【Abstract】Objective To investigate the expression of the mRNA of cancer-testis antigen 9 (CT9) gene in hepatocellular carcinoma. Methods The expression of CT9 mRNA was detected through RT-PCR in HCC tissues and their adjacent non-HCC tissues from 45 HCC patients. From CT9 RT-PCR positive products, 3 samples were selected randomly and were sequenced. ResultsCT9 mRNA was detectable in 51.1%(23/45) of HCC samples, and no expression of CT9 mRNA was detected in the adjacent non-HCC tissues. In addition, the RTPCR products were proved to be CT9 cDNA by DNA sequencing. No relationship was found between the expression of CT9 mRNA and clinical factors such as age, sex, tumor size, degree of tumor differentiation, serum αfetoprotein level and infection of hepatitis B virus or hepatitis C virus （Pgt;0.05）. ConclusionCT9 mRNA is expressed with high percentage and specificity in hepatocellular carcinomas. The CT9 gene product is a potential target for antigenspecific immunotherapy of HCC.
ObjectiveTo systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with partial splenic embolization (PSE) for hepatocellular carcinoma (HCC) with hypersplenism. MethodWe searched The Cochrane Library (Issue 11, 2015), PubMed, EMbase, CBM, VIP, CNKI and WanFang Data databases from inception to November 1st 2015, to collect randomized controlled trials (RCTs) about TACE combined with PSE in treating HCC with hypersplenism. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software. ResultsA total of 11 RCTs involving 708 patients were included. The results of meta-analysis showed that: Compared with TACE alone, TACE combined with PSE could significantly improve postoperative CD4 count (MD=6.99, 95%CI 4.60 to 9.38, P<0.00001), CD4/CD8 ratio (MD=0.64, 95% 0.45 to 0.84, P<0.00001), and the rate of half year survival (RR=1.16, 95%CI 1.02 to 1.32, P=0.02), decrease the incidences of spontaneous peritonitis (RR=0.20, 95%CI 0.05 to 0.48, P=0.03) and varices bleeding (RR=0.17, 95%CI 0.04 to 0.68, P=0.01). The two groups had similar incidence of post-embolization syndrome (RR=1.17, 95%CI 0.79 to 1.75, P=0.44). ConclusionTACE combined with PSE is more safe and effective than TACE alone in unresectable HCC with hypersplenism. Due to limited quantity and quality of the included studies, the above conclusion should be further verified by conducting more high quality, large scale RCTs.
ObjectiveTo identify the risk factors of postoperative recurrence and survival for patients with hepatocellular carcinoma within Milan criteria following liver resection. MethodsData of 267 patients with hepatocellular carcinoma within Milan criteria who received liver resection between 2007 and 2013 in our hospital were retrospectively analyzed. ResultsAmong the 267 patients, 123 patients suffered from recurrence and 51 patients died. The mean time to recurrence were (16.9±14.5) months (2.7-75.1 months), whereas the mean time to death were (27.5±16.4) months (6.1-75.4 months). The recurrence-free survival rates in 1-, 3-, and 5-year after operation was 76.8%, 56.3%, and 47.6%, respectively; whereas the overall survival rates in 1-, 3-, and 5-year after operation was 96.6%, 82.5%, and 74.5%, respectively. Multivariate analyses suggested the tumor differentiation, microvascular invasion, and multiple tumors were independent risk factors for postoperative recurrence; whereas the tumor differentiation, positive preoperative HBV-DNA load, and preoperative neutrophil-to-lymphocyte ratio adversely influenced the postoperative survival. ConclusionsFor patients with hepatocellular carcinoma within Milan criteria after liver resection, the tumor differentiation, microvascular invasion, and multiple tumors contribute to postoperative recurrence; whereas the tumor differentiation, positive preoperative HBV-DNA load, and preoperative neutrophil-to-lymphocyte ratio adversely influence the postoperative survival.
Objective To investigate the expression of multigenes mediated by adenovirus in liver cancer cells and the effects on growth of cells transducted with multigenes. MethodsBy construction of recombinant adenovirus containing human p53, B7-1, GM-CSF, and IL-2 genes (Ad-multigenes), the expression level of target genes in three human hepatocellular carcinoma cell lines and a human hepatocellular cell line L02 was detected using ELISA, immunohistochemistry and FACS assay and the change of growth of these cells and the tumor cell apoptosis were observed. Results The human hepatic cells and liver cancer cells were all sensitive to adenovirus infection. At a MOI of 50 PFU/cell, among the cells examined nearly 90% were positive expression and except IL-2, other three genes were expressed with high efficiency. The growth of Ad-multigenes-transduced liver cancer cell lines was inhibited and apoptosis was induced, but the growth of Ad-multigenes-transduced normal hepatic cell line L02 did not change. Conclusion These results indicate that the adenovirus is an efficient vector for gene transfer into human liver cancer cells. These liver cancer cell lines transduced with multigenes constructed on one recombinant adenoviral vector can highly express target genes and their growth was inhibited, and apoptosis appeared.
ObjectivesTo compare the survival outcomes between hepatocellular carcinoma and hepatic angiosarcoma, and to develop and validate a nomogram predicting the outcome of hepatic angiosarcoma.MethodsThe Surveillance, Epidemiology and End Results (SEER) database was electronically searched to collect the data of hepatic angiosarcoma patients and hepatocellular carcinoma patients from 2004 to 2016. Propensity score matching (PSM) was used to match the two groups by the ratio of 1:3. Cox regression analysis was used to compare the survival outcomes between hepatic angiosarcoma and HCC. In the angiosarcoma group, population was divided into training set and validation set by 6:4. Nomograms were built for the prediction of half- and one- year survival, and validated by concordance index (C-index) and calibration plots.ResultsA total of 210 histologically confirmed hepatic angiosarcoma patients and 630 hepatocellular carcinoma patients were included. The overall survival of HCC was significantly longer than angiosarcoma (3-year survival: 18.4% vs. 6.7%, median survival: 5 months vs. 1 month, P<0.001), and the nomogram achieved good accuracy with an internal C-index of 0.751 and an external C-index of 0.737.ConclusionsThe overall survival of HCC is significantly longer than angiosarcoma. The proposed nomograms can assist to predict survival probability in patients with hepatic angiosarcoma. Due to limitation of the data of included patients, more high-quality studies are required to verify above conclusions.
ObjectiveTo discuss the CT imaging differences between mass-forming intrahepatic cholangiocarcinoma (ICC) and poorly-differentiated hepatocellular carcinoma (HCC). MethodThe clinical and CT data of 28 patients with mass-forming ICC (mass-forming ICC group) and 27 patients with poorly-differentiated HCC (poorly-differentiated HCC group), who were confirmed by pathological diagnosis in the West China Hospital from February 2014 to August 2014, were collected and analyzed retrospectively. ResultsThe contour, margin, enhancement patterns in the arterial phase and portal vein phase of the tumor had significant differences between the mass-forming ICC group and poorlydifferentiated HCC group (P < 0.05), in other words, the lobulated shape (15/28, 53.6%), indistinct margin (17/28, 60.7%), peripheral enhancement in the arterial phase (21/28, 75.0%) and prolonged enhancement in the portal vein phase (14/28, 50.0%) were more often seen in the mass-forming ICC group, while the poorly-differentiated HCC group were mainly the round shape (17/27, 63.0%), partially well-defined margin (18/27, 66.7%), diffuse heterogeneous enhancement in arterial phase (20/27, 74.1%) and wash out in the portal vein phase (18/27, 66.7%). The presence of bile duct dilatation in the the mass-forming ICC group was significantly higher than that in the poorly-differentiated HCC group﹝57.1% (16/28) versus 14.8% (4/27), P=0.001﹞. The size and enhancement degree of lymph node in the mass-forming ICC group were significantly bigger or higher than those in the poorly-differentiated HCC group (average lymph node size: 1.7 cm versus 1.3 cm, P=0.009; average enhancement degree of lymph node: 62.6 HU versus 51.8 HU, P=0.031). ConclusionCT features, such as tumor contour, margin, enhancement characteristics, the presence of bile duct dilatation, and the size and enhancement degree of lymph node, might help for differentiating mass-forming ICC from poorly-differentiated HCC, so that more timely selection of appropriate treatment strategies would be made.
Objective To investigate the cell growth inhibition and apoptosis induced by rapamycin on human hepatocellular carcinoma Bel-7402 cells and to study the role of mitochondrium membrane potential in the process of apoptosis. Methods Bel-7402 cells in vitro were given 5, 10, 20, 30, 40 and 50 nmol/L different concentrations of rapamycin, and the cell growth inhibiting ratio of Bel-7402 was assessed by MTT assay. The changes of morphology of Bel-7402 were observed by Hoechst 33258 staining and flow cytometry (FCM), respectively; The cell mitochondrial membrane potential was detected by using JC-1 staining method. Results Rapamycin could inhibit the growth of Bel-7402 cells significantly by inducing apoptosis, and the growth suppression and the cell apoptosis both presented time-effect relationship and were also dose-dependent. The rates of inhibiting and cell apoptosis after 72 h exposure to 50 nmol/L rapamycin were significantly higher that those of other groups (P＜0.01). Typical morphological changes of cell apoptosis were observed very clearly after the Bel-7402 cells had been exposed to rapamycin for 48 hours using Hoechst 33258 staining method, and it was also observed that the mitochondrial membrane potential decreased when apoptosis occured (P＜0.01). Conclusion Rapamycin could inhibit the growth of Bel-7402 cells by inducing cell apoptosis, and the descent of mitochondrial membrane potential may play an important role in the process of cell apoptosis.
Objective To determine whether Rb gene is involved in the genesis of primary hepatocellular carcinoma(HCC). MethodsForty paraffin specimens of primary HCCs with corresponding adjacent liver tissues and normal liver tissues were investigated for Rb protein expression by tissue chip and SP immunohistochemical technique. ResultsLoss of Rb protein expression occurred in 17 of 40 tumor samples, whereas in 4 of 40 adjacent liver tissue samples, only 1 of 40 normal liver tissue specimens showed negative Rb staining.Rb protein deletion in HCC was higher than that in adjacent tissues and normal liver tissues (P＜0.05).Rb protein deletion rate doesn’t correlated remarkably with tumor size or phathology grade of HCC （Pgt;0.05）. ConclusionRb protein deletion may play an important role in the tumorigenesis of HCC.Tissue chip is an effective highthroughput technique platform for the study of tumor molecular pathology.
In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
ObjectiveTo investigate the survival of liver cancer cells in hypotonic solution, and provide a theoretical basis for the clinical application of warm distilled water to kill free intraperitoneal liver cancer cells. MethodsThe hepatocellular carcinoma cell line Hep3B were cultured by using different osmotic HEPES buffered solution (148 mOsmol/kg, 90 mOsmol/kg, and 0 mOsmol/kg) in vitro, and then the activity and status of the cells were observed by using the MTT assay and flow cytometry. ResultsOne hundred and forty-eight mOsmol/kg and 90 mOsmol/kg osmotic pressure solution had no obvious killing effect for hepatocellular carcinoma cell line Hep3B, the cells still had strong activity after 30 min. The 0 mOsmol/kg osmotic pressure distilled water had particular killing effect for hepatocellular carcinoma cells, with the prolongation of time and the killing effect was enhanced. It needs 10 min to destruct free cancer cells. ConclusionApplication of warm distilled water lavage in liver cancer surgery requires the continuing role of 10 min to kill the intraperitoneal free cancer cells, thereby preventing the occurrence of postoperative peritoneal metastasis.