• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1985-1988
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• 2013

Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases. Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital of Wenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry. Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in the HCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascular invasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantly shorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively). Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival (P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1 expression is correlated with a lower survival rate.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.179-183
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• 2016

A 59-year-old man presented with acute dyspnea following sudden productive cough and expectoration of a full cup of "blood-tinged" sputum. He had been diagnosed with hepatitis B virus-related hepatocellular carcinoma and had received transarterial chemoembolization 5 years ago for a 20-cm hepatic mass; he denied any history of hematemesis and the last esophagogastroduodenoscopy from a year ago showed absence of varix. Chest computed tomography (CT) with angiography showed new appearance of right basal lung consolidation but no bleeding focus. Despite the use of systemic antibiotics, the patient developed respiratory failure on day 7 of hospitalization. After intubation, a massive amount of brown sputum with anchovy-paste-like consistency was suctioned via the endotracheal tube. Bronchoscopic toileting was performed and the patient was extubated. In the ward, he continued to expectorate the brown sputum. On day 25 of hospitalization, a repeat CT scan showed simultaneous disappearance of the pneumonic consolidation and the necrotic fluid within the hepatic mass, suggesting the presence of a fistula. He has continued to receive systemic antibiotics, sorafenib, and entecavir, and follow up by respiratory and hepato-oncology specialists.

• BMB Reports
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• v.47 no.4
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• pp.221-226
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• 2014

Drug-resistance and imbalance of apoptotic regulation limit chemotherapy clinical application for the human hepatocellular carcinoma (HCC) treatment. The reactivation of p53 is an attractive therapeutic strategy in cancer with disrupted-p53 function. Nutlin-3, a MDM2 antagonist, has antitumor activity in various cancers. The post-translational modifications of p53 are a hot topic, but there are some controversy ideas about the function of phospho-$Ser^{392}$-p53 protein in cancer cell lines in response to Nutlin-3. Therefore, we investigated the relationship between Nutlin-3 and phospho-$Ser^{392}$-p53 protein expression levels in SMMC-7721 (wild-type TP53) and HuH-7 cells (mutant TP53). We demonstrated that Nutlin-3 induced apoptosis through down-regulation phospho-$Ser^{392}$-p53 in two HCC cells. The result suggests that inhibition of p53 phosphorylation on $Ser^{392}$ presents an alternative for HCC chemotherapy.

• Molecules and Cells
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• v.40 no.11
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• pp.847-854
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• 2017

Recent studies on molecular carcinogenesis suggest that the chemo-resistance of some cancers is largely due to presence of cancer stem cells (CSCs), which affect the chemotherapy outcome for hepatocellular carcinoma (HCC). However, currently no consensus on a CSC phenotype in HCC has been obtained. Here, we examined Sox12 as a novel CSC marker in HCC. Sox12+ versus Sox12- cells were purified from HCC cell lines. The Sox12+ cells were compared with Sox12- HCC cells for tumor sphere formation, chemo-resistance, tumor formation after serial adoptive transplantations in nude mice, and the frequency of developing distal metastasis. We found that compared to Sox12- HCC cells, Sox12+ HCC cells generated significantly more tumor spheres in culture, were more chemo-resistant to cisplatin, were detected in circulation more frequently, and formed distal tumor more frequently. Moreover, Sox12 appeared to functionally contribute to the stemness of HCC cells. Thus, we conclude that Sox12 may be a novel marker for enriching CSCs in HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3709-3713
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• 2015

Background: Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)-related HCC remain unknown. Materials and Methods: CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. Results: It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. Conclusions: CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7441-7447
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• 2015

Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6457-6461
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• 2015

MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6217-6220
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• 2012

Introduction: Up to present, EGF $61^*A$/G, TGF-${\beta}1$-$509^*T$/C and TNF-${\alpha}$-$308^*A$/G gene polymorphisms have been analysed in other cancer entities than hepatocellular carcinoma (HCC). We here investigated the frequency of these gene polymorphisms among HCC patients. Materials and Methods: A total of 73 HCC patients and 117 cancer-free healthy people were recruited at the Surgical Department of Zhongshan Hospital. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analyzed by PCR-RFLP. Results: The distribution of EGF $61^*G$/G homozygotes among HCC patients was more frequent than that in the control group (24.7% vs 11.1%, OR=2.618, 95%CI=1.195-5.738). In parallel, the frequency of the "G" allele in the HCC patient group was also higher than that in the control group (45.9% vs 33.3%, OR= 1.696, 95%CI=1.110-2.592). No difference could be found for the TGF-${\beta}1$-509 and TNF-${\alpha}$-308 genotypes. Conclusion: EGF $61^*G$/G genotype and G allele are significantly increased among patients with HCC. TGF-${\beta}1$-$509^*T$/C and TNF-${\alpha}$-$308^*A$/G gene polymorphisms are not related to this cancer entity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1745-1749
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• 2014

Background: Platycodin D (PD), a triterpenoid saponin isolated from the Chinese medicinal herb Platycodonis radix, possesses anti-cancer effects in several cancer cell lines. The aim of this study was to evaluate its anticancer activities in hepatocellular carcinoma cells. Materials and Methods: MTT and colony formation assays were performed to evaluate cell proliferation, along with flow cytometry and Western blotting for apoptosis. Cell adhesion was tested by observing cellular morphology under a microscope, while the transwell assay was employed to investigate the cell migration and invasion. Results: PD concentration-dependently inhibited cell proliferation in both HepG2 and Hep3B cells, and significantly suppressed colony formation and induced apoptosis in HepG2 cells. The protein levels of cleaved poly ADP-ribose polymerase (PARP) and Bax were up-regulated while that of survivin was down-regulated after treatment with PD. Moreover, PD not only obviously suppressed the adhesion of HepG2 cells to Matrigel, but also remarkably depressed their migration and invasion induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Conclusions: PD presents anti-cancer potential in hepatocellular carcinoma cells via inducing apoptosis, and inhibiting cell adhesion, migration and invasion, indicating promising features as a lead compound for anti-cancer agent development.

• 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.