• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5761-5767
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• 2013

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1961-1970
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• 2014

Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

• Journal of the Korean Society of Radiology
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• v.79 no.6
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• pp.340-347
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• 2018

Purpose: To evaluate value of image subtraction for identifying hepatocellular carcinoma (HCC) capsule on gadoxetic acid-enhanced MR images. Materials and Methods: This study involved 108 patients at risk of HCC preoperatively examined using gadoxetic acid-enhanced MRI with hepatic resection between May 2015 and February 2017. We evaluated qualities of subtraction images and presence of capsular appearance on portal venous or transitional phases conventional and subtraction images. We assessed effect of capsular appearance on subtraction images on HCC. Results: After excluding 1 patient who had treated by transarterial chemoembolization prior to surgery and 33 patients with unsatisfactory subtraction image qualities, 82 focal hepatic lesions (73 HCC, 5 non-HCC malignancies, and 4 benign) from 74 patients were analyzed. Regarding detection of capsules, sensitivity, accuracy, and area under the receiver operating characteristic curve (AUC) on subtraction images were significantly higher than those on conventional images (95.4%, 89.0%, and 0.80, respectively; p < 0.001), though specificities were same (64.7%). For diagnosis of HCC, sensitivity, accuracy, and AUC on subtraction images were significantly higher than on conventional images (82.2%, 79.3%, and 0.69, respectively; p = 0.011), though specificities were identical (55.6%). Conclusion: Portal venous or transitional phase gadoxetic acid-enhanced MRI subtraction images could improve detection of HCC capsule.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3811-3816
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• 2015

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

• Asian Oncology Nursing
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• v.3 no.2
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• pp.145-154
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• 2003

Purpose: The study was to furnish basic raw materials that evaluate the efficacy of meatal care according to the form and the relative importance of symptom distress which most of cancer sufferers have been experienced. For that, an investigation of five diverse major cancer symptom distress made a comparison between symptom distress and degree of suffering. Method: Study subjects were 138 inpatients with stomach cancer, lung cancer, hepatocellular carcinoma(HCC), large intestine cancer and breast cancer, except those in the terminal-stage, in 'H' university hospital in Seoul and 'K' center in Ilsan gathered from November 20, 2002 to February 20, 2003. To measure the correlation between feeling of discomfort and agony caused by cancer, 5 point scale (from zero to four), stood on the basis of Symptom Distress Scale (SDS, Rodes & Watson, 1987), was used for this study and the Cronbach's coefficient alpha was 0.95. Accumulated data was analyzed with SPSS 10.0 for window, also used by ANOVA and Duncan's Multiple Range Test. Pearson's Correlation Analysis. Results: 1. Symptom distress of cancer patients was noted and defined in their severity-fatigue, anorexia, pain, depression, dyspepsia, changing appearance and nausea. The degree of symptom distress was fatigue, dyspepsia, depression, anorexia, pain, changing appearance and the degree of suffering was nausea, pain, anorexia, dyspepsia, vomiting, breathing difficulty, changing appearance and fatigue. 2. Examining the difference of degree of symptom distress in each cancer cases, it takes the precedence of them. First, in case of stomach cancer, depression, pain, vomiting and nausea were shown in sequence. In case of lung cancer depression, pain, sleeping problem, anxiety, changing appearance, inattentiveness and vomiting were showed in sequence, depression, changing appearance, sleeping problem, pain in case of HCC, depression, pain in case of large intestine cancer and lastly in case of breast cancer changing appearance, depression, pain and anxiety were shown in sequence. The category of the degree of symptom distress that has a signifiant difference was anorexia, activity discomfort, fatigue, constipation or diarrhea, breathing difficulty, dyspepsia, caughing, fever or chillness, scotoma and urinary disorder. Verifying the highest degree of symptom distress in each cancer cases, anorexia was 1.94(F=4.00, p<.01) in stomach cancer, activity discomfort was 0.97(F=3.08, p<.01) in lung cancer and HCC, fatigue was 2.32(F=4.64, p<.01) in HCC, constipation or diarrhea was 1.83(F=22.31, p<.001) in large intestine cancer, breathing difficulty was 1.83(F=4.00, p<.01) in lung cancer, dyspepsia was 2.69(F=9.98, p<.001) in stomach cancer, coughing was 1.53(F=20.49, p<.001) in lung cancer, fever or chillness was 1.23(F=6.88, p<.001) in lung cancer, scotoma was 1.20(F=3.02, p<.05) in lung cancer and urinary disorder was 1.54(F=11.56, p<.001) in HCC. 3. Examining the difference degree of suffering on cancer cases, the result was as follows; depression of lung cancer was 1.17(F=3.76, p<.01), anorexia of stomach cancer was 1.61(F=3.89, p<.01), constipation or diarrhea of large intestine cancer was 1.42(F=10.43, p<.001), changing appearance of breast cancer was 1.65(F=5.43, p<.001), breathing difficulty of lung cancer was 2.27(F=18.57, p<.001), dyspepsia of stomach cancer was 1.97(F=13.56, p<.001), coughing of lung cancer was 1.70(F=22.07, p<.001), fever or chillness of lung cancer was 1.13(F=4.41, p<.01), scotoma of lung cancer was 0.87(F=3.34, p<.05), anxiety of lung cancer was 0.87(F=4.50, p<.001) and urinary disorder of HCC was 1.43(F=16.71, p<.001). 4. In consequence, comparing between symptom distress and degree of suffering on cancer patients undergoing chemotherapy, lung cancer patients showed the highest feeling of discomfort following stomach cancer, HCC, breast cancer and large intestine cancer(F=2.88, p<.05). On those undergoing radiotherapy, lung cancer, HCC, breast cancer, large intestine cancer was in sequence(F=3.78, p<.05) and those resisting radiotherapy, lung cancer, HCC, stomach cancer, large intestine cancer and breast cancer was in sequence(F=2.72, p<.05). 5. Correlation between symptom distress and degree of suffering on cancer patients was generally significant. Conclusion: this study not only defines a significant correlation between symptom distress and degree of suffering but also proffers basic data to evaluate the efficient meatal care depending upon diverse spectrums of symptom distress and degree of suffering.

• Biomedical Science Letters
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• v.11 no.4
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• pp.421-427
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• 2005

To evaluate the diagnostic significance of p16 overexpression in human hepatocellular carcinoma (HCC), we analyzed p16 status and growth inhibitory patterns by p16 overexpression in HCC cell lines having different pRE status. SKHep1 and SNU449 cells show homozygous deletion of p16. The p16 gene in SNU398 cell is inactivated at posttranscription level. Adenovira1-p16 (Ad-p16) infection inhibits the cell growth in Hep3B, SNU398, and SNU449. Failure of growth inhibition in SKHepl results from the low transduction efficiency of adenovirus. The p16-mediated growth inhibition shows G 1 phase arrest in pRE-positive SNU449 but not in pRE-negative Hep3B. These results suggest that therapeutic efficacy of p16 gene might be considered on the transduction efficiency and the toxicity of adenoviral vector. Beside, growth inhibitory effect of p16 could be exerted through either pRE-dependent or -independent pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1539-1544
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• 2014

Purpose: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). Methods: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. Results: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. Conclusions: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.207-214
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• 2019

Purpose: To identify the prognostic factors that could influence survival and to compare prognoses of the patients with the number of the risk factors that might assist in the adequate management of hepatocellular carcinoma (HCC) patients with bone metastases that showed a heterogeneous range of survival. Materials and Methods: A total of 41 patients, treated with radiotherapy (RT) for bone metastases from HCC from 2014 to 2017, were enrolled retrospectively. Survival was determined by the Kaplan-Meier method from the start of the RT for metastatic bone lesions. Pre-RT clinical features were evaluated and their influences on survival were analyzed. The significant factors were considered to compare survivals according to the number of prognostic factors. Results: Median follow-up was 6.0 months (range, 0.5 to 47.0 months). The median overall survival was 6.5 months, and the 1-year and 2-year survival rates were 35.5% and 13.5%, respectively. Multivariate analysis revealed that the Child-Pugh class A group, alpha-fetoprotein increased more than 30 ng/mL, and HCC size of more than 5 cm were associated with worse overall survival. The median survivals in HCC with none, 1, 2, and 3 of the aforementioned risk factors were 19.5, 9.0, 2.5, and 1.0 months, respectively (p < 0.05). Conclusion: Our results show that the overall survivals were significantly different according to the number of the risk factors among HCC patients with bone metastases who showed various lengths of survival.

• Radiation Oncology Journal
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• v.37 no.4
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• pp.286-292
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• 2019

Purpose: A mandibular metastasis is uncommon in patients with hepatocellular carcinoma (HCC). We report the clinical features of this rare lesion and evaluate the effectiveness of radiotherapy in affected patients. Materials and Methods: We retrospectively reviewed our institutional medical records for HCC patients who received radiotherapy for bone metastasis, and included cases of mandible metastasis. The clinical features of these cases, and the characteristics and outcomes of the treatments were assessed. Results: A total of 1,498 patients with a bone metastasis from HCC were treated with radiotherapy between July 1998 and April 2012 at our institution. We identified 9 patients (0.6%) in this cohort that received radiotherapy for a mandibular metastasis. The condyle was the most common location of mandibular metastasis. The median radiation dose was 40 Gy (range, 27.5 to 60 Gy), with a daily dose of 2-3 Gy. All of these 9 patients died during a median follow-up of 9 months (range, 1 to 19 months). Symptom relief was achieved in 7 of 8 patients who completed radiotherapy. Tumor size reduction was observed in 2 of 4 patients who underwent radiologic evaluation after radiotherapy. Conclusions: Metastasis to the mandible from HCC has a poor prognosis. Radiotherapy can be an effective local treatment option for symptomatic relief in these cases.