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1.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
2.
BMC Cancer ; 18(1): 310, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29558888

RESUMO

BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes. METHODS: Serum samples were prospectively collected from 57 patients receiving salvage chemotherapy and 70 non-EGFR mutated patients receiving erlotinib. Patients were classified as either VeriStrat good or poor based on the VeriStrat test. Luminex immunoassays were used to measure circulating levels of 102 distinct biomarkers implicated in tumor aggressiveness and treatment resistance. A Cox PH model was used to evaluate associations between biomarker levels and clinical outcome, whereas the association of VeriStrat classifications with biomarker levels was assessed via the Mann-Whitney Rank Sum test. RESULTS: VeriStrat was prognostic for outcome within the erlotinib treated patients (HR = 0.29, p < 0.0001) and predictive of differential treatment benefit between erlotinib and chemotherapy ((interaction HR = 0.25; interaction p = 0.0035). A total of 27 biomarkers out of 102 unique analytes were found to be significantly associated with OS (Cox PH p ≤ 0.05), whereas 16 biomarkers were found to be associated with PFS. Thrombospondin-2, C-reactive protein, TNF-receptor I, and placental growth factor were the analytes most highly associated with OS, all with Cox PH p-values ≤0.0001. VeriStrat status was found to be significantly associated with 23 circulating biomarkers (Mann-Whitney Rank Sum p ≤ 0.05), 6 of which had p < 0.001, including C-reactive protein, IL-6, serum amyloid A, CYFRA 21.1, IGF-II, osteopontin, and ferritin. CONCLUSIONS: Strong associations were observed between survival and VeriStrat classifications as well as select circulating biomarkers associated with fibrosis, inflammation, and acute phase reactants as part of this study. The associations between these biomarkers and VeriStrat classification might have therapeutic implications for poor prognosis NSCLC patients, particularly with new immunotherapeutic treatment options.


Assuntos
Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Resistencia a Medicamentos Antineoplásicos , Cloridrato de Erlotinib/uso terapêutico , Mediadores da Inflamação/sangue , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Proteômica , Taxa de Sobrevida
3.
J Proteome Res ; 16(1): 3-13, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27769114

RESUMO

Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and noncurable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential noninvasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. We provide an overview of differentially expressed protein, antigen, and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.


Assuntos
Antígenos de Neoplasias/sangue , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/sangue , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Autoanticorpos/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/diagnóstico por imagem , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/imunologia , Tomografia Computadorizada por Raios X
4.
Clin Lung Cancer ; 18(2): e99-e107, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27836219

RESUMO

BACKGROUND: Lung cancer screening using low-dose computed tomography reduces lung cancer mortality. However, the high false-positive rate, cost, and potential harms highlight the need for complementary biomarkers. We compared the diagnostic performance of modified aptamer-based protein biomarkers with Cyfra 21-1. PATIENTS AND METHODS: Participants included 100 patients diagnosed with lung cancer, and 100 control subjects from Asan Medical Center (Seoul, Korea). We investigated candidate biomarkers with new modified aptamer-based proteomic technology and developed a 7-protein panel that discriminates lung cancer from controls. A naive Bayesian classifier was trained using sera from 75 lung cancers and 75 controls. An independent set of 25 cases and 25 controls was used to verify performance of this classifier. The panel results were compared with Cyfra 21-1 to evaluate the diagnostic accuracy for lung nodules detected by computed tomography. RESULTS: We derived a 7-protein biomarker classifier from the initial train set comprising: EGFR1, MMP7, CA6, KIT, CRP, C9, and SERPINA3. This classifier distinguished lung cancer cases from controls with an area under the curve (AUC) of 0.82 in the train set and an AUC of 0.77 in the verification set. The 7-marker naive Bayesian classifier resulted in 91.7% specificity with 75.0% sensitivity for the subset of individuals with lung nodules. The AUC of the classifier for lung nodules was 0.88, whereas Cyfra 21-1 had an AUC of 0.72. CONCLUSION: We have developed a protein biomarker panel to identify lung cancers from controls with a high accuracy. This integrated noninvasive approach to the evaluation of lung nodules deserves further prospective validation among larger cohorts of patients with lung nodules in screening strategy.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteômica/métodos , Adenocarcinoma/sangue , Antígenos de Neoplasias/sangue , Aptâmeros de Peptídeos/metabolismo , Área Sob a Curva , Teorema de Bayes , Carcinoma de Células Grandes/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
5.
Clin Transl Oncol ; 18(4): 398-404, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26311076

RESUMO

INTRODUCTION: The possibility of detection of suppressor genes methylation in circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in healthy individuals makes this epigenetic alternation an ideal diagnostic marker of neoplastic processes. Moreover, hypermethylation in several genes promoter was described as a biomarker of lung cancer. Methylation in the gene encoding doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer and cholangiocarcinoma. However, there are no studies concerning DCLK1 methylation in lung cancer patients. The aims of the study was to evaluate the frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of healthy persons as well as the usefulness of this test for predicting the lung cancer course. MATERIALS AND METHODS: DCLK1 methylation status was evaluated in DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95 healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was correlated with the overall survival (OS) probability of lung cancer patients. RESULTS: DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2 %) and 8 healthy individuals (8.4 %). The methylation of the region before transcription start site (TSS) and the region after TSS of DCLK1 gene was detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1 promoter methylation in both regions was reported simultaneously. The methylation was observed slightly frequently in patients with small cell lung cancer (75 % of SCLC patients). The median overall survival of patients with DCLK1 promoter methylation was lower than that of patients without DCLK1 gene modification (p = <0.001, HR = 4.235). CONCLUSIONS: The evaluation of DCLK1 promoter region methylation may be useful in both early diagnosis and prediction of the course of lung cancer.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/patologia , Regiões Promotoras Genéticas/genética , Proteínas Serina-Treonina Quinases/genética , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Serina-Treonina Quinases/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida
6.
Zhonghua Zhong Liu Za Zhi ; 37(7): 508-11, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26463326

RESUMO

OBJECTIVE: To explore the value of serum neuron-specific enolase (NSE) before treatment in predicting brain metastases and prognosis of advanced non-small cell lung cancer (NSCLC). METHODS: A total of 128 hospitalized patients with advanced NSCLC from Jan 2012 to Mar 2012 were followed up, and their clinicopathological data, serum NSE, carcinoembryonic antigen, cytokeratin 21-1 (cyfra21-1) levels, albumin (ALB), white blood cell (WBC) before treatment were analyzed retrospectively to determine the factors affecting brain metastasis and prognosis of advanced NSCLC. RESULTS: Among the 128 NSCLC patients, 90 cases were of adenocarcinoma, 30 cases were of squamous cell carcinoma, and 8 cases were of large cell carcinoma. The median levels of pre-treatment NSE, CEA and cyfra21-1 were 13.6 ng/ml, 7.8 ng/ml and 6.1 ng/ml, respectively. The average levels of ALB and WBC were (35.41 ± 5.60) g/L and (8.16 ± 2.53) × 109/ml, respectively. Multi-variate logistic regression analysis showed that serum NSE before treatment was associated with brain metastasis of advanced NSCLC (P = 0.030). Pre-treatment NSE levels were (34.18 ± 28.48) ng/ml in 28 patients with brain metastasis and (13.87 ± 4.49) ng/ml in 98 patients without brain metastasis (P < 0.05). The median survival time were 3.5 months in patients with normal levels of NSE, and 10.7 months in patients with elevated levels of NSE pre-treatment (P < 0.05). CONCLUSIONS: A higher pre-treatment level of NSE is closely correlated with brain metastasis of advanced NSCLC, and can be used as a predictor of brain metastases in advanced NSCLC. High pre-treatment levels of NSE indicate a poor prognosis in advanced NSCLC patients.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/enzimologia , Fosfopiruvato Hidratase/sangue , Adenocarcinoma/sangue , Adenocarcinoma/enzimologia , Adenocarcinoma/secundário , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/enzimologia , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/secundário , Humanos , Queratina-19/sangue , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análise
7.
Eur Respir J ; 46(6): 1773-80, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26493785

RESUMO

Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies with larger sample sizes and including patients who receive more homogenous treatments. Our objective was to assess the predictive and prognostic value of plasma cfDNA concentration in a large series of patients with NSCLC and treated with a standard chemotherapy regimen.We included samples from lung cancer patients recruited into the Pharmacogenoscan study. The cfDNA of 218 patients was extracted and quantified by fluorometry before and after two or three cycles of platinum-based chemotherapy. The association between baseline and post-chemotherapy concentrations and treatment response, assessed by RECIST (response evaluation criteria in solid tumours) or patient survival was analysed.Patients with high cfDNA concentrations (highest tertile) at baseline had a significantly worse disease-free and overall survival than those with lower concentrations (lowest and middle tertiles) (median overall survival 10 months (95% CI 10.7-13.9) versus 14.2 months (95% CI 12.6-15.8), respectively; p=0.001). In multivariate analysis, increased baseline concentration of cfDNA was an independent prognostic factor. However, we did not find any association between cfDNA concentration and response to treatment.cfDNA may be a biomarker for the assessment of prognosis in NSCLC. However, total concentration of cfDNA does not appear to predict chemotherapy response.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , DNA/sangue , Neoplasias Pulmonares/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/sangue , Feminino , Fluorometria , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
8.
Cancer Biomark ; 15(6): 725-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26406401

RESUMO

BACKGROUND: Hyperlactatemia with or without type B lactic acidosis is a rare complication of cancer, previously observed most often in hematological malignancies. The aim of this study was to assess the prognostic value of lactic acid (LA) in patients with metastatic lung cancer. METHODS: Patients diagnosed with stage IV non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC), were included in this single center retrospective study. Arterial and venous LA level, anion gap (AG), serum LDH and presence of urine ketones were recorded for each patient and their associations with demographic and clinical data and overall survival (OS) were examined. RESULTS: Eighty-five patients (43 males, median age 74, range 45-96 years) were studied. The maximal levels of arterial or venous LA were significantly associated with presence of ≥ 2 metastatic sites (p= 0.001), ICU admission or transfer (p= 0.016), intubation (p= 0.029), elevated serum anion gap (p< 0.001) and LDH levels (p< 0.001). Hyperlactatemia (≥ 1.4 mmol/L) was associated with shorter OS (log-rank p< 0.001). In a multivariate model including LA, ICU, intubation, AG as well as other known prognostic factors of NSCLC and SCLC, including age, sex, smoking status, number and location of metastases, histologic type, performance status (PS), chemotherapy and LDH, LA retained its prognostic value (OR: 1.3; 95%CI: 1.082-1.561; p= 0.005), along with PS (p= 0.039) and chemotherapy (p= 0.039). CONCLUSIONS: The results of the study suggest that a high lactic acid level (≥ 1.4 mmol/L) is associated with significantly shorter overall survival in patients with metastatic non-small cell lung cancer and extensive stage small cell lung cancer. Hyperlactatemia is an independent predictor of poor survival in metastatic lung cancer patients.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/secundário , Ácido Láctico/sangue , Neoplasias Pulmonares/patologia , Adenocarcinoma/sangue , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/terapia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
9.
Clin Transl Oncol ; 17(10): 772-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26243392

RESUMO

BACKGROUNDS: Compared to pure small cell lung cancer (SCLC), combined small cell lung cancer (C-SCLC) has its own characteristics. High neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be related to poor prognosis in several types of tumors. The aim of this study was to explore the prognosis value of NLR and PLR in patients with C-SCLC. METHODS: A total of 112 patients diagnosed with C-SCLC between January 2000 and March 2009 were enrolled in the study. The clinicopathological parameters, laboratory analyses, and survival time were collected and analyzed. The correlation between NLR, PLR, and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. RESULTS: The pretreatment NLR was elevated in 37.5 % patients (NLR ≥ 4.15; n = 42; H-NLR). NLR was significantly related to disease stage (p = 0.033) and tumor recurrence (p = 0.014). The median overall survival (OS) and progression-free survival (PFS) were significantly worse in the H-NLR group (OS: 22.0 months vs 11.7 months, p = 0.001; PFS: 11.1 vs 6.0 months, p < 0.001). However, PLR at diagnosis was not associated with OS or PFS. Multivariate analyses indicated elevated NLR (HR = 1.6; p = 0.001), disease stage (HR = 1.6; p = 0.001), and performance status (HR = 1.8; p = 0.015) as independent prognostic factors. CONCLUSIONS: High pretreatment NLR (≥4.15) is a potential useful indicator for C-SCLC recurrence and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients.


Assuntos
Adenocarcinoma/sangue , Plaquetas , Carcinoma de Células Grandes/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Linfócitos , Recidiva Local de Neoplasia/sangue , Neoplasias Complexas Mistas/sangue , Neutrófilos , Carcinoma de Pequenas Células do Pulmão/sangue , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Irinotecano , Contagem de Leucócitos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/terapia , Contagem de Plaquetas , Compostos de Platina/administração & dosagem , Pneumonectomia , Prognóstico , Radioterapia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia
10.
Monoclon Antib Immunodiagn Immunother ; 34(3): 206-12, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26090599

RESUMO

SPLUNC1 (Short palate, lung and nasal epithelium clone1) protein is an abundant secretory product of epithelia present throughout the conducting airways. Although its function is still not fully known, most studies have focused on its defensive effect in the infection of human airways and its potential to serve as a molecular marker for lung cancer. In this study, we further evaluated the SPLUNC1 expression in patients with lung disease to explore its role in cancer or tuberculosis at the protein level. We generated a panel of antibodies by using protein from a eukaryotic expression system as the immunogen to mice. It was the panel of SPLUNC1 monoclonal antibodies that allowed us to comparatively determine SPLUNC1 protein in lung cancer and tuberculosis infection by detecting sera and pleural effusion other than airway surface. The results showed that the SPLUNC1 level was not significantly changed either from sera of lung cancer or control. There was a significant increase in pleural effusion from lung cancer when compared to tuberculosis. These results indicate that SPLUNC1 may be a useful marker for tracing lung cancer cells, based on its epithelial origin property in pleural effusion.


Assuntos
Anticorpos Monoclonais/imunologia , Biomarcadores/sangue , Glicoproteínas/sangue , Neoplasias Pulmonares/diagnóstico , Fosfoproteínas/sangue , Derrame Pleural/diagnóstico , Tuberculose/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/imunologia , Animais , Especificidade de Anticorpos , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/imunologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Seguimentos , Glicoproteínas/imunologia , Humanos , Hibridomas/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Camundongos , Fosfoproteínas/imunologia , Derrame Pleural/sangue , Derrame Pleural/imunologia , Prognóstico , Tuberculose/sangue , Tuberculose/imunologia
11.
Clin Lung Cancer ; 14(5): 513-20, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23810363

RESUMO

INTRODUCTION: The aim of this study was to develop a multiplex polymerase chain reaction (PCR)-based method for detection of circulating tumor cells in peripheral blood of lung cancer (LC) patients. PATIENTS AND METHODS: Peripheral blood was collected from 71 healthy donors and 125 LC patients at different pathological stages. Samples were analyzed using multiplex PCR, and specific primers for CK19, PTHrP, and LUNX mRNA. The sensitivity of our method was set at 10 LC cells (A549 cells) in 3 mL of peripheral blood of healthy donors using spiking experiments. RESULTS: The detection rates in LC patients for CK19, PTHrP, and LUNX were 45.6%, 64.8%, and 28%, and in healthy individuals were 7%, 7%, and 5.6%, respectively. Overall, our method produced 77.8% positive detections for at least 1 molecular marker. Twenty-eight (22.2%) were negative for expression of all markers, 39 (31.2%) were positive for expression of 1 marker, 42 (33.6%) were positive for expression of 2 markers, and 17 (13.6%) were positive for expression of all 3 markers. Detection of CK19 mRNA expression positively correlated with LC stage and distant metastases. PTHrP mRNA detection correlated positively with LC stage, presence of bone metastasis, and squamous cell carcinoma, and LUNX mRNA detection correlated with lymph node involvement. Combined detection of 2 or 3 markers was significantly correlated with metastatic disease, and negative detection of all 3 molecular markers was correlated with early stage nonmetastatic disease. CONCLUSION: Multiple PCR-based detection of CK19, PTHrP, and LUNX mRNA expression provides useful information for disease stage and dissemination in LC patients.


Assuntos
Glicoproteínas/genética , Queratina-19/genética , Neoplasias Pulmonares/diagnóstico , Reação em Cadeia da Polimerase Multiplex , Células Neoplásicas Circulantes/patologia , Proteína Relacionada ao Hormônio Paratireóideo/genética , Fosfoproteínas/genética , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Células Tumorais Cultivadas
12.
J Thorac Oncol ; 8(7): 947-51, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23777840

RESUMO

INTRODUCTION: Soluble mesothelin-related peptides (SMRP) have been reported as potential markers for the diagnosis of malignant pleural mesothelioma (MPM). We wondered, whether a combination with a carcinoembryonic antigen (CEA) test might improve the relatively low diagnostic yield of the SMRP test. METHODS: In a retrospective study, SMRP (mesothelin) and CEA serum concentrations were measured, using commercially available kits, in 93 previously untreated MPM patients, 75 patients with benign asbestos disease, and 139 patients suffering from lung cancer (LC). RESULTS: The differentiation between MPM, LC, and benign asbestos disease could be improved by applying the ratio mesothelin/CEA. Whereas CEA expression was found to be low in MPM, most LC patients had elevated CEA serum levels. The area under curve (AUC) of the receiver operator characteristics curve for mesothelin alone was found to be only 0.708. For mesothelin/CEA the AUC of the receiver operator characteristics curve increased to 0.978. The sensitivity was 93% (69%) at 95% (100%) specificity for the differentiation between MPM and LC. Comparison of MPM and benign asbestos disease showed that the AUC was 0.887 and the sensitivity 56% (47%) at 95% (100%) specificity. In contrast, the AUC for the mesothelin test alone was only 0.715, and for the CEA test alone it was 0.16. An average increment in sensitivity of 38% (range, 16%-63%) could be achieved by the quotient mesothelin/CEA compared with the sensitivity of mesothelin alone. CONCLUSION: The diagnostic yield of the mesothelin test can be considerably improved when combined with a CEA test with regard to the differential diagnosis between MPM and LC and between MPM and benign asbestos disease.


Assuntos
Asbestose/diagnóstico , Antígeno Carcinoembrionário/sangue , Proteínas Ligadas por GPI/sangue , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Asbestose/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Masculino , Mesotelioma/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pleurais/sangue , Prognóstico , Curva ROC , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue
13.
Clin Transl Oncol ; 15(11): 897-902, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23463593

RESUMO

PURPOSE: There is a need for biomarkers that may help in selecting the most effective anticancer treatments for each patient. We have investigated the prognostic value of a set of angiogenesis, inflammation and coagulation markers in patients treated for advanced non-small cell lung cancer. PATIENTS AND METHODS: Peripheral blood samples were obtained from 60 patients before first line platinum-based chemotherapy ± bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Angiogenesis, inflammation and coagulation markers vascular endothelial growth factor (VEGF), their soluble receptors 1 (VEGFR1) and 2 (VEGFR2), thrombospondin-1 (TSP-1), interleukin-6 (IL6), sialic acid (SA) and tissue factor (TF) were quantified by ELISA. RESULTS: Except for TSP-1, pre- and post-treatment levels of all markers were higher in patients than in controls (p < 0.05). There was a positive and significant correlation between VEGF and VEGFR2 before treatment. VEGF also correlated with inflammatory markers IL-6 and SA. Moreover, there was a positive and significant correlation between levels of VEGFR1 and TF. Decreased levels of TSP-1 and increased levels of VEGF were associated with shorter survival. Bevacizumab significantly modified angiogenesis parameters and caused a decrease of VEGF and an increase of TSP-1. CONCLUSION: Angiogenesis, inflammation and coagulation markers were increased in NSCLC patients. Increased levels of VEGF and low levels of TSP-1 correlated with a poor prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/sangue , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Docetaxel , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
14.
J Thorac Oncol ; 8(4): 443-51, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23370367

RESUMO

PURPOSE: In a multicenter randomized phase II trial of gemcitabine (arm A), erlotinib (arm B), and gemcitabine and erlotinib (arm C), similar progression-free survival (PFS) and overall survival (OS) were observed in all arms. We performed an exploratory, blinded, retrospective analysis of plasma or serum samples collected as part of the trial to investigate the ability of VeriStrat (VS) to predict treatment outcomes. METHODS: Ninety-eight patients were assessable, and the majority had stage IV disease (81%), adenocarcinoma histology (63%), reported current or previous tobacco use (84%), and 26% had a performance status (PS) of 2. RESULTS: In arm A, patients with VS Good (n = 20) compared with VS Poor status (n = 8) had similar PFS (hazard ratio [HR]: 1.21; p = 0.67) and OS (HR: 0.82; p = 0.64). In arm B, patients with VS Good (n = 26) compared with VS Poor (n = 12) had a statistically significantly superior PFS (HR: 0.33; p = 0.002) and OS (HR: 0.40; p = 0.014). In arm C, patients with VS Good (n = 17) compared with Poor (n = 1 5) had a superior PFS (HR: 0.42; p = 0.027) and a trend toward superior OS (HR: 0.48; p = 0.051). In the multivariate analysis for PFS, VS status was statistically significant (p = 0.011); for OS, VS status (p = 0.017) and PS (p = 0.005) were statistically significant. A statistically significant VS and treatment interaction (gemcitabine versus erlotinib) was observed for PFS and OS. CONCLUSIONS: Gemcitabine is the superior treatment for elderly patients with VS Poor status. First-line erlotinib for elderly patients with VS Good status may warrant further investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteômica , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida
15.
Clin Lung Cancer ; 14(4): 364-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23276824

RESUMO

BACKGROUND: Many cancers metastasize to bone, which may cause an increase in bone resorption because of the direct effects of the tumor itself or osteoclastic activation. PATIENTS AND METHODS: Levels of urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum cross-linked N-telopeptide of type I collagen (sNTx) were measured in 100 patients with lung cancer and 50 patients with benign respiratory disease using the Osteomark NTx urine and serum assays (Osteomark, Princeton, NJ). Bone metastasis was diagnosed by bone scintigraphy. Receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity to detect bone metastasis were calculated when cutoff points were set to 64 nmol bone collagen equivalents (BCE)/mmol Cr for uNTx and 22 nmol BCE/L for sNTx. RESULTS: Patients with lung cancer and bone metastasis had significantly higher levels of both uNTx and sNTx (uNTx median [range], 61.3 [22.7-593.1] nmol BCE/mmol creatinine [Cr]; sNTx median [range], 19.7 [10.7-97.1] nmol BCE/L) than did patients with lung cancer without bone metastasis (uNTx median [range], 45.2 [19.8-153.0] nmol BCE/mmol Cr; sNTx median [range], 16.7 [11.0-28.4] nmol BCE/L), or patients with benign respiratory diseases (uNTx median [range], 40.6 [15.2-155.9] nmol BCE/mmol Cr; sNTx median [range], 14.8 [9.5-55.5] nmol BCE/L.). There was good correlation between uNTx and sNTx (R = 0.807). Area under the curve (AUC) for ROC was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis were 48.0% and 86.0%, respectively, using uNTx, and 40.0% and 87.0%, respectively, using sNTx. CONCLUSION: This prospective study indicates equivalency between sNTx and uNTx in sensitivity and specificity to detect bone metastasis, and both uNTx and sNTx may have value as aids in the diagnosis of bone metastasis in patients with lung cancer.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Neoplasias Ósseas/secundário , Colágeno Tipo I/sangue , Colágeno Tipo I/urina , Neoplasias Pulmonares/patologia , Peptídeos/sangue , Peptídeos/urina , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/urina , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/urina , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/urina , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/urina , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/urina , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/urina
16.
Zhonghua Zhong Liu Za Zhi ; 35(12): 910-3, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24506960

RESUMO

OBJECTIVE: To analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance. METHODS: One hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed. RESULTS: The expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05]. CONCLUSION: Up-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.


Assuntos
Adenocarcinoma/sangue , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia , Adenocarcinoma/patologia , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Antígenos CD8/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Linfócitos T/metabolismo , Regulação para Cima
17.
Hormones (Athens) ; 12(4): 584-90, 2013 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24457407

RESUMO

OBJECTIVE: Serum calcitonin (CT) is a sensitive but not specific marker for medullary thyroid carcinoma (MTC). There are a large number of conditions that may elevate CT levels. CASE REPORT: Herein we present the case of a 47-year old woman with Hashimoto thyroiditis, goiter, cervical lymphadenopathy and high CT and CEA levels. After surgical extirpation of the lymph node neuroendocrine cancer metastasis was suspected. Computed tomography of the chest showed a tumor mass on the right lung. Bronchoscopy was performed and pathological and immunohistochemical analysis revealed large cell neuroendocrine lung cancer (LCNEC). After chemotherapy, significant reduction of tumor mass was achieved with a moderate decrease in CT levels in parallel. CONCLUSIONS: We present a female with LCNEC, a condition which is usually observed in older men (7(th) decade) and is not associated with CT secretion. Hashimoto thyroiditis is associated with increased incidence of different types of cancers (e.g. thyroid, colon). No reports at present exist on the incidence of lung cancers in patients with thyroid disease.


Assuntos
Calcitonina/sangue , Carcinoma de Células Grandes/sangue , Carcinoma Neuroendócrino/sangue , Hormônios Ectópicos/sangue , Neoplasias Pulmonares/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma Neuroendócrino/tratamento farmacológico , Comorbidade , Tratamento Farmacológico , Feminino , Bócio/epidemiologia , Bócio/cirurgia , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/cirurgia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Cancer Radiother ; 16(3): 179-82, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22521871

RESUMO

PURPOSE: This study was to evaluate the influence of radiotherapy on the selenium serum levels of non-small cell cancer patients with brain metastases. PATIENTS AND METHODS: This prospective study included 95 non-small cell cancer patients with brain metastases treated by radiotherapy from December 2007 until November 2010. Plasma selenium levels were determined before and at the end of the radiotherapy. Age, body mass index (BMI), prior chemotherapy, pathological type and personal habits (smoking and alcoholism) were recorded for each patient. RESULTS: The mean age was 63 years; the mean BMI was 27.6. Seventy-six patients (80%) were non-smokers. Sixty-two patients (65.3%) showed no drinking habits and 8 (8.4%) have no prior chemotherapy. Thirty-nine patients (41.1%) were adenocarcinoma, 51 (53.7%) were squamous cell carcinoma and five (5.3%) were large cell carcinoma. At the beginning of radiotherapy, the mean selenium level for all patients was 90.4 µg/l and after radiation this value dropped to 56.3 µg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P<0.001), BMI (P<0.001), smoking (P<0.001), alcoholism (P<0.001), prior chemotherapy (P<0.001) and pathological type (P<0.001). CONCLUSION: Significant reduction in plasma levels of selenium was recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.


Assuntos
Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares , Selênio/sangue , Adenocarcinoma/sangue , Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/sangue , Índice de Massa Corporal , Neoplasias Encefálicas/radioterapia , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/radioterapia , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Fumar/sangue
19.
Int J Oncol ; 40(6): 1957-62, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22426972

RESUMO

Aiming to identify novel sero-diagnostic markers for neuroendocrine carcinomas of the lung, the two-dimensional gel electrophoresis-immunoblot method was used to analyze tumor-associated autoantibodies in patients with small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Several autoantigens were revealed and anti-HuC autoantibody was detected only in sera of SCLC patients. Since Hu family proteins including HuC are well-known causes of paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/SN), the expression of HuC as well as HuD mRNAs and their proteins was studied in 11 lung cancer cell lines. The expression of HuC and HuD mRNAs and proteins was only detected in SCLC- and LCNEC-derived cells. To validate the existence of anti-HuC and -HuD auto-antibodies, we studied a large number of sera including those from lung cancer patients employing dot blot analysis. Anti-HuC and -HuD autoantibodies were detected only in SCLC cases with or without PEM/SN, and not in the sera of LCNEC patients. The mechanism leading to different anti-HuC and -HuD autoantibody production between SCLC and LCNEC is unclear; however, the results from the present and previous studies suggest that anti-HuC and -HuD auto-antibodies are novel differential sero-diagnostic markers for SCLC from LCNEC.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma Neuroendócrino/diagnóstico , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Área Sob a Curva , Carcinoma de Células Grandes/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma de Células Pequenas/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Diagnóstico Diferencial , Proteínas ELAV/imunologia , Proteína Semelhante a ELAV 3 , Proteína Semelhante a ELAV 4 , Eletroforese em Gel Bidimensional , Humanos , Neoplasias Pulmonares/sangue , Curva ROC
20.
Med Oncol ; 29(2): 582-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21327739

RESUMO

Bone morphogenetic proteins (BMPs) are members of the TGF-ß superfamily, and some studies demonstrated that BMPs enhance tumorigenesis and metastasis. The purpose of this study was to identify whether BMP-2 levels are elevated in the serum of non-small-cell lung cancer (NSCLC) patients and are associated with the stage and overall survival. Blood samples from 150 patients with NSCLC were analyzed. Also, 69 healthy volunteers were tested as control group. In NSCLC patients, whole blood was obtained before beginning any treatment modalities, and serum BMP-2 levels were quantified by commercially available ELISA kit. The NSCLC group demonstrated a significantly higher level of serum BMP-2 than the control group. (The median levels were 25.50 pg/ml for the control group and 72.23 pg/ml for the NSCLC group, P < 0.001). The median serum BMP-2 level in the advanced stage group (stage IIIb or IV) was significantly more elevated than that of the localized stage group (stage I, II, IIIa) (75.66 pg/ml and 44.36 pg/ml, P = 0.006). Patients with multiple metastatic sites (≥5) showed significantly higher level of serum BMP-2 than the patients with less than 5 metastatic sites. (79.39 pg/ml vs. 59.70 pg/ml, P = 0.013), and the median serum BMP-2 level from the patients with multiple metastatic organs (≥3) was significantly higher than that from the patients with single or two metastatic organs (<2) (89.39 pg/ml vs. 66.90 pg/ml, P = 0.001). Moreover, the patients with relatively lower BMP-2 level (≤70 pg/ml) had longer median overall survival than the patients with higher BMP-2 level (>70 pg/ml). (525 days vs. 260 days). One-year survival rate for the patients with lower BMP-2 level was also higher than that for the patients with higher BMP-2 level. (59.6% versus 40.2%, P = 0.034). The serum BMP-2 level is positively correlated with the stage and metastatic burden and maybe a probable predictor of survival in the NSCLC patients.


Assuntos
Adenocarcinoma/sangue , Proteína Morfogenética Óssea 2/metabolismo , Neoplasias Ósseas/sangue , Carcinoma de Células Grandes/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
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