• Genomics & Informatics
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• v.8 no.1
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• pp.9-18
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• 2010

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.1-13
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• 2024

Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide. Healthcare resource constraints may predispose treatment delays. We aim to review existing literature on whether delayed treatment results in worse outcomes in HCC. PubMed, Embase, The Cochrane Library, and Scopus were systematically searched from inception till December 2022. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included post-treatment mortality, readmission rates, and complications. Fourteen studies with a total of 135,389 patients (delayed n = 25,516, no delay n = 109,873) were included. Age, incidence of male patients, Child-Pugh B cirrhosis, and Barcelona Clinic Liver Cancer Stage 0/A HCC were comparable between delayed and no delay groups. Tumor size was significantly smaller in delayed versus no delay group (mean difference, -0.70 cm; 95% confidence interval [CI]: -1.14, 0.26; p = 0.002). More patients received radiofrequency ablation in delayed versus no delay group (OR, 1.22; 95% CI: 1.16, 1.27; p < 0.0001). OS was comparable between delayed and no delay in HCC treatment (hazard ratio [HR], 1.13; 95% CI: 0.99, 1.29; p = 0.07). Comparable DFS between delayed and no delay groups (HR, 0.99; 95% CI: 0.75, 1.30; p = 0.95) was observed. Subgroup analysis of studies that defined treatment delay as > 90 days showed comparable OS in the delayed group (HR, 1.04; 95% CI: 0.93, 1.16; p = 0.51). OS and DFS for delayed treatment were non-inferior compared to no delay, but might be due to better tumor biology/smaller tumor size in the delayed group.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1066-1076
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• 2021

Objective: To evaluate the performance of the 2018 Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) Practice Guidelines (hereafter, PG) for the diagnosis of hepatocellular carcinoma (HCC) using gadoxetic acid-enhanced MRI, compared to the Liver Imaging-Reporting and Data System (LI-RADS) version 2018 (hereafter, v2018). Materials and Methods: From January 2013 to October 2015, treatment-naïve hepatic lesions (≥ 1 cm) on gadoxetic acid-enhanced MRI in consecutive patients with chronic hepatitis B or cirrhosis were retrospectively evaluated. For each lesion, three radiologists independently analyzed the imaging features and classified the lesions into categories according to the 2018 KLCA-NCC PG and LI-RADS v2018. The imaging features and categories were determined by consensus. Generalized estimating equation (GEE) models were used to compare the per-lesion diagnostic performance of the 2018 KLCA-NCC PG and LI-RADS v2018 using the consensus data. Results: In total, 422 lesions (234 HCCs, 45 non-HCC malignancies, and 143 benign lesions) from 387 patients (79% male; mean age, 59 years) were included. In all lesions, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity and lower specificity than LR-5 (LI-RADS v2018) (87.2% [204/234] vs. 80.8% [189/234], p < 0.001; 86.2% [162/188] vs. 91.0% [171/188], p = 0.002). However, in lesions of size ≥ 2 cm, the definite HCC had a higher sensitivity than the LR-5 (86.8% [164/189] vs. 82.0 (155/189), p = 0.002) without a reduction in the specificity (80.0% [48/60] vs. 83.3% [50/60], p = 0.15). In all lesions, the sensitivity and specificity of the definite/probable HCC (2018 KLCA-NCC PG) and LR-5/4 did not differ significantly (89.7% [210/234] vs. 91.5% [214/234], p = 0.204; 83.5% [157/188] vs. 79.3% [149/188], p = 0.071). Conclusion: For the diagnosis of HCC of size ≥ 2 cm, the definite HCC (2018 KLCA-NCC PG) had a higher sensitivity than LR-5, without a reduction in specificity. The definite/probable HCC (2018 KLCA-NCC PG) had a similar sensitivity and specificity to that those of the LR-5/4.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5773-5775
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• 2012

Objective: To assess the diagnostic and prognostic value of AFP and des-gamma-carboxyprothrombin (DCP) in combination and alone for hepatocellular carcinoma. Materials and Methods: A case control study carried out in the Department of Biochemistry of Manipal College of Medical Sciences, Pokhara, Nepal between $1^{st}$ January 2010 and $31^{st}$ December 2011. The variables collected were age, gender, BMI, total proteins, albumin, AST, ALT, total bilirubin, DCP, AFP. Approval for the study was obtained from the institutional research ethical committee. Estimation of AFP was performed by ELISA reader for all cases. Analysis was done using descriptive statistics and confidence interval (CI). The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. Results:The mean age of HCC cases was $53.6{\pm}14.93$ yrs. The percentage of females was less than males in both cases (23%) and controls (29%). The specificity of DCP reached 100% when its values was equal or greater than 150 (MAU/ml) for 0, 3, 6, 9, 12 months preceding the diagnosis of HCC. Similarly, the specificity for AFP was also nearly 100% when its value was equal or greater than 200 ng/ml 0, 3, 6, 9, 12 months earlier to the finding of HCC. The specificity of DCP (${\geq}40MAU/mL$) and AFP(${\geq}20$ ng/mL) in combination was 93%, 97%, 95%, 96%, 97% in respect to 0, 3, 6, 9, 12 months prior to the diagnosis of HCC. Conclusion: The combination of both DCP and AFP will improve the finding of initial HCC and the sensitivity of these markers was utmost at the time of HCC identification and noticeably lesser at former time points.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2043-2049
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• 2015

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.3
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• pp.188-193
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• 2019

Transarterial chemoembolization (TACE) is a commonly used and rapidly evolving non-invasive treatment for hepatocellular carcinoma (HCC). It is important that understanding individual anatomical variants and planning for tumor-feeding artery access to acquire adequate treatment effectiveness. In this study, we will report acquired arteriovenous malformation which interferes with TACE for HCC. A 72-year-old man with persistent abdominal pain for 2 days visited our hospital. The patient was chronic hepatitis B carrier and had a history of HCC treated with conventional TACE 10 years ago. Hypervascular nodular HCC in the liver segment 8 and aberrant right hepatic artery from the superior mesenteric artery were detected on computed tomography (CT). When first TACE was performed, the tumor-feeding artery originating from the left hepatic artery was found and embolized. There was no tumor-feeding artery from the right hepatic artery but arteriovenous malformation was found. After a month, follow up CT showed necrotic lesion and residual HCC and we performed secondary TACE. On secondary TACE, we selected the right hepatic artery and passed through arteriovenous malformation. Superselective-angiogram showed remnant tumoral staining and remnant tumor was embolized using drug-eluting bead and Adriamycin. Final angiogram showed no remnant tumoral staining and the patient was discharged without complication. We found the rare case of arteriovenous malformation adjacent to HCC, and we performed superselective TACE beyond arteriovenous malformation to treat HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1649-1654
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• 2014

Background: Clinically significant portal hypertension (PHT) is considered as a contraindication for hepatectomy according to the guidelines of the European Association for Study of Liver and the American Association for Study of Liver Diseases. However, this issue remains controversial. Here we performed a metaanalysis to evaluate the impact of PHT on the results of hepatectomy for hepatocellular carcinoma (HCC). Methods: Cohort studies evaluating the impact of clinically significant PHT, defined as oesophageal varices and/or splenomegaly associated with thrombocytopenia, on the results of hepatectomy for HCC were identified using a predefined search strategy. Summary risk ratios (RRs) and 95% confidence intervals (95% CIs) for PHT and outcomes after hepatectomy for HCC were calculated. Results: Seven cohort studies which including 574 cases with PHT and 1,354 cases without PHT were considered eligible for inclusion. The meta-analysis showed that, in all patients, pooled RRs of post-operative liver failure, post-operative ascites, peri-operative blood transfusion, operative mortality, 3- and 5-year overall survival associated with PHT were 2.23 (95% CI: 1.48-3.34, P=0.0001), 1.77 (95% CI: 1.19-2.64, P=0.005), 1.23 (95% CI: 1.03-1.49, P=0.03), 2.58 (95% CI: 1.12-5.96, P=0.03), 0.82 (95% CI: 0.75-0.88, P<0.00001) and 0.76 (95% CI: 0.69-0.85, P<0.00001), respectively. In subgroup analysis, similar results were found in Child-Pugh class A patients. Conclusion: This meta-analysis suggests that presence of oesophageal varices and/or splenomegaly associated with thrombocytopenia is associated with higher rates of post-operative complications and poor long-term survival after hepatectomy for HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4853-4856
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• 2016

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.

• Journal of Digestive Cancer Reports
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• v.8 no.1
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• pp.65-70
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• 2020

Although being one of the major causes of malignancy related death globally, hepatocellular carcinoma (HCC) has not received much attention in respect of novel drug development. Fortunately, several new drugs were found to be effective and tolerable in patients with advanced HCC from a number of phase 3 studies during the recent several years. Novel multi-targeted kinase inhibitors and immune checkpoint inhibitors were approved for clinical use, and combination strategies to maximize the potent of drugs demonstrated promising antitumor activity and safety with high response rate and improved safety profile. The increased number of available agents for HCC will contribute to change of treatment strategies and prognosis of patients with advanced HCC. Still, there is a many critical questions remain unanswered. Currently ongoing trials and future studies will provide better understanding of tumor biology and optimized criteria for patient selection and combination therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.225-229
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• 2012

Background: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. Methods: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or ${\chi}^2$ tests was used to compare CNAs between females and males. Results: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). Conclusions: These findings suggest that CNAs may play a role in sex-related differences in HBVassociated HCC development.