• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.483-486
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• 2012

Background: The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. Methods: Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. Results: Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients' prognosis. Conclusion: Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4305-4309
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• 2012

Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3555-3559
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• 2013

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3509-3514
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• 2013

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1821-1825
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• 2015

Background: Associations between the NQO1 C609T polymorphism and hepatocellular carcinoma (HCC) risk are a subject of debate. We therefore performed the present meta-analysis to evaluate links with HCC susceptibility. Materials and Methods: Several major databases (PubMed, EBSCO), the Chinese national knowledge infrastructure (CNKI) and the Wanfang database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. Results: A total of 4 studies including 1,325 patients and 1,367 controls were identified. There was a significant association between NQO1 C609T polymorphism and HCC for all genetic models (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01; additive model: OR=1.96, 95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; and recessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis, similarly results were identified in Asians. For Asians, the combined ORs and 95% CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01; additive model: OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02, p<0.01; and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). Conclusions: The current meta-analysis suggested that the NQO1 C609T polymorphism could be a risk factor for developing HCC, particularly in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2395-2399
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• 2016

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

• Journal of Yeungnam Medical Science
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• 제33권2호
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• pp.155-158
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• 2016

Sorafenib (Nexavar) has been regarded as a treatment for unresectable hepatocellular carcinoma (HCC), with side effects that include hand-foot skin reaction, diarrhea, rash, fatigue, hypertension, nausea, anorexia, weight loss, and alopecia. Thyroid disorder, such as endocrine side effect, has also been reported. However no case involving adrenal insufficiency has been reported. Here, we report a case of adrenal insufficiency which occurred after taking sorafenib in a patient with HCC. A 56-year-old man visited our hospital due to right upper quadrant abdominal pain and he was diagnosed as multiple disseminated and unresectable HCCs with portal vein invasion; therefore transarterial chemoembolization was performed and sorafenib administration was started. Two months later, he was admitted to the hospital complaining of severe fatigue. The laboratory results showed cortisol of <$0.2{\mu}g/dL$ and adrenocorticotropic hormone of <1.00 pg/mL. The patient had no history of taking steroids or herbal medications. Secondary adrenal insufficiency was diagnosed and prednisolone 10 mg per day was started immediately; as a result, fatigue remarkably improved. This may be the first report indicating a possible association between sorafenib and adrenal insufficiency and it implies that the possibility of adrenal insufficiency should be considered in patients taking sorafenib who complain of severe fatigue.

• Radiation Oncology Journal
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• 제33권3호
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• pp.217-225
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• 2015

Purpose: To investigate the outcomes of patients with spinal metastases from hepatocellular carcinoma (HCC), who were treated by stereotactic body radiotherapy (SBRT). Materials and Methods: This retrospective study evaluated 23 patients who underwent SBRT from October 2008 to August 2012 for 36 spinal metastases from HCC. SBRT consisted of approximately 2 fractionation schedules, which were 18 to 40 Gy in 1 to 4 fractions for group A lesions (n = 15) and 50 Gy in 10 fractions for group B lesions (n = 21). Results: The median follow-up period was 7 months (range, 2 to 16 months). Seven patients developed grade 1 or 2 gastrointestinal toxicity, and one developed grade 2 leucopenia. Compression fractures occurred in association with 25% of the lesions, with a median time to fracture of 2 months. Pain relief occurred in 92.3% and 68.4% of group A and B lesions, respectively. Radiologic response (complete and partial response) occurred in 80.0% and 61.9% of group A and B lesions, respectively. The estimated 1-year spinal-tumor progression-free survival rate was 78.5%. The median overall survival period and 1-year overall survival rate were 9 months (range, 2 to 16 months) and 25.7%, respectively. Conclusion: SBRT for spinal metastases from HCC is well tolerated and effective at providing pain relief and radiologic response. Because compression fractures develop at a high rate following SBRT for spinal metastases from primary HCC, careful follow up of the patient is required.

• Radiation Oncology Journal
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• 제33권3호
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• pp.233-241
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• 2015

Purpose: To compare volumetric modulated arc therapy of RapidArc with robotic stereotactic body radiation therapy (SBRT) of CyberKnife in the planning and delivery of SBRT for hepatocellular carcinoma (HCC) treatment by analyzing dosimetric parameters. Materials and Methods: Two radiation treatment plans were generated for 29 HCC patients, one using Eclipse for the RapidArc plan and the other using Multiplan for the CyberKnife plan. The prescription dose was 60 Gy in 3 fractions. The dosimetric parameters of planning target volume (PTV) coverage and normal tissue sparing in the RapidArc and the CyberKnife plans were analyzed. Results: The conformity index was $1.05{\pm}0.02$ for the CyberKnife plan, and $1.13{\pm}0.10$ for the RapidArc plan. The homogeneity index was $1.23{\pm}0.01$ for the CyberKnife plan, and $1.10{\pm}0.03$ for the RapidArc plan. For the normal liver, there were significant differences between the two plans in the low-dose regions of $V_1$ and $V_3$. The normalized volumes of $V_{60}$ for the normal liver in the RapidArc plan were drastically increased when the mean dose of the PTVs in RapidArc plan is equivalent to the mean dose of the PTVs in the CyberKnife plan. Conclusion: CyberKnife plans show greater dose conformity, especially in small-sized tumors, while RapidArc plans show good dosimetric distribution of low dose sparing in the normal liver and body.