MultifunctionalNanocarrierTargetingSurvivinsiRNAInhibitsProliferation ofHepatocellularCarcinoma / 中山大学学报(医学科学版)

@#【Objective】 To investigate the inhibitory effect of RGD- modified，MRI visualized nanocarrier（RGD- PEG-g-PEI-SPION）targeting for Survivin siRNA（siRNA）delivery to hepatocellular carcinoma（HCC）in nude mice； and to investigate the MRI imaging function of RGD-PEG-g-PEI-SPION in nude mouse liver cancer. 【Methods】Nude mice were subcutaneously injected with Bel- 7402 cells to establish a subcutaneous tumor- bearing model. Tumor growth inhibition test，HE staining，immunohistochemical staining and tumor cell apoptosis test were used to evaluate the therapeutic effect of RGD-PEG-g-PEI-SPION targeted Survivin siRNA on liver cancer in nude mouse ；MRI imaging was used to analyze the targeting imaging function of RGD-PEG-g-PEI-SPION on hepatocellular carcinoma【Results】The subcutaneous tumor- bearing model of nude mice was successfully established，and the tumor volume of subcutaneous graft of RGD-PEG-g-PEI-SPION /siRNA，PEG-g-PEI-SPION/siRNA，RGD-PEG-g-PEI-SPION /siNC，PEG-g-PEI-SPION/ siNC and PBS solution in nude mice after first injection in the tail vein for 25 days was 59±8，156±7，202±7，212±9 and 220±8（mm3），respectively. Tumor histological examination showed that the RGD-PEG-g-PEI-SPION/siRNA group had the widest range of tumor necrosis，the lowest Survivin protein expression，and the number of apoptotic tumor cells significantly increased. Three hours after injection of RGD-PEG-g-PEI-SPION vector and PEG-g-PEI-SPION vector into the tail vein，the standardized MRI signal intensity of subcutaneous transplanted tumor decreased to（51.6±4.3）% and（88.5±3.2）% ，respectively ，compared with that before injection. 【Conclusion】 RGD- PEG- g- PEI- SPION delivers Survivin siRNA to hepatocellular carcinoma，promotes tumor cell apoptosis，inhibits tumor growth，and achieves good anti-tumor effect；RGD-PEG-g-PEI-SPION has a well targeted MRI imaging function in nude mouse liver cancer tissues.

Effects of KIF23 Gene Silencing on Proliferation,Migration and Invasion of Human Hepatocellular Carcinoma HepG2 cells / 中山大学学报(医学科学版)

[Objective]To investigate the effect of KIF23 gene expression on the proliferation,migration and invasion of human hepatocellular carcinoma HepG2 cells in vitro,and to explore the possible mechanism.[Methods]The KIF23 siRNA was transfected into HepG2 cells by lipofectamine 3000.The expression of KIF23 mRNA and protein in HepG2 cells was de-tected by qRT-PCR and Western blot.The effect of silencing KIF23 on the proliferation of HepG2 cells was studied by CCK-8 assay and plate clone formation assay.The tumor cell abilities of migration and invasion after transfection were measured by scratch assay and Transwell assay.The expression of protein kinase B(PKB/Akt)and phosphorylated Akt(p-Akt)protein in HepG2 cells transfected with KIF23-siRNA2 was detected by Western blot.[Results]KIF23-siRNA could effectively si-lence the expression of KIF23 mRNA and protein in HepG2 cells(P<0.01).The results of CCK-8 assay,plate clone forma-tion assay,scratch assay and Transwell assay demonstrated that the cell proliferation,migration and invasion ability of the KIF23-siRNA2 interference group were significantly inhibited,compared to the negative control group and the blank control group(P<0.05).The expression level of total Akt protein in HepG2 cells was not changed,but the expression level of phos-phorylated Akt protein was down-regulated(P<0.05).[Conclusions]KIF23 may promote the proliferation,migration and in-vasion of human hepatocellular carcinoma cells by activating Akt signal transduction pathway.KIF23 is expected to be a new target for gene therapy of hepatocellular carcinoma.

Transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate for gastric fundal varices / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the technique, safety and clinical efficacy of transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate (NBCA) for gastric fundal varices.</p><p><b>METHODS</b>Twenty-one patients with gastric fundal varices confirmed by endoscopy were enrolled in this study. The causes of the gastric varices were cirrhosis caused by hepatitis virus B or C (n = 16) and hepatocellular carcinoma with portal venous obstruction (n = 5). Percutaneous transhepatic or transplenic portography were performed on all 21 patients. The gastric varices were treated with NBCA-lipiodol mixture injected via a microcatheter introduced into the varices. For 8 patients who had large gastrorenal shunts (GRS), a balloon-occluded catheter was introduced into the GRS via the right femoral and left renal veins before injecting the NBCA-lipiodol. During the NBCA-lipiodol injection, the balloon was inflated to block the flow of GRS. Follow-up evaluations included findings of the laboratory liver function tests, upper intestinal endoscopies, and the occurrences of rebleeding.</p><p><b>RESULTS</b>In 20 patients (95.2%), the gastric varices were successfully obliterated with 2-8 ml of NBCA-lipiodol. In one patient with a large GRS, sclerotherapy was not successfully performed because a balloon-occluded catheter was not available during the procedure. In five patients, small amounts of NBCA-lipiodol entered into the distal pulmonary artery branches. Two of them suffered from transient irritable coughs; no patient developed severe pulmonary embolism. Embolization of portal venous branches occurred in two patients, which were not treated specifically. In comparison with the findings before the treatments, the serum alanine aminotransferase levels decreased at both 3 and 6 months after treatments (P less than 0.05); serum albumin levels increased at 6 months (P less than 0.05); the prothrombin times decreased at 6 months (P less than 0.05); but no significant changes were seen in the serum bilirubin levels. Fifteen patients were followed-up endoscopically for 3 months after the treatment. Gastric varices were completely resolved in 10 patients (66.7%) and were markedly smaller in 4 patients (26.6%). Worsening of the esophageal varices occurred in 3 patients (20%). All the patients were followed-up from 1 to 30 months [(16.7+/-8.8) months]. Rebleeding was observed in 4 patients, and the cumulative rebleeding rate at 1 year was 9.52%.</p><p><b>CONCLUSION</b>Transportal variceal sclerotherapy with NBCA is a safe and effective method for treating gastric varices. Microcatheter technique and occlusion of the large gastrorenal shunt with a balloon-occluded catheter are necessary to ensure obliteration of gastric varices and prevent pulmonary embolism.</p>

Radiofrequency ablation with or without transcather arterial chemoembolization for management of hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and complications of radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) for management of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A retrospective analysis was conducted for 62 small HCC cases undergoing RFA with or without TACE, and in each case, the tumors were not more than 3 with a diameter below 5 cm. Nineteen cases were managed with RFA alone (RFA group) while the other 27 underwent RFA combined with TACE (TACE+RFA group). Percutaneous RFA (RITA 1500) procedure was performed under CT guidance 1-3 weeks after TACE in TACE+RFA group.</p><p><b>RESULTS</b>The complete tumor necrosis rate was 77.8% (21/27) in TACE+RFA group, significantly higher than that in RFA group [57.9% (11/19), P<0.01], and the former group had a significantly lower local recurrence rate than the latter [22.2% (6/27) vs 42.1% (8/19), P<0.01]. Postoperative fever, local pain and temporary hepatic function abnormality were the common complications that were relieved after proper interventions, and mortality did not occur in these cases.</p><p><b>CONCLUSION</b>The combination of TACE and RFA significantly increases the complete tumor necrosis rate and decreases the recurrence rate of small HCC. CT-guided percutaneous RFA can be a safe and effective therapy for small HCC.</p>

Stent placement in treating hepatic artery stenosis after liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To evaluate the feasibility and effectiveness of stent placement in treating hepatic artery stenosis after orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>From November 2003 to September 2005, 14 patients who had hepatic artery stenosis after OLT underwent stent placement in their narrowed hepatic arteries. This included early interventional treatment in 10 patients and delayed interventional treatment in 4 patients. The technical results, clinical outcomes, and the hepatic artery patencies were reviewed.</p><p><b>RESULTS</b>Technical and immediate success was 100%. After a mean follow-up of 146 days (range, 9-345 days), all patients' hepatic arteries were patent, except that hepatic arterious restenosis occurred in 2 patients at 26 and 45 days after the stent placement. Of the 10 patients who received early treatment, 8 survived with normal results of liver function test and 2 patients died of septic multiple-organ failure at 9 and 30 days after the stent procedure. One patient received a retransplantation because of refractory biliary infection. Of the 4 patients who received a delayed interventional treatment, 1 patient survived for 345 days but with abnormal liver functional test results, the other 3 patients died of septic multiple-organ failure resulting from liver abscesses biliary infection.</p><p><b>CONCLUSION</b>Hepatic artery stenosis after OLT can successfully be treated with stent placement and an early interventional treatment is the key for a good clinical outcome.</p>

Long-term neurotoxic effects of MDMA result in cortical and hippocampal structural changes / 生理学报

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted amphetamine with stimulating and hallucinogenic properties. Since MDMA induces "ecstasy" it is extensively used as a "recreational" drug. It has been well established that MDMA is neurotoxic and can result in long-term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. The present study was undertaken to investigate the long-term neurotoxic effects of MDMA on cortical and hippocampal structures, by repeatedly administering MDMA in short time. Male Wistar rats were randomly assigned to control group and MDMA-treated group. MDMA (10 mg/kg) was administered to rats of MDMA-treated group, once per hour, total 40 mg/kg; rats of control group were treated with the same volume of saline. Thirty-two weeks after administering MDMA, the expression of serotonin transporter (SERT) mRNA and diazepam binding inhibitor (DBI) mRNA was detected by in situ hybridization. The expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry, and the degeneration of nerve terminals was demonstrated by Bielschowsky and Glee Marsland silver staining. The results showed that the expression of SERT mRNA in hippocampus decreased by 31.96%, while expression of DBI mRNA in neocortex increased by 40.51%, compared with the control group (P<0.05). The expression of GFAP in the brain tissue increased (P<0.05), while significant reduction of the nerve terminals in neocortex was demonstrated by silver staining, compared with the control group. These results suggest that the neurotoxicity of MDMA results in sustained cortical and hippocampal structural changes, which in turn result in disorder of the brain functions.

Superselective uterine arterial embolization with pingyangmycin-lipiodol emulsion for management of symptomatic uterine leiomyoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Uterine arterial embolization (UAE) is a safe and effective therapy for symptomatic uterine leiomyoma. This study was to assess the effectiveness and the feasibility of pingyangmycin-lipiodol emulsion (PLE) for the management of symptomatic uterine leiomyoma.</p><p><b>METHODS</b>One hundred consecutive patients (aged 21 - 53 years, with 38 in average) with symptomatic uterine leiomyoma underwent superselective UAE with PLE. Clinical symptoms of the patients (including menorrhagia, bulk-related symptoms, and postprocedure-related abdominal pain) and the changes in uterine volume and tumor size after the embolization were analyzed. The patients were followed up for 8 - 21 months (mean, 15 months).</p><p><b>RESULTS</b>Ninety-nine patients (99%, 99/100) were interviewed in their first menses circle after embolization, showing improvements in their abnormal bleeding and bulk-related symptoms to some extent. Imagiological results during follow-up showed a mean of 48% reduction in uterine volume at 6 months and a mean of 75% reduction in tumor size at 9 months. Eighty-three percent of the patients reported complete resolution of postprocedure pain within 7 days.</p><p><b>CONCLUSIONS</b>PLE is effective in the management of uterine leiomyoma, having superiority in alleviating postprocedure-related pain.</p>

Clinical application of endovascniar stent-graft in the treatment of portal stenosis of cancerous thrombus / 中华放射学杂志

Objective To explore the approach and early effects of endovascular stent-graft deployment in the treatment of portal stenosis of cancerous thrombus.Methods Six cases with portal vein stenosis of cancerous thrombus,which caused by primary hepatic carcinoma(5 cases)and eholangiocarcinoma(1 case)and the severity of stenosis showed on contrast enhanced CT were more than 75% or occluded,were performed percutaneous transhepatie or transsplenic portography.FLUENCY~(TM) endovascular stent-graft(10 mm diameter)was placed at the position of stenosis after gastroesophageal varices embolization.Portal pressure was measured pre-and post-deployment.Results Stents were successfully placed in all patients.The average portal pressure decreased from 50.7 cm H_2O(1 cm H_2O = 0.098 kPa)to 41.3 cm H_2O after endovascular stent-graft deployment.The restenosis were found in 2 cases after one month.Haematemesis and refractory aseites appeared in one case respectively,the other 4 cases showed no significant symptoms above caused by portal hypertension.Conclusion It is safe and feasible for endovaseular stent-graft deployment in the treatment of portal stenosis of cancerous thrombus.Selecting the suitable indications,the symptoms of portal hypertension can be controlled effectively.