Reciprocal cooperative signaling by integrins and growth factor receptors at G1 phase during cell cycle progression is well documented. By contrast, little is known about the cross-talk between integrin and transforming growth factor (TGF)-␤ signaling. Here, we show that integrin signaling counteracts the inhibitory effects of TGF-␤ on cell growth and that this effect is mediated by p130Cas (Crk-associated substrate, 130 kDa). Adhesion to fibronectin or laminin reduces TGF-␤-induced Smad3 phosphorylation and thus inhibits TGF-␤-mediated growth arrest; loss of p130Cas abrogates these effects. Loss and gain of function studies demonstrated that, once tyrosine-phosphorylated via integrin signaling, p130Cas binds to Smad3 and reduces phosphorylation of Smad3. That in turn leads to inhibition of p15 and p21 expression and facilitation of cell cycle progression. Thus, p130Cas-mediated control of TGF-␤/Smad signaling may provide an additional clue to the mechanism underlying resistance to TGF-␤-induced growth inhibition.

Excellent low field magnetoresistance (LFMR) properties could be achieved from the La0.7Sr0.3Mn1+dO3 (LSMO)-manganese oxide polycrystalline composites. While the improvement of LFMR properties in the perovskite maganite-oxide composites is commonly accompanied with a significant increase in their electrical resistivities, optimally processed LSMO-manganese composite in this study exhibits greatly enhanced LFMR of 1.7% at 0.5 kOe and unprecedentedly high maximum dMR/dH value of 28.3% kOe−1 at 300 K without an appreciable increase in its resistivity, which is attributable to the formation of sharp grain boundaries between neighboring LSMO ferromagnetic grains, acting as very effective spin-dependent scattering center.

Background/AimsLiver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.MethodsLSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.ResultsA strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.ConclusionsLSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.

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