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      • Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

        Zekri, Abd El-Rahman Nabawy,Nassar, Auhood Abdel-Monem,El-Rouby, Mahmoud Nour El-Din,Shousha, Hend Ibrahim,Barakat, Ahmed Barakat,El-Desouky, Eman Desouky,Zayed, Naglaa Ali,Ahmed, Ola Sayed,Youssef, A Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

        Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

      • Serum Biomarkers for Early Detection of Hepatocellular Carcinoma Associated with HCV Infection in Egyptian Patients

        Zekri, Abdel-Rahman,Youssef, Amira Salah El-Din,Bakr, Yasser Mabrouk,Gabr, Reham Mohamed,El-Rouby, Mahmoud Nour El-Din,Hammad, Ibtisam,Ahmed, Entsar Abd El-Monaem,Marzouk, Hanan Abd El-Haleem,Nabil, M Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

        Background: Early detection of hepatocellular carcinoma using serological markers with better sensitivity and specificity than alpha fetoprotein (AFP) is needed. Aims: The aim of this study was to evaluate the diagnostic value of serum sICAM-1, ${\beta}$-catenin, IL-8, proteasome and sTNFR-II in early detection of HCC. Materials and Methods: Serum levels of IL-8, sICAM-1, sTNFR-II, proteasome and ${\beta}$-catenin were measured by ELISA assay in 479 serum samples from 192 patients with HCC, 96 patients with liver cirrhosis (LC), 96 patients with chronic hepatitis C (CHC) and 95 healthy controls. Results: Serum levels of proteasome, sICAM-1, ${\beta}$-catenin and ${\alpha}FP$ were significantly elevated in HCC group compared to other groups (P-value<0.001), where serum level of IL-8 was significantly elevated in the LC and HCC groups compared to CHC and control groups (P-value <0.001), while no significant difference was noticed in patients with HCC and LC (P-value=0.09). Serum level of sTNFR-II was significantly elevated in patients with LC compared to HCC, CHC and control groups (P-value <0.001); also it was significantly higher in HCC compared to CHC and control groups (P-value <0.001). ROC curve analysis of the studied markers between HCC and other groups revealed that the serum level of proteasome had sensitivity of 75.9% and specificity of 73.4% at a cut-off value of $0.32{\mu}g/ml$ with AUC 0.803 sICAM-1 at cut off value of 778ng/ml, the sensitivity was 75.8% and the specificity was 71.8% with AUC 0.776. ${\beta}$-catenin had sensitivity and specificity of 70% and 68.6% respectively at a cut off value of 8.75ng/ml with an AUC of 0.729. sTNFR-II showed sensitivity of 86.3% and specificity of 51.8% at a cut off value of 6239.5pg/ml with an AUC of 0.722. IL-8 had sensitivity of 70.4% and specificity of 52.3% at a cut off value of 51.5pg/ml with AUC 0.631. Conclusions: Our data supported the role of proteasome, sICAM-1, sTNFR-II and ${\beta}$-catenin in early detection of HCC. Also, using this panel of serological markers in combination with ${\alpha}FP$ may offer improved diagnostic performance over ${\alpha}FP$ alone in the early detection of HCC.

      • SCIESCOPUSKCI등재

        THE USE OF SEAWEED MEAL IN FEEDING COMMON CARP (Cyprinus carpio L.)

        Zaki, M.A.,Nour, A.M.,Omar, E.,Tag El-Din, A.E. Asian Australasian Association of Animal Productio 1994 Animal Bioscience Vol.7 No.2

        Two experiments were made. In experiment 1, four diets containing 0, 5, 15 and 25% washed seaweed meal were prepared to study the effects of incorporating seaweed meal instead of equivalent amounts of berseem leaf meal in fish feeds on growth performance and feed utilization of common carp. The results showed that average daily gain (ADG), specific growth rate (SGR%), dry matter (DM) and ether extract (EE) of the carcasses were decreased (p<0.05) with the increasing level of seaweed meal in the feeds. Inclusion of 5% seaweed meal in the diet gave the best feed conversion ratio (FCR) among all diets, however, protein productive value (PPV) and energy utilization (EU) were decreased (p<0.05) with increasing level of seaweed meal in the diet. In experiment 2, washed seaweed meal was either steam cooked or sprayed with NaOH (0.5% or 1% NaOH) and incorporated in the diets at the level of 25% instead of equivalent amount of berseem leaf meal. The results showed that steam cooked seaweed gave the best (p<0.05) growth performance, FCR and protein efficiency ratios, PER and PPV, for other treatments in descending order were NaOH treated seaweed, washed seaweed and unwashed seaweed.

      • SCIESCOPUSKCI등재

        UTILIZATION OF EGYPTIAN MALLOW IN FEEDING COMMON CARP (Cyprinus carpio L.)

        Labib, E.,Omar, E.,Tag-El-Din, A.E.,Nour, A.M. Asian Australasian Association of Animal Productio 1994 Animal Bioscience Vol.7 No.2

        Two experiments were conducted to study the effect of using Egyptian mallow leaf meal (EMLM) on growth performance and feed utilization of common carp (Cyprinus carpio L.) in experiment 1. Four diets containing 0, 5, 15 and 25% EMLM were included at the expense of berseem leaf meal and fed to fingerlings of common carp for 98 days. The results showed that the average daily gain, feed intake and feed coefficient ratio (FCR) were improved (p<0.05) with increasing the level of EMLM in the diet. Fish fed 25% EMLM were similar to control fish (30% berseem leaf meal) in the productive value (PPV%). In experiment 2, five diets were prepared to contain: 1) 30% berseem leaf meal, 2) 25% untreated EMLM, 3) 25% cooked EMLM 4) 25% treated EMLM with 0.5% NaOH and 5) 25% treated EMLM with 1% NaOH. The results showed that diet containing EMLM gave the best growth performance and feed utilization. However, diet containing 1% NaOH treated EMLM superior to the other diets in PPV% and energy utilization. Diets containing 0.5% NaOH-treated EMLM or cooked EMLM decreased the protein utilization compared to those containing EMLM.

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