LEILA ANTONANGELO

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Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina - Líder

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Autor e Coautores FMUSP-HC Normalizados: FRANCISCO VARGAS SUSO ×

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Agora exibindo 1 - 10 de 29
  • 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.
  • 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.
  • article 6 Citação(ões) na Scopus
    Monoclonal antibodies anti-TGF beta 1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate
    (2012) MARCHI, Evaldo; VARGAS, Francisco S.; TAKEMURA, Renan L.; ACENCIO, Milena M.; ANTONANGELO, Leila; TEIXEIRA, Lisete R.; LIGHT, Richard W.
    Background. The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor beta (TGF beta 1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. Method. Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGF beta 1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). Results. Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGF beta 1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. Conclusions. We conclude that both TGF beta 1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.
  • article 10 Citação(ões) na Scopus
    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, Vera
    Inhibitors 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.
  • article 41 Citação(ões) na Scopus
    Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions
    (2011) CARTAXO, Ana Maria; VARGAS, Francisco S.; SALGE, Joao Marcos; MARCONDES, Bianca F.; GENOFRE, Eduardo H.; ANTONANGELO, Leila; MARCHI, Evaldo; TEIXEIRA, Lisete R.
    Background: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. Methods: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV, were analyzed before and 48 h after the removal of large pleural effusions. Results: The mean fluid removed was 1,564 +/- 695 mL. After the procedure, values of FVC, FEV and 6-min walk distance increased (P<.001), whereas dyspnea decreased (P<.001). Statistical correlations (P<.001) between 6-min walk distance and FVC (r=0.725) and between 6-min walk distance and FEV, (r=0.661) were observed. Correlations also were observed between the deltas (prethoracentesis X postthoracentesis) of the 6-min walk test and the percentage of FVC (r=0.450) and of FEV, (r=0.472) divided by the volume of fluid removed (P<.05). Conclusion: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities. CHEST 2011; 139(6):1424-1429
  • article 12 Citação(ões) na Scopus
    Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?
    (2012) ANTONANGELO, Leila; VARGAS, Francisco Suso; GENOFRE, Eduardo Flenrique; OLIVEIRA, Caroline Mans Neves de; TEIXEIRA, Lisete Ribeiro; SALES, Roberta Karla Barbosa de
    Objective: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. Methods: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of Sao Paulo School of Medicine Hospital das Clinicas Heart Institute, in the city of Sao Paulo, Brazil. Results: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. Conclusions: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.
  • conferenceObject
    Multiplex Ligation Probe-dependent Amplification (MLPA) as an ancillary method for the diagnosis of malignant pleural effusion
    (2012) PARRA, E.; ROSOLEN, D.; KULIKOWSKI, L.; DUTRA, R.; CAPELOZZI, V. L.; VARGAS, F.; ACENCIO, M.; ANTONANGELO, L.
    Objective: A definitive diagnosis provided by the finding of malignant cells in pleural fluid (PF) can be established in around 50 % of patients with pleural malignancy. However, underdiagnosis risk in cytological suspicious cases is high, which makes the cytological diagnosis quite limited. This is an important clinical problem, especially if we consider that some patients, in bad clinical conditions, can not be submitted to a guided thoracoscopic biopsy. Method: Using multiplex ligation probe-dependent amplification (P315-MRC-Holland) we have studied sequence variations of EGFR gene and amplifications/deletions of chromosomal regions frequently associated to tumors (ATG4B, PAHs, PROS, NSD1, and CDGIF genes). Results: Forty-three malignant PF samples from patients with different cancers were evaluated, even in those cases with scarce pellet cells. Four benign pleural effusions were used as control. Gene sequence changes were observed in 13 (30.2 %) cases, while others copy number abnormalities were found in 19 (44.2 %). Conclusion: The findings suggest that MLPA could be considered an alternative tool to detect molecular genetic changes in malignant pleural effusions, since this technique is relatively low expensive and not time consuming. Our next challenge is to find the best combination of probes capable to recognize malignant cells of any origin in fresh samples of PF.
  • article 3 Citação(ões) na Scopus
    Pleural tuberculosis: is radiological evidence of pulmonary-associated disease related to the exacerbation of the inflammatory response?
    (2012) ANTONANGELO, Leila; VARGAS, Francisco S.; PUKA, Juliana; SEISCENTO, Marcia; ACENCIO, Milena M. P.; TEIXEIRA, Lisete R.; TERRA, Ricardo M.; SALES, Roberta K. B.
    OBJECTIVE: Pleural tuberculosis is the most frequently occurring form of extra pulmonary disease in adults. In up to 40% of cases, the lung parenchyma is concomitantly involved, which can have an epidemiological impact. This study aims to evaluate the pleural and systemic inflammatory response of patients with pleural or pleuropulmonary tuberculosis. METHODS: A prospective study of 39 patients with confirmed pleural tuberculosis. After thoracentesis, a high resolution chest tomography was performed to evaluate the pulmonary involvement. Of the 39 patients, 20 exhibited only pleural effusion, and high resolution chest tomography revealed active associated-pulmonary disease in 19 patients. The total protein, lactic dehydrogenase, adenosine deaminase, vascular endothelial growth factor, interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta(1) levels were quantified in the patient serum and pleural fluid. RESULTS: All of the effusions were exudates with high levels of adenosine deaminase. The levels of vascular endothelial growth factor and transforming growth factor-beta(1) were increased in the blood and pleural fluid of all of the patients with pleural tuberculosis, with no differences between the two forms of tuberculosis. The tumor necrosis factor-alpha levels were significantly higher in the pleural fluid of the patients with the pleuropulmonary form of tuberculosis. The interleukin-8 levels were high in the pleural fluid of all of the patients, without any differences between the forms of tuberculosis. CONCLUSION: Tumor necrosis factor-alpha was the single cytokine that significantly increased in the pleural fluid of the patients with pulmonary involvement. However, an overlap in the results does not permit us to suggest that cytokine is a biological marker of concomitant parenchymal involvement. Although high resolution chest tomography can be useful in identifying these patients, the investigation of fast acid bacilli and cultures for M. tuberculosis in the sputum is recommended for all patients who are diagnosed with pleural tuberculosis.
  • article 16 Citação(ões) na Scopus
    Pulmonary involvement in pleural tuberculosis: How often does it mean disease activity?
    (2011) SEISCENTO, Marcia; VARGAS, Francisco S.; BOMBARDA, Sidney; SALES, Roberta K. B.; TERRA, Ricardo M.; UEZUMI, Kiyomi; TEIXEIRA, Lisete R.; ANTONANGELO, Leila
    Objective: To evaluate in chest X-rays and high-resolution computed tomographies of patients with pleural tuberculosis, the incidence of parenchymal and mediastinal lung lesions suggestive of active disease. Methods: Prospective study (2008-2009) evaluating the radiographic and tomographic abnormalities of 88 HIV-negative patients with pleural tuberculosis (unilateral effusion). The images were reviewed by 3 independent specialists, and the observed changes were classified according to previously established criteria: presence or absence of signs suggestive of disease activity, and nonspecific findings. Results: Abnormal changes were observed in chest X-rays of 22 (25%) patients and in the computed tomography of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by radiography in 9 (10%) patients and by tomography in 38 (43%). Only 4 (4.5%) patients had tomography images suggestive of residual disease. Conclusion: The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis. This finding is mainly observed in high-resolution computed tomography and has important epidemiological implications, since patients with pleural tuberculosis are significant sources of infection and disease dissemination.
  • article 5 Citação(ões) na Scopus
    Preanalytical conditions can interfere with M-tuberculosis detection by PCR in respiratory samples
    (2018) CARNEVALE, Gabriela Gaspar; VARGAS, Francisco Suso; CAIAFFA-FILHO, Helio Hehl; ACENCIO, Milena Marques Pagliarelli; MARCAL, Lia Junqueira; SALES, Roberta Karla Barbosa; TEIXEIRA, Lisete Ribeiro; ANTONANGELO, Leila
    OBJECTIVES: Tuberculosis is one of the most prevalent infections in humans. Although culture is the reference for diagnosis, its sensitivity is compromised, especially in paucibacillary samples. Because polymerase chain reaction (PCR) amplifies mycobacterial DNA, it is more sensitive than culture for the diagnosis of Mycobacterium tuberculosis (Mtb). However, its performance can be affected by intrinsic sample inhibitors and by the extraction/detection techniques used. METHODS: We evaluated the influence of preanalytical conditions on Mtb detection in samples of sputum (SPU), bronchoalveolar lavage (BAL), and pleural fluid (PF) using combinations of extraction/detection methods. Respiratory samples were prepared to contain different concentrations of red blood cells and nucleated cells to which increasing amounts of Mtb colonies were inoculated and submitted to PCR. RESULTS: Up to 10(2) CFU/ml of Mtb were detected in the SPU in all methods, except for the Roche extraction/detection method, regardless of the preanalytical sample condition. In BAL samples, medium and high concentrations of cells and high concentrations of red blood cells contributed to a lower Mtb detection, regardless of the extraction method used. In PF, red blood cells were the variable that most interfered with Mtb detection, with better recovery (10(2) CFU/ml) observed with the Qiagen/Nanogen combination. CONCLUSION: The choice of Mtb extraction and detection method is of fundamental importance for PCR analytical sensitivity, especially when paucibacillary samples and/or samples containing potential PCR inhibitors are analyzed.