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1.
Biomed Res Int ; 2020: 3054373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090075

RESUMO

Objectives: In this study, we aimed to conduct a 6-year follow-up and acquire a large sample dataset to analyze the most important demographic factors and cognitive function scale variables associated with mild cognitive impairment (MCI) progression for an elderly cohort (age ≥ 60 years old). Patients and Methods. We analyzed the subjects who had participated in a survey in 2011 and were successfully contacted in the later survey in 2017. For each subject, the basic demographic information was recorded, including sex, age, education level, marital status, working status, income level, and physical mental illness history. Cognitive assessments were performed using the following scales if possible: (1) the mini-mental state examination (MMSE) scale, (2) Montreal cognitive assessment (MoCA), (3) the clinical dementia rating (CDR) scale, and (4) Hamilton Depression Scale (HAMD-17). Results: The progression outcomes were different between sexes, among age brackets, education degrees, occupations types, and income levels; different progression groups had distinct children numbers (p < 0.001), heights (p < 0.001), heights (p < 0.001), heights (p < 0.001), heights (. Conclusions: In conclusion, the MCI progression outcomes were associated with sex, age, education degrees, occupations types, income level, children number, height, and weight. MoCA and MMSE scales are supporting tools to predict the progression outcomes, especially combined with the demographic data.

2.
J Cancer ; 10(25): 6374-6383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772670

RESUMO

Cisplatin-based chemotherapy is the foundation of treatment for major non-small cell lung cancer (NSCLC) patients. However, cisplatin resistance is still a challenging issue, and the molecular mechanisms underlying this resistance remain to be fully explored. CLEC4M, a Ca2+-dependent C-type lectin, has recently been found to correlate with tumourigenesis. This study mainly focused on whether CLEC4M impacts clinical prognosis and how CLEC4M contributes to cisplatin resistance in NSCLC. Our results found that CLEC4M was correlated with poor prognosis in patients with lung cancer. In addition, a positive association between CLEC4M expression and the IC50 values of cisplatin was found, which suggests that CLEC4M may impact cisplatin sensitivity. In vitro results from cultured A549 and H1299 cells confirmed that CLEC4M could enhance cisplatin resistance, while CLEC4M knockdown led to higher sensitivity to cisplatin in these cells. Further experiments showed that the underlying mechanisms included inhibition of cisplatin-induced cell apoptosis by CLEC4M and improved DNA repair capacity by upregulating XPA and ERCC1 expression. In addition, CLEC4M was able to promote cell migration with or without cisplatin treatment. Collectively, these findings suggest the potential clinical significance of CLEC4M inhibition in overcoming cisplatin resistance in NSCLC patients.

3.
Medicine (Baltimore) ; 98(27): e16284, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277157

RESUMO

RATIONALE: Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia. PATIENT CONCERNS: A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse. DIAGNOSIS: The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP. INTERVENTION: Withdrawal of PTU and the administration of methylprednisolone. OUTCOMES: The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions. LESSONS: Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.


Assuntos
Doenças Pulmonares Intersticiais/induzido quimicamente , Propiltiouracila/efeitos adversos , Adulto , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Propiltiouracila/uso terapêutico , Tomografia Computadorizada por Raios X
4.
Cancer Biol Ther ; 20(8): 1097-1104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30990107

RESUMO

Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on in cis compound EGFR mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of EGFR in cis compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had EGFR mutation; among them, 15 patients (1.2%) harboring in cis compound EGFR mutations, with 10 patients carrying EGFR L858R in combination with a rare mutation and five patients carrying two rare EGFR mutations. No patient with EGFR 19del was observed. Interestingly, no in trans configuration was identified in this cohort. All of the patients harboring in cis compound EGFR mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with in cis compound EGFR mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating EGFR mutation. This observation was further supported by in silico molecular modeling analyses which demonstrated in cis compound mutations do not alter the ATP-binding pocket of EGFR, thus having no effect on the interaction between gefitinib and EGFR.

5.
Int Arch Allergy Immunol ; 179(1): 43-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943513

RESUMO

BACKGROUND: The aim of this study was to investigate the role of Notch-1 signaling through Notch-1 ligands on bronchial epithelial cells (BECs) in regulating the development of T helper 2 (Th2) lymphocytes after RSV infection. METHODS: Firstly, we analyzed the expression of cytokines and Notch-1 ligands in BECs by using real-time PCR. Then, RSV-infected BECs were co-cultured with CD4+ T cells in a transwell chamber for 48 h, and differentiation of T cells in the lower chamber was determined using flow cytometry and real-time PCR. JAG1 siRNA was then used to determine the effects of Jagged/Notch-1 signaling on the differentiation of Th2. An RSV-infected mouse model was also used to analyze the secretion of Th differentiation-associated cytokines in serum and lung tissues using ELISA, the histopathological changes using HE staining, and the expression of JAG1 and JAG2 in BECs. RESULTS: The results showed that RSV promoted the expression of Th2-type cytokines and Jagged-1 and inhibited the expression of Jagged-2 in normal BECs. RSV-infected BECs induced Th2 differentiation. In addition, JAG1 downregulation inhibited the differentiation of Th2 and promoted differentiation of Th1. In the RSV-infected mouse model, the RSV titer, inflammation decreased with time. IL-4 and IL-17 increased on day 28 and 60, while IFNγ increased on day 7 and 28. Moreover, the expression of Jagged-1 increased and that of Jagged-2 decreased in BECs, which was consistent with IL-4 production in lung tissues. CONCLUSION: Our data showed that BECs had the potential to promote the differentiation of Th2 lymphocytes through Jagged-1/Notch-1 signaling.


Assuntos
Brônquios/fisiologia , Proteína Jagged-1/fisiologia , Proteína Jagged-2/fisiologia , Receptor Notch1/fisiologia , Infecções por Vírus Respiratório Sincicial/imunologia , Transdução de Sinais/fisiologia , Células Th2/citologia , Animais , Brônquios/imunologia , Brônquios/patologia , Diferenciação Celular , Citocinas/biossíntese , Células Epiteliais/fisiologia , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Cardiovasc Diabetol ; 18(1): 11, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691501

RESUMO

BACKGROUND: Increasing evidence has suggested that the presence of remnant lipoproteins is a significant risk factor for atherosclerosis. Remnant lipoproteins are lipoproteins that are rich in triglycerides (TGs), and the main components include very-low-density lipoprotein (VLDL) in the fasting state. Diabetic patients often have hypertriglyceridemia with elevated levels of VLDL cholesterol but normal levels of low-density lipoprotein cholesterol (LDL-C). The aim of the present study was to elucidate the potential role of remnant lipoproteins-induced atherosclerosis in the occurrence and development of in-stent restenosis (ISR) in diabetic patients with coronary artery disease. METHODS: The present study enrolled 2312 patients with type 2 diabetes mellitus who underwent percutaneous coronary intervention from January 2013 to December 2014 and who were followed up by angiography. Patients were divided into two groups based on the presence or absence of ISR, and multivariate Cox's proportional hazards regression modelling showed that remnant-like particle cholesterol (RLP-C) was an independent risk factor for ISR. According to the receiver operating characteristic curve, the optimal cutoff point of the RLP-C was identified, and the patients were further divided into 2 groups. Propensity score matching analysis was performed, and 762 pairs were successfully matched. Log-rank tests were used to compare Kaplan-Meier curves for overall follow-up to assess ISR. RESULTS: The multivariate Cox's proportional hazards regression analysis showed that RLP-C was independently associated with ISR, and the baseline RLP-C level at 0.505 mmol/L was identified as the optimal cutoff point to predict ISR. Patients were divided into 2 groups by RLP levels. After propensity score matching analysis, a total of 762 pairs matched patients were generated. Kaplan-Meier curves showed that the estimated cumulative rate of ISR was significantly higher in patients with RLP-C levels ≥ 0.505 mmol/L (log-rank P < 0.001; HR equal to 4.175, 95% CI = 3.045-5.723, P < 0.001) compared to patients with RLP-C levels < 0.505 mmol/L. CONCLUSIONS: The present study emphasized the importance of remnant-like particle cholesterol in cardiovascular pathology in diabetic patients. Physicians should take measures to control RLP-C below the level of 0.505 mmol/L to better prevent of in-stent restenosis in diabetic patients.


Assuntos
Colesterol/sangue , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/sangue , Diabetes Mellitus Tipo 2/sangue , Lipoproteínas/sangue , Intervenção Coronária Percutânea/efeitos adversos , Triglicerídeos/sangue , Idoso , Pequim/epidemiologia , Biomarcadores/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/instrumentação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
7.
Onco Targets Ther ; 11: 8565-8573, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30573970

RESUMO

Background: The global Phase III LUX-Lung 8 trial (ClinicalTrials.gov: NCT01523587) identified significant improvements in progression-free survival (PFS), overall survival (OS), and patient-reported outcomes (PROs) with second-line afatinib vs erlotinib in patients with advanced squamous cell carcinoma (SCC) of the lung. Materials and methods: We conducted a post hoc analysis of data for patients in LUX-Lung 8 from mainland China (n=67). Compared with erlotinib, afatinib reduced the risk of disease progression or death (PFS) in the Chinese subgroup by 30% (HR=0.70; 95% CI: 0.38-1.27). Results: The risk of death was reduced by 31% (HR=0.69; 95% CI: 0.39-1.21). The proportion of Chinese patients with improvements in PROs also favored afatinib vs erlotinib (global health status/quality of life [QoL], 52.8% vs 29.6%, P=0.072; dyspnea, 47% vs 26%, P=0.091; "dyspnea walked", 44% vs 15%, P=0.017; QoL rate, 53% vs 26%, P=0.037). Discussion: While this analysis was not powered to demonstrate differences compared to the overall trial population (OTP), and there were some differences in baseline characteristics (eg, the proportion of patients aged ≥65 years old), the benefits of afatinib treatment in Chinese patients with SCC of the lung appeared to be at least comparable to that observed in LUX-Lung 8. As with the OTP, the most common adverse events (AEs) with afatinib in the Chinese subgroup were diarrhea and rash/acne, and the incidence and type of the most frequently occurring AEs were similar. Conclusion: The results suggest that afatinib represents a feasible treatment option for Chinese patients with advanced SCC of the lung following progression on platinum-based chemotherapy.

8.
Onco Targets Ther ; 11: 8575-8587, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584317

RESUMO

Introduction: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in China. Four epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors - afatinib, erlotinib, icotinib, and gefitinib - are available for first-line treatment of NSCLC in China; however, there are few data to guide treatment choice. The Phase III LUX-Lung 6 trial compared afatinib with platinum-based chemotherapy for first-line treatment of patients from Southeast Asia with EGFR mutation-positive advanced NSCLC. This post hoc analysis assessed the findings from LUX-Lung 6 in Chinese patients. Clinical trial registration: ClinicalTrials.gov: NCT01121393. Materials and methods: Previously untreated patients with EGFR mutation-positive stage IIIB/IV lung adenocarcinoma were randomized 2:1 to receive afatinib or ≤6 cycles of gemcitabine/ cisplatin. The key outcomes were progression-free survival (PFS; primary), objective response rate, disease control rate, overall survival (OS), duration of response and disease control, patient-reported outcomes, and safety. Three hundred and twenty-seven patients from mainland China were treated (89.8% of overall LUX-Lung 6 population; afatinib 217, gemcitabine/cisplatin 110). Results: PFS was significantly longer with afatinib than gemcitabine/cisplatin (median 11.0 versus 5.6 months; hazard ratio [HR], 0.30 [95% CI, 0.21, 0.43]; P,0.0001). Overall, there was no significant difference in OS between treatment arms; however, in a subgroup analysis, afatinib significantly improved OS versus gemcitabine/cisplatin in patients with an EGFR Del19 mutation (median 31.6 versus 16.3 months; HR, 0.61 [95% CI, 0.41, 0.91]; P=0.0146). Afatinib was well tolerated, with most treatment-related adverse events (TRAEs) being of grade 1 or 2 severity. The most common grade 3/4 TRAEs with afatinib were rash/acne (15.9%/0.5%), stomatitis (6.1%/0%), and diarrhea (5.6%/0%). TRAEs leading to permanent discontinuation were reported in 12 patients (5.6%) receiving afatinib and 43 (41.7%) receiving gemcitabine/cisplatin. Afatinib significantly improved PFS compared with standard first-line chemotherapy in Chinese patients with EGFR mutation-positive NSCLC and demonstrated a manageable safety profile. Conclusion: The findings support the rationale for using afatinib as a first-line treatment option for this patient population.

9.
Chin Med J (Engl) ; 131(23): 2817-2826, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30511684

RESUMO

Background: Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown. Methods: A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV1) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1-/-) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB. Results: In asthmatic patients, the change of FEV1 was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type: GR: 0.769 vs. 1.000, P = 0.022; MKP-1: 0.493 vs. 1.000, P < 0.001. GLCCI1-/-: GR: 0.629 vs. 1.645, P < 0.001; MKP-1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1-/- asthmatic mice had less improvement (wild-type: GR: 1.517 vs. 0.769, P = 0.023; MKP-1: 1.036 vs. 0.493, P = 0.003. GLCCI1-/-: GR: 0.846 vs. 0.629, P = 0.116; MKP-1: 0.475 vs. 0.377, P = 0.388). GLCCI1-/- asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001). Conclusions: GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs. Trial Registration: ChiCTR.org.cn, ChiCTR-RCC-13003634; http://www.chictr.org.cn/showproj.aspx?proj=5926.


Assuntos
Asma/tratamento farmacológico , Asma/metabolismo , Glucocorticoides/uso terapêutico , Receptores de Glucocorticoides/deficiência , Receptores de Glucocorticoides/metabolismo , Animais , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Volume Expiratório Forçado/genética , Volume Expiratório Forçado/fisiologia , Camundongos , Camundongos Knockout , Fosforilação/genética , Fosforilação/fisiologia , Receptores de Glucocorticoides/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Sci Data ; 5: 180284, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30531820

RESUMO

Gene-gene (GXG) and gene-environment (GXE) interactions play important roles in pharmacogenetics study. Simultaneously incorporating multiple single nucleotide polymorphisms (SNPs) and clinical factors is needed to explore the association of their interactions with drug response and toxicity phenotypes. We genotyped 504 SNPs in a total of 490 Chinese non-small cell lung cancer (NSCLC) patients, and the correlation of GXG and GXE interactions with platinum-based chemotherapeutic efficacy and safety were analyzed. In this data descriptor, we shared our data set which could help others to reuse them. All kinds of file types needed for GXG and GXE analysis were supplied. The process of genotyping and data analysis was also introduced step by step.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Epistasia Genética , Interação Gene-Ambiente , Neoplasias Pulmonares/genética , Antineoplásicos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único
11.
Cancer Biol Ther ; 19(10): 898-903, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30067437

RESUMO

Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.


Assuntos
Biomarcadores Tumorais , Carcinoma Adenoide Cístico/genética , Evolução Clonal/genética , Heterogeneidade Genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Montagem e Desmontagem da Cromatina , Análise Mutacional de DNA , Epigênese Genética , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores Notch/metabolismo , Transdução de Sinais , Carga Tumoral , Adulto Jovem
12.
Transl Lung Cancer Res ; 7(3): 428-436, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30050780

RESUMO

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

13.
Chin Med J (Engl) ; 131(7): 757-763, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29578117

RESUMO

Background: It is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM. Methods: Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P25, P75) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows. Results: Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701, 95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]: 1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR: 4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI: 0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4: OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001). Conclusion: PDW is an independent predictor of ISR in patients with CAD and T2DM.


Assuntos
Plaquetas/metabolismo , Doença da Artéria Coronariana/metabolismo , Reestenose Coronária/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Idoso , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Retrospectivos
14.
Patient ; 11(1): 131-141, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29178024

RESUMO

INTRODUCTION: In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported. PATIENTS AND METHODS: Lung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory. RESULTS: Compared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations. CONCLUSIONS: These exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Quinazolinas/uso terapêutico , Afatinib , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Nível de Saúde , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Medidas de Resultados Relatados pelo Paciente , Polimorfismo de Nucleotídeo Único , Qualidade de Vida , Análise de Sobrevida
15.
Cancer Cell Int ; 17: 64, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28615992

RESUMO

BACKGROUND: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). METHODS: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan-Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells. RESULTS: The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC. CONCLUSIONS: Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial-mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

16.
Clin Respir J ; 11(4): 440-447, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26260022

RESUMO

BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.


Assuntos
Brônquios/patologia , Broncoscopia/instrumentação , Pulmão/patologia , Traqueia/patologia , Adulto , Idoso , Broncoscopia/métodos , Feminino , Granuloma/diagnóstico , Granuloma/patologia , Humanos , Inflamação/patologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/patologia , Estudos Retrospectivos , Sarcoidose/diagnóstico , Sarcoidose/patologia , Fumar/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/patologia , Tuberculose/diagnóstico , Tuberculose/patologia
17.
Biol Chem ; 398(7): 785-792, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28002023

RESUMO

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Histona Desacetilase 2/metabolismo , Neoplasias Pulmonares/patologia , Ácido Valproico/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Histona Desacetilase 2/genética , Humanos , Fator de Transcrição Sp1/metabolismo , Transcrição Genética/efeitos dos fármacos
18.
Br J Cancer ; 116(2): 175-185, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28006816

RESUMO

BACKGROUND: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). METHODS: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit. RESULTS: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA- (LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients. CONCLUSIONS: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status.


Assuntos
Adenocarcinoma/sangue , Análise Mutacional de DNA/métodos , DNA de Neoplasias/sangue , Receptores ErbB/genética , Neoplasias Pulmonares/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma de Pulmão , Adulto , Afatinib , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Química do Sangue/métodos , DNA de Neoplasias/análise , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Quinazolinas/administração & dosagem
19.
Respir Med ; 121: 48-58, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27888992

RESUMO

BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored. RESULTS: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain.


Assuntos
Asma/imunologia , Interleucina-17/análise , Obesidade/imunologia , Escarro/imunologia , Doença Aguda , Adulto , Asma/complicações , Índice de Massa Corporal , Depressão/imunologia , Feminino , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/imunologia , Escarro/citologia , Magreza/imunologia
20.
Oncotarget ; 7(36): 57832-57840, 2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27506936

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a known tumor suppressor in non-small cell lung cancer (NSCLC). By performing a systematic review and meta-analysis of the literature, we determined the prognostic value of decreased PTEN expression in patients with NSCLC. We comprehensively and systematically searched through multiple online databases up to May 22, 2016 for NSCLC studies reporting on PTEN expression and patient survival outcome. Several criteria, including the Newcastle-Ottawa Quality Assessment Scale (NOS), were used to discriminate between studies. In total, 23 eligible studies with a total of 2,505 NSCLC patients were included in our meta-analysis. Our results demonstrated that decreased expression of PTEN correlated with poor overall survival in NSCLC patients and was indicative of a poor prognosis for disease-free survival and progression-free survival in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Análise Multivariada , Prognóstico , Resultado do Tratamento
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