Objective To explore the relationship between the HBsAg positive patients suffering from hepatocellular carcinoma (HCC) and HBV DNA genotype. Methods By using PCR type-specific primers combined with sequencing of genotype, we analyzed the genotype of HBV DNA in the serum of 500 patients with positive HBsAg in our hospital. Among them, 150 cases suffered from HCC. Results Genotype B and C were both predominant genotypes in HBsAg positive patients. But in HCC group, the rate of genotype C was 65.33% （98/150）, which was significantly higher than that in non-HCC group (88/350, 25.14%), while genotype B, in contrast, was 28.67% （43/150） and 68.86% （241/350）， χ2=75.45， Plt;0.05. The distribution of HBV DNA genotype B or genotype C in different gender or different age groups were not statistically significantly different in cases of HCC (Pgt;0.05). Conclusion Genotype C of HBV DNA is more common in patients with HCC, and maybe there is relationship between genotype C and the occurrence of 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 determine the risk factors for recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). MethodsThe clinical data from seventysix consecutive HCC patients who underwent OLT were retrospectively analyzed. The patients were divided into nonrecurrence group (n=53) and recurrence group (n=23) based on recurrence, and the characteristics of tumor recurrence were analyzed. ResultsThe overall recurrence rate of tumor was 30.3% (23/76). By univariate analysis, gender (P=0.449), age (P=0.091), received preoperative therapy or not (P=0.958), tumor numbers (P=0.212), and HBV/HCV infection (P=0.220) were not closely related with tumor recurrence, while the integrality of tumor capsule (P=0.009), tumor stage (P=0.002), tumor diameter (Plt;0.001), vascular invasion (Plt;0.001), and AFP level before transplantation (P=0.044) were significantly related with tumor recurrence. Furthermore, the oneyear recurrence rate of tumor was higher in patients whose AFP level returned to normal within two months after transplantation (Plt;0.001) and tumor diameter was less than 5.0 cm (P=0.001). Multivariate analysis revealed that tumor diameter (P=0.001, OR=6.456, 95%CI: 2.356-17.680), vascular invasion (P=0.030, OR=10.653, 95%CI: 1.248-90.910), and AFP level before transplantation (P=0.017, OR=2.601, 95%CI: 2.196-5.658) were independent risk factors for tumor recurrence. ConclusionMore attentions shall be paid to these patients with tumor diameter gt;5.0 cm, vascular invasion, and AFP level before transplantation ≥400 μg/L, in particular AFP level is beyond normal within two months after transplantation, and antitumor therapy shall be given as soon as possible.
Objective To study the effect of HBeAg on recurrence and survival after radical resection of small (≤3 cm) hepatocellular carcinoma (HCC). Methods Two hundreds and twenty-three HCC patients undergone radical resection from 1999 to 2000 were divided into two groups according to serum HBeAg status， HBeAg positive group (n=73) and HBeAg negative group (n=150). The patients’ factors, operative factors and tumorous facors were studied retrospectively between the two groups. And risk factors of overall survival (OS) and disease-free survival (DFS) were analyzed. Results There were no significant differences in operative and tumorous factors between the two groups, but the HBeAg positive group were younger with more severe cirrhosis (P=0.004, P=0.008). The OS and DFS were significantly different between the HBeAg positive group and HBeAg negative group. The 1-, 3- and 5-year OS were 91.5%, 76.8%, 60.1% and 95.2%, 85.3%, 73.2%, respectively (P=0.053)； and the 1-, 3- and 5-year DFS were 73.3%, 53.7%, 40.3% and 86.6%, 65.5%, 54.5%, respectively (P=0.002). Multivariate analysis revealed that age ＞50 years, HBeAg positive and macronodular cirrhosis were significantly related to OS, and HBeAg positive, multiple tumor nodulars were significantly related to DFS. Positive serum HBeAg status was an independent risk factor for both OS and DFS. Conclusion Positive serum HBeAg is closely related to early recurrence and survival after radical resection of patients with small HCC.
【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.
ObjectiveTo study the relationship between expression of p27KIP1 and progression of hepatocellular carcinoma(HCC).MethodsThe expression of p27KIP1 in 52 cases of HCC was detected by immunohistochemistry of strept avidinbiotin complex and mRNA in situ hybridization.ResultsThe positive cells of p27KIP1 protein were diffused in HCC.The positive signal was localized in nuclei.The labeling index (LI) of p27KIP1 protein was significantly higher in tumorsurrounding tissues than that in tumor tissues. p27KIP1 protein LI showed a positive correlation with the differentiation grade of HCC.The better differentiation of cancer cells, the higher LI of p27KIP1 protein (P＜0.01).The positive cells of p27KIP1 mRNA were also diffused in HCC.The positive signal was localized in nuclei and cytoplasm. As to the expression of p27KIP1 at the mRNA level,there was no significant correlation with tumorsurrounding tissues and stages of HCC.Conclusionp27KIP1 protein is associated with progression and differentiation grade of hepatocellular carcinoma.
1术后生存41年，肝癌治疗史上的奇迹肝癌在我国是最常见的癌症之一，每年约10万人被夺去生命。此病进展迅速，预后很差，人们常将其称为“癌中之王”，或“不治之症”。 近年，肝癌研究不断取得突破进展，振奋人心。其中印象最深的是，复旦大学附属中山医院(原上海医科大学附属中山医院)在41年前为一肝癌患者成功施行了肝切除手术，至今已91岁高龄，仍健在。创造了肝癌外科治疗史上的奇迹。
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.
Objective To investigate the relationship between syndecan-1 protein and malignant phenotypes of hepatocellular carcinoma (HCC). Methods forty-seven formalin-fixed sections were obtained. The syndecan-1 was measured with immunohistochemistry assay (ABC method). Results Among 47 HCC tissues, 28 (59.6%) show negative staining, the syndecan-1 negative rate in HCC with poor differentiation was higher than those with good differentiation (78.3% vs 41.7%, Ｐ＜0.05), and negative rate in large HCC was higher than in small HCC (81.0% vs 42.3%, Ｐ＜0.01), and negative rate in HCC with the presence of tumor-cells in blood was greater than in those without tumor-cells in blood (84.2% vs 42.9%, P＜0.01). No correlation was found between syndecan-1 expression and serum AFP level and Child class. Conclusion Syndecan-1 expression is correlated with the growth, differentiation, invasiveness, metastasis and progression of HCC. It is possible that syndecan-1 is a negative regulator of these malignant phenotypes of HCC, can be regarded as suppressive gene.