• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6961-6967
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• 2014

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2619-2623
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• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1299-1306
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• 2014

Background: Nano-biotechnology is recognized as offering revolutionary changes in various fields of medicine. Biologically synthesized silver nanoparticles have a wide range of applications. Materials and Methods: Silver nanoparticles (AgNPs) were biosynthesized with an aqueous extract of Pterocladiella (Pterocladia) capillacea, used as a reducing and stabilizing agent, and characterized using UV-VIS spectroscopy, Fourier Transform Infra red (FT-IR) spectroscopy, transmission electron microscopy (TEM) and energy dispersive analysis (EDX). The biosynthesized AgNPs were tested for cytotoxic activity in a human hepatocellular carcinoma ($HepG_2$) cell line cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, 1% antibiotic and antimycotic solution and 2 mM glutamine. Bacterial susceptibility to AgNPs was assessed with Staphylococcus aureus, Bacillus subtilis [Gram+ve] and Pseudomonas aeruginosa and Escherichia coli [Gram-ve]. The agar well diffusion technique was adopted to evaluate the bactericidal activity of the biosynthesized AgNPs using Ampicillin and Gentamicin as gram+ve and gram-ve antibacterial standard drugs, respectively. Results: The biosynthesized AgNPs were $11.4{\pm}3.52$ nm in diameter. FT-IR analysis showed that carbonyl groups from the amino acid residues and proteins could assist in formation and stabilization of AgNPs. The AgNPs showed potent cytotoxic activity against the human hepatocellular carcinoma ($HepG_2$) cell line at higher concentrations. The results also showed that the biosynthesized AgNPs inhibited the entire panel of tested bacteria with a marked specificity towards Bacillus subtillus. Conclusions: Cytotoxic activity of the biosynthesized AgNPs may be due to the presence of alkaloids present in the algal extract. Our AgNPs appear more bactericidal against gram-positive bacteria (B. subtillus).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7331-7333
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• 2013

Aim: To investigate associations of fasting insulin and glucose levels in serum with hepatocellular carcinoma risk. Materials and Methods: This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalese Army Institute of Health Sciences, between 1st December, 2011 and 31st June, 2013. The variables collected were age, fasting plasma glucose, fasting plasma insulin and ALT. Quantitative determination of human insulin concentrations was accomplished by chemiluminescence enzyme immunoassay. Results: Of the total 220 subjects enrolled in our present study, 20 cases were of HCC and 200 were healthy controls. The maximum number of cases of hepatocellular carcinoma in category cutpoints of fasting insulin levels fell in the range of >6.10 ${\mu}U/ml$. The highest insulin levels (>6.10 ${\mu}U/ml$) were seen to be associated with an 2.36 fold risk of HCC when compared with fasting insulin levels of (<2.75 ${\mu}U/ml$). Furthermore, the insulin levels (2.75-4.10 ${\mu}U/ml$) of category cutpoints also conferred a 1.57 fold risk for HCC when compared with lowest fasting insulin levels of (<2.75 ${\mu}U/ml$). Conclusions: The effect of an insulin level in increasing HCC risk appeared consistent, influencing incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.36-41
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• 2015

Purpose: To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Materials and Methods: Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Results: Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. Conclusion: WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.116-124
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• 2014

Purpose: To investigate the frequency and clinical significance of detected incidental lung nodules found on computed tomography (CT) simulation images for hepatocellular carcinoma (HCC) using computer-aided diagnosis (CAD) and a physician review. Materials and Methods: Sixty-seven treatment-$na{\ddot{i}}ve$ HCC patients treated with transcatheter arterial chemoembolization and radiotherapy (RT) were included for the study. Portal phase of simulation CT images was used for CAD analysis and a physician review for lung nodule detection. For automated nodule detection, a commercially available CAD system was used. To assess the performance of lung nodule detection for lung metastasis, the sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were calculated. Results: Forty-six patients had incidental nodules detected by CAD with a total of 109 nodules. Only 20 (18.3%) nodules were considered to be significant nodules by a physician review. The number of significant nodules detected by both of CAD or a physician review was 24 in 9 patients. Lung metastases developed in 11 of 46 patients who had any type of nodule. The sensitivities were 58.3% and 100% based on patient number and on the number of nodules, respectively. The NPVs were 91.4% and 100%, respectively. And the PPVs were 77.8% and 91.7%, respectively. Conclusion: Incidental detection of metastatic nodules was not an uncommon event. From our study, CAD could be applied to CT simulation images allowing for an increase in detection of metastatic nodules.

• Journal of Korean Neurosurgical Society
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• v.59 no.1
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• pp.37-43
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• 2016

Objective : The aim of this multicenter, matched-pair study was to compare the outcomes of stereotactic radiosurgery (SRS) and conventional external radiation therapy (RT) when used as a primary treatment in spine metastasis from hepatocellular carcinoma (HCC). Methods : From 2005 to 2012, 28 patients underwent SRS as the primary treatment in spine metastasis from HCC. Based on sex, age, number of spine metastasis, Child-Pugh classification, interval from original tumor to spine metastasis, and year of treatment, 28 patients who underwent RT were paired. Outcomes of interest were pain relief, progression free survival, toxicities, and further treatment. Results : The perioperative visual analog scale (VAS) decrease was larger in SRS group than in RT group, but the difference was not significant (3.7 vs. 2.8, p=0.13). When pain medication was adjusted, the number of patients with complete (n=6 vs.3) or partial (n=12 vs.13) relief was larger in SRS group than in RT group; however, the difference was not significant (p=0.83). There was no significant difference in progression free survival (p=0.48). In SRS group, 32.1% of patients had 1 or more toxicities whereas the percentage in RT group was 63.0%, a significant difference (p=0.04). Six SRS patients and 7 RT patients received further intervention at the treated segment. Conclusion : Clinical and radiological outcome were not significantly different between the two treatments. Toxicities, however, were more prevalent in the RT group.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2771-2775
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• 2015

Background: Associations between ABO blood groups and risk of several malignancies have been reported, although there are limited data regarding hepatocellular carcinoma (HCC). The aim of this study was to investigate any possible association between the ABO genotype, especially blood group A, and HCC risk in Koreans. Materials and Methods: We conducted a case-control study of 1,538 patients with newly diagnosed HCC at Chonnam National University Hwasun Hospital and 1,305 randomly selected members of the general population. The ABO genotype was determined by multicolor real-time polymerase chain reaction (PCR) using displacing probes. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated using logistic regression models with adjustment for gender, age, smoking, alcohol drinking, and hepatitis B and C status. Results: The risk of HCC in genotype AA was significantly higher than in OO (aOR=1.773, 95% CI=1.161-2.705). The risk in blood group A was also higher than in blood group O (aOR=1.448, 95% CI=1.005 1.897). No significant difference was found for the AA, BO, BB, and AB genotypes, or blood group B and AB. Conclusions: Blood group A and genotype AA showed the highest risks of HCC in a Korean population. No significant difference was found for the AO, BO, BB, and AB genotypes, or blood group B and AB.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3009-3014
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• 2015

The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC). However, the conclusions of published reports on the relationship between the EGF $61^*A/G$ polymorphism and HCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on 14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August 1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the association. Meta-analysis results showed a significant association between the EGF $61^*A/G$ polymorphism and HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; ho-mozygous model: OR=1.59, 95%CI=1.33-1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology and genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF $61^*A/G$ polymorphism is associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from the source of controls or etiological diversity. Further studies with larger population sizes are needed to confirm these results.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8405-8410
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• 2016

Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR)=2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population.