Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.700
Filtrar
1.
Medicine (Baltimore) ; 99(40): e21965, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019389

RESUMO

BACKGROUND: The epidermal growth factor receptor (EGFR) mutation status related to the treatment approach for advanced non-small cell lung cancer (NSCLC) patients. This study aimed to evaluate the diagnostic accuracy of peripheral blood circulating tumor DNA (ctDNA) in EGFR mutated advanced NSCLC patients. METHOD: The related database was systematically searched with keywords until January 19, 2020. Studies contained the histopathological and cytological advanced NSCLC samples were included, and the diagnostic data were recorded for calculating sensitivity and specificity. I statistics were used for detecting heterogeneity across studies, and the meta-regression was performed to seek the source of heterogeneity. RESULT: A total of 32 studies with 4527 advanced NSCLC patients were included in our meta-analysis. Among them, 87% of the patients were diagnosed as stage IV. The pooled sensitivity of peripheral blood ctDNA was 0.70 (95% CI: 0.63-0.75, I = 81.76) and the pooled specificity was 0.98 (95% CI: 0.96-0.99, I = 88.33). The meta-regression showed that the prospective study design and the ARMS detection method were the main source of heterogeneity for sensitivity (P < .05), and the publication country (Asia or non-Asia) was the main source of heterogeneity for specificity (P < .01). CONCLUSION: ctDNA biopsy has high specificity and diagnostic accuracy in detection of EGFR mutation in advanced NSCLC patients. When the ctDNA gene test result is negative, we should fully consider the risk of missed diagnosis, and further tissue biopsy is still needed to undertake.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/genética , Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Receptores ErbB/sangue , Feminino , Testes Genéticos , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Sensibilidade e Especificidade
2.
Nat Commun ; 11(1): 4387, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873795

RESUMO

The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell tri-cell co-culture system, neutrophils are shown to potentially suppress the tumoricidal activity of NK cells, while neutrophils themselves are tumoricidal. Intriguingly, these two modulatory effects by neutrophils are both mediated by reactive oxygen species. Collectively, the absence or presence of NK cells, governs the net tumor-modulatory effects of neutrophils.


Assuntos
Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Mamárias Animais/imunologia , Neutropenia/prevenção & controle , Neutrófilos/imunologia , Animais , Linhagem Celular Tumoral/transplante , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Injeções Intravenosas , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/sangue , Neoplasias Mamárias Animais/complicações , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos NOD , Neutropenia/sangue , Neutropenia/etiologia , Neutropenia/imunologia , Neutrófilos/efeitos dos fármacos , Cultura Primária de Células
3.
BMC Pulm Med ; 20(1): 235, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873264

RESUMO

BACKGROUND: Osteopontin (OPN) is closely related to tumor occurrence and metastasis. This study explored the clinical value of serum OPN levels in small cell lung cancer (SCLC) patients. METHODS: The ELISA method was used to determine the OPN level of 96 SCLC patients before and after first-line chemotherapy, and compared with 60 healthy controls. RESULTS: The serum OPN level of SCLC patients before treatment was significantly higher than that of the healthy control (P < 0.001). Serum OPN levels were related to disease stage, tumor size, and lymph node metastasis (P = 0.012, 0.034, and 0.037, respectively). Serum OPN level decreased after first-line chemotherapy (P = 0.019), which was related to treatment response (P = 0.011). The serum OPN level was an independent predictor of overall survival. CONCLUSIONS: The serum OPN level can be used as a biomarker to predict treatment response and survival of SCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Osteopontina/sangue , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
4.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
5.
Medicine (Baltimore) ; 99(31): e21254, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756103

RESUMO

Retinol binding protein 4 (RBP4), as an adipokine, has been identified to be associated with several types of cancer. However, no studies have assessed its effect on non-small cell lung cancer (NSCLC) risk. The objective of this study was to assess the association between serum RBP4 levels and the risk of NSCLC.A case-control study design was used to recruit 256 confirmed NSCLC cases and 256 age- and gender-matched healthy controls by frequency between August 2017 and January 2019. Serum RBP4 was measured using enzyme-linked immune absorbent assay before treatment. Unconditional logistic regression analysis was applied to estimate the odds ratio and 95% confidence interval (CI).Serum RBP4 level was significantly higher in NSCLC patients than those in the healthy control group (36.05 ±â€Š8.28 vs 29.54 ±â€Š7.71 µg/mL, P < .05). Higher serum RBP4 level was associated with increased risk of NSCLC (P trend = .001). Compare with those in the lowest tertile, the adjusted odds ratios were 1.85 (95% CIs 1.07-3.2) (P = .029) for the second tertile and 2.18 (95% CIs 1.37-3.45) (P = .001) for the highest tertile after adjusting for confounding variables. No interactions were observed after stratified analyses by body mass index and smoking status (P for interaction: .584 and .357).Our study indicated that serum RBP4 level was positively related to the risk of NSCLC. Additional studies with prospective design are required to confirm this finding.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adulto , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
6.
PLoS One ; 15(8): e0237947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833961

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. METHODS: A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. RESULTS: RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). CONCLUSION: RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Eritrócitos/citologia , Hemoglobinas/metabolismo , Neoplasias Pulmonares/imunologia , Linfócitos/citologia , Neutrófilos/citologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
PLoS One ; 15(8): e0236966, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776968

RESUMO

Platelet-leukocyte aggregates (PLAs) are associated with increased thrombosis risk. The influence of PLA formation is especially important for cancer patients, since thrombosis accounts for approximately 10% of cancer-associated deaths. Our objective was to characterize and quantify PLAs in whole blood samples from lung cancer patients compared to healthy volunteers with the intent to analyze PLA formation in the context of lung cancer-associated thrombosis. Consenting lung cancer patients (57) and healthy volunteers (56) were enrolled at the Dana Cancer Center at the University of Toledo Health Science Campus. Peripheral blood samples were analyzed by flow cytometry. Patient medical history was reviewed through electronic medical records. Most importantly, we found lung cancer patients to have higher percentages of platelet-T cell aggregates (PTCAs) than healthy volunteers among both CD4+ T lymphocyte and CD8+ T lymphocyte populations. Our findings demonstrate that characterization of PTCAs may have clinical utility in differentiating lung cancer patients from healthy volunteers and stratifying lung cancer patients by history of thrombosis.


Assuntos
Plaquetas/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Linfócitos T/patologia , Trombose/sangue , Trombose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Estudos de Casos e Controles , Agregação Celular , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
8.
Nat Commun ; 11(1): 3556, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678093

RESUMO

Early cancer detection greatly increases the chances for successful treatment, but available diagnostics for some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA for large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning of serum metabolic patterns to detect early-stage LA. We extract direct metabolic patterns by the optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 s using only 50 nL of serum. We define a metabolic range of 100-400 Da with 143 m/z features. We diagnose early-stage LA with sensitivity~70-90% and specificity~90-93% through the sparse regression machine learning of patterns. We identify a biomarker panel of seven metabolites and relevant pathways to distinguish early-stage LA from controls (p < 0.05). Our approach advances the design of metabolic analysis for early cancer detection and holds promise as an efficient test for low-cost rollout to clinics.


Assuntos
Adenocarcinoma de Pulmão/sangue , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Aprendizado de Máquina , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Detecção Precoce de Câncer , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metabolômica , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
9.
Anticancer Res ; 40(7): 4023-4027, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620647

RESUMO

BACKGROUND/AIM: Different tumor markers and systemic inflammation have been linked with cancer development and poor outcome. We aimed to establish a novel non-invasive prognostic index for patients with resectable non-small cell lung cancer (NSCLC) based on serum carcinoembryonic antigen (CEA) and C-reactive protein (CRP). PATIENTS AND METHODS: Four hundred and sixty-two patients curatively resected for NSCLC between 2008 and 2014 were included. All patients with a follow-up period of less than 5 years were omitted. The geometric mean of the normalized serum CEA and CRP levels was used as a novel tumor marker and inflammation index (TMII). The cut-off value of TMII was determined by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify the relative risk factors for survival. RESULTS: ROC curve analysis revealed a TMII cut-off value of 0.46. The group with high TMII displayed more adverse clinical characteristics. Furthermore, compared to patients with low TMII, the group with high TMII had significantly poorer survival. On multivariate analysis, TMII was independently associated with survival. CONCLUSION: We established a novel prognostic index (TMII) based on serum CEA and CRP. Preoperative TMII may predict poor outcomes in patients with NSCLC.


Assuntos
Proteína C-Reativa/análise , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Inflamação/sangue , Neoplasias Pulmonares/sangue , Idoso , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Inflamação/mortalidade , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Prognóstico
10.
Anticancer Res ; 40(7): 3889-3896, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620629

RESUMO

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have an important role in lung cancer therapy. Although the programmed cell death protein-1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden are known prognostic factors, they are insufficient to predict clinical outcomes. This study was conducted to identify novel biomarkers for ICI treatment. PATIENTS AND METHODS: We performed univariable and multivariable analyses of 110 patients with advanced non-small-cell lung cancer (NSCLC) who were treated with an ICI to identify novel biomarkers related to prognosis. We assessed their backgrounds, such as performance status (PS), PD-L1 TPS, smoking status, and peripheral white blood cell counts at baseline and on the day the second course of ICI administration. RESULTS: In the multivariable analysis, PS, driver gene, immune-related adverse events, and post-treatment absolute neutrophil counts (post-ANCs) were significantly associated with progression-free survival. CONCLUSION: A high level of post-ANCs was associated with poor outcome in ICI-treated NSCLC patients.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Biomarcadores Tumorais/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Estudos Retrospectivos
11.
PLoS One ; 15(7): e0236523, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702075

RESUMO

BACKGROUND: Gefitinib is an orally potent and selective ATP-competitive inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase and is commonly used to treat locally advanced or metastatic non-small-cell lung cancer (NSCLC) with sensitive EGFR mutations. Multiple adverse effects associated with gefitinib, including liver and lung injuries, severe nausea, and diarrhea, have limited its clinical application. Xenobiotic-induced bioactivation is thought to be an important reason for gefitinib toxicity, which encouraged us to clarify the metabolism of gefitinib in NSCLC patients. MATERIALS AND METHODS: An ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry (UPLCQ-TOF-MS) method was established to tentatively identify the metabolites of gefitinib in human plasma. The extracted ion chromatogram peak intensity threshold was set at 1500 cps with minimum MS and MS/MS peak intensities of 400 and 100 cps, respectively. RESULTS: A total of 18 tentative metabolites were identified. Eight novel tentative metabolites with metabolic changes in dechlorination, defluorination, and hydrogenation on the quinazoline skeleton; removal of a partial or complete 3-chloro-4-fluoroaniline-substituted group; and sulfate conjugation and taurine conjugation were newly discovered in human plasma. Based on structural analysis of the tentative metabolites, the metabolic pathways were proposed. In addition, the pathways of dechlorination, defluorination, and hydrogenation on the quinazoline skeleton; removal of partial or complete 3-chloro-4-fluoroaniline-substituted groups; and sulfate conjugation and taurine conjugation in humans in vivo indicate that novel metabolic pathways exist in humans. CONCLUSIONS: In summary, the metabolism of gefitinib in humans in vivo is extensive and complex. Based on in vivo evidence, the propoxy-morpholine ring side chain and O-methyl group are the critical metabolic regions of gefitinib in humans. The novel metabolic pathways differ from those of in vitro studies, suggesting that intestinal floral metabolism might be involved.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Gefitinibe/química , Neoplasias Pulmonares/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Gefitinibe/sangue , Gefitinibe/metabolismo , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem
12.
PLoS One ; 15(7): e0235611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634139

RESUMO

Liquid biopsy has become widely applied in clinical medicine along with the progress in innovative technologies, such as next generation sequencing, but the origin of circulating tumor DNA (ctDNA) has not yet been precisely established. We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and both contained ctDNA. In this paper, we demonstrate that the total amount of cfDNA is higher when patients with lung cancer have extrathoracic metastases, and the amount of long fragment cfDNA is significantly higher in those patients. To investigate the origin of long fragment cfDNA, conditioned media isolated from lung cancer cell lines was fractionated. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs), but short fragment cfDNA was not observed in any fractions. However, in peripheral blood from a metastatic animal model both fragments were detected even with those same lung cancer cell lines. In human plasma samples, long fragment cfDNA was observed in the same fraction as that from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.


Assuntos
DNA Tumoral Circulante/análise , Neoplasias Pulmonares/diagnóstico , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , DNA Tumoral Circulante/química , Meios de Cultivo Condicionados/metabolismo , Modelos Animais de Doenças , Receptores ErbB/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Frequência do Gene , Humanos , Biópsia Líquida , Pneumopatias/sangue , Pneumopatias/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , Mutação , Metástase Neoplásica , Transplante Heterólogo
13.
J Cancer Res Clin Oncol ; 146(10): 2621-2630, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32661602

RESUMO

PURPOSE: The epithelial-to-mesenchymal transition (EMT) phenotype-based subsets of circulating tumor cells (CTCs) might be predictors of tumor progression. We evaluated the clinical properties of different phenotypic CTCs in patients with non-small cell lung cancer (NSCLC). Secondly, we explored the association between different phenotypic CTCs and the uptake of 18F-fluorodeoxyglucose (FDG) by the primary tumor on a positron emission tomographic (PET) scan. METHODS: Venous blood samples from 34 pathologically confirmed Stage IIB-IVB NSCLC patients were collected prospectively. CTCs were immunoassayed using a SE-i·FISH®CTC kit. We identified CTCs into cytokeratin positive (CK+) and cytokeratin negative (CK-) phenotypes. CTC classifications were correlated with the maximum standardized uptake value (SUVmax) measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Overall survival (OS) and progression-free survival (PFS) curves were produced using the Kaplan-Meier method. RESULTS: CTCs were detected in 91.2% of NSCLC patients. CTC counting was associated with TNM stage (P = 0.014) and distant metastasis (P = 0.007). The number of CK-CTCs was also positively associated with TNM stage (P = 0.022) and distant metastasis (P = 0.007). Both total CTC counting and CK-CTC counting did not show association with SUVmax value (P = 0.959, P = 0.903). Kaplan-Meier survival analysis demonstrated that patients with ≥ 7 CTCs had shorter OS (P = 0.003) and PFS (P = 0.001) relative to patients with < 7 CTCs). Notably, the number of CK-CTCs can act as independent risk factors for PFS (P = 0.044) and OS (P = 0.043) in NSCLC patients. However, SUVmax value was not associated with OS (P = 0.895) and PFS (P = 0.686). CONCLUSION: The CTC subpopulations could be useful evidence for testing metastasis and prognosis in NSCLC patients. The SUVmax value of the primary tumor was not related to prognosis in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Fenótipo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
14.
Nat Commun ; 11(1): 3662, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699280

RESUMO

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies.


Assuntos
Proteínas Sanguíneas/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Coroa de Proteína/análise , Proteômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/química , Carcinoma Pulmonar de Células não Pequenas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Diagnóstico Diferencial , Feminino , Voluntários Saudáveis , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Nanopartículas/química , Projetos Piloto , Coroa de Proteína/química , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Fatores de Tempo
15.
Medicine (Baltimore) ; 99(22): e20314, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481402

RESUMO

BACKGROUND: Previous studies have reported that microRNA 21 (mRNA 21) has involved in the procedure of lung cancer (LC). However, its conclusions are still unclear. Thus, this study will try to elaborate the association between mRNA 21 expression in serum and LC. METHODS: The electronic databases of Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine Database, WANGFANG database, and China National Knowledge Infrastructure will be retrieved from the inception to the present. All electronic databases will be searched without limitations of language and geographical location. Case-controlled studies reporting the association between mRNA 21 expression in serum and LC will be included. In addition, we will also identify other literature sources to avoid missing potential studies. All study selection, information collection, and study quality assessment will be performed by 2 independent authors. RevMan V.5.3 software and Stata V.12.0 software will be used for data synthesis and analysis. RESULTS: This study will summarize current evidence to investigate the association between mRNA 21 expression in serum and LC. CONCLUSION: The findings of this study will present comprehensive evidence to determine whether mRNA 21 expression in serum is relevant with LC or not. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040055.


Assuntos
Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , MicroRNAs/biossíntese , Biomarcadores Tumorais , Estudos de Casos e Controles , Detecção Precoce de Câncer , Humanos , Projetos de Pesquisa
16.
Gene ; 754: 144899, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32544494

RESUMO

Epithelial-mesenchymal transition (EMT) plays a crucial role in colorectal cancer (CRC) metastasis. Soluble E-cadherin (sE-cadherin) is a peptide degradation product of the E-cadherin, a key epithelial molecule of EMT. However, it is not known if elevated levels of sE-cadherin also occur during EMT. And the study of sE-cadherin in colorectal cancer is rare. The purpose of the study was to evaluate the relationship between sE-cadherin and EMT in CRC and to evaluate the diagnostic value of sE-cadherin as a serum marker for CRC. Transforming growth factor-ß1 (TGF-ß1) was used to induce EMT in HT29 and SW480 cells. The cells treated with TGF-ß1 showed morphological and biological behavior changes consistent with EMT. Western blot and ELISA showed the levels of sE-cadherin were increased during EMT in CRC cells. In addition, we intravenously injected luciferase-labeled SW480 cells into nude mice to construct CRC metastasis model. Following the elongation of time, the fluorescence intensity of the experimental group was gradually increased. Correspondingly, the serum concentration of sE-cadherin also increased during CRC metastasis in mice. Furthermore, compared to healthy subjects, significantly higher levels of serum sE-cadherin were also observed in CRC patients and correlated with clinicopathological features. For discriminating CRC from healthy controls, the area under the receiver operating characteristic (ROC) curve (AUC) of sE-cadherin was 0.853, while the optimal cut-off point was set at 5928.16 ng/ml, the diagnostic sensitivity was 73.9% and the specificity was 80%. Compared with current commercial biomarkers (CEA, CA19-9 and CA125), the diagnostic performance of sE-cadherin was highest. Combined sE-cadherin and CEA raised the sensitivity to 82.4%. Serum sE-cadherin level can be used as a potential diagnostic biomarker of CRC.


Assuntos
Antígenos CD/sangue , Biomarcadores Tumorais/sangue , Caderinas/sangue , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/secundário , Animais , Apoptose , Neoplasias Colorretais/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Prognóstico , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Asia Pac J Clin Oncol ; 16(4): 280-286, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32525285

RESUMO

AIM: To assess the exosomal miR-21/Let-7a ratio, a noninvasive method, in distinguishing non-small cell lung cancer (NSCLC) from benign pulmonary diseases. METHODS: The exosomes were extracted from the peripheral blood serum using serum exosomal extraction kit. miR-21 and Let-7a levels were evaluated by quantitative reverse transcription polymerase chain reaction. RESULTS: We found that miR-21/Let-7a ratio of NSCLC patients was significantly higher than that of healthy people, patients with pulmonary inflammation diseases, and benign pulmonary nodules, respectively. Receiver-operating characteristic analysis revealed that as compared with healthy controls, miR-21/Let-7a produced the area under the curve (AUC) at 0.8029 in patients with NSCLC, which helped to distinguish NSCLC from healthy controls with 81.33% sensitivity and 69.57% specificity. In addition, the AUC of miR-21/Let-7a in NSCLC patients was 0.8196 in comparison to patients with pulmonary inflammation diseases. Meanwhile, the sensitivity and specificity were 56.00% and 100%, respectively. Furthermore, compared with patients with benign pulmonary nodules, the AUC of miR-21/Let-7a in NSCLC patients was 0.7539. The sensitivity and specificity were 56.00% and 82.61%, respectively. CONCLUSION: In the present study, our findings revealed that exosomal miR-21/Let-7a ratio holds considerable promise as a noninvasive biomarker for the diagnosis of NSCLC from benign pulmonary diseases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade
18.
J Cancer Res Ther ; 16(2): 222-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474505

RESUMO

Aims: The aim of this study is to investigate patients with unresectable Stage III non-small-cell lung cancer (NSCLC) receiving radiotherapy with induction and concurrent pemetrexed or docetaxel plus cisplatin (PP/DP) chemotherapy and to identify the subgroup most likely to benefit from induction chemotherapy (IC). Subjects and Methods: Patients with unresectable measurable Stage III NSCLC received two cycles of PP/DP IC followed by concurrent chemoradiotherapy at a dose of 60-66 Gy. Statistical Analysis Used: Cox regression analysis was performed to evaluate the prognostic factors for survival; logistic regression analysis was used to evaluate the predictors for response to IC, and the receiver operating characteristic curves were used to evaluate the independent factors predicting response. Results: Eighty patients were included; the median survival time (MST) was 22.1 months. Partial response (PR) to IC was an independent prognostic factor for overall survival. For patients in the PR and stable disease groups, the MST was 36.7 and 19.5 months, respectively. The independent predictors of PR to IC included classification as stage N3 cancer, baseline carcinoembryonic antigen (CEA) levels >10 ng/ml, and cytokeratin fragment 19 (CYFRA21-1) levels >6 ng/ml. With each additional independent predictor, the likelihood of having have PR to IC increased. Conclusions: Radiotherapy with induction and concurrent PP/DP chemotherapy is feasible for patients with unresectable Stage III NSCLC. IC may improve the survival of IC responders, as predicted by elevated CEA and CYFRA21-1 levels and classification as stage N3 cancer. Additional randomized trials on IC may consider these predictors to tailor individualized treatments.


Assuntos
Antígenos de Neoplasias/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia/mortalidade , Quimioterapia de Indução/mortalidade , Queratina-19/sangue , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Curva ROC , Taxa de Sobrevida
19.
Medicine (Baltimore) ; 99(20): e20263, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443368

RESUMO

BACKGROUND: This study aims to identify the association between microRNA 25 (mRNA 25) expression in serum and lung cancer (LC). METHODS: This planned study will cover all eligible case-controlled studies that report association between mRNA 25 expression in serum and LC. It will include published studies from inception to the present in Cochrane Library, PUBMED, EMBASE, Web of Science, Allied and Complementary Medicine Database, VIP database, and China National Knowledge Infrastructure regardless language and geographical location. We will also search other sources, such as conference abstracts and reference lists of related known studies and experts in the domain consulted to avoid missing potential studies. Two contributors will independently examine and select studies, collect all necessary data, and judge study quality for all included studies. We will perform statistical analysis using RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will summarize current evidence to present first systematic review of research on the association between mRNA 25 expression in serum and LC. CONCLUSION: This study will present comprehensive evidence to determine whether mRNA 25 expression in serum is associated with LC, and will provide helpful evidence for the future studies. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040056.


Assuntos
Neoplasias Pulmonares/sangue , MicroRNAs/sangue , Biomarcadores Tumorais , Estudos de Casos e Controles , Detecção Precoce de Câncer , Humanos , MicroRNAs/biossíntese , Projetos de Pesquisa
20.
Cancer Immunol Immunother ; 69(9): 1813-1822, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350592

RESUMO

BACKGROUND: Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. METHODS: A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. RESULT: NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. CONCLUSION: In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antineoplásicos/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos/métodos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA