Utility of ECG-Gated CTA for Detecting and Classifying Coronary Artery Involvement in Patients With Type A Aortic Dissection and Sinus of Valsalva Involvement.

BACKGROUND. Extension of type A aortic dissection (TAAD) from the sinus of Valsalva (SV) into the coronary arteries is associated with a poor prognosis and requires direct coronary repair or coronary artery bypass grafting (CABG) depending on the extent of involvement. OBJECTIVE. The purpose of this study was to assess the diagnostic performance of ECG-gated aortic CTA with surgical findings as the reference for detection and classification of coronary artery involvement in patients with TAAD involving the SV. METHODS. This retrospective study included 112 patients who underwent preoperative ECG-gated aortic CTA that showed TAAD with SV involvement. Two radiologists independently reviewed CTA images for right coronary artery (RCA) and left coronary artery (LCA) involvement. Involvement was classified according to a previously described system as type A (coronary ostial dissection), B (dissection with coronary false channel), or C (complete detachment from aortic root with dissection encircling the coronary artery). The diagnostic performance of CTA was calculated with surgical findings as the reference; interreader agreement was assessed; and surgical interventions were summarized. RESULTS. At surgery, the RCA was uninvolved in 33 patients and had type A involvement in 45, type B involvement in 19, and type C involvement in 15 patients. The LCA was uninvolved in 70 patients and had type A involvement in 34 patients, type B involvement in eight patients, and type C involvement in no patient. For the two readers, sensitivity in making the diagnosis in the RCA was 86.7% and 91.1% for type A, 79.0% and 89.5% for type B, 86.7% and 93.3% for type C, and 97.5% and 98.7% for any involvement. Sensitivity for the LCA was 85.3% and 91.2% for type A, 87.5% and 100% for type B, and 100% for any involvement. Specificity for the RCA was 94.0% and 97.0% for type A, 95.7% and 96.7% for type B, 96.9% and 96.9% for type C, and 93.9% and 97.0% for any involvement. Specificity for the LCA was 96.2% and 98.7% for type A, 96.2% and 97.1% for type B, and 97.1% and 98.6% for any involvement. Interreader agreement for types of involvement ranged from a kappa value of 0.85 to 0.96. The most common interventions were aortic repair for SV involvement alone (55.7-63.6%), coronary artery repair for types A and B involvement (53.3-87.5%), and CABG for type C involvement (86.7%). CONCLUSION. ECG-gated CTA has high diagnostic performance in the detection and classification of coronary involvement in TAAD with SV involvement. CLINICAL IMPACT. CTA findings may help guide presurgical planning for patients with TAAD.

Notch1 downregulation combined with interleukin-24 inhibits invasion and migration of hepatocellular carcinoma cells.

AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin (IL)-24 in hepatocellular carcinoma (HCC) cells. METHODS: γ-secretase inhibitors (GSIs) were used to down-regulate Notch1. HepG2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h. Cell viability was measured by MTT assay. The cellular and nuclear morphology was observed under a fluorescence microscope. To further verify the apoptotic phenotype, cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining. The expression of Notch1, SNAIL1, SNAIL2, E-cadherin, IL-24, XIAP and VEGF was detected by Western blot. The invasion and migration capacities of HCC cells were detected by wound healing assays. Notch1 and Snail were down-regulated by RNA interference, and the target proteins were analyzed by Western blot. To investigate the mechanism of apoptosis, we analyzed HepG2 cells treated with siNotch1 or siCON plus IL-24 or not for 48 h by caspase-3/7 activity luminescent assay. RESULTS: GSI-I at a dose of 2.5 µmol/L for 24 h caused a reduction in cell viability of about 38% in HepG2 cells. The addition of 50 ng/mL IL-24 in combination with 1 or 2.5 µmol/L GSI-I reduced cell viability of about 30% and 15%, respectively. Treatment with IL-24 alone did not induce any cytotoxic effect. In SMMC7721 cells with the addition of IL-24 to GSI-I (2.5 µmol/L), the reduction of cell viability was only about 25%. Following GSI-I/IL-24 combined treatment for 6 h, the apoptotic rate of HepG2 cells was 47.2%, while no significant effect was observed in cells treated with the compounds employed separately. Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in HepG2 cells. Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I. Furthermore, the increased GSI-I and IL-24 in HepG2 cell was associated with downregulation of MMP-2, XIAP and VEGF. In the absence of treatment, HepG2 cells could migrate into the scratched space in 24 h. With IL-24 or GSI-I treatment, the wound was still open after 24 h. And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I. Treatment of Notch-1 silenced HepG2 cells with 50 ng/mL IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination. Caspase-3/7 activity was increased in the presence of siNotch1 plus IL-24 treatment. CONCLUSION: Down-regulation of Notch1 by GSI-I or siRNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of HepG2 cells.