The dual mTORC1/2 inhibitor AZD2014 inhibits acute graft rejection in a rat liver transplantation model / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation.@*METHODS@#Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema.@*RESULTS@#Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ2=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01).@*CONCLUSIONS@#AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

Value of detection of serum glypican-3 level in diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the clinical value of detecting serum glypican-3 in the diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma (PHC).</p><p><b>METHODS</b>Using sandwich ELISA, we detected serum glypican-3 levels in 60 patients with PHC, 60 with metastatic liver cancer, 50 with liver cirrhosis, 50 with chronic viral hepatitis, 20 with hepatic cyst, 20 with fatty liver, 20 with hepatic hemangioma and 20 with drug-induced hepatitis as well as in 40 healthy subjects (control). We also analyzed the changes in serum levels of glypican-3 and alpha fetoprotein (AFP) in PHC patients after treatment.</p><p><b>RESULTS</b>PHC patients had significantly higher serum levels of glypican-3 than patients with other liver diseases and the control subjects (P<0.05). The levels of serum glypican-3 were significantly higher in patients with metastatic liver cancer, liver cirrhosis and viral hepatitis than in those with other benign liver diseases and the control subjects (P<0.05). Glypican-3 level was not associated with AFP level or liver function in PHC patients, in whom the positivity rates for glypican-3 and AFP were 65% and 56.7%, respectively. The detection rate of PHC increased to 85% by a combined detection of AFP and glypican-3. In the 23 PHC patients who responded positively to treatments, serum glypican-3 level showed a steady decline compared with that in 15 patients before treatment, while serum AFP level showed a similar decrease only in 10 patients.</p><p><b>CONCLUSION</b>Combined detection of glypican-3 and AFP is expected to improve the early diagnosis rate of PHC. The different thresholds of serum glypican-3 may play a role in the differential diagnosis of PHC and other various liver diseases. Glypican-3 may serve as a better marker than AFP with a high specificity and sensitivity for evaluating the therapeutic effect in PHC patients.</p>

Sequential study of liver collagen fibers in diethylnitrosamine-induced hepatocarcinogenesis in rats / 第二军医大学学报

Objective: To observe the sequential changes of collagen fibers in rats with diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), so as to provide a reference for pathogenesis research of HCC. Methods: Fifty male Wistar rats, weighing 100-120 g, were randomly divided into normal group and HCC model group. The model group was intraperitoneally administered with 50 mg/kg DEN (0.1 mL), twice a week for 4 weeks, then once a week for another 10 weeks. The control group was given normal saline (0.1 mL) in the same manner. Finally the rats were sacrificed; the normal and diseased liver tissues were observed by H-E, Masson and argyrophilic fiber staining. The expression of collagen type I and type III mRNA was detected by fluorogenic quantitative PCR; the expression of matrix metalloproteinase (MMP) was examined by gelatinases spectrometry. Results: Cirrhosiswas found in rats 5 weeks after treatment with DEN and HCC was induced 14 weeks after DEN treatment; collagen deposition in liver tissues increased in a progressive manner, and the collagen contents in the HCC tissues was greatly less than that in the adjacent tissues, showing a decreasing trend. The contents of MMP-2 and MMP-9 in the HCC and adjacent tissues had opposite changes compared with collagen. Conclusion: Collagen deposition in cirrhosis liver tissue is increased during the process of DEN-induced HCC, but it is decreased in HCC tissues in a progressive manner, which indicates that collagen might be degraded during the progression from cirrhosis to HCC.

Percutaneous transhepatic biliary radiofrequency and endoprothesis: a new therapy for malignant biliary obstruction / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore a new approach to the management of malignant biliary obstruction using percutaneous transhepatic biliary radiofrequency and endoprothesis.</p><p><b>METHODS</b>Percutaneous transhepatic biliary radiofrequency and endoprothesis were performed in 2 cases of malignant biliary obstruction, including 1 of hilar cholangiocarcinoma and 1 of pancreatic head carcinoma. The tumor was ablated with radiofrequency followed by placement of matched metal stents into the biliary duct.</p><p><b>RESULTS</b>The surgical procedures were carried out smoothly in the 2 cases. The symptoms of the patients were obviously improved after the operation with a significant decrease in the serum levels of total bilirubin, and CA-199 level decreased to the normal level in 1 case.</p><p><b>CONCLUSIONS</b>This new approach is safe for management of malignant biliary obstruction. Compared with the more conventional interventional therapy, radiofrequency can reduce the intraoperative bleeding and arrest the local tumor growth to promote the patency of the stent as well as the postoperative survival of the patients.</p>