GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma

While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N-acetylgalactosaminyltransferase (GalNAc-T14), is highly inversely correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here, we showed that GalNAc-T14 expression was positively associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9, the expression of which was increased in a GalNAc-T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the β-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of β-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival and increased hazard risk, suggesting that targeting β-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.     

Quantitative Ultrasound Imaging to Assess the Biceps Brachii Muscle in Chronic Post-Stroke Spasticity: Preliminary Observation

We prospectively investigated the feasibility of using quantitative ultrasound imaging (QUI) to assess the biceps brachii muscle (BBM) in individuals with chronic post-stroke spasticity. To quantify muscle echogenicity and stiffness, we measured QUI parameters (gray-scale pixel value and shear wave velocity [SWV, m/s]) of the BBM in three groups: 16 healthy BBMs; 12 post-stroke, non-spastic BBMs; and 12 post-stroke, spastic BBMs. The QUI results were compared with the Modified Ashworth Scale and Tardieu Scale. A total of 20 SWVs were measured in each BBM, once at elbow in 90° flexion and again at maximally achievable extension using acoustic radiation force impulse imaging. BBM pixel value was measured in gray-scale images captured at 90° elbow flexion using ImageJ software. Statistical analyses included analysis of variance for examining the difference in SWV and pixel values among the three groups; Bonferroni correction for testing the difference in SWV and pixel values in a paired group; t-test for examining the difference in SWV values measured at two elbow angles; and Pearson correlation coefficient for analyzing the correlation of QUI to Modified Ashworth Scale and Tardieu Scale. SWV significantly differed between spastic BBMs and non-spastic or healthy BBMs. For pixel values, each of the three groups significantly differed from the others at elbow 90° flexion. The difference in SWV measured between the two elbow angles was also significant (p?<0.01). A strong negative correlation was found between SWV and passive range of motion (R²?=??0.88, p?<0.0001) in spastic upper limbs. These results suggest that the use of QUI is feasible in quantitative assessment of spastic BBM.