To elucidate bcl-2 protein expression in hepatic carcinogenetic process and its relationship with apoptotic changes. bcl-2 protein was evaluated immunohistochemically while apoptosis was approached with terminal deoxynucleotidyl transferase (TdT)mediated dUTP nick end labeling (TUNEL) technique in 8 normal livers (NL), 17 liver cirrhosises (LC) and 77 hepatocellular carcinomas (HCC). The results showed that bcl-2 protein was expressed in 3 of 8 NLs(37.5%), 5 of 17 LCs(29.4%) and 7 of 77 HCCs(9.1%) with significant differences between group NL and HCC and between LC and HCC (Ｐ＜0.05). Apoptosis rates of 1.18±0.42%, 4.85±2.78%, 12.89±2.33% in NL, LC, HCC group respectively were demonstrated with significant differences among them (Ｐ＜0.01). Compared the bcl-2 expression with the apoptosis rate in this hepatocarcinogenetic process, reversed trends were presented. Conclusion: bcl-2 expression could be detected in NL, LC and HCC, and its decreasing expression was related to the inhibition attenuation of hepatocellular apoptosis in the process of hepatocarcinogenesis.
ObjectiveTo investigate the impact of elevated fasting blood glucose (FBG) level after open radical hepatectomy on the early recurrence of hepatocellular carcinoma (HCC).MethodsThe clinical data of 112 patients with HCC who underwent the open radical hepatecomy from January 2013 to December 2014 in the Affiliated Hospital of Qingdao University were retrospectively analyzed. After the radical resection of HCC, 86 patients with level of FBG 3.9–6.1 mmol/L and 26 patients with level of FBG≥6.1 mmol/L were design into a normal FBG group and an elevated FBG group, respectively. The recurrence rates of HCC were compared between the two groups at 1- and 2-year after the opreation.ResultsThere were no significant differences between the 2 groups in the gender, age, history of alcohol drinking, hepatitis B history, preoperative ALT, AST, AFP and Child-Pugh classification, scope of hepatectomy, intraoperative hemorrhage, hepatic blood flow occlusion, diameter of maximal tumor, histopathological differentiation, tumor number, cirrhosis, satellite lesion, postoperative adjuvant TACE treatment or not (P>0.05). The postoperative 1- and 2-year recurrence rates of HCC were 19.8% (17/86) and 33.7% (29/86) in the normal FBG group and 42.3% (11/26) and 61.5% (16/26) in the elevated FBG group, respectively, showing significant differences between the 2 groups (P<0.05). The results of multivariate analysis showed that the level of FBG≥6.1 mmol/L, low histopathological differentiation, and no postoperative TACE treatment were the independent risk factors affecting tumor-free survival rate after the open radical resection of HCC (P<0.05). ConclusionsElevated FBG level after open radical resection has a stimulative effect on early recurrence of HCC. As a result, monitoring and controlling of FBG level after operation is helpful in decreasing early recurrence rate of patients with HCC.
ObjectiveTo investigate the expressions and clinical significance of human telomerase reverse transcriptase (hTERT) mRNA and γglutamyl transpeptidase mRNA-H (GGT mRNA-H) in the peripheral blood of small hepatocellular carcinoma (HCC) patients. MethodsThe expressions of hTERT mRNA and GGT mRNA-H were detected in the peripheral blood of thirty patients with small HCC by RT-PCR, eighteen patients with benign liver diseases, and twelve normal volunteers. ResultsThe positive rate of hTERT mRNA and GGT mRNA-H expression in patients with small HCC were 80.0% (24/30) and 46.7%(14/30), respectively. In patients with hepatitic cirrhosis the positive rate of hTERT mRNA expression was 33.3% (6/18), while the expression of GGT mRNA was not detected. Both the expressions of hTERT mRNA and GGT mRNA-H were negative in all normal volunteers. The combination analysis of hTERT mRNA and GGT mRNA-H expression achieved positive rate of 86.7% in the diagnosis of small HCC, which was significantly higher than the positive rate of AFP (26.7%)， Plt;0.05. ConclusionThe hTERT mRNA and GGT mRNA-H are significantly expressed in small HCC patients, the combination analysis of hTERT mRNA and GGT mRNA-H seems to be useful in the early diagnosis of small HCC.
ObjectiveTo investigate the expression of IQ motif-containing GTPase activating protein 1 (IQGAP1) in hepatocellular carcinoma (HCC) tissues, and to analyze the relationship of IQGAP1 and patient's clinical characteristics and prognosis after liver resection. MethodsData of 79 patients who received liver resection between 2007 and 2009 in our hospital were collected. The expression of IQGAP1 was examined by immunohistochemical tests. The clinical characteristics and prognosis were compared. ResultsIQGAP1 was detected in 43 patients (54.4%). Patients with IQGAP1 expression had more poor differentiation and microvascular invasion. The cumulative recurrence-free rate and overall survival rate in 1-, 3-, and 5-year after operation of patients with IQGAP1 expression (cumulative recurrencefree rate:67.4%, 39.5%, and 23.3%; cumulative overall survival rate:97.7%, 71.5%, and 53.3%) were poor than patients without IQGAP1 expression (cumulative recurrence-free rate:100%, 94.4%, and 83.3%; cumulative overall survival rate:1007%, 97.2%, and 88.9%), P < 0.001. ConclusionsHCC patients with IQGAP1 expression had a poor prognosis after liver resection. IQGAP1 may be a prognostic indicator for hepatocellular carcinoma.
ObjectiveTo summary the progress and status of downstaging therapy in treating hepatocellular carcinoma. MethodsThe related literatures were reviewed and analyzed by searching PubMed and MEDLINE. ResultsAlthough the clinical prognosis of advanced hepatocellular carcinoma was poor, the liver resection or liver transplantation after downstaging therapy could significantly improve the prognosis of patients. However, differences were existed if different downstaging therapies and selections of standard were used. ConclusionTo improve the prognosis of patients with advanced hepatocellular carcinoma, the downstaging therapy should be ingeniously selected based on the situation of the patients.
Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). MethodsThe monoclonal antiVEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling (TUNEL) assay. ResultsIn the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm2 vs (105.77±17.40) mm2 (P＜0.001) and (45.20±23.02) mm2 vs (150.77±77.41) mm2 (P＜0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm2 vs (3 900±328)/mm2(P＜0.001 ) and AI being (15.31% vs 6.83%), P＜0.005. Conclusion The antiVEGF antibody can suppress the xenograft tumour growth of the human SMMC7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.
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.
【Abstract】Objective To construct a recombinant adenoviral vector carrying antisense matrix metalloproteinase2 (MMP2) for use in the gene therapy to inhibit the invasiveness and migratory capacity of hepatocellular carcinoma (HCC) cell line HepG2 in vitro and in vivo models. Methods Total RNA was extracted from HCC, and then a 500 bp fragment at the 5′ end of human MMP2 cDNA was synthesized by polymerase chain reaction (PCR) and was reversely inserted into the multiclone site (MCS) of the shuttle plasmid pAdTrack-CMV,with the resultant plasmid and the backbone plasmid pAdEasy-1,the homologous recombination took place in the E.coli BJ5183 and the recombinant adenoviral plasmid carrying the antisense MMP2 gene was constructed and generated. The adenoviruses(Ad-MMP2AS) were packaged and amplified in the HEK 293 cells.Then the viral titer was checked by GFP. Results The recombinant adenovirus vector carrying antisense MMP2 was constructed successfully, the b green fluorescence was observed in HEK 293 cells under a fluorescence microscopy. The viral titer was 1×108/ml. Conclusion The recombinant adenovirus Ad-MMP2AS constructed by us could introduce the antisense MMP2 into HepG2 effectively,which would provide experimental basis for reversing the overexpression of MMP2 in HCC and for inhibiting the invasiveness and migratory capacity of HepG2 in vitro and in vivo models.
Objective To explore the clinical value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid （Gd-EOB-DTPA） enhanced magnetic resonance （MR） imaging for cirrhosis-related nodules. Methods Nineteen patients who were suspected cirrhosis with lesions of liver were prospectively included for Gd-EOB-DTPA enhanced MR imaging test between Nov. 2011 and Jan. 2013. The hepatobiliary phase （HBP） images were taken in 20 minutes after agents’ injection. The images were diagnosed independently in two groups： group A， including the plain phase and dynamic phase images； group B， including plain phase， dynamic phase， and HBP phase images. The signal intensity （SI） of lesions in HBP images， background liver SI， and background noise standard deviation were measured by using a circular region of interest， then the lesion signal to noise ratio （SNR） and contrast signal to noise ratio （CNR） were calculated. Results Nineteen patients had 25 tumors in all， including 18 hepatocelluar carcinoma （HCC） and 7 regenerative nodule （RN） or dysplastic nodule （DN）， with the diameter ranged from 0.6 cm to 3.2 cm （average 1.3 cm） . Sixteen HCC manifested hypo SI relative to the normal liver， while 2 HCC manifested hyper SI at HBP. Five HCC had cystic necrosis with the necrotic area， and there were no enhancement in artery phase， while performed flocculent enhancement at HBP. Six RN or DN showed hyper SI while another 1 showed iso SI to background liver at HBP. The diagnostic accuracy rates of group A and group B were 80.0% （20/25） and 92.0% （23/25）. SNR of RN or DN at HBP was 132.90±17.21， and of HCC was 114.35±19.27， while the CNR of RN or DN was 19.47±8.20， and of HCC was 112.15±33.52. Conclusion Gd-EOB-DTPA enhanced MR imaging can improve the diagnosis capacity of cirrhosis-related nodules， so as to develop more accurate and reasonable treatment options.