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Pigment epithelium-derived factor (PEDF) could bind to vascular endothelial growth factor receptor 2 (VEGFR2) and inhibit its activation induced by VEGF. But how PEDF affects VEGFR2 pathway is still poorly understood. In this study, we elucidated the precise mechanism underlying the interaction between PEDF and VEGFR2, and subsequently corroborated our findings using a rat AMI model. PEDF prevented endocytosis of VE-cadherin induced by hypoxia, thereby protecting the endothelium integrity. A three-dimensional model of the VEGFR2-PEDF complex was constructed by protein-protein docking method. The results showed that the VEGFR2-PEDF complex was stable during the simulation. Hydrogen bonds, binding energy and binding modes were analyzed during molecular dynamics simulations, which indicated that hydrogen bonds and hydrophobic interactions were important for the recognition of VEGFR2 with PEDF. In addition, the results from exudation of fibrinogen suggested that PEDF inhibits vascular leakage in acute myocardial infarction and confirmed the critical role of key amino acids in the regulation of endothelial cell permeability. This observation is also supported by echocardiography studies showing that the 34mer peptide sustained cardiac function during acute myocardial infarction. Besides, PEDF and 34mer could inhibit the aggregation of myofiber in the heart and promoted the formation of a dense cell layer in cardiomyocytes, which suggested that PEDF and 34mer peptide protect against AMI-induced cardiac dysfunction. These results suggest that PEDF inhibits the phosphorylation of downstream proteins, thereby preventing vascular leakage, which provides a new therapeutic direction for the treatment of acute myocardial infarction.Communicated by Ramaswamy H. Sarma.
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<p><b>OBJECTIVE</b>To explore the efficacy and determine the risk factors of survival for recurrent hepatocellular carcinoma(HCC) treated by percutaneous radiofrequency ablation (PRFA).</p><p><b>METHODS</b>From January 1999 to December 2008, 82 patients with recurrent HCC, with the diameter less than 7 cm for solitary tumor, or the largest tumor less than 5 cm for multiple tumors(the number of tumors less than 3), were treated by PRFA. The significance of 12 clinical or pathological variables in the risk factors of overall survival were assessed.</p><p><b>RESULTS</b>The overall survival 1-, 3-, and 5-year survival rates were 75.8%, 43.9% and 34.5% (from the date of PRFA), and 95.1%, 63.2% and 46.6% (from initial hepatectomy), respectively. Univariate analysis indicated that tumor size before initial hepatectomy, recurrence interval from initial hepatectomy, number of recurrent tumors, diameter of largest recurrent tumor, serum glutamyl transpeptidase (GGT) and serum albumin (ALB) level were significant prognostic factors (P < 0.05, Kaplan-Meier Log-rank test). Multivariate analysis showed recurrence interval from initial hepatectomy, diameter of largest recurrence tumor, serum GGT and ALB level were significant prognostic (P < 0.05).</p><p><b>CONCLUSION</b>PRFA is effective for recurrent HCC. Recurrence interval from initial hepatectomy, diameter of largest recurrent tumor, serum GGT and ALB level are significant prognostic factors.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Hepatocelular , Patología , Cirugía General , Ablación por Catéter , Estudios de Seguimiento , Estimación de Kaplan-Meier , Neoplasias Hepáticas , Patología , Cirugía General , Recurrencia Local de Neoplasia , Cirugía General , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
<p><b>BACKGROUND AND OBJECTIVE</b>Single mode of radiofrequency ablation (RFA) often leads to limited ablation in the zone of necrosis. This study clarifies the efficacy of combining temperature- and power-controlled RFA for malignant liver tumors.</p><p><b>METHODS</b>Between April 2008 and August 2008, 58 patients with malignant liver tumors received RFA at Sun Yat-sen University Cancer Center. The patients were divided into 2 groups using a random number table: one group received combined temperature- and power-controlled RFA (the combination group), and the other group received power-controlled RFA alone (the control group).</p><p><b>RESULTS</b>Three patients were lost to follow-up and 55 patients were included for evaluation. Twenty-five patients with 29 tumors were treated by the combination RFA, and 27 tumors (93.1%) achieved either complete response (CR) or partial response (PR). One patient had a seriously decreased heart rate. In the control group, 30 patients with 32 tumors received power-controlled RFA, and 29 tumors (90.6%) achieved CR or PR. There were no serious complications. There was no difference between the combination and control groups in treatment time ((13.3 +/- 1.3) min vs. (10.2 +/- 2.3) min, P = 0.459). The number of sessions of RFA for the combination group was less than that of control group (1.3 sessions vs. 2.4 sessions), but the difference was not significant (P = 0.579).</p><p><b>CONCLUSION</b>RFA controlling both temperature and power is effective and safe for patients with malignant liver tumors, and the number of sessions of RFA for the combination group was less than that of the control group.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ablación por Catéter , Métodos , Neoplasias del Colon , Estudios de Seguimiento , Neoplasias Hepáticas , Sangre , Patología , Terapéutica , Inducción de Remisión , Temperatura , alfa-Fetoproteínas , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of percutaneous radiofrequency ablation (PRFA) and combined with other minimally invasive treatments for recurrent hepatocellular carcinoma (RHCC) after hepatectomy.</p><p><b>METHODS</b>Eighty-four patients with RHCC after hepatectomy who were treated with PRFA or combined with other minimally invasive therapies between August 1999 and February 2008 were analyzed retrospectively.</p><p><b>RESULTS</b>There was no treatment related mortality in the study population, and the morbidity was 2.4% (2/84). The complete ablation rate was 94.0% (79/84), and the 1-, 3- and 5-year overall survival rates were 74.9%, 54.9% and 48.2%, respectively. The 1-, 3- and 5-year overall survival rates of patients with recurrent interval after hepatectomy less than 1 year and over 1 year were 72.1%, 36.2%, 24.2% and 76.8%, 70.6% and 65.1%, respectively (P = 0.040). The 1-, 3- and 5-year overall survival rates of patients with tumor size <or= 3 cm and > 3 cm were 83.2%, 67.7%, 67.7% and 59.1%, 24.2%, 12.1%, respectively (P = 0.003). The 1-, 3- and 5-year overall survival rates of patients treated with PRFA alone and combined with percutaneous ethanol injection (PEI) were 66.7%, 33.3%, 22.2% and 76.5%, 57.3%, 57.3%, respectively (P = 0.017). The 1-, 3- and 5-year overall survival rates of patients treated with PRFA alone and combined with transcatheter hepatic arterial chemoembolization (TACE) were 55.6%, 24.7%, 24.7% and 81.6%, 66.0%, 57.5%, respectively (P = 0.001).</p><p><b>CONCLUSIONS</b>PRFA is an effective and safe treatment for RHCC, and tumor size and recurrent interval after hepatectomy are important prognostic factors. Combination with PEI or TACE may improve the efficacy of PRFA for treatment of RHCC.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Hepatocelular , Patología , Cirugía General , Ablación por Catéter , Estudios de Seguimiento , Hepatectomía , Métodos , Neoplasias Hepáticas , Patología , Cirugía General , Recurrencia Local de Neoplasia , Cirugía General , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
<p><b>OBJECTIVE</b>To summarize the 8-year experience of radiofrequency ablation (RFA) on liver malignancies and explore the effect and prognostic factors.</p><p><b>METHODS</b>From August 1999 to February 2007, 803 patients with liver malignancies, among which there were 672 with primary liver cancer (PLC) and 131 with liver metastasis, were treated with RFA. There were 781 cases who were performed percutaneously under the guidance of ultrasound, 8 cases under CT, 9 cases with laparoscopy and 5 cases with laparotomy. And there were 117 cases who were treated by RFA combined with percutaneous ethanol injection and 108 cases by RFA combined with trans-catheter arterial chemoembolization.</p><p><b>RESULTS</b>In the treatment of all the 803 patients with liver malignancies, the mortality was 0.25%, the rate of severe complications was 0.37%. The rate of complete ablation was 92.5%, the loco-recurrence rate was 13.8% and the 1, 2, 3, 4, 5-year survivals were 95.1%, 85.6%, 75.7%, 60.7% and 47.5%, respectively. For the 672 patients with PLCs, the 1, 2, 3, 4, 5-year survivals with stage Ia (Chinese staging system) were 97.8%, 91.5%, 84.6%, 77.1% and 61.9%, respectively, with stage Ib were 93.9%, 83.7%, 69.8%, 45.1% and 42.2%, respectively, with stage II were 86.2%, 67.3%, 47.3%, 17.2% and 0, respectively, and the 1, 2-year survivals with stage III were 67.8% and 0, respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>RFA is a safe and effective method for liver malignancy, and the tumor size and stage are important prognostic factors.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ablación por Catéter , Estudios de Seguimiento , Neoplasias Hepáticas , Mortalidad , Terapéutica , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
<p><b>OBJECTIVE</b>To compare percutaneous radiofrequency ablation (RFA) alone and RFA combined with percutaneous absolute ethanol injection (RFA-PEI) in the treatment of single hepatocellular carcinoma smaller than 5.0 cm in diameter.</p><p><b>METHODS</b>From Jan. 2002 till Dec. 2003, eighty-six patients were put on a randomized clinical trial. For RFA, the American Radiotherapeutics RF 2000 machine and 3.5 cm/LEE VEEN + electroradiofrequency needle was introduced under ultra-beta sound guide. For tumor < 3 cm, the needle was left in center of tumor and for tumor > 3 cm, the needle was first left in situ and twisted by 180 as it was withdrawn for every 1 cm, till the surface border was reached. Power output was increased from 20 W and raised by 10-20 W per minute until the impedance became rapidly raised and the output decreased. Forty-five patients were treated with RFA-PEI and 41 with RFA, with each group divided into group A (diameter < or = 3.0 cm) and group B (diameter = 3.1-5.0 cm) according to tumor size. The overall and local recurrence-free survival was used to evaluate the treatment effect.</p><p><b>RESULTS</b>There was no mortality or serious morbidity in either group. The 6-, 12-, 18-, 24-month survival rate of RFA-PEI and RFA was 88.9%, 84.0%, 80.6%, 73.9% and 87.7%, 78.3%, 73.7%, 61.4% (P = 0.6181), respectively; and the local recurrence-free survival rates was 95.4%, 95.4%, 87.8%, 73.7% and 94.9%, 72.7%, 68.4%, 57.1% (P = 0.0393), respectively. The local recurrence-free survival rate in group A was 95.7%, 95.7%, 79.1%, 79.1% and 92.3%, 83.2%, 81.3%, 65.9% (P = 0.3679), respectively; while in group B was 95.0%, 95.0%, 95.0%, 72.6% and 100.0%, 58.3%, 45.4%, 45.4% (P = 0.0440).</p><p><b>CONCLUSION</b>Percutaneous radiofrequency ablation combined with percutaneous absolute ethanol injection is safe, and more effective and easily practiced than percutaneous radiofrequency ablation alone in the treatment of small hepatocellular carcinoma, especially when the tumor is greater than 3 cm in diameter, for which RFA-PEI may be able to reduce local recurrence and improve long-term survival.</p>