RESUMO

Introdution: To determine the role of Pleural Mesothelial Cells (PMC) and/or Neoplasic Cells (NC) in the initiation and regulation of acute inflammatory response after exposure to talc for evaluating inflammatory mediators and cellular alterations. MATERIALS AND METHODS: PMC cultures, human lung (A549) and breast (MCF7) adenocarcinoma cells were divided in 5 groups: 100% PMC, 100% NC, 25% PMC + 75% NC, 50% of each type and 75% PMC + 25% NC. All groups were exposed to talc and measured IL-6, IL-1ß, IL-10, TNF-α, TNFRI, pH, LDH, apoptosis and necrosis. STATISTICAL ANALYSIS: One-way Anova. RESULTS: High IL-6, IL-1ß and TNFRI levels were found in PMC and NC exposed to talc. IL-6 was higher at the points of more confluence of PMC. The highest levels of IL-1ß and TNFRI were found in mixed cultures. In pure cultures TNFRI was higher in A549 followed by PMC and MCF7. LDH was higher in A549 than PMC. The lowest pH was found in 100% NC. All cell line exposed to talc reduced viability and increased necrosis. Apoptotic cells exposed to talc were higher in pure cultures of NC than in PMC. Mixed cultures of PMC and A549 showed lower levels of apoptosis in cultures with more NC. CONCLUSIONS: PMC after talc exposure participates in the inflammatory process contributing to production of molecular mediators, necessary for effective pleurodesis. Talc acted in NC causing higher rates of apoptosis, contributing in a modest way to tumoral decrease. Different types of tumor cells may respond differently to exposure to talc.

RESUMO

INTRODUCTION: Serum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement. METHODS: We conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels. RESULTS: One hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404-1588) versus 162 (117-232) pg/mL, respectively (p < 0.001). Patients with tuberous sclerosis complex-LAM, TSC-LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641-2732) vs. 772 (370-1383), p = 0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r = - 0.26, p = 0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800 pg/mL (35% vs. 13%, p = 0.02). CONCLUSIONS: In LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.

Assuntos

Linfangioleiomiomatose/sangue , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Brasil , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/fisiopatologia , Sistema Linfático/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Regulação para Cima

RESUMO

RATIONALE: Malignant pleural effusion has few options of treatment and drugs administrated by different routes can lead to a less permissive microenvironment for the development of malignant pleural disease. OBJECTIVES: To analyze therapies administered intrapleurally in malignant pleural disease and to study EGFR and KRAS mutations in adenocarcinoma. METHODS: Mice received LLC cells and were treated intrapleurally with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline. Animal survival, weight and mobility, volume, biochemistry and immunology of fluid, gene expression, KRAS and EGFR mutation were evaluated. RESULTS: All animals developed malignant effusion and presented progressive weight loss without difference between groups; however, groups treated with anti-EGFR were more active. No difference in mortality was observed. Temporal increase of volume and inflammatory markers was observed mainly in the untreated group. Gene expression in tumors was overexpressed in VEGF, EGFR and KRAS compared with normal tissue. Mutation in exon 2 of the KRAS gene was observed. CONCLUSIONS: Intrapleural Anti-VEGF and/or anti-EGFR reduced volume and inflammatory mediators in pleural fluid. Anti-EGFR and anti-VEGF+anti-EGFR decreased morbidity although without impact on survival. LLC tumors presented KRAS mutation, this could have influenced the action of these therapies.