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1.
Crit Rev Oncol Hematol ; 143: 148-152, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31675543

RESUMO

Soluble PD-1 and PD-L1 are detected in the serum and plasma of lung cancer patients. The significance of these soluble proteins as prognostic or predictive markers in lung cancer is uncertain. The testing methods used to detect soluble PD1/PD-L1 are variable with no agreement on a common definition of a positive test. The advantages of validating soluble PD1/PD-L1 relevance in lung cancer include easiness of obtaining blood samples for testing, serial measurements to assess response to treatments such as immunotherapy, and potentially early identification of cancer relapse in cases treated with curative intent. In this review, we present the available data published on soluble PD1 and PD-L1 in lung cancer.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/imunologia
2.
Medicine (Baltimore) ; 98(42): e17335, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626089

RESUMO

BACKGROUND: Previous studies have shown that microRNA-32 (miRNA-32) is an exosome microRNA that affects the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. In this study, our goal was to assess the expression of plasma microRNA-32 and its potential as a biomarker to predict the tumor response and survival of patients with NSCLC undergoing platinum-based chemotherapy. METHODS: Plasma microRNA-32 levels before and after 1 cycle of platinum-based chemotherapy in 43 patients with NSCLC were measured using a quantitative real-time polymerase chain reaction assay (qPCR). In addition, the demographic and survival data of the patients were collected for analysis. RESULTS: A significant correlation was observed between the changes in microRNA-32 levels before and after 1 chemotherapy cycle and the treatment response (P = .035). In addition, Kaplan-Meier analysis showed that the level of microRNA-32 after 1 chemotherapy cycle was significantly correlated with the prognosis of patients. The median progression-free survival (P = .025) and overall survival (P = .015) of patients with high microRNA-32 levels (≥7.73) after 1 chemotherapy cycle was 9 and 21 months, respectively. In contrast, the median survival of patients with low microRNA-32 levels (<7.73) was 5 and 10 months, respectively. CONCLUSIONS: The plasma levels of microRNA-32 correlated with the efficacy of platinum-based chemotherapy and survival, indicating that microRNA-32 may be useful for predicting the effectiveness of platinum-based chemotherapy and prognosis in NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma de Pequenas Células do Pulmão/genética , Idoso , Biomarcadores Tumorais/genética , Estudos Controlados Antes e Depois , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Resultado do Tratamento
3.
J Cancer Res Clin Oncol ; 145(11): 2713-2723, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31552488

RESUMO

BACKGROUND: During the development of tumors, tumors "educate" platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. METHODS: Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. RESULTS: Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with "favorable" first chemotherapy response. CONCLUSIONS: A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Plaquetas/metabolismo , Antígenos HLA-B/genética , Neoplasias Pulmonares/diagnóstico , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Feminino , Perfilação da Expressão Gênica , Antígenos HLA-B/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Prognóstico , RNA Mensageiro/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/genética
5.
Asian Pac J Cancer Prev ; 20(8): 2405-2407, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450913

RESUMO

Background: To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods: 90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results: The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , /análise , Adenocarcinoma de Pulmão/sangue , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Escamosas/sangue , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Carcinoma de Pequenas Células do Pulmão/sangue
6.
Medicine (Baltimore) ; 98(26): e16130, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261534

RESUMO

Pro-gastrin-releasing peptide (ProGRP) is the promising molecular tumor marker of small cell lung cancer (SCLC). Here we study the influence of different blood samples treatment methods on ProGRP.Serum with and without separation gel and heparin plasma from 10 SCLC patients and 5 healthy individuals were assayed for ProGRP immediately and 2, 4, 6, 8, 24, and 48 hours after collection.ProGRP of serum with and without separation gel and heparin plasma detected immediately was basically consistent, whereas there was a significant difference in the level of them assayed after 2 hours. No significant variation with time was observed in heparin plasma, but in serum with and without separation gel, ProGRP concentrations gradually declined with time, with statistical significance. When assayed within 2 hours, each time point of ProGRP in heparin plasma had no significant difference and the difference of PrpGRP in serum separating gel existed at 1.5 hours.Heparin plasma is the best option for clinical test of ProGRP. If serum with separation gel is used, optimization methods of turn-around-time which guarantee samples detected within 1 hour after collection can make results more instructive for clinical treatment.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Peptídeo Liberador de Gastrina/sangue , Biomarcadores Tumorais/sangue , Humanos , Neoplasias Pulmonares/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Fatores de Tempo
7.
Oncol Res Treat ; 42(10): 506-515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336378

RESUMO

PURPOSE: To determine whether hemogram parameters have prognostic effects on survival in patients with extensive-stage small cell lung cancer (ED-SCLC). METHODS: This retrospective analysis included 113ED-SCLC patients, who were followed in an oncology clinic. The data regarding the baseline patient demographic characteristics, complete blood count (white blood cell, red blood cell, hemoglobin, hematocrit, mean platelet volume, platelet, total neutrophil, total lymphocyte, total monocyte, neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and monocyte-to-lymphocyte ratio [MLR]), and survival were analyzed. According to the ROC curve drawn for overall survival (OS) analysis, the cutoff values were determined as follows: NLR ≥3, with 71.4% sensitivity and 63.6% specificity; PLR ≥0.150, with 68.1% sensitivity and 52.4% specificity; and MLR ≥0.367, with 64.4% sensitivity and 71.4% specificity. RESULTS: Of the 113 patients with ED-SCLC, 92 (81.4%) were men and 21 (18.6%) were women. The median age was 65 years (range, 35-81 years). NLR was <3 in 40 (65.4%) patients. Patients with NLR <3 had significantly higher OS than those with NLR ≥3 (15 vs. 5 months, respectively, p < 0.001). Patients with PLR <150 had significantly higher median OS than those with PLR ≥150 (14 vs. 6 months, respectively, p = 0.014). The median OS was significantly greater in patients with MLR <0.367 compared to that in patients with MLR ≥0.367 (11 vs. 6 months, respectively, p = 0.016). In multivariate analysis, NLR was the only factor associated with OS (HR = 2.26, 95% Cl 1.24-4.10). CONCLUSION: NLR was determined as an independent negative prognostic factor for OS in ED-SCLC patients at diagnosis, thus may help determine disease prognosis as a useful prognostic marker.


Assuntos
Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida
8.
Medicine (Baltimore) ; 98(25): e15721, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232917

RESUMO

Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown.Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan-Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in lung cancer patients. Patients with lower MLH1 expression levels had worse prognoses. In a cohort of 32 randomly selected patients with lung cancer, the patients with poorer treatment responses had more MLH1-negative CTCs. The total CTCs, MLH1-negative CTCs and mesenchymal markers-expressing CTCs levels were negatively correlated with prognosis in the lung cancer patients.Our data showed the clinical significance of MLH1 expression in lung cancer tissues. The characterization and numeration of CTCs based on the expression of MLH1 and mesenchymal markers may be a convenient approach for predicting treatment response and prognosis in lung cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/patologia , Proteína 1 Homóloga a MutL/metabolismo , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , China , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida
9.
Asian Pac J Cancer Prev ; 20(6): 1879-1885, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31244313

RESUMO

Background: The aim of this study was to investigate the effect of platelet parameters before concurrent chemoradiotherapy (CCRT) on survival of patients with limited disease small cell lung cancer (LD-SCLC). Methods: This study consisted of patients who received CCRT due to LD-SCLC in the oncology clinic between 1997-2017. Examined platelet parameters included total platelet count (TPC), mean platelet volume, platelet distribution width, and platelet-lymphocyte ratio. The cut-off value for TPC was determined as 306x109/U (sensitivity: 62%, specificity: 75.5%), where patients below or equal to this level was classified as Group I, and those above as Group II. Results:The study included 90 patients whose mean age was 59 years (range: 42-83) and male ratio was 80.0% (n=72). Near three-fourths of patients (74.4%) were at clinical stage III. Among stage I-II patients, mOS was found as 126 months for Group I whereas it had not been reached in Group II (p=0.158). Stage III patients showed significantly lower mOS for Group 1 (16 [range: 14.1-17.8] months) compared to that in Group 2 (19.0 [range: 15.6-62.8] months; p=0.002). In multivariate analysis, Eastern Cooperative Oncology Group performance score (p=0.003), clinical stage (p<0.001), prophylactic cranial irradiation (p=0.004), and TPC (p=0.031) was determined as the most significant factors affecting survival. Conclusion: Our study suggests association of high baseline levels of TPC to improved survival in patients scheduled to undergo CCRT for LD-SCLC. Considering easiness and universal availability of TPC measurement, potential utilization of this biomarker may be promising to predict survival, albeit requiring validation by further well-designated prospective studies.


Assuntos
Plaquetas/fisiologia , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/mortalidade , Volume Plaquetário Médio , Recidiva Local de Neoplasia/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
10.
ACS Comb Sci ; 21(6): 465-472, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31022347

RESUMO

Diagnosis of lung cancer patients with indeterminate pulmonary nodules (IPNs) presents a significant clinical challenge, with morbidity and management costs of $28 billion/year. We show that a quantitative free-solution assay (FSA), coupled with a compensated interferometric reader (CIR), improves the diagnostic performance of CYFRA 21-1 as a lung cancer biomarker. FSA-CIR is a rapid, mix-and-read, isothermal, label- and enzyme-free, matrix-insensitive, and target and probe-agnostic assay. Operating FSA-CIR at ∼40, 0.75 µL samples/day delivered a serum CYFRA 21-1 limit of quantification (LOQ) of 81 pg/mL with intra-assay and interassay CVs of 4.9% and 9.6% for four-day replicate determinations. Blinded analysis of a 225 patient cohort, consisting of 75 nonmalignant nodules, 45 adenocarcinomas, 44 squamous cell carcinomas, and 61 small cell lung cancers, gave a clear separation of cases and controls, not observed in the Cobas ECL analysis. The area under the curve (AUC) for the Mayo model increased from 0.595 to 0.923 when combined with the FSA-CIR CYFRA 21-1 measurements. In a population with nodules between 6 and 30 mm, the AUC increased from 0.567 to 0.943. In this subgroup, the positive predictive value (PPV) for all tumors by the CYFRA 21-1 assay was 98.7%. Our results demonstrate increased performance of the CYFRA 21-1 assay using FSA-CIR and represents a proof of concept for redefining the performance characteristics of this important candidate biomarker.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Interferometria , Queratina-19/sangue , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/sangue , Idoso , Carcinoma de Células Escamosas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/sangue
11.
Dis Markers ; 2019: 8170759, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944671

RESUMO

Background: Histidine-rich glycoprotein (HRG) displays anticoagulant and antifibrinolytic properties in animal models, but its effects in humans are unclear. We investigated serum HRG levels and their associations with the disease stage and prothrombotic alterations in lung cancer (LC) patients. Methods: In 148 patients with advanced LC prior to anticancer therapy (87 non-small-cell LC and 61 small-cell LC) versus 100 well-matched controls, we measured HRG levels in association with clot permeability (K s), clot turbidimetry (lag phase and maximum absorbance), and clot lysis time (CLT). Results: Compared to controls, LC patients had 45.9% lower HRG levels with no associations with demographics and comorbidities. Decreased HRG, defined as the 90th percentile of control values (<52.7 µg/ml), was 16 times more common in subjects with than without LC (OR = 16.4, 95% CI 9.2-23.5, p < 0.01). HRG < 38 µg/ml discriminated stage IIIAB/limited disease from IV/extensive disease (ED) LC. In LC patients, HRG correlated inversely with CLT (r = -0.41, p < 0.001), but not with other fibrin variables. Among stage IV/ED LC, HRG correlated significantly with K s and lag phase (r = 0.28 and r = 0.33, respectively, both p < 0.001). LC patients with low K s (10th percentile of control values) combined with prolonged CLT (90th percentile of control values) had reduced HRG levels compared to the remainder (p = 0.003). No such observations were noted in controls. Conclusions: Our study is the first to show that decreased HRG levels occur in advanced LC and are associated with the disease stage and hypofibrinolysis.


Assuntos
Coagulação Sanguínea , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Proteínas/análise , Carcinoma de Pequenas Células do Pulmão/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina
12.
Int J Biol Markers ; 34(2): 163-167, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30994045

RESUMO

BACKGROUND: Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers. METHODS: We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis. RESULTS: At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP. CONCLUSIONS: ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/sangue , Idoso , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Diagnóstico Diferencial , Feminino , Seguimentos , Peptídeo Liberador de Gastrina/sangue , Humanos , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Masculino , Fragmentos de Peptídeos/sangue , Prognóstico , Curva ROC , Proteínas Recombinantes/sangue , Carcinoma de Pequenas Células do Pulmão/sangue
14.
Int J Med Sci ; 16(3): 403-408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911274

RESUMO

The death receptor 5 (DR5) is a member of the tumor necrosis factor receptor superfamily that can transduce the apoptosis signal in cells. This study assessed serum levels of soluble death receptor 5 (sDR5) in small-cell lung cancer (SCLC) patients compared with those in healthy controls. Clinicopathological features of patients, treatment responses, and overall survival of patients were also recorded and analyzed. The sDR5 levels were analyzed using ELISA in 50 healthy controls and 82 SCLC patients before and after first-line chemotherapy. The statistical data showed that pre-treatment levels of serum sDR5 in SCLC patients were higher than those of healthy controls (P<0.001). Pre-treatment levels of serum sDR5 were significantly associated with smoking history of patients, Veterans Administration Lung Study Group (VALSG) stage, tumor size, and lymph node (N) metastasis (P=0.028, 0.001, 0.028, and 0.01, respectively). After treatment with the first-line chemotherapy, the post-treatment levels of serum sDR5 were obviously decreased (P<0.001), and correlated with treatment responses (P<0.001), although there was no significant difference in their pretreatment sDR5 levels (P=0.62). Cox proportional hazard analysis demonstrated that the post-treatment levels of serum sDR5, VALSG stage, and PS status were all independent predictors for overall survival of patients. The results from the current study indicate that serum level of sDR5 could be further confirmed as a biomarker to predict treatment responses and survival of SCLC patients.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Análise de Sobrevida , Resultado do Tratamento
15.
Molecules ; 24(4)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781735

RESUMO

Progastrin-releasing peptide (ProGRP), which is known to be highly specific and sensitive to small cell lung cancer (SCLC), has been proven to be a valuable substitute for neuron-specific enolase in SCLC diagnostics and monitoring, especially in its early stages. The detection of ProGRP levels also facilitates a selection of therapeutic treatments. For the fabrication of our proposed biosensor, titanium (IV) oxide microparticles were first used, followed by dispersing gold nanoparticles into chitosan and immobilizing them onto a carbon paste electrode (CPE) surface. The developed immunosensor exhibits a much higher biosensing performance in comparison with current methods, when it comes to the detection of ProGRP. Therefore, the proposed CPE/TiO2/(CS+AuNPs)/anti-ProGRP/BSA/ProGRP is excellent for the development of a compact diagnostics apparatus.


Assuntos
Biomarcadores Tumorais/sangue , Técnicas Biossensoriais , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Ouro/química , Humanos , Nanocompostos/química , Fosfopiruvato Hidratase/genética , Proteínas Recombinantes/sangue , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Titânio/química
16.
Clin Lab ; 65(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30775876

RESUMO

BACKGROUND: High serum neuron-specific enolase (NSE) level has been in use as a tumor marker; however, some physicians may ignore NSE levels in serum, especially when the patients are asymptomatic. Here we report a case that a 51 year old female patient with no respiratory symptoms who had a NSE level which increased extremely over three months and was eventually diagnosed small cell lung cancer (SCLC). METHODS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in right pulmonary hilar enlarged lymph node was performed for diagnosis. RESULTS: EBUS showed right pulmonary hilar lymph node enlargement. A TBNA biopsy histopathology diagnosed SCLC. CONCLUSIONS: We should pay attention to high serum NSE levels, especially when the index increased extremely over a short time.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Fosfopiruvato Hidratase/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Linfonodos/patologia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/diagnóstico
17.
Future Oncol ; 15(9): 995-1006, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30644319

RESUMO

AIM: To dynamically investigate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in limited stage small-cell lung cancer. MATERIALS & METHODS:  The AAPR within 1 week before and after chemoradiation therapy (pre- and post-AAPR) was collected and analyzed. RESULTS: Patients with low pre- or post-AAPR had shorter overall survival and progression-free survival than the high groups (p-values all <0.05). Post-AAPR was an independent prognostic factor for progression-free survival (p = 0.007) and overall survival (p = 0.003). The integration of pre- or post-AAPR improved the prognostic ability of Tumor, Node, Metastasis stage alone (0.55-0.64 and 0.68, respectively). CONCLUSION:  Post-AAPR is a reliable prognostic factor for limited stage small-cell lung cancer patients. The complementary value of AAPR to Tumor, Node, Metastasis stage is worth further validation in the future.


Assuntos
Fosfatase Alcalina/sangue , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/mortalidade , Albumina Sérica Humana/análise , Carcinoma de Pequenas Células do Pulmão/mortalidade , Quimiorradioterapia/métodos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Análise de Sobrevida
18.
Asian Pac J Cancer Prev ; 20(1): 53-57, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30678380

RESUMO

Purpose: This study aimed to evaluate the impact of tumor volume on platelet counts (PLT) and mean platelet volume (MPV) and involve these parameters on overall survival. Methods: It is a retrospective study of 99 patients with lung cancer (confirmed histologically or cytologically). Sixty-six patients underwent radical operating treatment and 33 patients had only biopsies ­ due to the inoperable status of tumor According to the histopathology profile: non-small cell carcinoma ­ 23%, adenocarcinoma - 23 %, squamous - 36%, small cell carcinoma -11%, carcinoid ­ 6%. The overall survival was measured from the time of surgery to last observation or death. The tumor's size was established based on information from histopathology protocol by using model for the ellipsoid (V=4/3 π r abc). Results: KM median survival time after surgery was 20 months (95% C.I. = 16­42). The survival time depends significantly on: Tumor feature, MPV (p=0.03, p=0.04). Patients with normal PLT levels have longer survival time (median: 11 months) than thrombocytosis group (9.5) (p=0.6). Following both the PLT and MPV, a change-point that is equal to approximately 18.5 cm3 (approx. 3.3 cm in diameter) stands for a segmented relationship between tumor volume and analyzed blood indicators. Conclusions: After an overstepping of the change-point of tumor volume inflammatory processes start and they are associated with poor prognosis. MPV may be a valuable biomarker for the diagnosis and follow up of various types of carcinoma.


Assuntos
Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Taxa de Sobrevida
19.
J Neuroimmunol ; 326: 14-18, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445363

RESUMO

Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were detectable in 61% of patients with LEMS-SCLC, and in other paraneoplastic disorders, such as opsoclonus-myoclonus and paraneoplastic cerebellar degeneration, only when there was an underlying SCLC. SOX2 antibodies are specific (>90%) markers for SCLC, but are rarely found in patients with other tumours, whether neurological symptoms are present or not.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/diagnóstico , Síndromes Paraneoplásicas/etiologia , Fatores de Transcrição SOXB1/imunologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/imunologia , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/imunologia , Adulto Jovem
20.
Cancer Biol Ther ; 20(1): 52-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183476

RESUMO

Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high mortality. Effective new therapy for advanced SCLC patients is urgently needed. By screening a FDA-approved drug library, we identified a cardiac glycoside (CG), namely digoxin (an inhibitor of cellular Na+/K+ ATPase pump), which was highly effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl supplement markedly enhanced the anti-tumor activities of digoxin in both in vitro and in vivo models of SCLC. Subsequent analysis revealed that this novel combination of digoxin/NaCl caused an up-regulation of intracellular Na+ and Ca2+ levels with an induction of higher resting membrane potential of SCLC cells. We also found that this combination lead to morphological shrinking of SCLC cells, together with high levels of cytochrome C release. Lastly, our data revealed that NaCl supplement was able to induce the expression of ATP1A1 (a Na+/K+ ATPase subunit), in which contributes directly to the increased sensitivity of SCLC cells to digoxin. Thus, this is the first demonstration that NaCl is a potent supplement necessitating superior anti-cancer effects of digoxin for SCLC. Further, our study suggests that digoxin treatment could need to be combined with NaCl supplement in future clinical trial of SCLC, particularly where low Na+ is often present in SCLC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Digoxina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Cloreto de Sódio/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Digoxina/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Potenciais da Membrana/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Sódio/sangue , Cloreto de Sódio/uso terapêutico , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
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