.; NIEMAN, Gary; ROCCO, Patricia Rieken Macedo; SILVA, Pedro LemeThe time-controlled adaptive ventilation (TCAV) method attenuates lung damage in acute respiratory distress syndrome. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury (VILI) and cardiac function in emphysema. We hypothesized that the use of the TCAV method to achieve an expiratory flow termination/expiratory peak flow (E-FT/E-PF) of 25% could reduce VILI and improve right ventricular function in elastase-induced lung emphysema in rats. Five weeks after the last intratracheal instillation of elastase, animals were anesthetized and mechanically ventilated for 1 h using TCAV adjusted to either E-FT/E-PF 25% or E-FT/E-PF 75%, the latter often applied in acute respiratory distress syndrome (ARDS). Pressure-controlled ventilation (PCV) groups with positive end-expiratory pressure levels similar to positive end-release pressure in TCAV with E-FT/E-PF 25% and E-FT/E-PF 75% were also analyzed. Echocardiography and lung ultrasonography were monitored. Lung morphometry, alveolar heterogeneity, and biological markers related to inflammation [interleukin 6 (IL-6), CINC-1], alveolar pulmonary stretch (amphiregulin), lung matrix damage [metalloproteinase 9 (MMP-9)] were assessed. E-FT/E-PF 25% reduced respiratory system peak pressure, mean linear intercept, B lines at lung ultrasonography, and increased pulmonary acceleration time/ pulmonary ejection time ratio compared with E-FT/E-PF 75%. The volume fraction of mononuclear cells, neutrophils, and expression of IL-6, CINC-1, amphiregulin, and MMP-9 were lower with E-FT/E-PF 25% than with E-FT/E-PF 75%. In conclusion, TCAV with E-FT/E-PF 25%, compared with E-FT/E-PF 75%, led to less lung inflammation, hyperinflation, and pulmonary arterial hypertension, which may be a promising strategy for patients with emphysema. NEW & NOTEWORTHY The TCAV method reduces lung damage in ARDS. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury and cardiac function in experimental emphysema. The TCAV method at E-FT/E-PF ratio of 25%, compared with E-FT/E-PF of 75% (frequently used in ARDS), reduced lung inflammation, alveolar heterogeneity and hyperinflation, and pulmonary arterial hypertension in elastase-induced emphysema. TCAV may be a promising and personalized ventilation strategy for patients with emphysema.
- Editorial: Multiplexed image analysis for translational research project applications(2022) CAPELOZZI, Vera Luiza; PARRA, Edwin Roger
- Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions(2022) BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; MACHADO-RUGOLO, Juliana; MIRANDA, Jurandir Tomaz de; OLIVEIRA, Lizandre Keren Ramos de; VELOSA, Ana Paula Pereira; TEODORO, Walcy Rosolia; AB'SABER, Alexandre; TAKAGAKI, Teresa; CAPELOZZI, Vera LuizaLung cancer still represents a global health problem, being the main type of tumor responsible for cancer deaths. In this context, the tumor microenvironment, and the extracellular matrix (ECM) pose as extremely relevant. Thus, this study aimed to explore the prognostic value of epithelial-to-mesenchymal transition (EMT), Wnt signaling, and ECM proteins expression in patients with non-small-cell lung carcinoma (NSCLC) with clinical stages I-IIIA. For that, we used 120 tissue sections from patients and evaluated the immunohistochemical, immunofluorescence, and transmission electron microscopy (TEM) to each of these markers. We also used in silico analysis to validate our data. We found a strong expression of E-cadherin and beta-catenin, which reflects the differential ECM invasion process. Therefore, we also noticed a strong expression of chondroitin sulfate (CS) and collagens III and V. This suggests that, after EMT, the basal membrane (BM) enhanced the motility of invasive cells. EMT proteins were directly associated with WNT5A, and collagens III and V, which suggests that the WNT pathway drives them. On the other hand, heparan sulfate (HS) was associated with WNT3A and SPARC, while WNT1 was associated with CS. Interestingly, the association between WNT1 and Col IV suggested negative feedback of WNT1 along the BM. In our cohort, WNT3A, WNT5A, heparan sulfate and SPARC played an important role in the Cox regression model, influencing the overall survival (OS) of patients, be it directly or indirectly, with the SPARC expression stratifying the OS into two groups: 97 months for high expression; and 65 for low expression. In conclusion, the present study identified a set of proteins that may play a significant role in predicting the prognosis of NSCLC patients with clinical stages I-IIIA.