Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 269
Filtrar
1.
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
2.
Mol Med Rep ; 21(1): 51-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746355

RESUMO

Matrix­assisted laser desorption/ionization time­of­flight mass spectrometry (MALDI­TOF­MS) was employed to analyze differential serum and urine peptides in patients with small cell lung cancer (SCLC) and healthy individuals, and SCLC diagnostic classification models were constructed. Serum and urine samples from 72 patients with SCLC, age­ and gender­matched with 72 healthy individuals, were divided into training and testing sets in a 3:1 ratio. Serum and urine peptides were extracted using copper ion­chelating nanomagnetic beads, and mass spectra were obtained using MALDI­TOF­MS. Peptide spectra for the training set were analyzed, and the classification model was constructed using ClinProTools (CPT). The testing set was used for blinded model validation. For training­set sera, 122 differential peptide signal peaks with a mass of 0.8­10 kDa were observed, and 19 peptides showed significantly different expression [P<0.0005; area under curve (AUC) ≥0.80]. CPT screened 5 peptide peaks (0.8114, 0.83425, 1.86655, 4.11133 and 5.81192 kDa) to construct the classification model. The testing set was used for the blinded validation, which had 95.0% sensitivity and 90.0% specificity. For the training­set urine, 132 differential peptide signal peaks with m/z ratios of 0.8­10 kDa were observed, and 8 peptides had significantly different expression (P<0.0005; AUC ≥0.80). Then, 5 peaks (1.0724, 2.37692, 2.7554, 4.75475 and 4.7949 kDa) were used for classification model construction. The testing set was used for 36 blinded validation, which had 85.0% sensitivity and 80.0% specificity. Among the differential peptides, 3 had the same significant peaks at 2.3764, 0.8778 and 0.8616 kDa, identified as fibrinogen α, glucose­6­phosphate isomerase and cyclin­dependent kinase­1, respectively. The present study highlighted the differences that exist in serum and urine peptides between patients with SCLC and healthy individuals. Serum and urine peptide diagnostic classification models could be constructed using MALDI­TOF­MS, and showed high sensitivity and specificity.


Assuntos
Neoplasias Pulmonares , Proteínas de Neoplasias , Peptídeos , Carcinoma de Pequenas Células do Pulmão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/urina , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/urina , Peptídeos/sangue , Peptídeos/urina , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/urina
3.
Int J Cancer ; 146(9): 2394-2405, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Inflamação/complicações , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/etiologia , Adulto , Idoso , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/etiologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/imunologia , Cinurenina/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/etiologia , Triptofano/sangue
4.
J Transl Med ; 17(1): 402, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796037

RESUMO

BACKGROUND: Immunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression. METHODS: This study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured. RESULTS: CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324-14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = - 0.379; p = 0.0003, r = - 0.464). CONCLUSION: The present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Movimento Celular , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Proliferação de Células , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto Jovem
5.
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
6.
Crit Rev Biomed Eng ; 47(3): 217-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679257

RESUMO

Early detection is crucial to the proper and effective treatment of two metastatic cancers, prostate cancer and small cell lung cancer. Currently, preventative screenings for these conditions are restricted to high-risk populations and extremely expensive. The discovery of clinically indicative biomarkers has been revolutionary in advancing screening and diagnostic capabilities. Prostate-specific antigen (PSA), an extracellular secreted protein of the prostate gland, and neuron-specific enolase (NSE), an enzyme of neuronal origin, have reported reputable specificity for prostate cancer and small cell lung cancer (SCLC). Current efforts are underway to develop a rapid, label-free means of measuring both PSA and NSE levels in a clinical environment for early screening applications of highly metastatic cancers. Electrochemical impedance spectroscopy (EIS) and impedance time (Z-t) are rapid, sensitive electrochemical techniques previously validated in the detection of several clinically relevant biomarkers, including cardiovascular disease and diabetes mellitus. Herein, we determine the optimal frequencies of PSA (81.38 Hz) and NSE (14.36 Hz) using EIS that are robust across analytical platforms and in the presence of potentially interfering species. The reported empirical evidence supports the prevalence of electrostatic interactions in electrochemical systems and provides alternative theoretical support of previous findings. Finally, Z-t was implemented for its utility in continuous monitoring applications and to lay the foundation for future improvements to continuous sensor platforms.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/instrumentação , Neoplasias Pulmonares/diagnóstico , Neoplasias da Próstata/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Técnicas Biossensoriais/métodos , Detecção Precoce de Câncer/métodos , Impedância Elétrica , Eletrodos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Conformação Molecular , Fosfopiruvato Hidratase/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Eletricidade Estática
7.
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
8.
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
9.
Clin Exp Pharmacol Physiol ; 46(12): 1074-1083, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31381177

RESUMO

The present study was designed to evaluate the percentage of different programmed cell death-1 (PD-1)+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD-1+ T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD-1+ T cell subsets. These present results revealed that the percentage of circulating PD-1+ Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non-small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD-1+ Tfh cells were also significantly enhanced in patients in the extensive-stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD-1+ Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD-1+ Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL-2 and IFN-γ derived from PD-1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD-1+ T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target.


Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Carcinoma de Pequenas Células do Pulmão/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/terapia , Evasão Tumoral/fisiologia
11.
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 , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/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
12.
Thorac Cancer ; 10(10): 1962-1972, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441580

RESUMO

BACKGROUND: Previous studies have reported that soluble fms-like tyrosine kinase-1 (sFlt-1) possesses anti-tumor effects by inhibiting angiogenesis in many cancers. Exosomes can be engineered as delivery vehicles for transferring functional biomolecules, such as proteins, lipids, and nucleic acids (DNA, mRNA, and miRNA) to target cells to affect inflammation, apoptosis, and angiogenesis. The purpose of this study was to investigate whether exosomes can function as efficient carriers of sFlt-1 in vitro and in vivo, to play a role in SCLC therapy. METHODS: We adopted three different methods: TEM, NTA and western blot analysis to characterize the cell-derived exosomes from NCI-H69 SCLC cell line and normal bronchial epithelial BEAS-2B cell line. we next explored the effects of these exosomes on HUVE cell proliferation and migration in vitro.To verify sFlt-1-loaded exosomes suppress the tumor growth in vivo,we established subcutaneous xenografts in nude mice using the NCI-H69 cell line. RESULTS: We observed that NCI-H69-exo significantly increased human umbilical vein endothelial cells (HUVEC) migration compared to BEAS-2B-exo in vitro and in vivo. sFlt-1 protein expression was statistically higher in BEAS-2B-exo than NCI-H69-exo. sFlt-1 protein or sFlt-1-enriched exosomes can inhibit the migration of HUVECs. Furthermore, sFlt-1-enriched exosomes exhibited higher inhibition efficacy on pro-angiogenesis of NCI-H69-exo in comparison with the same concentration of sFlt-1 protein. Intriguingly, sFlt-1-loaded exosomes showed marked anti-tumor activity by inhibiting the growth of NCI-H69 tumor xenografts. CD31 staining revealed that sFlt-1-loaded exosomes significantly reduced the vascular density of experimental mice. sFlt-1-loaded exosomes markedly induced tumor apoptosis and inhibited tumor cell proliferation in mice. CONCLUSION: Exosomes from a SCLC cell line contain low levels of sFlt-1 and significantly increased the migration of HUVECs. SFlt-1-enriched exosomes can inhibit NCI-H69-exo-induced HUVEC migration. Exosomes enriched in sFlt-1 have the potential to be effective therapeutic agents for SCLC.


Assuntos
Células Endoteliais/metabolismo , Exossomos/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Animais , Apoptose , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Exossomos/ultraestrutura , Feminino , Humanos , Neoplasias Pulmonares/sangue , Camundongos , Carcinoma de Pequenas Células do Pulmão/sangue
13.
Clin Cancer Res ; 25(20): 6119-6126, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31300452

RESUMO

PURPOSE: Patients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC. EXPERIMENTAL DESIGN: ctDNA test results were prospectively collected from patients with SCLC between 2014 and 2017 and analyzed. ctDNA profiles of SCLC at diagnosis and relapse were also compared. RESULTS: A total of 609 samples collected from 564 patients between 2014 and 2017 were analyzed. The median turnaround time for test results was 14 days. Among patients with data on treatment status, there were 61 samples from 59 patients and 219 samples from 206 patients collected at diagnosis and relapse, respectively. The number of mutations or amplifications detected per sample did not differ by treatment status. Potentially targetable alterations in DNA repair, MAPK and PI3K pathways, and genes such as MYC and ARID1A were identifiable through ctDNA testing. Furthermore, our results support that it may be possible to reconstruct the clonal relationship between detected variants through ctDNA testing. CONCLUSIONS: Patients with relapsed SCLC rarely undergo biopsies for molecular testing and often require prompt treatment initiation. ctDNA testing is less invasive and capable of identifying alterations in relapsed disease in a clinically meaningful timeframe. ctDNA testing on an expanded gene panel has the potential to advance our knowledge of the mechanisms underlying treatment resistance in SCLC and aid in the development of novel treatment strategies.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Reparo do DNA/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Estudos de Viabilidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida/métodos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Adulto Jovem
14.
Eur J Cancer ; 118: 82-90, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31326730

RESUMO

BACKGROUND: Coagulation activation is a hallmark of cancer, and anticoagulants have shown tumour-inhibiting properties. However, recent trials have failed to demonstrate improved survival with low-molecular-weight heparin (LMWH) in cancer populations. This has raised the question of suboptimal adherence as a possible explanation for the lack of benefit. Still, there is no standardised method to directly monitor LMWH in patient plasma. Here, we directly determine LMWH levels in patients using the Heparin Red assay to objectively assess adherence and how this associates with the patient outcome in the RASTEN trial. METHODS: RASTEN is a multicentre, randomised phase III trial investigating if the addition of LMWH to standard therapy can improve survival in small-cell lung cancer. LMWH was measured in plasma (N = 258) by the Heparin Red assay and compared with the anti-factor Xa (anti-FXa) activity assay. RESULTS: Both methods could differentiate patients in the LMWH arm from the control arm and patients receiving therapeutic LMWH owing to thrombosis. Receiver Operating Characteristic (ROC) analysis yielded adherence rates of 85% for anti-FXa and 68% for Heparin Red. No survival benefits were found in the adherent subgroup compared with the control arm (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.95-1.67; P = 0.105 and HR: 1.19; 95% CI: 0.89-1.60; P = 0.248 for anti-FXa and Heparin Red, respectively). Heparin Red could define patients with high probability of adherence to LMWH treatment, which warrants prospective studies for further validation. Our finding that the LMWH-adherent subpopulation did not show improved survival excludes that the negative outcome of RASTEN was due to poor adherence.


Assuntos
Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Enoxaparina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adesão à Medicação , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Trombose/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Testes de Coagulação Sanguínea , Monitoramento de Medicamentos , Enoxaparina/efeitos adversos , Enoxaparina/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Suécia , Trombose/sangue , Trombose/mortalidade , Fatores de Tempo , Resultado do Tratamento
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...