RESUMO
Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Cofilina 1/análise , Neoplasias Pulmonares/química , Escarro/química , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Escarro/química , Carcinoma de Células Escamosas/química , Biomarcadores Tumorais/análise , Cofilina 1/análise , Neoplasias Pulmonares/química , Prognóstico , Ensaio de Imunoadsorção Enzimática , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Curva ROC , Sensibilidade e Especificidade , Proliferação de Células , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
BACKGROUND: The presence of tumour cells in pleural fluid or tissue defines an effusion as malignant. Cytology analysis of the pleural fluid has about 60% diagnostic sensitivity. Several tests have been proposed to improve diagnosis-among them, the concentrations of tumour markers in pleural fluid. We evaluated whether the concentrations of tumour markers in pleural fluid could improve the diagnosis of malignant pleural effusion (mpe) when cytology is doubtful. METHODS: Lymphocytic pleural fluids secondary to tuberculosis or malignancy from 156 outpatients were submitted for cytology and tumour marker quantification [carcinoembryonic antigen (cea), cancer antigen 15-3 (ca15-3), carbohydrate antigen 19-9 (ca19-9), cancer antigen 72-4 (ca72-4), cancer antigen 125 (ca125), and cyfra 21-1). Oneway analysis of variance, the Student t-test or Mann-Whitney test, and receiver operating characteristic curves were used in the statistical analysis. RESULTS: Concentrations of the tumour markers cea, ca15-3, ca125, and cyfra 21-1 were higher in mpes than they were in the benign effusions (p < 0.001), regardless of cytology results. The markers ca19-9 and ca72-4 did not discriminate malignant from benign effusions. When comparing the concentrations of tumour markers in mpes having positive, suspicious, or negative cytology with concentrations in benign effusions, we observed higher levels of cea, ca15-3, cyfra 21-1, and ca125 in malignant effusions with positive cytology (p = 0.003, p = 0.001, p = 0.002, and p = 0.001 respectively). In pleural fluid, only ca125 was higher in mpes with suspicious or negative cytology (p = 0.001) than in benign effusions. CONCLUSIONS: Given high specificity and a sensitivity of about 60%, the concentrations of tumour markers in pleural effusions could be evaluated in cases of inconclusive cytology in patients with a high pre-test chance of malignancy or a history of cancer.
RESUMO
OBJECTIVE: Despite the methodological variability in preparation techniques for pleural fluid cytology, it is fundamental that the cells should be preserved, permitting adequate morphological classification. We evaluated numerical and morphological changes in pleural fluid specimens processed after storage at room temperature or under refrigeration. METHODS: Aliquots of pleural fluid from 30 patients, collected in ethylenediaminetetraacetic acid-coated tubes and maintained at room temperature (21 °C) or refrigeration (4 °C) were evaluated after 2 and 6 hours and 1, 2, 3, 4, 7 and 14 days. Evaluation of cytomorphology and global and percentage counts of leucocytes, macrophages and mesothelial cells were included. RESULTS: The samples had quantitative cellular variations from day 3 or 4 onwards, depending on the storage conditions. Morphological alterations occurred earlier in samples maintained at room temperature (day 2) than in those under refrigeration (day 4). CONCLUSIONS: This study confirms that storage time and temperature are potential pre-analytical causes of error in pleural fluid cytology.
Assuntos
Líquidos Corporais/citologia , Pleura/patologia , Preservação Biológica , Temperatura , Núcleo Celular/metabolismo , Forma Celular , Humanos , Coloração e Rotulagem , Fatores de TempoRESUMO
SETTING: A tertiary care research centre in São Paolo, Brazil. OBJECTIVE: To quantify interleukin (IL) 8, tumour necrosis factor alpha (TNF-alpha), vascular endothelial growth factor (VEGF) and transforming growth factor beta(1) (TGF-beta(1)) in pleural fluid from tuberculous patients, correlating its values with the histopathological patterns in pleural biopsies. DESIGN: Cytokines were quantified in patients with transudates secondary to congestive heart failure (n = 8) and exudates secondary to tuberculosis (TB; n = 39). In parietal pleural biopsies from TB patients, the histological patterns of the inflammatory response were quantified by morphometric analysis (stereological point-counting method). RESULTS: IL-8, TNF-alpha, VEGF and TGF-beta(1) levels were higher in TB than in transudates. A positive correlation existed between components of the fibrinoid exudative phase with pleural fluid IL-8 (R = 0.52, P = 0.004) and VEGF (R = 0.42, P = 0.0021) levels. A negative correlation existed between pleural fluid IL-8 (R = -0.37, P = 0.048) and VEGF (R = -0.44, P = 0.0015) levels with tissue components of fibroproliferation. CONCLUSION: The high pleural levels of TNF-alpha, IL-8, VEGF and TGF-beta(1) suggest the involvement of these cytokines in the TB immunological response. The positive correlation between pleural fluid IL-8 and VEGF with the components of the acute exudative phase and the negative correlation between these cytokines with the fibroproliferative components suggest a temporary inflammatory response in the pleural space.
Assuntos
Citocinas/metabolismo , Exsudatos e Transudatos/metabolismo , Derrame Pleural/metabolismo , Tuberculose Pleural/imunologia , Adulto , Idoso , Brasil , Exsudatos e Transudatos/imunologia , Feminino , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/patologia , Humanos , Inflamação/etiologia , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural/imunologia , Estudos Prospectivos , Tuberculose Pleural/patologia , Adulto JovemRESUMO
BACKGROUND: Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently. OBJECTIVE: To evaluate the pleural inflammatory response after surgery. PATIENTS AND METHODS: Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test. RESULTS: All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1beta, IL-6, and IL-8 were undetectable at all time points. CONCLUSIONS: There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.
Assuntos
Citocinas/análise , Hepatopatias/cirurgia , Transplante de Pulmão/fisiologia , Adulto , Citocinas/sangue , Exsudatos e Transudatos/metabolismo , Feminino , Humanos , Inflamação/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-8/análise , Interleucina-8/sangue , Hepatopatias/classificação , Masculino , Pessoa de Meia-Idade , Derrame Pleural/metabolismo , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto JovemRESUMO
Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 mum) and 50 with MT (median 21.15 mum); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.
Assuntos
Pleura/efeitos dos fármacos , Pleurodese/métodos , Talco/farmacologia , Animais , Proteína C-Reativa/biossíntese , Inflamação , Interleucina-8/sangue , L-Lactato Desidrogenase/sangue , Tamanho da Partícula , Pleura/patologia , Pleurodese/efeitos adversos , Coelhos , Talco/administração & dosagem , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.
Assuntos
Células Epiteliais/imunologia , Derrame Pleural/imunologia , Pleurodese , Talco/farmacologia , Animais , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Inflamação , Interleucina-8/metabolismo , Masculino , Modelos Animais , Coelhos , Talco/imunologia , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Pleurodesis is a useful therapeutic tool when local treatment of a recurrent malignant pleural effusion or pneumothorax is needed. We have previously demonstrated that the intrapleural injection of 0.5% silver nitrate (SN) produces a significant pleurodesis, while 0.25% SN has no sclerosing effect in a rabbit model. The objective of this study was to determine the minimum concentration of SN needed to induce pleurodesis in our experimental model. One hundred twenty male New Zealand white rabbits received 0.3, 0.4, or 0.5% SN (40 animals per group) in a total volume of 2 mL instilled intrapleurally. These animals were sacrificed 3, 7, 14 or 28 days after the intrapleural injection (n = 10 animals per group), and the pleural spaces were then assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. By 28 days, all concentrations of SN had produced a pleurodesis. There was evidence of a gross pleurodesis 7 days post-injection in animals that received 0.5% SN (score of 2.8 +/- 0.2 on a scale of 0-4). After 14 days, significant pleural adhesions were evident in the groups that received 0.4 or 0.5% SN. We conclude that SN concentrations as low as 0.3% can effectively produce a pleurodesis within 28 days of intrapleural injection. However, the precocious pleurodesis development observed 7 days after the intrapleural injection of 0.5% SN suggests that this concentration may be optimal when a fast result is necessary.