Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and migration of endothelial cells and some types of tumor cells. In this study, we evaluated the efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II trial. Sixty-eight patients with core-biopsy confirmed breast cancer were allocated randomly to two groups to receive 3 cycles of intravenous administration of either neoadjuvant DE (docetaxel: 75 mg/m2, d1, epirubicin: 75 mg/m2, d1, every 3 weeks), or neoadjuvant DE combined with rh-endostatin (7.5 mg/m2, d1-d14, every 3 weeks). The primary end point was clinical response based upon Response Evaluation Criteria in Solid Tumors, and the secondary end point was safety and quality of life. All patients were assessable for toxicity and 64 (94.2%) were assessable for efficacy evaluation. The objective response rate was 67.7% for chemotherapy (n = 31) and 90.9% for rh-endostatin plus chemotherapy (n = 33) (P = 0.021). A retrospective subset analysis revealed that rh-endostatin was more effective in premenopausal patients and patients with ECOG score of zero (P = 0.002 and P = 0.049, respectively). Five patients in the rh-endostatin plus chemotherapy arm achieved pathologic complete response compared with 2 in the chemotherapy arm (P = 0.428). No significant difference was identified in quality of life score and side effects (P > 0.05). The combination of rh-endostatin with chemotherapy produced a higher tumor response rate without increasing toxicity in breast cancer patients. ClinicalTrials.gov Identifier, NCT00604435
1 February 2005 in American Journal of Physiology-Heart and Circulatory Physiology
Recent studies have demonstrated that cerebral arteries from rats fed a high-salt (HS) diet exhibit impaired vasodilation and altered electrophysiological response to reduction in Po2. The present study examined whether an increase in salt intake alters the response of vascular smooth muscle cells (VSMC) to prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an HS (4% NaCl) or a low-salt diet (0.4% NaCl) for 3 days. The stable prostacyclin analog iloprost (10 ng/ml) inhibited serotonin (0.1–10 μM)-induced contractions and the increase in intracellular Ca2+concentration ([Ca2+]i) in VSMC isolated from arteries of animals fed the low-salt diet. In contrast, iloprost had no effect on serotonin-induced contractions and increases in [Ca2+]iin VSMC isolated from arteries of rats fed the HS diet. Preventing the fall in ANG in rats fed the HS diet by infusion of a low dose of ANG II (5 ng·kg−1·min−1iv) restored the inhibitory effect of iloprost on serotonin-induced contractions and increases in [Ca2+]iin VSMC from animals fed the HS diet. These effects were reversed by AT1receptor blockade with losartan. These results indicate that ANG II suppression secondary to elevated dietary salt intake impairs vascular relaxation and Ca2+regulation by prostacyclin.
Background: Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound elastography technique that uses shear waves to quantitatively measure tissue stiffness and it has recently been developed as a safe, real-time, and noninvasive imaging technique. The purpose of this study was to investigate the value of 2D-SWE in the diagnosis and treatment of acute compartment syndrome (ACS). Methods: 2D-SWE was used to measure the elasticity values of the main muscles in the superficial compartments of the calf in 212 healthy volunteers, and the difference in the muscle elasticity values between different gender and age groups were analyzed. Nine patients with clinical suspicion of ACS were included in this study and 2D-SWE was used to measure the elasticity values of the muscles on the affected and unaffected sides, and a comparative analysis was performed. Results: The mean elasticity values of the tibialis anterior (TA), peroneus longus (PL), and gastrocnemius medialis (GA) muscles in the relaxed state of the 212 healthy volunteers were 25.4 ± 3.2 kPa, 15.7 ± 1.5 kPa, and 12.1 ± 2.1 kPa, respectively. No statistically significant differences was observed in the elasticity values of the same muscle under the state of relaxation in different gender and age groups (p > 0.05). A statistically significant difference in the elasticity values of the muscle between the affected and unaffected sides in the fasciotomy group (p < 0.05, n = 5) was observed. In contrast, no difference in the elasticity values of the muscle between the affected and unaffected sides in the conservative group (p > 0.05, n = 4) was observed. There was a statistically significant difference in the elasticity values of the muscle on the affected side in the two treatment groups (p < 0.05). Conclusions: When the ACS occurs, the muscle elasticity of the affected limb increases significantly. 2D-SWE is expected to be a new noninvasive technique for the assessment of ACS and may provide a potential basis for clinical diagnosis and treatment.
Noninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV). A retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV. In patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters. SS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.