• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3275-3279
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• 2012

Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclear. Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC.

• Journal of Veterinary Science
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• v.24 no.3
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• pp.36.1-36.7
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• 2023

Platelet to lymphocyte ratio (PLR) is a prognostic marker in human hepatocellular carcinoma (HCC) however, its utility in canine HCC has not been explored. The aim of the study was to determine if PLR could predict survival outcomes in 42 dogs with HCC. PLR was not a significant predictive factor (p = 0.15) but lymphopenia alone was significantly correlated with a reduced probability of survival (p = 0.024). Further studies are needed to evaluate if peripheral lymphocyte count mirrors that of the tumor microenvironment in canine HCC.

• 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.15 no.11
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• pp.4443-4448
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• 2014

Background: A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2985-2990
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• 2012

Background: Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. Materials and methods: In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. Results: A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. Conclusions: According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

• The Korean Journal of Nuclear Medicine
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• v.20 no.1
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• pp.33-37
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• 1986

It is well known that $^{99m}Tc-sulfur$ colloid or phytate hepatic scintigraphy is highly sensitive but not specific. Both $^{99m}Tc-DISIDA$ and bilirubin have been shown to share the same anionic transport pathway in the liver. Hepatocellular carcinoma(HCC) retains the ability to produce bile but has marked limitation to excreting it resulting in accumulation of bile within the tumor cells. Based upon such a fact, $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy is used for the diagnosis of HCC. The present communication deals with our experience of DISIDA scintigraphic exploration of 9 cases of HCC in a retrospective way. We have made an observation on intensity of positive radio nuclide accumulation in the cold area of HCC as it is demonstrated by phytate scintigraphy. In addition we have semi quantitatively analyzed time-activity pattern and the following results were obtained. (1) All of 9 cases showed an increased uptake of $^{99m}Tc-DISIDA$ in delayed scintigrams. Of these 5 cases showed accumulation less than, 3 equal to, 1 more than the surrounding liver tissue. (2) The mean of the first appearing time of $^{99m}Tc-DISIDA$ activity in tumoral region was 2 hours and 20 minutes. (3) DISIDA scintigraphy provides us with positive informations of diagnostic value.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4451-4456
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• 2015

Background: The aim of our present study was to compare quality of life (QoL) between intermediate-stage (BCLC-B) HCC patients who had undergone either liver resection or transcatheter arterial chemoembolization (TACE). Materials and Methods: A total of 102 intermediate-stage HCC patients participated in our study, including 58 who had undergone liver resection and 44 who had undergone TACE. Baseline demographic characteristics, tumor characteristics, and long-term outcomes, such as tumor recurrence, were compared and analyzed. QoL was assessed using the Short Form (SF)-36 health survey questionnaire with the mental and physical component scales (SF-36 MCS and PCS). This questionnaire was filled out at HCC diagnosis and 1, 3, 6, 12, 24 months after surgery. Results: For the preoperative QoL evaluation, the 8 domains related to QoL were comparable between the two groups. The PCS and MCS scores were significantly decreased in both the TACE and resection groups at1 month after surgery, and this decrease was greater in the resection group. These scores were significantly lower in the resection group compared with the TACE group (P<0.05). However, these differences disappeared at 3 and 6 months following surgery. One year after surgery, the resection group showed much higher PCS scores than the TACE patients (P=0.018), and at 2 years after surgery, the PCS and MCS scores for the resection group were significantly higher than those for the TACE group (P<0.05). Eleven patients (19.0%) in the resection group and 17 (38.6%) in the TACE group suffered HCC recurrence (P<0.05). Univariate and multivariate analyses indicated that tumor recurrence (HR=1.211, 95%CI: 1.086-1.415, P=0.012) was a significant risk factor for poorpostoperative QoL in the HCC patients.Conclusions: Due to its effects on reducing HCC recurrence and improving long-term QoL, liver resection should be the first choice for the treatment of patients with intermediate-stage HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4077-4082
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• 2016

Background: Hepatocellular carcinoma (HCC) is a dreadful complication of end stage liver disease with high morbidity and mortality. Aim: The aim was to assess the role of serum talin-1 and non-invasive fibrosis in patients with HCC. Materials and Methods: A total of eighty seven subjects were enrolled, with 22 two healthy individuals as a control group (n=22), 22 patients in the cirrhosis group and finally 43 in the group with HCC diagnosed with positive triphasic CT abdomen criteria. Serum talin-1 and noninvasive fibrosis parameters were assessed in all subjects. Results: Compared to the cirrhosis group, patients with HCC had higher serum talin-1 ($32.9{\pm}12.6$ vs. $11.1{\pm}2.79ng/ml$), FIB4 ($9.96{\pm}15.3$ vs. $2.90{\pm}1.87$) and $fibro-{\alpha}$ ($10.9{\pm}18.1$ vs. $1.55{\pm}0.28$) but not fibrosis index scores ($4.47{\pm}0.95$ vs. $4.98{\pm}0.96$; p=0.046). Patients with large focal lesions (${\geq}5cm$) had different ALBI scores ($-1.02{\pm}0.63$ vs. $-1.72{\pm}0.59$; p=0.001) serum talin-1 ($9.72{\pm}13.81$ vs. $28.6{\pm}38.89ng/ml$; p=0.007) and fibrosis index scores ($0.85{\pm}0.99$ vs. $4.20{\pm}4.85$; p=0.026). No statistical differences were noted between patients with and without portal vein thrombosis. For detection of HCC, serum talin-1 had 97.7% sensitivity and 100% specificity with a 17.2 ng/ml cutoff. AFP at a 13.7 ng/ml cutoff had 72.1% sensitivity and 6.3.6% specificity. The cutoff for the $fibro-{\alpha}$ score was 1.61 with 81.4% sensitivity and 77.3% specificity. Serum talin-1 (odds=1.08; C.I=1.016-1.150; p=0.014), fibrosis index score (odds=2.35; C.I=1.055-5.217; p=0.037) and the ALBI score (odds=6.9; C.I=1.924-24.708; p=0.003) were predictors of large focal lesions. Conclusions: Serum talin-1, AST/ALT ratio, $fibro-{\alpha}$ score are useful for the assessment of HCC patients.

• Journal of Life Science
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• v.30 no.5
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• pp.460-467
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• 2020

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the word. Although radiation and chemotherapy are generally effective, there are various side effects that greatly limit the effectiveness of these treatments. Therefore, traditional herbs may have potential as important resources for the discovery of liver cancer therapeutics. In this study, we selected three Korean herbal medicine formulas from the Donguibogam, namely Bigihwan (BGH), Daechilgithang (DCGT), and Mokwhyangbinranghwan (MHBRH), and evaluated their anti-cancer effects on HCC cells. According to our results of three ethanol extracts, BGH was more effective at suppressing HCC growth than DCGT or MHBRH. Furthermore, flow cytometry analysis showed that inhibition of HCC proliferation by the three extracts was associated with the induction of apoptosis and autophagy. In particular, BGH significantly increased mitochondrial impairment and showed the possibility of inducing mitophagy in comparison with the other two extracts. BGH prominently upregulated the levels of microtubule-associated protein light chain-3 which was accompanied by a decrease in the expression of anti-apoptotic Bcl-2 without altering the expression of pro-apoptotic Bax. In addition, the levels of PTEN-induced kinase 1 were also markedly increased in BGH-treated HCC cells. Moreover, autophagy blocking improved cell viability and reduced apoptosis after the three treatments, indicating that autophagy by these extracts enhances HCC cells against cytotoxicity. In conclusion, our findings show that BGH demonstrates the highest anti-cancer activity among the three formulas and inhibits the proliferation of HCC cells through autophagy induction.