RESUMO
Progranulin is a growth and survival factor implicated in tumorigenesis and drug resistance. Several studies showed that progranulin is expressed in breast cancer tissue and inversely correlates with survival. B lymphocyte chemoattractant, also known as B cell-attracting chemokine 1 (BCA-1), is a member of the CXC subtype of the chemokine superfamily. BCA-1 is critical for secondary lymphoid tissue development and navigation of lymphocytes within the microcompartments of the tissue. There are no data on the content of progranulin and BCA-1 in bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients. To study this issue, we measured BALF content of progranulin and BCA-1 in 46 NSCLC patients before chemotherapy and 15 healthy subjects. Both markers were elevated in cancer patients compared to healthy subjects (progranulin: 61.4 (1.6-384.0) vs. 6.5 (0.6-12.9) ng/ml, p = 0.001 and BCA-1: 30.8 (24.3-70.8) vs. 15.4 (13.3-19.5) pg/ml, p = 0.0001). The cut-off BALF level concerning NSCLC vs. controls, investigated using the receiver-operating characteristic (ROC) curve, yielded 6.5 ng/ml for progranulin and 15.4 pg/ml for BCA-1. We failed to find any association between the BALF content of progranulin or BCA-1 and the stage of tumor or prospectively assessed treatment response. However, BALF progranulin associated with time to tumor progression (r = 0.61; p = 0.04). In addition, a higher BALF content of BCA-1 in NSCLC patients associated with shorter overall survival. We conclude that progranulin and BCA-1 in BALF of NSCLC patients before chemotherapy may be prognostic factors of cancer progression.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Quimiocina CXCL13/análise , Neoplasias Pulmonares/metabolismo , Progranulinas/análise , Linfócitos B , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , Quimiocina CXCL13/metabolismo , Quimiocinas , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Prognóstico , Taxa de SobrevidaRESUMO
Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor-kappa B ligand (sRANKL). OPG promotes endothelial cell survival and neoangiogenesis. Dysregulation of the OPG/RANKL system has been detected in several tumors. In the present study, we evaluated the clinical usefulness of OPG and sRANKL assessment in bronchoalveolar lavage fluid (BALF) of patients with advanced non-small cell lung cancer (NSCLC). We measured the concentration of OPG and sRANKL in BALF of 44 NSCLC patients and 15 healthy volunteers taken as control subjects. The OPG content was higher in the NSCLC group than that in controls [0.48 (0.12-1.45) vs. 0.23 (0.14-0.75) pmol/l; p = 0.0001]. There were no significant differences in sRANKL content between the NSCLC and control groups [1.22 (0.74-23.00) vs. 1.12 (0.79-4.39) pmol/l; p = 0.67]. However, we found that the greater the level of sRANKL in NSCLC patients, the shorter the overall survival. We found a correlation between the content of sRANKL and the percentage of lymphocytes in BALF of NSCLC patients (r = 0.52; p = 0.041). We conclude that NSCLC patients have a higher content of OPG in BALF than healthy people. A high level of sRANKL in BALF of NSCLC patients may predict worse survival.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Osteoprotegerina/análise , Ligante RANK/análise , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Osteoprotegerin (OPG), a soluble tumor necrosis factor receptor family molecule, protects endothelial cells from apoptosis in vitro and promotes neovascularization in vivo. Angiogenesis may be crucial for the course and outcome of sarcoidosis. In this study, we evaluated the clinical usefulness of OPG and its ligand, a soluble receptor activator of nuclear factor-kappaB (sRANKL), in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis (BBS, Besniera-Boeck-Schaumann disease). We studied 22 BBS patients and 15 healthy volunteers as a control group. The levels of OPG, sRANKL, and interleukin-18 (IL-18) were measured by the Elisa method. The BALF levels of sRANKL and IL-18 were higher in the BBS patients compared with controls [sRANKL: 2.12 (0.82-10.23) vs. 1.12 (0.79-4.39) pmol/l, p = 0.03; IL-18: 34.29 (12.50-133.70) vs. 13.05 (12.43-25.88) pg/ml, p = 0.001]. There were no significant differences between the concentration of OPG in the BBS patients and healthy controls [0.22 (0.14-0.81) vs. 0.23 (0.14-0.75) pmol/l]. In the BBS patients we found correlations between sRANKL and IL-18 in BALF (r = 0.742, p = 0.0001) and between OPG and lung diffusing capacity for carbon monoxide (DLCO) (r = -0.528, p = 0.029). Receiver-operating characteristic (ROC) curve was applied to find the cut-off for the BALF level of sRANKL (BBS vs. healthy: 1.32 pmol/l). We conclude that OPG and sRANKL may have usefulness in clinical evaluation of BBS patients.
Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Sarcoidose Pulmonar/metabolismo , Transdução de Sinais/fisiologia , Lavagem Broncoalveolar/métodos , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-18/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Hepatocyte growth factor (HGF) is involved in tumorigenesis, interleukin-20 (IL-20) is an inhibitor of angiogenesis, and interleukin-22 (IL-22) stimulates tumor growth. The aim of this study was to determine the level of HGF, IL-20, and IL-22 in both serum and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients before onset of chemotherapy, the nature of the interrelationships between these markers, and their prognostic significance regarding post-chemotherapy survival time. We studied 46 NSCLC patients and 15 healthy subjects as a control group. We found significantly higher serum levels of HGF and IL-22 in the NSCLC patients than those in controls [pg/ml: HGF - 1911 (693-6510) vs. 1333 (838-3667), p = 0.0004; IL-22 - 10.66 (1.44-70.34) vs. 4.69 (0.35-12.29), p = 0.0007]. In contrast, concentrations of HGF and IL-22 in BALF were lower in NSCLC patients than those in controls [pg/ml: HGF - 72 (6-561) vs. 488 (14-2003), p = 0.0002; IL-22 - 2.28 (0.70-6.52) vs. 3.72 (2.76-5.64), p = 0.002]. In the NSCLC patients, there was a negative correlation between the serum level of IL-20 and time to tumor progression (r = -0.405, p = 0.04) and between the serum level of HGF and survival time (r = -0.41, p = 0.005). In addition, a higher serum level of HGF and a higher BALF level of IL-22 in patients were linked with a shorter overall survival. We conclude that HGF, IL-20, and IL-22 in the serum and BALF of NSCLC patients before chemotherapy may be a prognostic of cancer progression.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Fator de Crescimento de Hepatócito/análise , Interleucinas/análise , Neoplasias Pulmonares/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucinas/sangue , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Gencitabina , Interleucina 22RESUMO
The mechanisms of sarcoidosis (Besniera-Boeck-Schaumann disease, BBS) remain incompletely understood, although recent observations suggested an important contribution of interleukin-33 (IL-33). So far, there are no data about bronchoalveolar lavage fluid (BALF) concentration of IL-33 in patients with BBS. In the present study we attempted to relate the concentration of IL-33 to IL-18, a well-known marker of BBS activity, in BALF of BBS patients. We examined 24 BBS patients (stage II). The age-matched control group consisted of 24 healthy subjects. The levels of IL-33 and IL-18 in BALF were higher in BBS patients than in the control group [IL-33: 4.8 (0.1-12.5) vs. 3.4 (0.6-56.9) pg/ml, p=0.024; IL-18: 33.2 (5.7-122.0) vs. 10.8 (1.9-45.8) pg/ml, p=0.002]. In the BBS group, the correlations between IL-33 and IL-18 (r=0.606, p=0.002), and between IL-33 and diffusion lung capacity for carbon monoxide (DLCO) (r=-0.500, p=0.035) were found. The receiver-operating characteristic curves were applied to find the cut-off serum levels of IL-33 and IL-18 in BALF (BBS vs. healthy: IL-33 2.7 pg/ml and IL-18 16.4 pg/ml). We conclude that IL-33 appears an important factor of pulmonary BBS activity.
Assuntos
Interleucina-33/análise , Sarcoidose Pulmonar/imunologia , Adulto , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Interleucina-18/análise , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnósticoRESUMO
Lung cancer is associated with poor prognosis. The aim of this study was to evaluate the clinical usefulness of HMGB-1 (high-mobility group protein B1) and TGF-ß (transforming growth factor beta) in patients with advanced non-small cell lung cancer (NSCLC). We studied 45 patients with NSCLC prior to chemotherapy, 23 patients with Besnier-Boeck-Schaumann (BBS) disease (sarcoidosis), and 15 healthy volunteers. HMGB-1 and TGF-ß levels were measured in serum and BALF samples using ELISA method. A higher serum HMGB-1 and TGF-ß levels were in NSCLC patients compared with the other groups. TGF-ß concentration in BALF was significantly higher in NSCLC than in healthy controls (p=0.047) but lower than in BBS (p=0.016). Serum HMGB-1 in NSCLC correlated with age and gender while its level in BALF was associated with distant metastasis. A higher levels of HMGB-1 in the serum of NSCLC patients with progressive disease was linked with shorter overall survival and disease-free survival. We found a positive correlation between HMGB-1 and TGF-ß in BALF of IIIB NSCLC group and overall survival (p=0.04; p=0.003). Our findings confirmed that the measurement of HMGB-1 and TGF-ß levels in serum and BALF of patients with NSCLC prior to treatment may have clinical usefulness and predict poor prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Líquido da Lavagem Broncoalveolar , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína HMGB1/análise , Proteína HMGB1/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/sangueRESUMO
Recently, it has been reported that lack of cathepsins prevent the development of lung granulomas in a mouse model of Besnier-Boeck-Schaumann (BBS) disease, sarcoidosis. There is no data about cathepsin V (Cath V) in bronchoalveolar lavage fluid (BALF) in humans. Endostatin is a novel inhibitor of lung epithelial cells. The role of this protein in BBS is not determined. The aim of this study was to evaluate the concentration of endostatin, Cath V, and IL-18 in BALF of BBS patients. We studied 22 BBS patients (Stage 2). The control group consisted of 20 healthy subjects. Cath V concentration was lower in BBS than in healthy group (16.03±8.60 vs. 32.25±21.90 pg/ml, p=0.004). Both endostatin and IL-18 levels were higher in BBS than in the control group (0.88±0.30 vs. 0.29±0.04 ng/ml, p=0.028; 40.37±31.60 vs. 14.61±1.30 pg/ml, p=0.007, respectively). In BBS there were correlations between the levels of endostatin and IL-18 (r=0.74, p=0.001) as well as endostatin and DLCO (diffusing capacity for carbon monoxide) (r=-0.6, p=0.013). Receiver-operating characteristic (ROC) curves were applied to find the cut-off for the BALF levels of Cath V, endostatin, and IL-18. We conclude that Cath V and endostatin may represent an index of pulmonary sarcoidosis activity.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Catepsinas/análise , Cisteína Endopeptidases/análise , Endostatinas/análise , Sarcoidose Pulmonar/metabolismo , Adulto , Feminino , Humanos , Interleucina-18/análise , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Thrombospondin-2 (TSP-2) is an endogenous negative regulator of vascularization in human cancer. TSP-2 regulates angiogenesis through binding and sequestration of the proangiogenic fibroblast growth factor-2 (FGF-2). However, it is unclear whether TSP-2 and FGF-2 are related to prognosis in non-small cell lung cancer (NSCLC). To study this issue, we measured serum (Elisa) levels of TSP-2 and FGF-2 in 40 NSCLC patients (before chemotherapy) and 22 healthy subjects. Both TSP-2 and FGF-2 concentrations were elevated in the NSCLC group compared with control (TSP-2: 26.72±8.00 vs. 18.64±5.50 ng/ml, p=0.002; FGF-2: 11.90±5.80 vs. 7.26±3.90 pg/ml, p=0.01). Receiver-operating characteristic (ROC) curves were applied to find the cut-off serum levels of TSP-2 and FGF-2 (NSCLC vs. healthy: TSP-2=15.09 ng/ml, FGF-2=2.23 pg/ml). Patients before treatment with the TSP-2 level<24.15 ng/ml had a median survival of 23.7 months, but those with TSP-2>24.15 ng/ml had only 9 months' median survival (p=0.007). Patients with FGF-2 level>11.21 pg/ml had significantly shorter survival than patients with FGF-2<11.21 pg/ml (7.5 months vs. 16 months, p=0.034). We conclude that NSCLC patients have higher serum concentrations of TSP-2 and FGF-2 than healthy people. High levels of TSP-2 and FGF-2 may predict worse survival.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Neoplasias Pulmonares/sangue , Trombospondinas/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), ligands for the Tie-2 receptor expressed on endothelial cells, play a critical role in angiogenesis, in concert with vascular endothelial growth factor (VEGF). Angiogenesis is important for tumor growth and development and also is implicated in the pathogenesis of interstitial lung diseases. The aim of this study was to evaluate the concentration of Ang-1, Ang-2, Tie-2, interleukin-18 (IL-18), transforming growth factor beta-1 (TGF ß1), and VEGF domain in both serum and bronchoalveolar lavage fluid (BALF) of lung cancer patients before chemotherapy. We studied 45 non-small cell lung cancer (NSCLC) patients (M/F; 38/7; mean age 62 ± 4 years). The age-matched control groups consisted of 15 sarcoidosis (BBS), 15 hypersensivity pneumonitis (HP), and 15 healthy subjects. The patients with NSCLC had a significantly higher level of Ang-1 compared with the BBS and healthy subjects, and a higher level of Ang-2 compared with the healthy subjects in both serum and BALF. BALF level of IL-18 was lower in the NSCLC than that in the HP group, but higher than that in the BBS patients. Serum level of IL-18 was higher in the NSCLC than in the healthy subjects. The NSCLC group had lower VEGF in BALF than that in healthy subjects. Receiver-operating characteristics (ROC) curves were applied to find the cut-off the serum levels of Ang-1 and Ang-2 levels in BALF. We did not find any correlation between the levels of Ang-1, Ang-2, Tie-2, and the stage of tumor or treatment response (prospectively). We conclude that the angiogenic axis Ang-1 and Ang-2/Tie-2 may play an important role in lung cancer development and their concentrations may be a useful marker at the time of initial diagnosis of lung cancer.
Assuntos
Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neovascularização Fisiológica , Idoso , Alveolite Alérgica Extrínseca/metabolismo , Líquido da Lavagem Broncoalveolar , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-18/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Sarcoidose/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
UNLABELLED: There are several antiproliferative and angiogenic factors, recently have been discovered (IL-27, IL-29, IL-31 and IL-33), but they have not been tested yet in lung cancer patients. The aim of this pilot study was to assess the clinical usefulness of determination of IL-27, IL-29, IL-31 and IL-33 in advanced stages of lung cancer. PATIENTS AND METHODS: The study included 45 patients (38 males; mean age 62 years; 45 with advanced NSCLC). Serum and BALF cytokine concentrations were evaluated by ELISA method before chemotherapy. The comparative groups consisted of patients with sarcoidosis (BBS, n = 15), hypersensivity pneumonitis (HP, n = 8) and healthy subjects (n = 15). RESULTS: The serum IL-29 levels were higher in NSCLC patients than in the sarcoidosis group. However, serum IL-27, IL-31 and IL-33 did not differ markedly between: NSCLC, BBS, HP and the control group. Concentrations of IL-29 and IL-31 in BALF did not differ significantly between investigated groups. In all groups levels of IL-27 and IL-29 are significantly higher in serum than in BALF. Concentrations of IL-31 in BBS, HP and control groups tended to higher in BALF than in serum. These differences were significantly in NSCLC patients. Patients in stage IIIB of NSCLC had higher serum levels of IL-29 than these in stage IV. Lung cancer patients with partial remission (PR) after chemotherapy had significantly higher concentration of IL-27 in BALF than patients with SD. However, patients with SD had higher levels of IL-29 in BALF than patients with PD. A negative correlation was found between serum IL-31 levels before therapy and time to progression of NSCLC. CONCLUSION: Determination of IL-27, IL-29 and IL-31 in serum and BALF can be useful in clinical practice, but their practical significance needs further studies.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Citocinas/análise , Neoplasias Pulmonares/diagnóstico , Líquido da Lavagem Broncoalveolar/química , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interferons , Interleucina-33 , Interleucinas/análise , Interleucinas/biossíntese , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Vascular endothelial growth factors C (VEGF-C) and D (VEGF-D) are important lymphangiogenic factors in human cancers. We studied the expression of VEGF-C and VEGF-D using immunohistochemistry in 73 resected esophageal cancer specimens, and correlated the results with patient clinicopathologic features and survival. High expression of VEGF-C was identified in 40 (54.7%) patients, and it correlated positively with histological grade (p=0.038), tumor stage (p=0.01), depth of tumor invasion (p=0.036) and lymph node metastasis (p=0.001). In 48 of 73 (65.7%) tumors, the VEGF-D protein was also expressed at high levels. VEGF-D immunoreactivity significantly correlated with tumor location (p=0.027), size of tumor (p=0.015), histological grade (p=0.02), depth of invasion (p=0.001) and lymph node metastasis (p=0.018). In logistic multivariate analysis, high expression of VEGF-C (OR 1.941, 95% CI 1.263-7.289, p=0.024) was associated with lymph node metastasis. Calculating the prognostic relevance revealed that both VEGF-C and VEGF-D correlated with decreased overall survival (p=0.01, p=0.003), disease free survival (p=0.02, p=0.006), and cancer-specific survival (p=0.03, p=0.005). In conclusion, our results suggest that high levels of both VEGF-C and VEGF-D proteins are associated with lymph node involvement, and that VEGF-C expression is an independent predictor of risk for lymph node metastasis in esophageal cancer. In locally advanced disease, overexpression of VEGF-C and VEGF-D may be useful in identifying patients who are more likely to have a poor prognosis even after curative resection.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Metástase Linfática/patologia , Fator C de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
UNLABELLED: THE AIM of this study was to assess the clinical usefulness of determination of soluble Fas (sFas) and soluble Fas Ligand (sFasL) during chemotherapy of lung cancer. METHODS: The study included 80 patients (69 males; 11 females; mean age 64 years; 48 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC). The control group consisted of 15 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. sFas and sFasL levels were assessed by Elisa method. RESULTS: The serum sFas and sFasL levels observed at the end of the chemotherapy were higher in all patients with lung cancer compared to healthy volunteers. The levels of sFas and sFasL were higher after chemotherapy than before therapy. The levels of sFasL were significantly higher in SCLC patients than in NSCLC ones. There were no significant differences in serum sFasL levels in relation to clinical stage of lung cancer. After chemotherapy the levels of sFas were higher in patients with metastases. There were no significant differences in serum sFasL levels in relation to response to therapy. At the end of the therapy the serum levels of sFas were higher in Partial Response group than in Progressed patients. Before chemotherapy the levels of sFas were higher in Progressive Disease group than in No Change one. The levels of sFas observed after chemotherapy were higher in Partial Response group than in No Change one. CONCLUSION: Determination of serum sFas and sFasL levels can be useful in clinical practice, but their practical significance needs further studies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Pequenas/sangue , Proteína Ligante Fas/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Receptor fas/sangue , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , SolubilidadeRESUMO
UNLABELLED: The purpose of our study was to evaluate the clinical usefulness of serum endostatin levels during chemotherapy of lung cancer in relation to the histopathological type of the tumor, clinical stage and response to therapy. MATERIALS AND METHODS: Serum concentrations of endostatin were determined in 37 patients (24 with non-small cell lung cancer and 13 with small cell lung cancer), 10 healthy subjects constituted controls. To determine endostatin levels (ELISA), venous blood samples were collected from each patient before treatment and after 4-6 courses of chemotherapy. RESULTS: The serum concentrations of endostatin were found significantly higher in patients in comparison with controls (p=0.003). No statistically significant differences were established between the concentrations of endostatin with regard to such clinical features, as: performance status, clinical stage (III and IV) and histopathological type (non-small cell lung cancer and small cell lung cancer). The concentrations of endostatin did not change after chemotherapy. There was no change of endostatin concentration caused by the response to treatment. CONCLUSIONS: The serum endostatin concentrations were elevated in lung cancer patients.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Pequenas/sangue , Endostatinas/sangue , Neoplasias Pulmonares/sangue , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
UNLABELLED: The AIM of this study was to assess the influence of chemotherapy on the serum levels of IGF-I and IGF-II in patients with lung cancer. METHODS: The study included 38 patients (33 males and 5 females) at mean age of 59.8, diagnosed histologically with lung cancer. Twenty five patients had non-small cell lung cancer (NSCLC) including 11 patients with squamous cell carcinoma (SCC), 5 patients with adenocarcinoma and 9 patients without an essential histological type of NSCLC. A total of 13 patients had small cell lung cancer (SCLC). The control group consisted of 10 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. IGF-I and IGF-II levels were assessed by ELISA method. RESULTS: Serum levels of IGF-I and IGF-II measured before chemotherapy were significantly higher in both NSCLC and SCLC groups in comparison with controls. There were no significant differences of serum levels of both growth factors before and after 4 cycles of chemotherapy. Serum levels of IGF-I and IGF-II were still high after chemotherapy in patients with NSCLC and SCLC. Patients with SCC and adenocarcinoma had similar serum levels of IGF-I and IGF-II without statistical differences. CONCLUSION: Serum levels of IGF-I and IGF-II were significantly higher in patients with NSCLC and SCLC before chemotherapy than in controls. Chemotherapy had no influence on the serum levels of insulin-like growth factors (IGFs). Serum levels of IGF-I and IGF-II did not depend on a histological type of NSCLC either.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like I/análise , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
PURPOSE: We evaluated the clinical usefulness of interleukin-18 (IL-18) and soluble interleukin-2 receptor (sIL-2R) during chemotherapy of lung cancer in relation to the histological type of the tumor, clinical stage, response to therapy and time survival. MATERIAL AND METHODS: Serum levels of IL-18 and sIL-2R were determined in 73 patients (62 males; mean age 64 years; 41 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC); 12 healthy subjects served as controls. To determine IL-18 serum concentrations (Elisa), venous blood samples were collected from each patient before and after chemotherapy. RESULTS: The mean serum IL-18 level in all patients with lung cancer was significantly higher compared with healthy volunteers (p = 0.0001; NSCLC vs control p = 0.0001; SCLC vs control p = 0.004). In NSCLC group with stage IV the mean IL-18 level was significantly higher than those with stage IIIB (p = 0.04). Regarding tumor stage and response to therapy, no significant differences in IL-18 were observed. Using cut-off serum IL-18 concentration of 319.6 pg/ml, the prognoses of the two groups were different, but it was not statistically significant. The serum levels of sIL-2R in NSCLC patients were significantly higher than in controls (p = 0.018). There were no significant differences in serum sIL-2R levels in relation to clinical stage of lung cancer and response to therapy. The cut-off value between high and low serum sIL-2R concentration was defined as 582.27 U/ml. The difference in survival rate between the high and low sIL-2R groups was not significant. CONCLUSIONS: Serum IL-18 and sIL-2R levels can be useful in clinical practice, but their practical significance needs further studies.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Pequenas/sangue , Interleucina-18/sangue , Neoplasias Pulmonares/sangue , Receptores de Interleucina-2/sangue , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
The aim of our study was to evaluate the usefulness of serum OPG and ProGRP during chemotherapy of lung cancer in relation to the histological type of the tumour, its clinical stage and the response to therapy. The levels of OPG and ProGRP were determined in 39 patients (20 NSCLC, 19 SCLC) and 10 healthy subjects. Blood samples were collected from each patient before and after chemotherapy. OPG and ProGRP levels in all the patients with lung cancer were higher than those in the controls. ProGRP were higher in SCLC group than in those NSCLC. In NSCLC group (after chemotherapy), OPG level in patients with Stage IV tumour was higher than in those with Stage IIIB (p=0.03). OPG in ED SCLC were higher than those in LD SCLC (p=0.04). In SCLC group, ProGRP were higher in LD patients than those with ED (p=0.04). Concluding, the measuring of OPG and ProGRP in lung cancer patients may be useful in clinical practice.
Assuntos
Glicoproteínas/sangue , Neoplasias Pulmonares/tratamento farmacológico , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Receptores Citoplasmáticos e Nucleares/sangue , Proteínas Recombinantes/sangue , Biomarcadores Tumorais/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Osteoprotegerina , Receptores do Fator de Necrose TumoralRESUMO
The origins of the various histological types of primary lung cancer are not well understood. Numerous recent studies have indicated that lung cancer is not a result of a sudden transforming event in the bronchial and alveolar epithelium and in the neuroendocrine cells, but a multistep process in which a sequence of morphological and genetic changes is occurring. New modern technical approaches like fluorescence bronchoscopy techniques and microdissection, provide facilities to obtain valuable specimens for morphological and genetic verification of the sequentional changes in lung cancerogenesis. With their help, cells with morphologically recognized changes thought to be preneoplastic, may be removed and prepared for molecular and genetic studies. Therefore, the knowledge of the morphological aspects of lung preneoplastic lesions is crucial to make progress in molecular studies of lung carcinogenesis. Presently the knowledge about the sequence of molecular events in the lung carcinogenesis and their relationship to morphology is not perfect. In this review we will describe morphological aspects of various preneoplastic lesions occurring in the bronchial and bronchiolo-alveolar compartments including neuroendocrine cells.
Assuntos
Transformação Celular Neoplásica , Neoplasias Pulmonares/fisiopatologia , Pulmão/patologia , Lesões Pré-Cancerosas/fisiopatologia , Diferenciação Celular , Predisposição Genética para Doença , Humanos , Hiperplasia , Pulmão/citologiaRESUMO
We focused our studies on single endothelial cells (ECs) scattered in extracellular matrix in lung cancer tumors. Neovascularization was evaluated in 100 tumors obtained from patients operated for lung cancer, in relation to histological type, tumor differentiation and clinical stage of the disease. Angiogenic objects (single endothelial cells and microvessels) were identified by immunohistochemistry using monoclonal antibodies against von Willebrand factor. The count of angiogenic objects per 1 mm2 in each section was determined in a "hot spot" located at the margin of the tumor. We used an arbitrary scale of angiogenesis intensity: 1 - 0-200, 2 - 201-400, 3 - >400 angiogenic objects/mm2. A majority (57%) of the examined cases belonged to the group 2. The angiogenesis intensity measured by the single EC numbers/mm2 correlates with the histological type and the differentiation of the tumors. There was no such a correlation when the angiogenesis intensity was measured by counting total angiogenic objects (microvessels + EC) number/mm2. Single EC number/mm2 in different histological types of cancer were as follows: 162+/-121 in squamous cell (SqCC), 194+/-71 in adenocarcinoma (AdC), 225+/-145 in large cell (LCC), 264+/-52 in small cell (SCC), 279+/-173 in combined cancer. The differences between the EC counts in the different histological types of lung cancers were statistically significant in the following pairs: SqCC vs SCC (p=0.0233) and AdC vs SCC (p=0.0409). The correlation between EC count in the "hot spot" and the grade of tumor differentiation was statistically significant for G1 vs G4 (p=0.0007) and G1 vs G2 (p=0.0411). Our results suggest that higher numbers of EC/mm2 may confirm rapid development of angioneogenesis. These relations should be examined in larger series of cases.
Assuntos
Endotélio Vascular/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neovascularização Patológica , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/patologia , Adulto , Idoso , Antígenos/análise , Biomarcadores Tumorais/análise , Carcinoma de Células Grandes/irrigação sanguínea , Carcinoma de Células Grandes/patologia , Carcinoma de Células Pequenas/irrigação sanguínea , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/patologia , Endotélio Vascular/química , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estatística como Assunto , Fator de von Willebrand/imunologiaRESUMO
Aspergillus fumigatus can cause a number of lung diseases. One of them is allergic bronchopulmonary aspergillosis (ABPA) characterized by pulmonary eozynophilia, asthma, an allergic type of immune response in the bronchi and proximal bronchiectases. ABPA was recognised in 28-years old man (round shadows in the lung, obturated bronchus with mucoid impaction, positive skin tests with aspergillin and presence of precipitins to Aspergillus fumigatus, elevated serum IgE level). Patient was treated for 6 months with corticosteroids. After 2 years of regression there was an exacerbation of ABPA was recognised. The steroid therapy was repeated.
Assuntos
Aspergilose Broncopulmonar Alérgica/diagnóstico , Adulto , Aspergilose Broncopulmonar Alérgica/complicações , Asma/etiologia , Progressão da Doença , Humanos , Imunoglobulina E/sangue , Pulmão/diagnóstico por imagem , Masculino , Radiografia , Recidiva , Testes CutâneosRESUMO
Human papillomavirus (HPV) infection is one of the risk factors contributing to the pathogenesis of lung cancer. The aim of the study was to determine the presence of HPV in non-small cell carcinomas of the lung. The study included 40 tumors: 22 squamous cell carcinomas, 13 adenocarcinomas and 5 large cell carcinomas. HPV was found in 4 cases (10%). High risk HPV was present in 3 tumors: in one squamous cell carcinoma, one large cell carcinoma and one adenocarcinoma, while low risk HPV was detected in one adenocarcinoma.