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.

Expression of Wnt5b in patients with HBV-related hepatocellular carcinoma and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of Wnt5b in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological parameters.</p><p><b>METHODS</b>Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were employed to measure Wnt5b mRNA and protein expressions in two groups of HBV-related HCC patients (100 cases in each) selected from a cohort of 289 cases with HBV-related HCC using simple random sampling method. The correlation of Wnt5b expression with the clinicopathological parameters and the prognosis of HCC patients was analyzed.</p><p><b>RESULTS</b>Wnt5b mRNA expression was significantly higher in HCC tissues than that of adjacent noncancerous tissues in 65.0% (65/100) of the cases, and the positivity rate of Wnt5b protein was significantly higher in HCC tissues than that of adjacent noncancerous tissues (58.0% vs 22.0%, P<0.05). Wnt5b expression was significantly correlated with the tumor size (P<0.05), tumor number (P<0.01, only at the protein level), tumor differentiation (P<0.01, only at the protein level), TNM stage (P<0.05), BCLC stage (P<0.05), metastasis (P<0.05) and recurrence (P<0.01). The patients with up-regulated Wnt5b mRNA and protein had a shorter relapse-free survival (P<0.01).</p><p><b>CONCLUSION</b>s Up-regulated Wnt5b might contribute to the progression of HBV-related HCC and predicts a poor prognosis.</p>

Positive circulating tumor cells in the peripheral blood may indicate a poor prognosis in patients with hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.</p><p><b>RESULTS</b>s CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).</p><p><b>CONCLUSION</b>Positive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.</p>

Safety and efficacy of Sorafenib in treatment of tumor recurrence in liver transplantation recipients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the therapeutic effect and safety of Sorafenib in the treatment of tumor recurrence after orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>Between January, 2009 and June, 2011, 10 patients with tumor recurrence after OLT were treated with Sorafenib (group A) and another 8 recipients received no Sorafenib treatment (group B); 25 patients with hepatocellular carcinoma (HCC) also received Sorafenib treatment (group C). The tumor-bearing survival time, adverse effect and toxicity associated with sorafenib were compared between the 3 groups.</p><p><b>RESULTS</b>In group A, the median tumor-bearing survival time was 10 months (5-22 months), as compared to 4 months (1-8 months) in group B and 4 months (2-21 months) in group C, showing a significant difference in the survival time among the 3 groups (Kaplan-Meier, log-rank test, P=0.045). No recipient experienced acute graft rejection, but one recipient in group A died due to gastrointestinal bleeding. No significant difference was found in adverse effects associated with Sorafenib between groups A and C (P<0.05).</p><p><b>CONCLUSION</b>Sorafenib can prolong the survival time of patients with tumor recurrence after OLT without increasing the risk of acute graft rejection.</p>

Adult-to-adult living-related donor liver transplantation: report of 2 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft.</p><p><b>METHODS</b>The clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed.</p><p><b>RESULTS</b>Liver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively.</p><p><b>CONCLUSION</b>Adult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.</p>

Expression of special AT-rich sequence-binding protein 1 mRNA in hepatocellular carcinoma and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of special AT-rich sequence binding protein 1 (SATB1) mRNA in hepatocellular carcinoma (HCC) and explore its correlation to the clinicopathological features, surgical outcomes and metastasis of HCC.</p><p><b>METHODS</b>The total RNA was extracted from 102 HCC tissues and the adjacent tissues, and the expression of SATB1 mRNA was detected using quantitative real-time PCR. The correlations of SATB1 mRNA expression to the clinicopathological features, postoperative recurrence and metastasis of the tumor were analyzed.</p><p><b>RESULTS</b>The expression of SATB1 mRNA in HCC tissues was 3.27 folds higher than that in the adjacent tissues (P<0.001). The expression of SATB1 mRNA in HCC was associated with liver cirrhosis, AFP level, tumor size, tumor thrombi, histological differentiation, TNM classification, postoperative recurrence and metastasis (P<0.05), but not to the patients' gender, age, HbsAg positivity, HCV-Ab positivity, tumor number, or the presence of tumor encapsulation (P>0.05). In patients with significant high expression, high expression, and low expression of SATB1 mRNA, the postoperative recurrence rates were 82.68%, 0, and 0, with the 3-year survival rate of 0, 52.63%, and 100%, respectively.</p><p><b>CONCLUSION</b>SATB1 mRNA expression is associated with the postoperative recurrence and metastasis of HCC, and can be used as an indicator for predicting the recurrence and metastasis of HCC.</p>

Expression and mutations of PIK3CA gene in hepatocellular carcinomas / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression and mutation of PIK3CA gene in hepatocellular carcinomas (HCC).</p><p><b>METHODS</b>HCC samples and the corresponding adjacent tissues were collected from the surgical patients with pathologically verified diagnosis. The exons 1, 9 and 20 of PIK3CA gene were detected by PCR-SSCP and DNA sequencing. Immnohistochemistry was employed to test the expression of PIK3CA gene in these samples.</p><p><b>RESULTS</b>No mutation was found in exons 1, 9 or 20 of PIK3CA gene in the HCC tissue and the adjacent tissues by PCR-SSCP and DNA sequencing, while abnormal superimposed peaks were found on the sequence map of exon 9 in 25 cases of HCC tissue. Immunohistochemistry showed that expression of PIK3CA was higher in the HCC tissue than in the corresponding adjacent tissue (50.81% vs 14.75%).</p><p><b>CONCLUSION</b>PIK3CA gene mutation may exist in HCC in Guangxi, which can be associated with the development of HCC, but the ratio of hotspot mutations is low.</p>

Transfection with virus interleukin-10 to prolong murine heart allograft / 中华外科杂志

<p><b>OBJECTIVE</b>To prolong murine heart allograft by modifying hematopoietic stem cells with virus interleukin-10 (vIL-10).</p><p><b>METHODS</b>The recombinant of murine stem cell virus (MSCVneo) vIL-10 was composed of MSCVneo and vIL-10 cDNA and transduced hematopoietic stem cells from CBA (H-2(K)) mice's bone marrow in vitro. The transduced hematopoietic stem cells were transplanted into a syngenic CBA (H-2(K)) mouse with lethal irradiation (900 rad) in the same day through penis vein. The mouse's heterotopic heart transplantation was conducted using CBA (H-2(K)) mice as recipients, which vIL-10 in serum were positive by enzyme-linked immunosorbent assay, and donors hearts from C57BL/6 (H-2b) mice. Five animals in each group were sacrificed to test histopathology changes, the expression of interleukin (IL)-2, IL-4, IL-6, mIL-10, interferon (IFN)-gamma, inducible nitric oxide synthase (iNOS), B7-1, B7-2 and CD(4)(+) and CD(8)(+) T cells subset infiltration in heart transplants with reverse transcriptase polymerase chain reaction, immunohistochemistry and regular pathology.</p><p><b>RESULTS</b>Survival time of mice's allografts experimental group was (80.0 +/- 33.3) days. And survival time of control groups were (10.4 +/- 1.0) days, (11.6 +/- 1.1) days and (11.2 +/- 1.7) days, respectively (P < 0.01). Heart transplants from experimental group were characterized by sparse lymphocytes infiltration, mild endocarditis and vasculitis and preserved myocardial architecture, which had acute rejection of grade I. Cardiac allografts from other control groups developed severe cellular rejection with severe infiltrating lymphocytes, myocyte injury and necrosis, interstitial edema and hemorrhage, which had acute rejection of grade III. The expression of IL-2, INF-gamma, B7-1, B7-2 and iNOS mRNA in allografts in experimental group markedly down-regulated, whereas that in allografts in control groups markedly upregulated (P < 0.05). CD(4)(+) and CD(8)(+) T cell subsets infiltration in heart transplants from experimental group decreased, and that in control groups increased (P < 0.05).</p><p><b>CONCLUSION</b>Engineering Hematopoietic stem cells with vIL-10 can protect cardiac allografts from acute rejection and prolong cardiac allografts survival.</p>