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Vol.8 No.1 – 3: 8-hydroxy-2′-deoxyguanosine and TP53 in Egyptian Patients with Hepatitis C Viral Chronic Liver Diseases: Insight into the Pathogenesis and Predictive Force

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By : Hoda M. El-Emshaty1,*, Somaia M. Osman 2, Fathy M. El-Taweel2, Mohamed M. El-Hemaly1, Hisham Ismail 3

1Gastrointestinal Surgery Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

2Chemistry Dept., Faculty of Science, Damietta University, New Damietta, Egypt.

3Biochemistry Division, Chemistry Dept., Faculty of Science, Minia University, Minia, Egypt.

Abstract

Reactive oxygen species (ROS) is excessively generated during tumor development yielding the oxidatively modified products of proteins and DNA. These DNA alterations could contribute to the development of cancer through the activation of oncogenes and inactivating tumor suppressor genes (TSGs). Therefore, 8-OHdG DNA oxidative damage and TP53 protein expression were evaluated amongst HCV-Chronic liver disease patients to explore their possible role in hepatocarcinogenesis and to predict HCC development at early stages. A total of 141 patients with HCV-related liver diseases; 69 with hepatocellular carcinoma and 72 with liver cirrhosis were enrolled in this study in addition to 56 healthy subjects.Serum 8-OHdG and TP53 expression by ELISA were markedly elevated in HCC patients compared to LC and healthy individuals (p<0.0001). A significant correlation was noted for 8-OHdG and TP53 with disease progression and tumor differentiation but not with tumor site. 8-OHdG and TP53 were highly (p<0.05) predicting for HCC at early stages and the diagnostic performance for discriminating HCC from LC by ROC curve showed the best AUC was recorded for 8-OHdG (0.745) followed by TP53 (0.667) with accuracy (87.2% and 82% respectively). Therefore, HCV-induced oxidative DNA damage could increase the carcinogenic potential of HCC development through the activation of TP53.

8-hydroxy-2-deoxyguanosine-and-TP53-in-Egyptian-Patients-with-Hepatitis-C-Viral-Chronic-Liver-Diseases-Insight-into-the-Pathogenesis-and-Predictive-Force-converted

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Vol.2 No.6 -1 : Study the association between glutathione peroxidase-1 gene in patients with hepatocellular carcinoma in Egypt.

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By : Ibrahim A. Elelaimy1, Eman L. Shehata2, Mohamed A. Abdel-Hamid3

Abstract

cancer in the world. The main risk factors associated with HCC are hepatitis B and hepatitis C viral infections and other factors that play a role in HCC development. Oxidative stress is an imbalance between production and elimination of reactive metabolites of oxygen and nitrogen, in favor of their production leading to potential damage. During oxidative stress, biologically important molecules and cells can be damaged, and this can be significant in the pathogenesis of many diseases. Reactive oxygen species (ROS) is known to activate the apoptosis of some hepatocytes and therefore contribute to inflammation, regeneration, fibrogenesis, and carcinogenesis. The enzyme generally considered to be the frontline defense against ROS is glutathione peroxidase (GPX).The present study aims to investigate the association of progression of HCC with GPX1 (Pro198Leu) gene polymorphisms in HCC Egyptian patients. One hundred HCC cases and matched 100 controls were recruited from National Cancer Institute and Kasr El-Aini respectively. The detection of the genetic polymorphisms of GPX1 (Pro198Leu) were determined by single nucleotide polymorphisms (SNPs) using real time PCR technique. The results showed that there is a significant association between the GPX1 polymorphisms and the progression of HCC, the distribution of different GPX1 polymorphisms in HCC patients infected with HCV was (47.5% CC, 47.0% CT and 81.3% TT) respectively and in controls was (52.5% CC, 53.0% CT and 18.8% TT) respectively (P=0.033). Our findings suggested that the genetic polymorphisms in GPX1 play a role in the etiology of hepatocellular carcinoma.Conclusion: AFP is highly significant in relation to HCC cases and in also with GPX1 gene mutation. Our findings suggested that the genetic polymorphisms in GPX1 play a role in the etiology of hepatocellular carcinoma.

1. Study the association between glutathione peroxidase-1 gene in patients with hepatocellular carcinoma in Egypt.
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Vol.1 No.5 -6 : Study of the effect of silver nanoparticles encapsulated by doxorubicin drug in the treatment of hepatocellular carcinoma.

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By : Rasha Said Shams El-Dine1, Samir Ali Abd El Kaream2

Abstract

Hepatocellular carcinoma (HCC) is the third deadliest and fifth most common cancer worldwide. Many drugs that have the potential to treat cancers have had limited success due to their lack of efficient and safe delivery mechanisms that allow the drug molecules to cross cell membranes. Electrical pulses-mediated drug delivery, known as electroporation, is gaining attention as a possible approach to enhance uptake of chemotherapy. The present work studied the effect of silver nanoparticles encapsulated by doxorubicin drug in the treatment of hepatocellular carcinoma. The study was conducted on 40 albino mice weighting 20-25 g of 8-10 weeks of age, and were divided into two major groups. Group A:10 mice were used as a control , group B: 40 mice have induced HCC by DABE this group were subdivided into three subgroups; sub groupB1 10 mice which were not received any treatment, and were kept at room environment and, sub group B2: 10 mice were injected i.p with a dose of 50 mg/kg body weight of doxorubicin only every day for 21days, sub group B3 :10 mice were injected i.p. with a dose of 50 mg/kg body weight of doxorubicin encapsulated by the silver nanoparticles every day for 21days.Parts of liver tissue and blood samples were collected from all from mice of each group for histopathological examination; the nanocapsules were of the size range 200 ± 20 nm and loaded with the positively charged anticancer drug doxorubicin with an efficiency of 89%. The loading of the drug into the capsule occurs by virtue of the pH-responsive property of the capsule wall, which is determined by the pKa of the polyelectrolytes. As the pH is varied, about 64% of the drug is released in acidic pH while 77% is released in neutral pH. Molecular detection of Alpha-fetoprotein (AFP) and Glypican-3 (gly3) mRNAs by RT-PCR before and after treatment by silver nanoparticles encapsulated doxorubicin drug were studied in mice with HCC. Silver nanoparticles encapsulated doxorubicin drug showed effective results for treatment of HCC compared to results obtained with doxorubicin drug resulting in reduced tumor growth, and induction of apoptosis in the treated cells by enhancing of delivering chemotherapy and anticancer drugs with enhanced efficacy and fewer adverse effects.

6. Study of the effect of silver nanoparticles encapsulated by doxorubicin drug in the treatment of hepatocellular carcinoma.
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