EDWIN ROGER PARRA CUENTAS
Projetos de Pesquisa
Unidades Organizacionais
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- 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.
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.- 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.
article 10 Citação(ões) na Scopus Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis(2012) PARRA, E. R.; ARAUJO, C. A. L.; LOMBARDI, J. G.; AB'SABER, A. M.; CARVALHO, C. R. R.; KAIRALLA, R. A.; CAPELOZZI, V. L.Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.conferenceObject Elastic-Collagen Profile in Emphysematous Airspaces from Different Chronic Fibrosing Lung Disorders(2013) MARCAL, L. J.; ANTONANGELO, L.; PARRA, E. R.; VARGAS, F. S.; TEODORO, W. R.; NASCIMENTO, E. C. T.; CAPELOZZI, V. L.Background: Parenchyma elastic and collagen components of chronic fibrosing lung disorders has been exhaustively investigated, but little attention has been aimed at the emphysematous airspaces present in bullous disease, smoking-related interstitial disease and usual interstitial pneumonia. The aim of this study was to evaluate whether elastic deposition accompanies collagen deposition in the repairing process of emphysematous airspaces in chronic fibrosing lung injuries. Design: The elastic and collagen fibers distribution were evaluated in emphysematous airspaces of bullous type I and II disease, smoking-related interstitial fibrosis and of usual interstitial pneumonia (UIP). Lung specimens obtained by surgical lung biopsy or by bullectomy divided the patients into four groups: 1) type I bullous disease (SPT-I; n=7); 2) type II bullous disease (SPT-II; n=12); 3) smoking-related interstitial pneumonia (SRIP; n=5) and 4) usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF; n=5). Collagen and elastic fibers were identified respectively by Picrosirius-polarization and Weigert's resorcin-fucsin staining and quantified by image analysis.The results were expressed in percentual area. Descriptive ResultsStaining Disease Mean Std. Deviation Std. Error Minimum Maximum Picro-sirius STP-I 40.71 15.87 6.00 18.56 61.67 Picro-sirius STP-II 40.58 15.95 4.60 15.67 63.35 Picro-sirius SRIP 30.18 9.23 4.13 25.31 46.64 Picro-sirius UIP/IPF 40.99 13.99 6.26 24.76 60.07 Resorcina STP-I 19.97 10.63 4.02 3.71 33.76 Resorcina STP-II 18.42 6.17 1.78 10.19 26.70 Resorcina SRIP 11.86 9.72 4.35 1.87 25.62 Resorcina UIP/IPF 18.49 9.95 4.45 12.43 35.77 Results: The proportion of collagen fibers was two times higher when compared with the elastic component in the four groups. In addition, a lower percentage of elastic and collagen fibers were observed in SRIP when compared with UIP/IPF, SPT-I and SPT-II. Table 1. Conclusions: A smaller amount of elastic and collagen fibers accompanies the remodeling of the emphysematous airspaces in smoking-related interstitial pneumonia when compared to the other fibrosing diseases, suggesting a different remodeling spectrum in chronic fibrosing lung diseases.- Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation(2013) SANTOS, G. C. dos; PARRA, E. R.; STEGUN, F. W.; CIRQUEIRA, C. S.; CAPELOZZI, V. L.Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.
- Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance(2012) PARRA, E. R.; FALZONI, R.; CAPELOZZI, V. L.In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1) and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP) using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF). Telomerase+, myofibroblasts alpha-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci), severe ( mural) fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.
conferenceObject Down Regulation of Angiotensin II Receptor Type 1 (AGTR1) Contrast with Up Regulation of Type 2 (AGTR2) in Idiopathic Pulmonary Fibrosis(2013) PARRA, E. R.; RUPPERT, A. D. P.; RANGEL, M. P.; CAPELOZZI, V. L.Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. IPF represents a progressive and lethal disorder and is of major concern due to its unresolved pathogenesis and limited responsiveness to currently available therapies. IPF is characterized by alveolar injury, fibroblast proliferation and extracellular matrix (ECM) accumulation with severe loss of respiratory function. Angiotensin II (ANGII) signaling, mediated via angiotensin II receptor type 1 (AGTR1) or type 2 (AGTR2), controls tissue remodeling in fibrosis, but the relevance of AGTR2 and AGTR1 remains elusive. Design: Twenty-seven patients with biopsy-proven IPF disease with pulmonary evaluation by high-resolution computed tomography (HRCT) and pulmonary function tests were studied. Ten normal lung tissues (NLT) were included with controls. AGTR1 and AGTR2 in lung parenchyma were detected by immunohistochemistry and quantified by histomorphometry. Results: Quantitative analysis revealed a significant increase of AGTR2 expression in epithelial, endothelial and fibroblastic cells from patients with IPF when compared to NLT group. In contrast, AGTR1 expression levels are decreased in these cells from patients with IPF when compared with NTL. Pulmonary function tests no showed correlation with expression of AGTR1 or AGTR2. The median follow-up was 42.70 months. Ten patients were still alive, 17 died from causes related to IPF. Kaplan Meier curve, showed that the 5-year survival rate in patients with <0.05% of AGTR1 levels was 58.20% versus 24.66% in the group with ≥ 0.05% of AGTR1 levels (p < 0.05). Conclusions: In summary, we demonstrated increased expression of AGTR2 and decreased expression of AGTR1 in lung tissues from patients with IPF suggesting that they may be promising markers of prognosis in these patients.conferenceObject COLVa2 a Biomarker of Vasculopathy in Scleroderma?(2013) MORAIS, J.; MARTIN, P.; CAMARGO, I. C.; KATAYAMA, M. L.; CARRASCO, S.; GOLDEINSTEIN-SCHAINBERG, C.; PARRAS, E. R.; BARRENCE, F.; VELOSA, A. P.; CAPELOZZI, V. L.; TEODORA, W. R.