Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells.

The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis.

Cardiac cine CT approaching 1 mSv: implementation and assessment of a 58-ms temporal resolution protocol.

Clinical use of cardiac cine CT imaging is limited by high radiation dose and low temporal resolution. To evaluate a low radiation dose, high temporal resolution cardiac cine CT protocol in human cardiac CT and phantom scans. CT scans of a circulating iodine target were reconstructed using the conventional single heartbeat half-scan (HS, approx. 175 ms temporal resolution) and the 3-heartbeat multi-segment (MS, approx. 58 ms) algorithms. Motion artifacts were quantified by the root-mean-square error (RMSE). Low-dose cardiac cine CT scans were performed in 55 subjects at a tube potential of 80 kVp and current of 80 mA. Image quality of HS and MS scans was assessed by blinded reader quality assessment, left ventricular (LV) free wall motion, and LV ejection rate. Motion artifacts in phantom scans were higher in HS than in MS reconstructions (RSME 188 and 117 HU, respectively; p = 0.001). Median radiation dose in human scans was 1.2 mSv. LV late diastolic filling was observed more frequently in MS than in HS images (42 vs. 26 subjects, respectively; p < 0.001). LV free wall systolic motion was more physiologic and had less error in MS than in HS reconstructions (sum-of-squared errors 34 vs. 45 mm2, respectively; p < 0.001), and LV peak ejection rate was higher in MS than in HS reconstructions (166 vs. 152 mL/s, respectively; p < 0.001). Cardiac cine CT imaging is feasible at a low radiation dose of 1.2 mSv. MS reconstruction showed improved imaging of rapid motion in phantom studies and human cardiac CTs.