Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.284
Filtrar
1.
Recent Results Cancer Res ; 215: 299-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605236

RESUMO

Lung cancer is the number one cause of cancer-related mortality worldwide. To improve disease outcome, it is crucial to implement biomarkers into the clinics which assist physicians in their decisions regarding diagnosis, prognosis, as well as prediction of treatment response. Liquid biopsy offers an opportunity to obtain such biomarkers in a minimal invasive manner by retrieving tumor-derived material from body fluids of the patient. The abundance of circulating microRNAs is known to be altered in disease and has therefore been studied extensively as a cancer biomarker. Circulating microRNAs present a variety of favorable characteristics for application as liquid biopsy-based biomarkers, including their high stability, relatively high abundance, and presence is nearly all body fluids. Although the application of circulating microRNAs for the management of lung cancer has not entered the clinics yet, several studies showed their utility for diagnosis, prognosis, and efficacy prediction of various treatment strategies, including surgery, radio-/chemotherapy, as well as targeted therapy. To compensate for their limited tumor specificity, several microRNAs are frequently combined into microRNA panels. Moreover, the possibility to combine single microRNAs or microRNA panels with tumor imaging or other cancer-specific biomarkers has the potential to increase specificity and sensitivity and could lead to the clinical application of novel multi-marker combinations.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , RNA Neoplásico/sangue , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Prognóstico , RNA Neoplásico/genética
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.
Anticancer Res ; 39(9): 5195-5201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519633

RESUMO

BACKGROUND/AIM: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and anti-programmed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. MATERIALS AND METHODS: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. RESULTS: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). CONCLUSION: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/sangue , Biomarcadores Tumorais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(37): e17179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517874

RESUMO

We investigated oxidative stress parameters in the sera of patients with lung cancer and healthy individuals to evaluate their correlations with lung cancer.Ninety-four lung cancer patients and 64 healthy controls were enrolled after obtaining informed consent. Their sera oxidative stress parameters were measured.Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were significantly different between patients and healthy groups (all P < .001). TAS gradually decreased and TOS and OSI gradually increased from stage I to III, but it did not reach statistical significance (all P > .05). TAS and OSI were significantly different between the nonsmoking and smoking groups, radiotherapy and without radiotherapy groups, chemotherapy and without chemotherapy groups (P < .05), but not TOS (P > .05). In a receiver operating characteristic curve analysis comparing patients with lung cancer with healthy controls, the Youden indices of TOS, TAS, and OSI were 0.541, 0.532, and 1, respectively.The oxidative stress may be correlation with lung cancer staging. Smoking, surgery, radiotherapy, and chemotherapy showed correlation with parts oxidative stress parameters.


Assuntos
Antioxidantes/metabolismo , Neoplasias Pulmonares/sangue , Oxidantes/sangue , Biomarcadores Tumorais/sangue , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Curva ROC , Fumar/sangue
5.
Chem Commun (Camb) ; 55(76): 11458-11461, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31535684

RESUMO

We report a polymer-based sensor that rapidly detects cancer based on changes in serum protein levels. Using three ratiometric fluorescence outputs, this simple system identifies early stage and metastatic lung cancer with a high level of accuracy exceeding many biomarker-based assays, making it an attractive strategy for point-of-care testing.


Assuntos
Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Corantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagem , Polímeros/química , Animais , Fluorescência , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Neoplasias Experimentais/sangue , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/secundário , Testes Imediatos
6.
Medicine (Baltimore) ; 98(31): e16712, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374064

RESUMO

Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Adenocarcinoma/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Proteínas Nucleares/sangue , Proteína Nuclear Ligada ao X/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
7.
Medicine (Baltimore) ; 98(32): e16764, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393394

RESUMO

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Fibrinogênio/análise , Neoplasias Pulmonares/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais , Antígeno Ca-125/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfopiruvato Hidratase/sangue , Estudos Retrospectivos , Serpinas/sangue , Fatores Sexuais
8.
Zhonghua Zhong Liu Za Zhi ; 41(8): 633-637, 2019 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-31434457

RESUMO

Objective: To investigate whether elevated levels of C-reactive protein (CRP) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence. Methods: From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow-up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer. Results: A total of 92 735 participants were enrolled in this study. During the follow-up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg/L and NE≤4×10(9)/L(Group A), CRP≤3 mg/L and NE>4×10(9)/L(Group B), CRP>3 mg/L and NE≤4×10(9)/L(Group C), CRP>3 mg/L and NE>4×10(9)/L(Group D). The cumulative incidence of lung cancer were 950/100 000, 1 030/100 000, 1 081/100 000 and 1 596/100 000 in these four groups, respectively (P<0.001). Multivariate Cox proportional risk model showed that participants from Group D had an significantly increased 72% risks of lung cancer when compared to Group A (95% CI: 1.40~2.12, P<0.001). Stratified analyses gender showed that males in Group D had higher risk of lung cancer when compared with participants in Group A (HR=1.73, 95% CI: 1.40~2.15, P<0.001). Conclusion: Elevated levels of CRP and NE might increase the risk of lung cancer.


Assuntos
Neoplasias Pulmonares/epidemiologia , Proteína C-Reativa/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Masculino , Neutrófilos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
9.
Anticancer Res ; 39(8): 4517-4523, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366554

RESUMO

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. PATIENTS AND METHODS: PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. RESULTS: Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. CONCLUSION: The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample.


Assuntos
Biomarcadores Tumorais/sangue , Imunoterapia , Neoplasias Pulmonares/sangue , Proteínas de Neoplasias/genética , Idoso , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
10.
Wien Klin Wochenschr ; 131(17-18): 419-426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31440821

RESUMO

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin­2 and nectin­4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin­2 and nectin­4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin­2 and nectin­4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin­2 was found superior to both serum nectin­4 and serum nectin-2 + nectin­4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin­2 and nectin­4 might be used in lung cancer diagnosis but the diagnostic importance of nectin­2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.


Assuntos
Moléculas de Adesão Celular , Neoplasias Pulmonares , Nectinas/sangue , Microambiente Tumoral , Moléculas de Adesão Celular/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Prognóstico , Estudos Retrospectivos
11.
Cancer Treat Rev ; 78: 31-41, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326635

RESUMO

Current classification and treatment of lung cancer rely increasingly on molecular and genetic testing. Obtaining tumor tissue is not always feasible and multiple biopsies are undesirable. In response to the demand for non-invasive molecular and genetic testing in cancer care, several liquid biopsy technologies, including circulating DNA (ctDNA), have been developed. ctDNA analysis is now technically feasible to be carried out in large scales and integrated into clinical practice owing to the advances in technology. Despite the challenges in improving test accuracy and cost-effectiveness, there are huge potentials for ctDNA analysis in lung cancer management. This review focuses on the clinical utility of ctDNA analysis in lung cancer, including early detection, monitoring treatment response and detecting residual disease, identification of genetic determinants for targeted therapy, and predicting efficacy of immune checkpoint blockade.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , DNA de Neoplasias/sangue , Neoplasias Pulmonares/diagnóstico , Humanos , Biópsia Líquida , Neoplasias Pulmonares/sangue
12.
Isr Med Assoc J ; 21(6): 394-398, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31280508

RESUMO

BACKGROUND: The main acquired resistance mechanism to first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR mutant non-small cell lung cancer (NSCLC) is the propagation of T790M clones, which can be detected in circulating tumor DNA (ctDNA). OBJECTIVES: To analyze osimertinib outcomes according to T790M testing method. METHODS: The study comprised 33 consecutive patients with advanced EGFR mutant NSCLC who were diagnosed with a T790M mutation after progression on first- or second-generation EGFR TKIs and treated with osimertinib. The patients were divided into groups A (diagnosed by tumor testing) and B (by ctDNA testing). Osimertinib outcomes were compared between the groups. RESULTS: Objective response rate with osimertinib comprised 54% and 62% in groups A and B, respectively (P = 0.58). Median progression-free survival (PFS) with osimertinib was 8.9 months (95% confidence interval [95%CI] 1.8-17.5) and 9.1 months (95%Cl 5.3-12.6) in groups A and B, respectively (log-rank test 0.12, P = 0.73). Median overall survival (OS) was 13.8 months (95%CI 4.9-25.5) and 13.8 months (95%Cl 7.7-27.7) in groups A and B, respectively (log-rank test 0.09, P = 0.75). T790M testing technique did not affect PFS (hazard ratio [HR] 1.16, 95%CI 0.50-2.69, P = 0.73) or OS (HR = 1.16, 95%CI 0.45-3.01, P = 0.76). The proportion of patients diagnosed by ctDNA grew from 56% in 2015 to 67% in 2016-2017. CONCLUSIONS: Our study provides a ctDNA validation for the purpose of T790M testing in EGFR mutant NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/tratamento farmacológico , Piperazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Humanos , Israel , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Resultado do Tratamento
13.
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
14.
Medicine (Baltimore) ; 98(26): e16238, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261584

RESUMO

This study tries to evaluate the associations between circulating C-reactive protein (CRP) and the overall survival of patients with non-small cell lung cancer (NSCLC).One hundred ninety-two patients with advanced NSCLC who treated with chemotherapy were enrolled in this study. The cut-off value of CRP concentration was 5.0 mg/L. The patients were divided into low, intermediate and high 3 groups respectively according to the baseline level of CRP before the treatment. Kaplan-Meier analysis and Cox proportional-hazard models were used to evaluate the relationship between the CRP and overall survival time of patients.After adjusting for age, gender, smoking history, pathologic type, CRP was a significant independent impact which predicts the survival prognosis of patients with NSCLC. For all patients, the hazard ratio with high CRP levels for NSCLC-specific survival was 1.83 [95%confidenceinterval (CI) = 0.96, 3.48] compared with low CRP levels. The level of CRP was significantly correlated with survival time (hazard ratio = 1.77; 95% CI = 0.73, 4.26) for the patient with first-line chemotherapy. Patients with high level of circulating CRP also responded poorly to chemotherapy.A high level of circulating CRP was associated with a poor response and worse survival in patients with NSCLC.


Assuntos
Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
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
16.
J Cancer Res Clin Oncol ; 145(8): 2071-2082, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154543

RESUMO

PURPOSE: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. METHODS: ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. RESULTS: Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. CONCLUSION: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.


Assuntos
Quinase do Linfoma Anaplásico/genética , Plaquetas/química , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/diagnóstico , Plasma/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/métodos , Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA de Neoplasias/análise , Resistencia a Medicamentos Antineoplásicos/genética , Estudos de Viabilidade , Feminino , Humanos , Hibridização in Situ Fluorescente , Biópsia Líquida , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Células Neoplásicas Circulantes/patologia , Plasma/citologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
BMC Cancer ; 19(1): 410, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039766

RESUMO

BACKGROUND: Systemic treatment of advanced non-small cell lung cancer (NSCLC) has changed dramatically since the introduction of targeted therapies. The analysis of circulating tumor DNA (ctDNA) is a valuable approach to monitor the clonal evolution of tumors during treatment with EGFR-tyrosine kinase inhibitors (TKIs) and to detect resistance mutations. CASE PRESENTATION: A NSCLC patient with exon 19 deletion (ex19del) of EGFR was treated with osimertinib after multiple lines of treatment and obtained a partial response that lasted over 26 months. Blood was collected at each visit and ctDNA was extracted to monitor ex19del by digital droplet PCR. Within a few weeks from the beginning of osimertinib, ex19del disappeared from plasma but appeared again and steadily increased a few months later anticipating tumor progression. Interestingly, the change in ex19del was much more pronounced than other mutations, since T790M appeared 3 months after the increase of ex19del, and C797S was detectable a few weeks before clinical disease progression. Then the patient received cytotoxic chemotherapy, which was associated with a decrease in ex19del and disappearance of T790M and C797S; however, at disease progression, all EGFR mutations increased again in plasma together with MET amplification which was detected by NGS. CONCLUSIONS: The measurement of ex19del changes in ctDNA is a simple and sensitive approach to monitor clinical outcome to osimertinib and, potentially, to other therapeutic interventions.


Assuntos
Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Deleção de Sequência , Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Receptores ErbB/sangue , Receptores ErbB/genética , Feminino , Amplificação de Genes , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-met/genética , Resultado do Tratamento
18.
Yonsei Med J ; 60(6): 525-534, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124335

RESUMO

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biópsia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/genética , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
19.
World J Surg Oncol ; 17(1): 78, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060563

RESUMO

BACKGROUND: Inconsistent results according to numerous studies that had investigated the association between serum zinc levels and lung cancer risk were reported. The aim of this study was to explore whether serum zinc levels were lower in lung cancer patients than that in controls. METHODS: We systematically retrieved the databases of PubMed, Wanfang, Cochrane, ScienceDirect website, CNKI, and SinoMed databases for comprehensive relevant studies published before December 2018 and conducted a meta-analysis. Standard mean differences (SMD) were pooled using a random effects model. RESULTS: Thirty-two articles were eligible to investigate the correlation between serum zinc levels and lung cancer risk, involving 2894 cases and 9419 controls. The pooled results showed sufficient evidence approving the association between serum zinc levels and lung cancer risk. And the serum zinc levels in lung cancer were significantly lower than that in controls (summary SMD = - 0.88, 95% confidence interval (CI) = - 0.94, - 0.82). Meanwhile, consistent results were obtained both in European populations and Asian populations. No publication bias was detected in our analysis. CONCLUSIONS: The present meta-analysis suggested that serum zinc levels were significantly lower in lung cancer patients than that in controls.


Assuntos
Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Zinco/sangue , Estudos de Casos e Controles , Bases de Dados Factuais , Humanos , Estudos Observacionais como Assunto , Prognóstico , Fatores de Risco
20.
BMC Cancer ; 19(1): 427, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068179

RESUMO

BACKGROUND: Several studies have documented that blood biomarkers can improve basic prognostic models in radiotherapy and radio-chemotherapy for non-small cell lung cancer. The current study evaluated the prognostic impact of six markers focusing on their utility in homogenous subsets, compared to the significance in a large heterogeneous group. METHODS: Blood samples of 337 patients who were referred for curative or palliative external beam thoracic radiotherapy for non-small cell lung cancer were collected. The concentration of osteopontin (OPN), vascular endothelial growth factor (VEGF), erythropoetin (EPO), high mobility group box 1 protein (HMGB1), insulin-like growth factor 1 (IGF-1) and platelet-derived growth factor (PDGF) in serum were measured by ELISA assay and the prognostic potential was assessed using univariable and multivariable survival models. RESULTS: Multivariable analysis revealed that out of several variables studied six dichotomized features: namely: cigarette smoking, lack of chemotherapy, palliative doses of radiotherapy, high OPN concentration, advanced T stage and high VEGF concentration had a highly significant (p < 0.005) and independent influence on overall survival in the group of 337 patients. In a subset of patients treated with curative radio-chemotherapy or radiotherapy (N = 148) tumor pathology, EPO concentration and VEGF concentration, significantly and independently influenced overall survival. In a subset of patients with squamous cell cancer (N = 206) OPN had a highly significant impact on overall survival. In contrast, in a subset of patients with nonsquamous histology (N = 131) only VEGF had a significant influence on survival. CONCLUSIONS: Blood serum proteins appear to be clinically useful prognosticators of overall survival in radio-chemotherapy and radiotherapy for non-small cell lung cancer. In unselected heterogeneous groups, dichotomized concentrations of OPN and VEGF emerged among the strongest independent prognosticators of overall survival. VEGF and EPO concentration (dichotomized) were found to be independent prognostic factors among the patients treated with curative doses of radiotherapy. The utility of OPN as a prognostic marker appeared restricted to the patients with squamous histology.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Eritropoetina/sangue , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA