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
43 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 43
- Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis(2013) PARRA, E. R.; AGUIAR, A. C. Junior; SILVA, L. O.; SOUZA, H. S. P.; ESPINOZA, J. D.; CAPELOZZI, V. L.Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc- NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.
- Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort(2023) 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.TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early -stage resected EGFR-mutated NSCLC.
- Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation(2011) PRADO, C. M.; ROCHA, G. Z. da; LEICK-MALDONADO, E. A.; STARLING, C. M.; CAPELOZZI, V. L.; MARTINS, M. A.; TIBERIO, I. F. L. C.Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 +/- 0.9; 13.8 +/- 1.2), vessels (19.8 +/- 0.8; 13.4 +/- 0.5) and lung parenchyma (18.8 +/- 1.1; 25.31 +/- 1.1) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 +/- 1.1; 7.9 +/- 1.5), vessels (2.8 +/- 1.1; 4.4 +/- 1.1) and lung tissue (12.46 +/- 1.0; 15.05 +/- 1.5) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.
conferenceObject Combining Inhibitor of DNA - Binding Proteins and Angigenic Markers Expression Predict Long Term Survival of Patients with Non-Small Cell Lung Cancer(2013) ANTONANGELO, L.; TUMA, T. S.; VARGAS, F. S.; PARRA, E. R.; TERRA, R. M.; ACENCIO, M.; CAPELOZZI, V. L.Background: Inhibitor of DNA binding (Id) proteins is an emerging promise as biologic marker on oncogenic transformation, cancer progression and tumor angiogenesis, the last, by the regulation of vascular endothelial growth factor (VEGF) expression. Design: We evaluated Ids (1, 2 and 3), VEGF expression and microvessel density (CD34+) in tumor and stromal cells and their impact on survival of 85 patients with surgically excised lung squamous cell carcinoma and adenocarcinoma. Immunohistochemistry and morphometry were used for the quantitation and Kaplan-Meyer survival curves and Cox regression for the statistical analyses. Results: It was found that high Id-1 and VEGF expression and high microvessel density were associated with worse prognosis (Log Rank Test, p<0.001). The Cox model controlled for histological type, age, lymph node stage, Ids, VEGF and microvessel density demonstrated that age, lymph node stage, Id1 and Id3 expression and vascular density were significantly associated with overall survival. A point at the median for Id1, Id3 and vascular density divided patients into 2 groups of different prognosis. Those with higher expression of Id1, Id3 and vascular density had a higher risk of death than those with lower Id-1, Id-3 and microvessel density. Conclusions: Inhibitor of DNA binding (Id) proteins and vascular density are strongly related to prognosis, suggesting that treatment strategies aimed for preventing high Ids synthesis, or local responses to angiogenesis may have impact on NSLC survival.- Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria(2015) SOUZA, Mariana C.; SILVA, Johnatas D.; PADUA, Tatiana A.; TORRES, Natalia D.; ANTUNES, Mariana A.; XISTO, Debora G.; ABREU, Thiago P.; CAPELOZZI, Vera L.; MORALES, Marcelo M.; PINHEIRO, Ana A. Sa; CARUSO-NEVES, Celso; HENRIQUES, Maria G.; ROCCO, Patricia R. M.Introduction: Malaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria. Methods: Forty C57BL/6 mice were injected intraperitoneally with 5 x 10(6) Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1x10(5)) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed. Results: In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-a, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-gamma, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group. Conclusions: BM-MSC treatment increased survival and reduced parasitemia and malaria pigment accumulation in spleen, liver, kidney, and lung, but not in brain. The two main organs associated with worse prognosis in malaria, lung and kidney, sustained less histological damage after BM-MSC therapy, with a more pronounced improvement in lung function.
- Role of the extracellular matrix in variations of invasive pathways in lung cancers(2013) SA, V. K. de; CARVALHO, L.; GOMES, A.; ALARCAO, A.; SILVA, M. R.; COUCEIRO, P.; SOUSA, V.; SOARES, F. A.; CAPELOZZI, V. L.Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor beta (TGF-beta) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-beta profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P, 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P, 0.01). Hyal, HAS, E-cadherin, and TGF-beta modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-beta and E-cadherin, may have a greater impact in lung cancer prognosis.
- Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy(2016) ANTONANGELO, Leila; TUMA, Taila; FABRO, Alexandre; ACENCIO, Milena; TERRA, Ricardo; PARRA, Edwin; VARGAS, Francisco; TAKAGAKI, Teresa; CAPELOZZI, VeraInhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.
- Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia(2014) PARRA, E. R.; PINCELLI, M. S.; TEODORO, W. R.; VELOSA, A. P. P.; MARTINS, V.; RANGEL, M. P.; BARBAS-FILHO, J. V.; CAPELOZZI, V. L.Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.
- Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer A Perspective From Members of the Pulmonary Pathology Society(2018) JAIN, Deepali; ALLEN, Timothy Craig; AISNER, Dara L.; BEASLEY, Mary Beth; CAGLE, Philip T.; CAPELOZZI, Vera Luiza; HARIRI, Lida P.; LANTUEJOUL, Sylvie; MILLER, Ross; MINO-KENUDSON, Mari; MONACO, Sara E.; MOREIRA, Andre; RAPARIA, Kirtee; REKHTMAN, Natasha; RODEN, Anja Christiane; ROY-CHOWDHURI, Sinchita; SANTOS, Gilda da Cunha; THUNNISSEN, Erik; TRONCONE, Giancarlo; VIVERO, MarinaContext.-Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. Objective.-To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer. Data Sources.-An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review. Conclusions.-Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.
- Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome A Perspective From Members of the Pulmonary Pathology Society(2017) CAPELOZZI, Vera Luiza; ALLEN, Timothy Craig; BEASLEY, Mary Beth; CAGLE, Philip T.; GUINEE, Don; HARIRI, Lida P.; HUSAIN, Aliya N.; JAIN, Deepali; LANTUEJOUL, Sylvie; LARSEN, Brandon T.; MILLER, Ross; MINO-KENUDSON, Mari; MEHRAD, Mitra; RAPARIA, Kirtee; RODEN, Anja; SCHNEIDER, Frank; SHOLL, Lynette M.; SMITH, Maxwell LawrenceAcute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches.