Roles of eIF3m in the tumorigenesis of triple negative breast cancer.

BACKGROUND: Without targets, triple negative breast cancer (TNBC) has the worst prognosis in all subtypes of breast cancer (BC). Recently, eukaryotic translation initiation factor 3 m (eIF3m) has been declared to be involved in the malignant progression of various neoplasms. The aim of this study is to explore biological functions of eIF3m in TNBC. METHODS: Multiple databases, including Oncomine, KM-plotter and so on, were performed to analyze prognosis and function of eIF3m in TNBC. After transfection of eIF3m-shRNA lentivirus, CCK-8, colony formation assay, cell cycle analysis, wound healing assay, transwell assays, mitochondrial membrane potential assay and cell apoptosis analysis were performed to explore the roles of eIF3m in TNBC cell bio-behaviors. In addition, western blotting was conducted to analyze the potential molecular mechanisms of eIF3m. RESULTS: In multiple databases, up-regulated eIF3m had lower overall survival, relapse-free survival and post progression survival in BC. EIF3m expression in TNBC was obviously higher than in non-TNBC or normal breast tissues. Its expression in TNBC was positively related to differentiation, lymph node invasion and distant metastasis. After knockdown of eIF3m, cell proliferation, migration, invasion and levels of mitochondrial membrane potential of MDA-MB-231 and MDA-MB-436 were all significantly suppressed, while apoptosis rates of them were obviously increased. In addition, eIF3m could regulate cell-cycle, epithelial-mesenchymal transition and apoptosis-related proteins. Combined with public databases and RT-qPCR, 14 genes were identified to be modulated by eIF3m in the development of TNBC. CONCLUSIONS: eIF3m is an unfavorable indicator of TNBC, and plays a vital role in the process of TNBC tumorigenesis.

Quantitative assessment of hyperacute cerebral infarction with intravoxel incoherent motion MR imaging: Initial experience in a canine stroke model.

PURPOSE: To evaluate the feasibility of intravoxel incoherent motion (IVIM) for the measurement of diffusion and perfusion parameters in hyperacute strokes. MATERIALS AND METHODS: An embolic ischemic model was established with an autologous thrombus in 20 beagles. IVIM imaging was performed on a 3.0 Tesla platform at 4.5 h and 6 h after embolization. Ten b values from 0 to 900 s/mm2 were fitted with a bi-exponential model to extract perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D*. Additionally, the apparent diffusion coefficient (ADC) was calculated using the mono-exponential model with all the b values. Statistical analysis was performed using the pairwise Student's t test and Pearson's correlation test. RESULTS: A significant decrease in f and D was observed in the ischemic area when compared with those in the contralateral side at 4.5 h and 6 h after embolization (P < 0.01 for all). No significant difference was observed in D* between the two sides at either time point (P = 0.086 and 0.336, respectively). In the stroke area, f at 6 h was significantly lower than that at 4.5 h (P = 0.016). A significantly positive correlation was detected between ADC and D in both stroke and contralateral sides at 4.5 h and 6 h (P < 0.001 for both). Significant correlation between ADC and f was only observed in the contralateral side at 4.5 h and 6 h (P = 0.019 and 0.021, respectively). CONCLUSION: IVIM imaging could simultaneously evaluate the diffusion and microvascular perfusion characteristics in hyperacute strokes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:550-556.

Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. Current evidence shows that the CD40-CD40L system plays a crucial role in the development, progression and outcome of SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to SLE and its impact on CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205 patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 T variant allele were associated with increased CD40 levels compared with the homozygous wild-type genotype in patients with SLE. The rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. These data suggest that CD40 gene may play an essential role in the development of SLE.