• BMB Reports
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• v.41 no.2
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• pp.158-163
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• 2008

Hepatitis B virus X protein (HBx) is essential for hepatitis B virus infection and exerts a pleiotropic effect on various cellular machineries. HBx has been also demonstrated as an indirect transcriptional transactivator of various different viral and cellular promoters. In addition, HBx is involved in the development of various liver diseases including hepatocellular carcinoma. However the mechanism of HBx in hepatocellular carcinogenesis remains largely unknown. In this study, to identify possible new cellular proteins interacting with HBx, we carried out yeast two-hybrid assay. We obtained several possible cellular partners including VBP1, a binding factor for VHL tumor suppressor protein. The direct physical interaction between HBx and VBP1 in vitro and in vivo was confirmed by immunoprecipitation assay. In addition, we found that VBP1 facilitates HBx-induced $NF{\kappa}B$ activation and cell proliferation. These results implicate the important role of HBx in the development of hepatocellular carcinoma through its interaction with VBP1.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2165-2170
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• 2016

Background: The survival of hepatocellular carcinoma (HCC) patients is usually low due to late diagnosis. Cipto Mangunkusumo Hospital as the largest tertiary referral hospital in Indonesia, has recently improved its modalities for advanced HCC management, but there has not been any evaluation on any improvement in HCC patient survival. Materials and Methods: A retrospective analysis on 114 HCC patients in 2013-2014 were conducted and compared with the database for 77 HCC patients in 1998-1999. Clinical characteristics and treatment received were recorded and the survival of both groups was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results: The percentage of HBV positive patients had increased after fifteen years from 32.5% to 67.5%. Only two patients (1.8%) in 2013-2014 were diagnosed with HCC during surveillance program. Proportions of Barcelona Clinic Liver Cancer A, B, C, and D in 2013-2014 were 1.8%, 42%, 28.1%, and 28.1%, respectively. There was an increase in the use of potentially curative treatment, such as surgical resection or combination of loco-regional therapies. The one-year survival rate increased from 24.1% in 1998-1999 to 29.4% in 2013-2014, while the median survival decreased from 146 days to 138 days, but the difference was not statistically significant (p=0.913). Conclusions: There was no improvement in the median survival of HCC patients after fifteen years because most continued to present at late stages. There is an urgent need for a nationwide implementation of a hepatitis screening program and HCC surveillance education.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1823-1828
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• 2016

Background: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. Materials and Methods: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. Results: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and $75{\mu}g/mL$ dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. Conclusions: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3479-3483
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• 2015

Objective: Patients with hepatocellular carcinoma (HCC) in stage Barcelona Clinic Liver Cancer (BCLC)-A were grouped based on whether they were accompanied with hepatitis B virus (HBV) infection or not so as to explore the clinical characteristics and prognostic conditions of HCC patients with non-HBV/hepatitis C virus (HCV). Materials and Methods: Clinical data of 64 stage BCLC-A HCC patients with non-HBV/HCV infection (observation group) who received radical hepatectomy in the Affiliated Cancer Hospital of Guangxi Medical University from January, 2006 to November, 2014 were retrospectively analyzed and compared with those of 409 stage BCLC-A HCC patients with HBV infection (control group) in corresponding period. Results: The postoperative 1-, 3- and 5-year recurrent rates of the observation group were 25%, 38.6% and 48.8%, with postoperative mean and median disease-free survival time being 49.1 months and 62.0 months, respectively. Additionally, the postoperative 1-, 3- and 5-year survival rates of observation group were 90.1%, 72.7% and 62.0%, with the mean and median survival times being 54.4 months and 70.0 months, respectively. Conclusions: The 1-year recurrent rate is the highest in HCC patients with non-HBV/HCV, and almost half of the patients have recurrence within 1 year, after which the recurrent rate decreases along with the time.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4303-4310
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• 2015

Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9 % normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and ${\gamma}$-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1771-1777
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• 2012

The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3045-3050
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• 2013

Purpose: Hepatic resection is arguably the preferred treatment for huge hepatocellular carcinoma (H-HCC). Estimating the remnant liver volume is therefore essential. This study aimed to evaluate the feasibility of using computer-assisted volumetric analysis for this purpose. Methods: The study involved 40 patients with H-HCC. Laboratory examinations were conducted, and a contrast CT-scan revealed that 30 cases out of the participating 40 had single-lesion tumors. The remaining 10 had less than three satellite tumors. With the consensus of the team, two physicians conducted computer-assisted 3D segmentation of the liver, tumor, and vessels in each case. Volume was automatically computed from each segmented/labeled anatomical field. To estimate the resection volume, virtual lobectomy was applied to the main tumor. A margin greater than 1 cm was applied to the satellite tumors. Resectability was predicted by computing a ratio of functional liver resection (R) as (Vresected-Vtumor)/(Vtotal-Vtumor) x 100%, applying a threshold of 50% and 60% for cirrhotic and non-cirrhotic cases, respectively. This estimation was then compared with surgical findings. Results: Out of the 22 patients who had undergone hepatectomies, only one had an R that exceeded the threshold. Among the remaining 18 patients with non-resectable H-HCC, 12 had Rs that exceeded the specified ratio and the remaining 6 had Rs that were < 50%. Four of the patients who had Rs less than 50% underwent incomplete surgery due to operative findings of more extensive satellite tumors, vascular invasion, or metastasis. The other two cases did not undergo surgery because of the high risk involved in removing the tumor. Overall, the ratio of functional liver resection for estimating resectability correlated well with the other surgical findings. Conclusion: Efficient pre-operative resectability assessment of H-HCC using computer-assisted volumetric analysis is feasible.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3109-3116
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• 2013

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3381-3384
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• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5361-5365
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• 2013

The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR=2.22, 95% CI 1.51-3.27, ${\chi}^2$=16.90, P<0.001), dominant model (AA/GA vs. GG: OR=1.25, 95% CI 1.00-1.55, ${\chi}^2$=3.98, P=0.046), recessive model (AA vs. GA/GG: OR=2.14, 95% CI 1.47-3.09, ${\chi}^2$=16.68, P<0.001) and allele comparison (A vs. G: OR=1.33, 95% CI 1.13-1.57, ${\chi}^2$=11.66, P=0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility.