JNK2 is activated during ER stress and promotes cell survival

Adaptation to endoplasmic reticulum (ER) stress relies on activation of the unfolded protein response (UPR) and induction of autophagy. Indeed, cells die if ER stress is not countered by the UPR. Here we show in U937 cells that the ER stressors tunicamycin and thapsigargin cause increased expression of c-Jun N-terminal kinase 2 (JNK2), which allows regulation of the UPR, whose silencing or pharmacological inhibition delays BiP (immunoglobulin heavy-chain binding protein) upregulation, and causes earlier and greater expression of CCAAT/enhancer-binding protein-homologous protein (CHOP). Furthermore, we show that pharmacological inhibition or silencing of JNK2 causes accumulation of both p62 and the acidic compartment, caspase 3 activation and apoptosis. Our results reveal that JNK2 prevents accumulation of the acidic compartment in U937 cells undergoing autophagic flux and, by this mechanism, it keeps stressed cells alive. Our findings highlight a potential role for JNK2 in tumor cell survival, senescence and neurodegenerative diseases, in which ER stress, autophagy and lysosome activity are known to interplay

Ultrasound vector flow imaging â\u80\u93 Could be a new tool in evaluation of arteriovenous fistulas for hemodialysis?

Abstract INTRODUCTION: We report the use of a new ultrasound technique to evaluate the axial and lateral components of a complex flow in the arteriovenous fistula (AVF). Vector Flow Imaging (VFI) allows to identify different components of the flow in every direction, even orthogonal to the flow streamline, represented by many single vectors. VFI could help to identify flow alterations in AVF, probably responsible for its malfunction. METHODS: From February to June 2016, 14 consecutive patients with upper-limb AVF were examined with a Resona 7 (Mindray, Shenzhen, China) ultrasound scanner equipped with VFI. An analysis of mean velocity, angular direction and mean number of vectors impacting the vessel wall was carried out. We also identified main flow patterns present in the arterial side, into the venous aneurysm and in correspondence of significant stenosis. RESULTS: A disturbed flow with the presence of vectors directed against the vessel walls was found in 9/14 patients (64.28%): in correspondence of the iuxta-anastomotic venous side (4/9; 44.4%), into the venous aneurysmal tracts (3/9; 33.3%) and in concomitance of stenosis (2/9; 22.2%). The mean velocity of the vectors was around 20-25 cm/s, except in presence of stenosis, where the velocities were much higher (45-50 cm/s). The vectors directed against the vessel walls presented high angle attack (from 45° to 90°, with a median angular deviation 65°). CONCLUSIONS: VFI was confirmed to be an innovative and intuitive imaging technology to study the flow complexity in the arteriovenous fistulas

High-frame rate vector flow imaging of the carotid bifurcation

Abstract Carotid artery atherosclerotic disease is still a significant cause of cerebrovascular morbidity and mortality. A new angle-independent technique, measuring and visualizing blood flow velocities in all directions, called vector flow imaging (VFI) is becoming available from several vendors. VFI can provide more intuitive and quantitative imaging of vortex formation, which is not clearly distinguishable in the color Doppler image. VFI, as quantitative method assessing disturbed flow patterns of the carotid bifurcation, has the potential to allow better understanding of the diagnostic value of complex flow and to enhance risk stratification. This pictorial review article will show which new information VFI adds for the knowledge of hemodynamics in comparison to the conventional ultrasound techniques. Teaching points • VFI is an angle-independent technique measuring flow velocities in all directions. • This kind of VFI is based on a plane wave multidirectional excitation technique. • VFI allows quantitative assessment of carotid streamlines progression and visualizes vorticity. • VFI does not allow a precise comprehension of streamlines’ 3D shape. • VFI allows a better understanding of carotid artery complex flows

High-Frame Rate Vector Flow Imaging of the Carotid Bifurcation in Healthy Adults: Comparison With Color Doppler Imaging

To evaluate the carotid bifurcation in healthy adults using a commercial system equipped with high-frame rate vector flow imaging (VFI) based on the plane wave and to compare VFI with color Doppler imaging. METHODS: Carotid bifurcation diameters and flow characteristics of 60 vessels in 60 healthy volunteers were evaluated quantitatively and qualitatively to assess complex flow patterns and their extension and duration. RESULTS: Complex flow in the internal carotid artery (ICA) was associated with a statistically significant difference in the ΔICA sinus-to-common carotid artery (CCA) diameter ratio (the relative change in diameter between the CCA and ICA sinus.) Vector flow imaging and color Doppler imaging were in accordance when detecting complex flow in 96.7% of cases; in 3.3% of cases, only VFI identified small recirculation areas of short duration. Vector flow imaging highlighted a larger extension of the complex flow (mean ± SD, 47.7 ± 28.5 mm2 ; median, 45.5 mm2 ) compared with color Doppler imaging (mean, 29.2 ± 19.9 mm2 ; median, 29.5 mm2 ) and better depicted different complex flow patterns; a strong correlation (r = 0.84) was found between the ΔICA sinus-to-CCA diameter ratio and the complex flow extension. Vector flow imaging showed a longer duration of the flow disturbances (mean, 380 ± 218 milliseconds; median, 352.5 milliseconds) compared with color Doppler imaging (mean, 325 ± 206 milliseconds; median, 333 milliseconds), and there was a strong correlation (r = 0.92). CONCLUSIONS: Vector flow imaging is as effective as color Doppler imaging in the detection of flow disturbances, but it is more powerful in the assessment of complex flow patterns

Median nerve evaluation by shear wave elastosonography: impact of "bone-proximity" hardening artifacts and inter-observer agreement

Peripheral nerves frequently travel close to the bone surface and are, therefore, prone to elastosonographic "bone-proximity" hardening artifacts. The impact of these artifacts on quantitative measurements of median nerve stiffness performed by shear wave elastosonography has not been explored. Our aim was to assess normal median nerve stiffness values at various locations

Muscle ultrasound elastography and MRI in preschool children with Duchenne muscular dystrophy

The aim of this study was to determine muscle tissue elasticity, measured with shear-wave elastography, in selected lower limb muscles of patients affected by Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those recorded in healthy children and with muscle magnetic resonance imaging (MRI) data from the same DMD children, specifically the pattern on T1-weighted (w) and short-tau inversion recovery (STIR) sequences. Five preschool DMD children and five age-matched healthy children were studied with shear-wave elastography. In the DMD children, muscle stiffness was moderately higher compared with the muscle stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in 3/5 patients at the level of the GM, while thigh and leg muscles were affected in 2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant correlation was observed between stiffness values and MRI scoring. Our study demonstrated that lower limb muscles of preschool DMD patients show fatty replacement and patchy edema on muscle MRI and increased stiffness on shear-wave elastography. In conclusion, although further studies in larger cohorts are needed, shear-wave elastography could be considered a useful non-invasive tool to easily monitor muscle changes in early stages of the disease

Correlation of the tumour-stroma ratio with diffusion weighted MRI in rectal cancer

Imatges per ressonància magnètica; Neoplàsies rectals; Microambient tumoralImagen de resonancia magnética; Neoplasias rectales; Microambiente tumoralMagnetic Resonance Imaging; Rectal neoplasms; Tumor MicroenvironmentObjective This study evaluated the correlation between intratumoural stroma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer. Methods This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients. Two observers measured the mean and minimum ADCs based on single-slice and whole-volume segmentations. The TSR was determined on diagnostic haematoxylin & eosin stained slides of rectal tumour biopsies. The correlation between TSR and ADC was assessed by Spearman correlation ( r s ). Results The ADC values between stroma-low and stroma-high tumours were not significantly different. Intra-class correlation (ICC) demonstrated a good level of agreement for the ADC measurements, ranging from 0.84–0.86 for single slice and 0.86–0.90 for the whole-volume protocol. No correlation was observed between the TSR and ADC values, with ADC mean r s = -0.162 ( p= 0.38) and ADC min r s = 0.041 ( p= 0.82) for the single-slice and r s = -0.108 ( p= 0.55) and r s = 0.019 ( p= 0.92) for the whole-volume measurements in the training cohort, respectively. Results from the validation cohort were consistent; ADC mean r s = -0.022 ( p= 0.86) and ADC min r s = 0.049 ( p= 0.69) for the single-slice and r s = -0.064 ( p= 0.59) and r s = -0.063 ( p= 0.61) for the whole-volume measurements. Conclusions Reproducibility of ADC values is good. Despite positive reports on the correlation between TSR and ADC values in other tumours, this could not be confirmed for rectal cancer.This study received financial support from “ Genootschap Landgoed Keukenhof .” Author R.P.L.’s work is supported by a PCF-Young Investigator Award . The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript

Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5

Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/ or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value = 0.04) and distant metastases (p-value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients (p-value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC