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1.
Clin Cancer Res ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413010

RESUMO

PURPOSE: Preclinical and retrospective studies suggested a role for metformin in sensitizing diabetic non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs). We therefore examined its effects in combination with gefitinib in non-diabetic patients harboring EGFR mutations (EGFRm). EXPERIMENTAL DESIGN: 224 non-diabetic patients with treatment naïve stage IIIB-IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of interleukin-6 were also examined in an exploratory analysis. RESULTS: The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2%(95% confidence interval [CI] 30.0-52.2) with gefitinib plus metformin and 42.9% (95% CI 32.6-52.7) with gefitinib plus placebo (p=0.6268). Median PFS (10.3 months versus 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of interleukin-6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared to the control arm (78.38% vs 43.24%). CONCLUSIONS: Our study showed that addition of metformin resulted in non-significantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in non-diabetic EGFRm NSCLC patients.

2.
Eur Respir J ; 54(2)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31164430

RESUMO

Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population.Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups.In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26-2.84), 0.72 (95% CI 0.26-1.98), 1.00 (95% CI 0.63-1.58) and 1.05 (95% CI 0.66-1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13-1.91).The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.

3.
Exp Cell Res ; 382(1): 111461, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31194977

RESUMO

Emerging evidence indicates that long noncoding RNAs (LncRNAs) are new players in gene regulation but their mechanisms of action are mainly undocumented. In this study, we investigated LncRNA alterations that contribute to lung cancer by analyzing published microarray data in Gene Expression Obminus (GEO) and The Cancer Genome Atlas RNA (TCGA) sequencing data. Here, we reported that HAGLR (also called HOXD-AS1) was frequently down-regulated in lung adenocarcinoma (LUAD) tissues, and decreased HAGLR expression was clinically associated with shorter survival of LUAD patients. Preclinical studies using multiple LUAD cells and in vivo mouse model indicated that HAGLR could attenuate LUAD cell growth in vitro and in vivo. Mechanistically, HAGLR could physically interact with DNMT1, and recruit DNMT1 on E2F1 promoter to increase local DNA methylation. Overall, our study demonstrated that HAGLR promoted LUAD progression by recruiting DNMT1 to modulate the promoter methylation and expression of E2F1, which expanded potential therapeutic strategies for LUAD treatment.

4.
Cell Tissue Res ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31214773

RESUMO

Fibrosis in the lungs usually occurs in the initial phase of acute respiratory distress syndrome (ARDS), which exacerbates poor prognosis among patients. MicroRNAs (miRs) have the ability to modulate the expression profiles of many genes, thus essentially altering cell phenotypes. We hypothesize that miRs may be involved in the development of lung fibrosis in mice. In this study, mice were treated with lipopolysaccharide (LPS) to establish the lung fibrosis animal model. Hematoxylin and eosin (H&E) staining and western blot (WB) were performed to confirm the successful establishment of the model. Quantitative PCR (qPCR) and WB were utilized to monitor the expression of miRs and proteins. A dual-luciferase reporter assay was used to detect the interaction between miR and genes. We observed miR-506 downregulation in lung tissues during lung fibrosis after ARDS rat modeling by LPS exposure. We also observed that its expression level was similar to that observed in TGF-ß1-induced human MRC-5 cells. The proportion of apoptotic cells decreased, while levels of inflammatory cytokines were upregulated in lung tissues during lung fibrosis and in fibroblasts after TGF-ß1 treatment. In order to elucidate the possible role of miR-506, it was overexpressed in mice with ARDS. It was revealed that miR-506 significantly ameliorated the degree and spread of pulmonary damage stimulated by LPS. miR-506 also induced apoptosis in vivo and in vitro, while also ameliorating the inflammatory response. Notably, p65, a subunit of NF-κB, acts as a target of miR-506. p65 expression was downregulated in TGF-ß1-treated MRC-5 cells upon transfection with miR-506 mimic. Indeed, the 3'-UTR of human p65 contained functional human miR-506-responsive sequences. LPS induction and TGF-ß1 stimulation in mice led to p65 upregulation. In addition, p65 knockdown in the ARDS mouse model partially ameliorated the severity of lung lesions, induced apoptosis and reduced inflammation in lung tissue. Our findings revealed that miR-506 could be an important modulator of apoptosis and inflammation and a regulator of lung fibrosis.

5.
Biomed Pharmacother ; 116: 109023, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31150989

RESUMO

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.

6.
Thorac Cancer ; 10(5): 1303-1309, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31016875

RESUMO

According to multiple studies, the objective response rate of PD-1/PD-L1 inhibitors in the second-line treatment of unscreened non-small cell lung cancer (NSCLC) is only approximately 20%. Predictive biomarkers of treatment efficacies are still under investigation. In selected NSCLC patients with PD-L1 expression ≥ 50%, the response rate of pembrolizumab in first-line treatment can reach 44.8%. Moreover, patients with a higher tumor mutation burden (TMB) tend to achieve a better response with nivolumab. Besides PD-L1 expression and TMB, taking all these indicators into consideration would hypothetically maximize the clinical response in a specific subgroup of patients. Our study aims to accumulate large and complete samples and clinical data to verify the biomarkers and their cutoff values related to the efficacy of PD-1/PD-L1 inhibitors in Chinese NSCLC patients, and to construct a comprehensive predictive model by combining multi-omics data with contemporary machine learning techniques. NSCLC patients administered treatment of anti-PD-1/PD-L1 antibodies or a combination with other drugs have been enrolled. The estimated enrollment is 250 participants. A sophisticated predictive model of immunotherapy response in the Chinese population has not yet been developed. It is clinically and practically imperative to comprehensively evaluate the possible indicators of Chinese NSCLC patients through multiple test platforms, such as next generation sequencing, PCR, or immunohistochemistry. This study is registered in the Chinese Clinical Trial Registry (ChiCTR1900021395).

8.
Brief Bioinform ; 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30815677

RESUMO

MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.

9.
Nucleic Acids Res ; 47(3): 1164-1177, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30576464

RESUMO

Synonymous codons provide redundancy in the genetic code that influences translation rates in many organisms, in which overall codon use is driven by selection for optimal codons. It is unresolved if or to what extent translational selection drives use of suboptimal codons or codon pairs. In Saccharomyces cerevisiae, 17 specific inhibitory codon pairs, each comprised of adjacent suboptimal codons, inhibit translation efficiency in a manner distinct from their constituent codons, and many are translated slowly in native genes. We show here that selection operates within Saccharomyces sensu stricto yeasts to conserve nine of these codon pairs at defined positions in genes. Conservation of these inhibitory codon pairs is significantly greater than expected, relative to conservation of their constituent codons, with seven pairs more highly conserved than any other synonymous pair. Conservation is strongly correlated with slow translation of the pairs. Conservation of suboptimal codon pairs extends to two related Candida species, fungi that diverged from Saccharomyces ∼270 million years ago, with an enrichment for codons decoded by I•A and U•G wobble in both Candida and Saccharomyces. Thus, conservation of inhibitory codon pairs strongly implies selection for slow translation at particular gene locations, executed by suboptimal codon pairs.


Assuntos
Códon , Biossíntese de Proteínas , Saccharomyces/genética , Sequência de Bases , Candida/genética , Sequência Conservada , Genes Fúngicos , Saccharomyces cerevisiae/genética
10.
Clin Respir J ; 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30480362

RESUMO

INTRODUCTION: Tumors are more likely to metastasize after development of resistance to EGFR TKIs. CD146 is a multi-functional molecule and is implicated in tumor invasion and metastasis; however, its role in lung cancer has not been clearly established. OBJECTIVE: Here we aimed to explore the relationship between CD146-pathway and stem cell phenotype after EGFR-TKI resistance in lung cancer. METHODS: EGFR-TKI resistance cell lines were established by exposing parental cells to Erlotinib/Gefitinib. CD146 level was measured by western blot, RT-PCR and immunocytochemistry fluorescent. Cell migration was examined by transwell assay and scratch assay. Stemness phenotype genes were evaluated by RT-PCR and stem cell phenotype was observed by microsphere formation assay. RESULTS: CD146 and stemness phenotype genes were increased while ß-catenin was decreased in acquired EGFR-TKI resistance cell lines. CD146 over-expression induced up-regulation of stemness related genes and inversely correlated with ß-catenin expression, which further increased the migration capability of the resistance cancer cells. CD146 knockdown suppressed cell migration and stemness phenotype. CONCLUSIONS: CD146 molecule contributes to the stemness phenotype and migration in EGFR-TKI resistance cells. CD146 might be a potential therapeutic target for EGFR-TKI resistance lung cancer or metastasis prevention. This article is protected by copyright. All rights reserved.

11.
Respiration ; 96(6): 571-587, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308515

RESUMO

The mechanisms of idiopathic pulmonary fibrosis (IPF), a rare, devastating disease with a median survival of 3-5 years, are not fully understood. Gastroesophageal reflux disease (GERD) is a frequent comorbidity encountered in IPF. Hypothetically, GERD-associated microaspiration may lead to persistent inflammation impairing lung infrastructure, thereby possibly accelerating the progression of IPF. IPF may increase intrathoracic pressure, which can aggravate GERD and vice versa. On the basis of the possible beneficial effects of antireflux or antacid therapy on lung function, acute exacerbation, and survival, the recent international IPF guideline recommends antacid therapies for patients with IPF, regardless of symptomatic GERD. However, due to newer conflicting data, several national guidelines do not support this recommendation. Elucidation of these questions by further clinical and bench-to-bedside research may provide us with rational clinical diagnostic and therapeutic approaches concerning GERD in IPF. The present review aims to discuss the latest data on the controversial association of IPF and GERD.

12.
Front Immunol ; 9: 1898, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30177934

RESUMO

Background: Acute lung injury (ALI) is characterized by suppressed fibrinolytic activity in bronchoalveolar lavage fluid (BALF) attributed to elevated plasminogen activator inhibitor-1 (PAI-1). Restoring pulmonary fibrinolysis by delivering tissue-type plasminogen activator (tPA), urokinase plasminogen activator (uPA), and plasmin could be a promising approach. Objectives: To systematically analyze the overall benefit of fibrinolytic therapy for ALI reported in preclinical studies. Methods: We searched PubMed, Embase, Web of Science, and CNKI Chinese databases, and analyzed data retrieved from 22 studies for the beneficial effects of fibrinolytics on animal models of ALI. Results: Both large and small animals were used with five routes for delivering tPA, uPA, and plasmin. Fibrinolytics significantly increased the fibrinolytic activity both in the plasma and BALF. Fibrin degradation products in BALF had a net increase of 408.41 ng/ml vs controls (P < 0.00001). In addition, plasma thrombin-antithrombin complexes increased 1.59 ng/ml over controls (P = 0.0001). In sharp contrast, PAI-1 level in BALF decreased 21.44 ng/ml compared with controls (P < 0.00001). Arterial oxygen tension was improved by a net increase of 15.16 mmHg, while carbon dioxide pressure was significantly reduced (11.66 mmHg, P = 0.0001 vs controls). Additionally, fibrinolytics improved lung function and alleviated inflammation response: the lung wet/dry ratio was decreased 1.49 (P < 0.0001 vs controls), lung injury score was reduced 1.83 (P < 0.00001 vs controls), and BALF neutrophils were lesser (3 × 104/ml, P < 0.00001 vs controls). The mortality decreased significantly within defined study periods (6 h to 30 days for mortality), as the risk ratio of death was 0.2-fold of controls (P = 0.0008). Conclusion: We conclude that fibrinolytic therapy may be effective pharmaceutic strategy for ALI in animal models.

13.
Lung Cancer ; 123: 44-51, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30089594

RESUMO

OBJECTIVES: Early and accurate diagnosis of lung cancer is crucial for effective treatment. This study aimed to identify plasma microRNAs for diagnosis of lung cancer and for further discrimination of small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Plasma microRNA expression was investigated using three independent cohorts including 1132 participants recruited between October 2008 and September 2014 from five medical centers. The subjects were healthy individuals and patients with NSCLC or SCLC. Microarrays were used to screen 723 human microRNAs in 106 plasma samples for candidate selection. Quantitative reverse-transcriptase PCR was applied to evaluate the expression of selected microRNAs. Two logistic regression models were constructed based on a training cohort (n = 565) and then validated using an independent cohort (n = 461). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS: Plasma panel A with six microRNAs (miR-17, miR-190b, miR-19a, miR-19b, miR-26b, and miR-375) provided high diagnostic accuracy in discriminating lung cancer patients from healthy individuals (AUC 0.873 and 0.868 for training and validation cohort, respectively). Moreover, plasma panel B with three microRNAs (miR-17, miR-190b, and miR-375) demonstrated high diagnostic accuracy in discriminating SCLC from NSCLC (AUC 0.878 and 0.869 for training and validation cohort, respectively). CONCLUSION: We constructed and validated two plasma microRNA panels that have considerable clinical value in diagnosis of lung cancer, and could play an important role in determining optimal treatment strategies based on discrimination between SCLC and NSCLC.

14.
Biomed Res Int ; 2018: 6057589, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018981

RESUMO

Insulin-like growth factor-1 (IGF-1) was firstly identified as a hormone that mediates the biological effects of growth hormone. Accumulating data have indicated the role of IGF-1 signaling pathway in lung development and diseases such as congenital disorders, cancers, inflammation, and fibrosis. IGF-1 signaling modulates the development and differentiation of many types of lung cells, including airway basal cells, club cells, alveolar epithelial cells, and fibroblasts. IGF-1 signaling deficiency results in alveolar hyperplasia in humans and disrupted lung architecture in animal models. The components of IGF-1 signaling pathways are potentiated as biomarkers as they are dysregulated locally or systemically in lung diseases, whereas data may be inconsistent or even paradoxical among different studies. The usage of IGF-1-based therapeutic agents urges for more researches in developmental disorders and inflammatory lung diseases, as the majority of current data are collected from limited number of animal experiments and are generally less exuberant than those in lung cancer. Elucidation of these questions by further bench-to-bedside researches may provide us with rational clinical diagnostic approaches and agents concerning IGF-1 signaling in lung diseases.

15.
Hum Mutat ; 39(9): 1238-1245, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29920840

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P = 2.34 × 10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.

16.
Adv Exp Med Biol ; 1068: 59-71, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29943296

RESUMO

In the past two decades, super-resolution fluorescence microscopy has undergone a dynamic evolution. Following proof-of-concept studies with stimulated emission depletion (STED) microscopy, several new approaches such as structured illumination microscopy (SIM), photoactivation localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), have been developed for imaging of nanoscale structural details and fast cellular dynamics in biological research. In this chapter, after briefly explaining their principles, we will describe the recent application of these super-resolution techniques in single cell imaging. In addition, the extension of super-resolution microscopy to 3D, multicolor, live-cell imaging and multimodal imaging are also discussed, significantly improving the precision of single cell imaging. Combining with molecular biology, biochemistry and bio-computing algorithms, super-resolution fluorescence microscopy continues to expand its capabilities and provide comprehensive insights into the details of single cells.

17.
Adv Exp Med Biol ; 1068: 73-87, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29943297

RESUMO

In the proteomic and genomic era, lung cancer researchers are increasingly under challenge with traditional protein analyzing tools. High output, multiplexed analytical procedures are in demand for disclosing the post-translational modification, molecular interactions and signaling pathways of proteins precisely, specifically, dynamically and systematically, as well as for identifying novel proteins and their functions. This could be better realized by single-cell proteomic methods than conventional proteomic methods. Using single-cell proteomic tools including flow cytometry, mass cytometry, microfluidics and chip technologies, chemical cytometry, single-cell western blotting, the quantity and functions of proteins are analyzed simultaneously. Aside from deciphering disease mechanisms, single-cell proteomic techniques facilitate the identification and screening of biomarkers, molecular targets and promising compounds as well. This review summarized single-cell proteomic tools and their use in lung cancer.

18.
J Pain Symptom Manage ; 56(1): 113-121, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29627566

RESUMO

CONTEXT: Comprehensive symptom assessment is crucial for symptom management. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) has been validated for symptom assessment in cancer patients, but there is no simplified Chinese version. OBJECTIVES: To present the validation procedures and results for the simplified Chinese version of the Memorial Symptom Assessment Scale-Short Form (MSAS-SF-SC) among cancer patients in mainland China. METHODS: The MSAS-SF was translated and culturally adapted into simplified Chinese. About 359 cancer patients completed the MSAS-SF-SC, the Chinese Functional Assessment of Cancer Therapy-General, the Chinese Brief Fatigue Inventory, the Chinese Hospital Anxiety and Depression Scale, and the Chinese Medical Outcomes Study Social Support Survey. Reliability was assessed by internal consistency and test-retest coefficients. Convergent and divergent validity were analyzed by Pearson's correlation coefficients between MSAS-SF-SC subscales and the other instruments. Known-groups validity used Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site. RESULTS: The MSAS-SF-SC was reliable with Cronbach's alpha coefficients for subscales ranging from 0.782 to 0.874 and test-retest coefficients ranging from 0.819 to 0.872. MSAS-SF-SC subscales correlated with corresponding Chinese Functional Assessment of Cancer Therapy-General subscales (-0.557 to -0.680; P < 0.001), Chinese Brief Fatigue Inventory (0.620; P < 0.001), and Chinese Hospital Anxiety and Depression Scale (0.663; P < 0.001) indicating convergent validity. MSAS-SF-SC subscales showed low or no correlations with the Chinese Medical Outcomes Study Social Support Survey (-0.146 to -0.165; P < 0.01), indicating divergent validity. MSAS-SF-SC subscales showed appropriate differences by Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site. CONCLUSION: The MSAS-SF-SC demonstrated good psychometric properties and is culturally adapted. The instrument could be a valuable tool for Chinese health care professionals and researchers.

19.
Cancer ; 124(2): 262-270, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28940455

RESUMO

BACKGROUND: The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS: The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS: The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS: Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.

20.
RNA ; 24(3): 410-422, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29259051

RESUMO

Microorganisms have universally adapted their RNAs and proteins to survive at a broad range of temperatures and growth conditions. However, for RNAs, there is little quantitative understanding of the effects of mutations on function at high temperatures. To understand how variant tRNA function is affected by temperature change, we used the tRNA nonsense suppressor SUP4oc of the yeast Saccharomyces cerevisiae to perform a high-throughput quantitative screen of tRNA function at two different growth temperatures. This screen yielded comparative values for 9243 single and double variants. Surprisingly, despite the ability of S. cerevisiae to grow at temperatures as low as 15°C and as high as 39°C, the vast majority of variants that could be scored lost half or more of their function when evaluated at 37°C relative to 28°C. Moreover, temperature sensitivity of a tRNA variant was highly associated with its susceptibility to the rapid tRNA decay (RTD) pathway, implying that RTD is responsible for most of the loss of function of variants at higher temperature. Furthermore, RTD may also operate in a met22Δ strain, which was previously thought to fully inhibit RTD. Consistent with RTD acting to degrade destabilized tRNAs, the stability of a tRNA molecule can be used to predict temperature sensitivity with high confidence. These findings offer a new perspective on the stability of tRNA molecules and their quality control at high temperature.


Assuntos
Fatores de Terminação de Peptídeos/genética , Estabilidade de RNA/genética , RNA de Transferência/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Biblioteca Gênica , Genes Reporter , Mutação , RNA de Transferência/química , Saccharomyces cerevisiae/fisiologia , Análise de Sequência de DNA , Temperatura Ambiente
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