• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4757-4761
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• 2012

Objectives: To explore the impact of low- vs conventional-dose chemotherapy via transcatheter arterial chemo-embolization (TACE) on serum fibrosis indicators and treatment efficacy of hepatocellular cancer patients (HCC). Materials and Methods: Patients fulfilling the eligibility criteria were assigned to TACE in Group A (with low-dose chemotherapy) or Group B (conventional-dose chemotherapy). Four serum fibrosis related indicators, hyaluronic acid(HA), human pro-collagen type-III (hPC-III), laminin (LN), and collagen type-IV(IV-C) before TACE were compared with the values 7 days after TACE. The response rate and survival time were also compared between the two groups. Results: Fifty patients with HCC were enrolled in this study, including 25 in Group A and 25 in Group B. No significant differences were detected between the two groups in the four indicators before TACE. After TACE, the value of the four serum indicators increased significantly in Group B. However, no significant differences regarding these four indicators were found in Group A after TACE. Significant differences were demonstrated between the two groups after TACE, but median survival time and 1 or 2 year overall survival rates did not differ (P>0.05). Conclusions: Low-, compared with conventional-dose chemotherapy exerts the same impact on the variation of fibrosis related indicators and has no influence on median survival time and survival rate after TACE in HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2753-2758
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• 2014

Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8665-8670
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• 2016

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7213-7218
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• 2014

Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

• Korean Journal of Radiology
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• v.21 no.9
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• pp.1077-1086
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• 2020

Objective: To evaluate the effect of perfluorobutane microbubbles (Sonazoid^®, GE Healthcare) on steam popping during radiofrequency (RF) ablation for treating hepatocellular carcinoma (HCC), and to assess whether popping affects treatment outcomes. Materials and Methods: The institutional review board approved this retrospective study, which included 90 consecutive patients with single HCC, who received percutaneous RF ablation as the first-line treatment. The patients were divided into two groups, based on the presence or absence of the popping phenomenon, which was defined as an audible sound with a simultaneous sudden explosion within the ablation zone as detected via ultrasonography during the procedure. The factors contributing to the popping phenomenon were identified using multivariable logistic regression analysis. Local tumor progression (LTP) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with the log-rank test for performing comparisons between the two groups. Results: The overall incidence of the popping phenomenon was 25.8% (24/93). Sonazoid^® was used in 1 patient (4.2%) in the popping group (n = 24), while it was used in 15 patients (21.7%) in the non-popping group (n = 69). Multivariable analysis revealed that the use of Sonazoid^® was the only significant factor for absence of the popping phenomenon (odds ratio = 0.10, p = 0.048). There were no significant differences in cumulative LTP and DFS between the two groups (p = 0.479 and p = 0.424, respectively). Conclusion: The use of Sonazoid^® has a suppressive effect on the popping phenomenon during RF ablation in patients with HCC. However, the presence of the popping phenomenon may not affect clinical outcomes.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.40-46
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• 2022

Backgrounds/Aims: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC). Methods: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated. Results: Serum alpha-fetoprotein levels > 100 ng/mL (p = 0.014) and lymphovascular emboli in the specimen (p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score (p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS. Conclusions: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.483-486
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• 2012

Background: The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. Methods: Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. Results: Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients' prognosis. Conclusion: Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4363-4368
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• 2012

The epidermal differentiation complex (EDC) contains a large number of gene products which are crucial for the maturation of the human epidermis and can contribute to skin diseases, even carcinogenesis. It is generally accepted that activation of oncogenes and/or inactivation of tumor suppressor genes play pivotal roles in the process of carcinogenesis. Here, NICE-3, a novel EDC gene, was found to be up-regulated in human hepatocellular carcinoma (HCC) by quantitative real-time RT-PCR. Furthermore, overexpression of exogenous NICE-3 by recombinant plasmids could significantly promote cell proliferation, colony formation and soft agar colony formation in Focus and WRL-68 HCC cell lines. Reversely, NICE-3 silencing by RNA interference could markedly inhibit these malignant phenotypes in YY-8103 and MHCC-97H cells. Moreover, cell cycle analysis of MHCC-97H transfected with siRNA by flow cytometry showed that NICE-3 knockdown may inhibit cell growth via arrest in G0/G1 phase and hindering entry of cells into S phase. All data of our findings indicate that NICE-3 may contribute to human hepatocellular carcinoma by promoting cell proliferation.

• Journal of Yeungnam Medical Science
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• v.33 no.2
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• pp.155-158
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• 2016

Sorafenib (Nexavar) has been regarded as a treatment for unresectable hepatocellular carcinoma (HCC), with side effects that include hand-foot skin reaction, diarrhea, rash, fatigue, hypertension, nausea, anorexia, weight loss, and alopecia. Thyroid disorder, such as endocrine side effect, has also been reported. However no case involving adrenal insufficiency has been reported. Here, we report a case of adrenal insufficiency which occurred after taking sorafenib in a patient with HCC. A 56-year-old man visited our hospital due to right upper quadrant abdominal pain and he was diagnosed as multiple disseminated and unresectable HCCs with portal vein invasion; therefore transarterial chemoembolization was performed and sorafenib administration was started. Two months later, he was admitted to the hospital complaining of severe fatigue. The laboratory results showed cortisol of <$0.2{\mu}g/dL$ and adrenocorticotropic hormone of <1.00 pg/mL. The patient had no history of taking steroids or herbal medications. Secondary adrenal insufficiency was diagnosed and prednisolone 10 mg per day was started immediately; as a result, fatigue remarkably improved. This may be the first report indicating a possible association between sorafenib and adrenal insufficiency and it implies that the possibility of adrenal insufficiency should be considered in patients taking sorafenib who complain of severe fatigue.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6455-6461
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• 2012

Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031). ${\chi}^2$ tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P=0.012), rather than later stage recurrence. Conclusion: The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC.