Pooled analysis of prognostic significance of CX3CL1 mRNA expression level in patients with non-small cell lung cancer / 医学研究生学报

Objective The prognostic expression level and prognostic significance of CX3CL1 in patients with non-small cell lung cancer(NSCLC) need further investigation. The purpose of this paper was to investigate the effects of various CX3CL1 mRNA expression levels on patients with NSCLC.Methods By retrieving lung-cancer related gene expression profile data in NCBI GEO database and TCGA of UCSC Cancer Browser, 8 datasets were included based on inclusion and exclusion criteria. All the datasets were collated and standardized through R statistical software. Univariate and multivariate Cox models were conducted for prognosis analysis of CX3CL1 in each dataset. HR values of all the datasets were pooled by meta algorithm.Results High-expression of CX3CL1 mRNA in tumor tissues of lung adenocarcinoma was a positive prognostic factor for overall survival(pooled HR=0.53; 95% CI=0.43-0.65 in univariate analysis; pooled HR=0.52; 95% CI=0.42-0.64 in multivariate analysis). However, in lung squamous cell carcinoma, there was no significant association between CX3CL1 expression and overall survival (pooled HR=1.09; 95% CI=0.82-1.45 in univariate analysis; pooled HR=1.18; 95% CI=0.88-1.58 in multivariate analysis).Conclusion The mRNA level of CX3CL1 in lung adenocarcinoma was positively correlated with better prognosis, but there was no correlation between CX3CL1 mRNA level and prognosis in patients with lung squamous cell carcinoma. CX3CL1 may be used as a potential prognostic marker for patients with lung adenocarcinoma.

Triazole Resistance inClinical Isolates Obtained in Nanjing, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>During the past decades, the incidence of invasive aspergillosis (IA) caused by Aspergillus fumigatus has increased dramatically. The aims of this study were to investigate the susceptibility of clinical isolates of A. fumigatus to triazole and the underlying cyp51A mutations in triazole-resistant A. fumigatus.</p><p><b>METHODS</b>A total of 126 A. fumigatus clinical isolates from 126 patients with proven or probable IA were obtained from four large tertiary hospitals in Nanjing, China, between August 2012 and July 2015. The determination of minimal inhibitory concentrations (MICs) for itraconazole, voriconazole, and posaconazole was performed by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing reference method.</p><p><b>RESULTS</b>A total of 4 A. fumigatus isolates (3.17%) were confirmed to be itraconazole resistant, with MICs of ≥8 mg/L, and one isolate (0.8%) was confirmed to be voriconazole resistant and posaconazole resistant, with MICs of 4 mg/L and 0.5 mg/L, respectively. We found that two of the 4 isolates of triazole-resistant A. fumigatus had the L98H amino acid substitution in combination with a 34-base pair tandem repeat in the promoter region, one isolate had an M220I mutation, and another itraconazole-resistant isolate did not have a substitution in the cyp51A gene.</p><p><b>CONCLUSIONS</b>This study shows that triazole-resistant A. fumigatus clinical isolates are present in Nanjing, China, which is a new challenge to the clinical management of IA.</p>

Effect of hypoxia on HIF-1α, GLUT-1, and MMP-2 in human lung adenocarcinoma cells / 肿瘤

Objective: To explore the changes of hypoxia-inducible factor 1α(HIF-1α), glucose transporter protein-1(GLUT-1), and matrix metalloproteinase-2 (MMP-2) in hypoxic human lung adenocarcinoma A549 cells. Methods: The human lung adenocarcinoma A549 cells were cultured in normoxic and CoCl2-induced hypoxic conditions respectively. MTT assay was used to test the effect of hypoxia on the proliferation of lung cancer cells, and Transwell assay to determine the invasive capacity of hypoxic cells. Reverse transcription-polymerase chain reaction analyses (RT-PCR) was used to detect the mRNA expression of HIF-1α, GLUT-1 and MMP-2 under hypoxia. The protein levels of HIF-1α, GLUT-1, and MMP-2 were measured with immunohistochemical staining and western blot at different time points after hypoxia. Results: The proliferative and invasive capabilities of lung cancer cells increased under hypoxia condition. HIF-1α, GLUT-1, and MMP-2 were expressed at certain levels in A549 cells under normoxic condition. After hypoxia exposure, the mRNA and protein expression of the three proteins increased in a time-dependent manner. The difference was significant between hypoxia group and normal control group (P <0.05). Conclusion: Hypoxia induced by CoCl2 up-regulates the expression of HIF-1α, GLUT-1 and MMP-2 in lung adenocarcinoma A549 cells and stimulates the proliferation and metastasis of lung cancer cells, thus further promotes their tolerance to hypo-xia.