• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7345-7349
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• 2013

Background: Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markers with better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. The aim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probable diagnostic markers for HCC among Egyptian patients. Materials and Methods: A total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markers were compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. Results: Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and 90%) for Glypican3 mRNA, and (80% and 95%) for double combination between sGPC3 and AFP respectively. Conclusion: Both serum GPC-3 and GPC-3mRNA are promising diagnostic markers for early detection of HCC in Egyptian patients. RT- PCR proved to be more sensitive (100%) than ELISA (95%) in detecting glypican3.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.30-38
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• 2008

Objectives: The main goals of cancer treatment are improvement of quality of life and survival prolongation. There is a limitation to prolonging the survival time in hepatobiliary and pancreatic cancer. The purpose of this study was to evaluate the quality of life of hepatobiliary and pancreatic cancer patients who visited for traditional Korean cancer treatment. Methods: We evaluated the quality of life of 23 hepatobiliary and pancreatic cancer patients who visited for oriental medicine treatment at East-West Neo Medical Center from June to October of 2007. FACT-G (Functional Assessment Cancer Therapy-General), used in this study, is a scale for evaluation of QOL confirmed validity and reliability, popularly used in many countries to evaluate QOL of cancer patients. Results: The average age of enrolled patients was 57. There were 10 hepatocellular carcinoma patients, 7 pancreatic cancer patients, 6 biliary tract cancer patients. Twenty one patients were in stage IV and 20 patients had distant metastases. By Sasang constitution, Taeumin were 7, Soyangin were 8, and Soeumuin were 8. The baselines of FACT-G score in the first visit were from 34.33 to 85, and the mean score was 67.3. The mean score of FACT-G in hepatocellular carcinoma patients was 67.5, that of pancreatic cancer patients was 62.5, and that of biliary tract cancer patients was 71. Conclusions: This study is valuable as an initial QOL study of hepatobiliary and pancreatic cancer patients who visited an oriental medical clinic. We believe that consistent studies will be necessary to demonstrate oriental treatment-related quality of life with hepatobiliary and pancreatic cancer.

• Korean Journal of Veterinary Research
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• v.38 no.2
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• pp.386-393
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• 1998

The study was performed to investigate the histological findings and the appearances of positive cells by immunohistochemical methods using proliferating cell nuclear antigen (PCNA) antibody and apoptotic kit in diethylnitrosamine (DEN) -induced rat liver cancer model. Forty four male rats (Sprague Dawley), initially 5 to 6 weeks of age and 120 to 150gm in body weight were continuously were given with water containing 0.01% DEN for 13 weeks and 3~6 rats per week were randomly sacrified at intervals of a week from 8 weeks to 17 weeks. The interlobular connective tissues in the rat livers were proliferated at early 8 weeks. The vaccuolated or fatty degenerated liver cells were focally distributed and then widely distributed with the passage of weeks and the liver cells with large vacuoles tended to be crowded in focal areas, and the liver cells in some lobules were transformed into small or eosinophilic polyhedral large cells. The hepatocellular carcinoma and the cholangiocarcinoma were simultaneously developed in same liver and tended to be markedly developed after 12 weeks but the development of carcinoma in some livers at same week were less or more advanced as 3~5 week intervals. The regions with more number of positive cells by PCNA antibody or apoptotic kits in livers were ranked as following order ; small hepatocellular carcinoma regions, cholangiocarcinoma regions, trabecular or acinar type carcinoma regions, and large liver cell regions. The numbers of the positive cells by PCNA antibody were more numerous than those by apoptotic kit. So these findings suggested that the volumes and weights of the livers were increasing by more many proliferating of carcinoma cells on the above ordered regions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8377-8382
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• 2016

Background: The aim of this study was to evaluate any association between a single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409, C>G) and the development and prognosis in patients with hepatocellular carcinoma (HCC). Materials and Methods: Two hundred heathy controls and 388 HCC cases were included: 211 with HBV, 98 patients with HCV, 29 with alcoholic steatohepatitis (ASH) and 52 with non-alcoholic steatohepatitis (NASH). The SNP was determined by real-time PCR based on TaqMan assays. Results: The prevalence of rs738409 genotypes CC, CG and GG in controls was 91 (45.5%), 88 (44.0%), and 21 (10.5%), respectively, while the corresponding genotypes in all patients with HCC was 158 (40.7%), 178 (45.9%), and 52 (13.4%). The GG genotype had significantly higher distribution in patients with ASH/NASH-related HCC compared with controls (OR=2.34, 95% CI=1.16-4.71, P=0.018), and viral-related HCC cases (OR=2.15, 95% CI=1.13-4.08, P=0.020). However, the frequency of the GG genotype was similar between controls and patients with viral-related HCC. At initial diagnosis, HBV-related HCC were larger and at more advanced BCLC stage than the other HCC groups. There were no significant differences between the GG and non-GG groups regarding clinical characteristics, tumor stage and overall survival. Conclusions: These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis. However, the polymorphism was not associated with the prognosis of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8271-8279
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• 2016

Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1649-1654
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• 2013

Objective: This work aimed to evaluate the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with c-arm cone-beam CT guided synchronous radiofrequency ablation (RFA) in treatment of large hepatocellular carcinoma (HCC). Methods: 21 patients with large HCC were studied from January 2010 to March 2012. TACE combined with synchronous C-arm cone-beam CT guided RFA were performed on a total of 25 lesions. Conventional imaging examination (CEUS, enhanced CT or MRI) and AFP detection were regularly conducted to evaluate the technical success rate of combined treatment, complications, treatment response, time without disease recurrence and survival rate. Results: The technical success rate of combined treatment was 100%, without any significant complication. After 1 month, there were 19 cases with complete response and 2 cases with partial response, with an complete response rate of 90.4% (19/21) and a clinical effective rate of 100% (21/21). The complete response rates of single nodular lesions (100%, 17/17) was significantly higher than that of multiple nodular lesions (50%, 2/4) (P<0. 05). During 2 to 28 months of follow-up, in 19 cases with complete response, the average time without disease recurrence was $10.8{\pm}6$ months. The total survival rates of 6, 12 and 18 months in 21 patients were 100%, respectively. Conclusion: TACE combined with synchronous C-arm CT guided RFA is safe and effective for treatment of large HCC. The treatment efficacy for single nodular lesion is better than that for multiple nodular lesions.

• Genomics & Informatics
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• v.1 no.2
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• pp.101-107
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• 2003

Loss of heterozygosity (LOH) has been used to detect deleted regions of a specific chromosome in cancer cells. LOH on chromosome 16q has been reported to occur frequently in progressed hepatocellular carcinoma (HCC). Liver tissues from 37 Korean HCC patients were analyzed for LOH by using 25 polymorphic microsatellite markers distributed along 16q. Out of the 37 HCC patients studied, 21 patients (56.8%) showed LOH in various regions of 16q with at least one polymorphic marker. Puring the analysis of these 21 LOH cases, 6 patients showed interstitial LOHs in which the boundary of the LOH region was defined. With two rounds of LOH analysis, five commonly occurring interstitial LOH regions were identified; 16q21-22.1, 16q22.2 - 22.3, 16q22.3, 16q23.2 and 16q23.3 - 24.1. Among the five LOH regions the 16q23.3 - 24.1 region has been reported to be related with chromosome instability. A complete physical map, which covers the 3.2 Mb region of 16q23.3 - 24.1 (D16S402 and D16S486), was constructed to identify novel candidate tumor suppressor genes. We provide the minimally tiling path map consisting of 28 BAC clones. There was one gap between NT_10422.11 and NT_019609.9 of the human genome sequence contig (NCBI sequence build 33, April 29, 2003). This gap can be filled by sequencing the R-1425M20 clone which bridges these sequence contigs.

• Advances in Traditional Medicine
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• v.9 no.1
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• pp.67-73
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• 2009

Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.77-77
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• 2003

Sepsis remains common surgical problems with high morbidity and mortality despite improvement in the management for septic patient. Although hepatocellular dysfunction occurs during sepsis, the mechanism responsible for this remains unclear. In sepsis, a state of severe oxidative stress is encountered, with host endogenous antioxidant defenses overcome. Therefore, the aim of this study was to determine the effect of a-tocopherol (AT) vasoregulatory gene expression during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). AT (15 mg/kg) was intraperitonealy injected for 3 days prior to CLP. Blood samples were taken 24 h after CLP for measurement of the extent of hepatocellular damage. Liver samples were taken for RT-PCR analysis of mRNA for genes of interest: endothelin-l (ET-l), its receptors $ET_{A}$ and $ET_{B}$, nitric oxide synthases (iNOS and eNOS), cyclooxygenase-2 (COX -2), heme oxygenase-l (HO-l), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The activities of serum alanine aminotransferase and lipid peroxidation level were significantly increased; an increase which was prevented by AT pretreatment. CLP significantly increased the mRNA levels of ET-1 and $ET_{B}$; an increase that was prevented by AT pretreatment. However, the level of $ET_{A}$ mRNA significantly decreased after CLP; a decrease that was not prevented by AT pretreatment. There were significant increases in the mRNA expression of iNOS, HO-l and COX -2 in CLP groups. This increase was prevented by AT pretreatment. The expression of eNOS and TNF-$\alpha$ mRNA significantly increased in CLP, which was not prevented by AT pretreatment. Our findings suggest that there was an imbalanced vasoregulatory gene expression in sepsis, and AT ameliorates this change through its free radical scavenging activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4103-4107
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• 2015

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. Materials and Methods: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. Results: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). Conclusions: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.