Waleed Seif - Academia.edu (original) (raw)
Papers by Waleed Seif
Acta Scientific Medical Sciences, Jul 1, 2022
The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a ... more The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a major public health problem in Egypt. The objective of this study was to detect the clearance of HCV-RNA in Egyptian patients who were recommended for combination therapy of pyglated interferon α 2a and ribavirin (PEG-interferon/Ribavirin). Ninety-five positive HCV-IgG cases were tested for HCV-RNA at baseline and at weeks 4, 12, 24, 48 and 72 of treatment with PEG-interferon α 2a/Ribavirin. The correlations between the viral parameters during and after treatment were evaluated. Patients recommended receiving PEG-interferon 2a/ribavirin combination therapy showed high response rate determined as 71.9% achieved Sustained Virological Response (SVR) from total patients, and 71.4% from patients who received 48 weeks therapy. In general, the employment of TMA provided us the accuracy of results with confidence in our work. There was a significant relation (p < 0.001) between results of Transcription mediated amplification (TMA) and response to therapy that indicate to positive correlation. The development of sensitive accurate assays for HCV-RNA detection and quantification is necessary to improve not only the assessment of the response to antiviral therapy but also our understanding of the mechanism underlying antiviral resistance.
Epigenetics involved in multiple normal cellular processes. Previous research have revealed the r... more Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis. Clin Mol Hepatol 2019 Oct 22.
Clinical and Molecular Hepatology, 2019
Background/Aims: Epigenetics involved in multiple normal cellular processes. Previous research ha... more Background/Aims: Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. Methods: A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Results: Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. Conclusions: To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis.
The Egyptian Journal of Hospital Medicine, 2014
Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC... more Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in the absence of HCV RNA in serum, designated as 'occult HCV infection', has been a matter of controversy in the recent years. Occult hepatitis C virus (HCV) infection has not been investigated in haemodialysis patients. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) patients in a single heamodialysis center at Al-Taif, KSA. Methods: We enrolled 84 CHD patients, whose sera are negative for HCV markers. HCV RNA was tested in PBMC using a sensitive commercial real time assay. In this study, real-time PCR was used to test for the presence of genomic HCV-RNA in peripheral blood mononuclear cells of all of these patients. For comparison, 20 patients on HD with evidence of chronic hepatitis C virus infection were included as a control group. Results: In CHD patients, occult HCV infection, determined by the presence of genomic HCV-RNA in peripheral blood mononuclear cells (PBMNCs), was found in 13.4 % of the patients; 83 % of these patients had ongoing HCV replication, indicated by the presence of HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on heamodialysis and had significantly higher mean alanine aminotransferase levels during the 3 months before study entry. Compared to CHCV patients, those with occult HCV have less elevated bilirubin, AST and ALT. Conclusions: The prevalence of occult HCV infection was moderate in our CHD patients, and it did not appear to be clinically relevant. Further studies in other geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups. Abbreviations HCV, Hepatitis C Virus ; antibody against HCV; PBMC, peripheral blood mononuclear cells; rRT-PCR, real time reverse transcriptase polymerase chain reaction; CHD, chronic hemodialysis.
DOI: 10.21276/sjpm.2018.3.10.11 Abstract: Herpes viruses as CMV, EBV and HHV-6 are the most commo... more DOI: 10.21276/sjpm.2018.3.10.11 Abstract: Herpes viruses as CMV, EBV and HHV-6 are the most common cause severe morbidity and mortality in immunocompromised individuals. Reactivation of the virus is seen during periods of down-regulation of the immune system, such as coinfection with other pathogens. So, this study was conducted to detect the presence of Human herpes virus-6 infection in patients with chronic hepatitis C virus (HCV) infection and to point out the effect of HHV 6 -HCV co-infection on Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) liver enzymes. Nested polymerase chain reaction was carried out on extracted DNA from sera of both groups with hepatitis C and control group. Serological investigations were carried out as well. Fifty-three serum samples with HCV-RNA were examined, (25%) were positive HHV-6 DNA, (82%) were positive for HHV-6 IgG antibodies and (22%) were positive for HHV-6 IgM antibodies; among control specimens (18.5%) were positive f...
Egyptian Journal of Medical Human Genetics, 2010
Objective Monocyte chemoattractant protein-1 (MCP-1) is a member of CC chemokine that plays an im... more Objective Monocyte chemoattractant protein-1 (MCP-1) is a member of CC chemokine that plays an important role in the recruitment of monocytes/macrophages into renal tubulointerstitium. A biallelic A/G polymorphism at position 2518 in the MCP-1 gene was found to regulate MCP-1 expression. MCP-1 and its A/G gene polymorphism have been implicated in the pathogenesis of some renal diseases. The aim of this study was to evaluate the role of circulating MCP-1 level and the relevance of functional genetic variations of MCP-1 as early predictors of the development of glomerulonephropathy (GN) in Egyptian patients. Methods This is a case control study that was conducted in 50 GN patients, 20 non-GN cases and 20 ethnically matched healthy controls. MCP-1 serum level was detected by ELISA technique, while genotyping of polymorphisms in the MCP-1 genes was performed using a polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) detection. Results High MCP-1 circulating levels and subsequently MCP-1 2518G polymorphism are associated with the developing of nephropathy irrespective to the underlying etiology. MCP-1 serum level was significantly high when compared with healthy controls (P = 0.0007) and non-GN cases (P = 0.01). There was predominance of A allele at 2518 of MCP-1 gene in healthy controls (87.5%) and non-GN cases (77.5%). The frequency of the 2518G MCP-1 polymorphism was significantly higher in GN patients than in healthy controls (P < 0.0001; OR = 15.6) and non-GN cases (P < 0.0001; OR = 7.7). Interestingly, homozygosity for G allele plays the main role in such association. Conclusion A/G polymorphism in MCP-1 gene and subsequently high circulating MCP-1 level confer a relevant role in the susceptibility to the development of nephropathy in the Egyptian population denoting that MCP-1 system could be an early predictor of such renal complication.
Transplant …, 2004
To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-B... more To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV),
Leukemia & …, 2007
SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV4... more SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV40 and NHL is biologically plausible since SV40 causes hematological malignancies in laboratory rodents. We investigated 266 Egyptian cases of hematological malignancies (158 NHL, ...
Experimental and Molecular Pathology, 2011
Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We so... more Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC.Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined
Abstract: Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threa... more Abstract: Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening infection in immunocompromised patients. Therefore, sensitive and reliable diagnostic test is essential for choice line of antiviral therapy and patients ’ management. Methods. HCMV detection was investigated by serological assay, PCR assay in both WBC’s and plasma samples, antigenemia assay in PMBLs in 32 leukemia patients, 20 bladder cancer patients and 20 apparently healthy controls. Results. HCMV IgG was detected in 100 % of our cancer patients. High HCMV IgG Ab titer was found to be less frequent in leukemia patients than solid tumor patients. In other words, low HCMV Ab titer was most common in leukemia patients. Antigenemia assay was positive in 8/32 (25%) of leukemia patients but viremia was positive in only 2/32 (6%) of leukemia patients. High level of antigenemia was associated with development of severe HCMV disease in leukemia patients. Conclusion. Antigenemia test is ...
International journal of health sciences, 2008
BACKGROUND Chronic HBV and HCV infections are the major risk factors for the development of HCC t... more BACKGROUND Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. METHODS Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II. RESULTS Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC c...
International Journal of …, 2007
Your browser version may not work well with NCBI's web applications. More information here..... more Your browser version may not work well with NCBI's web applications. More information here... ...
Evaluation of SV-40 as a biological prognostic factor in Egyptian patients with malignant pleural... more Evaluation of SV-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma Bahnassy, Abeer A.1 Gaafar, Rabab M.2 Zekri, Abdel-Rahman N.3 Hassan, Nelly A.4 Aboulkassem, Fatma2 Abdel-Rahman, Mohamed5 Mohammad, Waleed S.6 1 Pathology, NCI, Cairo, Egypt 2 Medical Oncology, NCI, Cairo, Egypt 3 Cancer Biology Dpt., NCI, Cairo, Egypt 4 Epidemiology & Biostatistics, NCI, Cairo, Egypt 5 Surgery, NCI, Cairo, Egypt 6 Virology & Immunology, NCI, Cairo, Egypt Background: Malignant Mesothelioma is a highly aggressive primary neoplasm of the pleural, peritoneal, and pericardial surfaces. It is a challenging disease in all aspects, from presentation and diagnosis to staging and treatment. In the past 50 years, the incidence of malignant pleural mesothelioma (MPM) has been increasing especially in developing countries, along with industrial development. The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological rol...
Background/aim Infection with hepatitis C virus (HCV) frequently results in a persistent infectio... more Background/aim Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus infection results in activation or direct induction of the interferon regulatory factors (IRFs), which are a family of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been shown to play an essential role in virus-dependent signaling, whereas IRF-1 is critical for proper IFN-dependent gene expression. This study has been performed to show the expression profile of IRF-1, IRF-3, and IRF-7 in Egyptian patients with HCV-related liver diseases and hepatocellular carcinoma (HCC). Materials and methods This study included 90 patients, who were positive for HCV infection by reverse transcription PCR, divided into three groups: group I (Gr I) included 30 patients with chronic hepatitis C, group II (G...
Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening inf... more Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening infection in immunocompromised patients. Therefore, sensitive and reliable diagnostic test is essential for choice line of antiviral therapy and patients’ management. Methods. HCMV detection was investigated by serological assay, PCR assay in both WBC’s and plasma samples, antigenemia assay in PMBLs in 32 leukemia patients, 20 bladder cancer patients and 20 apparently healthy controls. Results. HCMV IgG was detected in 100% of our cancer patients. High HCMV IgG Ab titer was found to be less frequent in leukemia patients than solid tumor patients. In other words, low HCMV Ab titer was most common in leukemia patients. Antigenemia assay was positive in 8/32 (25%) of leukemia patients but viremia was positive in only 2/32 (6%) of leukemia patients. High level of antigenemia was associated with development of severe HCMV disease in leukemia patients. Conclusion. Antigenemia test is a reliable d...
Pathology …, 2007
The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an ... more The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.
Journal of Biosciences and Medicines
The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a ... more The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a major public health problem in Egypt. The objective of this study was to detect the clearance of HCV-RNA in Egyptian patients who were recommended for combination therapy of pyglated interferon α 2a and ribavirin (PEG-interferon/Ribavirin). Ninety-five positive HCV-IgG cases were tested for HCV-RNA at baseline and at weeks 4, 12, 24, 48 and 72 of treatment with PEG-interferon α 2a/Ribavirin. The correlations between the viral parameters during and after treatment were evaluated. Patients recommended receiving PEG-interferon 2a/ribavirin combination therapy showed high response rate determined as 71.9% achieved Sustained Virological Response (SVR) from total patients, and 71.4% from patients who received 48 weeks therapy. In general, the employment of TMA provided us the accuracy of results with confidence in our work. There was a significant relation (p < 0.001) between results of Transcription mediated amplification (TMA) and response to therapy that indicate to positive correlation. The development of sensitive accurate assays for HCV-RNA detection and quantification is necessary to improve not only the assessment of the response to antiviral therapy but also our understanding of the mechanism underlying antiviral resistance.
Asian Journal of Medical Sciences, 2011
Objective: This work is designed to study the possible role of chronic inflammation induced by E.... more Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis. Material & Methods: This study was done on one hundred and fifty adult male albino rats (50 - 60 gm) that divided into five groups; a) Normal control group, b) Dibutyl amine and sodium nitrate treated group, c)E.Coli treated group, d) Dibutyl amine and sodium nitrate treated group plus E. coli, and e) Dibutyl amine and sodium nitrate treated group plus soy bean flour. Survival rate and histopatholgical changes during the period of treatment were recorded. Level of malondialdhyde, glutathione, catalase, hydrogen peroxide, Total anti-oxidant capacity and nitric oxide were measured. RNA extracted from bladder tissues was determined in addition to P16 level and caspase-3 expression. Results: Survival analysis showed a signifi...
Asian Journal of …, 2011
Objective: This work is designed to study the possible role of chronic inflammation induced by E.... more Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis. Material & Methods: This study was done on one hundred and fifty adult male albino rats (50-60 gm) that divided into five groups; a) Normal control group, b) Dibutyl amine and sodium nitrate treated group, c)E.Coli treated group, d) Dibutyl amine and sodium nitrate treated group plus E. coli, and e) Dibutyl amine and sodium nitrate treated group plus soy bean flour. Survival rate and histopatholgical changes during the period of treatment were recorded. Level of malondialdhyde, glutathione, catalase, hydrogen peroxide, Total anti-oxidant capacity and nitric oxide were measured. RNA extracted from bladder tissues was determined in addition to P16 level and caspase-3 expression. Results: Survival analysis showed a significant decrease (p< 0.001) in E.Coli and dibutyl amine plus sodium nitrate treated groups in comparing with the normal and other treated groups. Also, E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors, and enhances oxidative and nitrosative stresses via increasing levels of nitric acid, hydrogen peroxide and malondialdhyde. Regarding the molecular changes, extra bands have been found in E. coli and E. coli + carcinogen treated groups approximately at 16-18KD which are not present in the other groups. Conclusion: Bacterial infection of the urinary bladder may play a major additive and synergistic role in bladder carcinogenesis. Our results have also shown that soy bean flour may have a protective action during induction of urinary tumors.
Acta Scientific Medical Sciences, Jul 1, 2022
The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a ... more The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a major public health problem in Egypt. The objective of this study was to detect the clearance of HCV-RNA in Egyptian patients who were recommended for combination therapy of pyglated interferon α 2a and ribavirin (PEG-interferon/Ribavirin). Ninety-five positive HCV-IgG cases were tested for HCV-RNA at baseline and at weeks 4, 12, 24, 48 and 72 of treatment with PEG-interferon α 2a/Ribavirin. The correlations between the viral parameters during and after treatment were evaluated. Patients recommended receiving PEG-interferon 2a/ribavirin combination therapy showed high response rate determined as 71.9% achieved Sustained Virological Response (SVR) from total patients, and 71.4% from patients who received 48 weeks therapy. In general, the employment of TMA provided us the accuracy of results with confidence in our work. There was a significant relation (p < 0.001) between results of Transcription mediated amplification (TMA) and response to therapy that indicate to positive correlation. The development of sensitive accurate assays for HCV-RNA detection and quantification is necessary to improve not only the assessment of the response to antiviral therapy but also our understanding of the mechanism underlying antiviral resistance.
Epigenetics involved in multiple normal cellular processes. Previous research have revealed the r... more Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis. Clin Mol Hepatol 2019 Oct 22.
Clinical and Molecular Hepatology, 2019
Background/Aims: Epigenetics involved in multiple normal cellular processes. Previous research ha... more Background/Aims: Epigenetics involved in multiple normal cellular processes. Previous research have revealed the role of hepatitis C virus infection in accelerating methylation process and affecting response to treatment in chronic hepatitis patients. This work aimed to elucidate the role of promoter methylation (PM) in response to antiviral therapy, and its contribution to the development of fibrosis through hepatocarcinogenesis-related genes. Methods: A total of 159 chronic hepatitis Egyptian patients versus 100 healthy control group were included. The methylation profile of a panel 9 genes (SFRP1, p14, p73, APC, DAPK, RASSF1A, LINE1, O6MGMT, and p16) was detected in patients' plasma using methylation-specific polymerase chain reaction (MSP). Results: Clinical and laboratory findings were gathered for patients with combined pegylated interferon and ribavirin antiviral therapy. Regarding the patients' response to antiviral therapy, the percentage of non-responders for APC, O6MGMT, RASSF1A, SFRP1, and p16 methylated genes were significantly higher versus responders (P<0.05). Of the 159 included patients, the most frequent methylated genes were SFRP1 (102/159), followed by p16 (100/159), RASSF1A (98/159), then LINE1 (81/159), P73 (81/159), APC (78/159), DAPK (66/159), O6MGMT (66/159), and p14 (54/159). A total of 67/98 (68.4%) cases of RASSF1A methylated gene (P=0.0.024), and 62/100 (62%) cases of P16 methylated gene (P=0.03) were associated with mild-degree fibrosis. Conclusions: To recapitulate, the PM of SFRP1, APC, RASSF1A, O6MGMT, and p16 genes increases in chronic hepatitis C patients, and can affect patients' response to antiviral therapy. The RASSF1A and P16 genes might have a role in the distinction between mild and marked fibrosis.
The Egyptian Journal of Hospital Medicine, 2014
Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC... more Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in the absence of HCV RNA in serum, designated as 'occult HCV infection', has been a matter of controversy in the recent years. Occult hepatitis C virus (HCV) infection has not been investigated in haemodialysis patients. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) patients in a single heamodialysis center at Al-Taif, KSA. Methods: We enrolled 84 CHD patients, whose sera are negative for HCV markers. HCV RNA was tested in PBMC using a sensitive commercial real time assay. In this study, real-time PCR was used to test for the presence of genomic HCV-RNA in peripheral blood mononuclear cells of all of these patients. For comparison, 20 patients on HD with evidence of chronic hepatitis C virus infection were included as a control group. Results: In CHD patients, occult HCV infection, determined by the presence of genomic HCV-RNA in peripheral blood mononuclear cells (PBMNCs), was found in 13.4 % of the patients; 83 % of these patients had ongoing HCV replication, indicated by the presence of HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on heamodialysis and had significantly higher mean alanine aminotransferase levels during the 3 months before study entry. Compared to CHCV patients, those with occult HCV have less elevated bilirubin, AST and ALT. Conclusions: The prevalence of occult HCV infection was moderate in our CHD patients, and it did not appear to be clinically relevant. Further studies in other geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups. Abbreviations HCV, Hepatitis C Virus ; antibody against HCV; PBMC, peripheral blood mononuclear cells; rRT-PCR, real time reverse transcriptase polymerase chain reaction; CHD, chronic hemodialysis.
DOI: 10.21276/sjpm.2018.3.10.11 Abstract: Herpes viruses as CMV, EBV and HHV-6 are the most commo... more DOI: 10.21276/sjpm.2018.3.10.11 Abstract: Herpes viruses as CMV, EBV and HHV-6 are the most common cause severe morbidity and mortality in immunocompromised individuals. Reactivation of the virus is seen during periods of down-regulation of the immune system, such as coinfection with other pathogens. So, this study was conducted to detect the presence of Human herpes virus-6 infection in patients with chronic hepatitis C virus (HCV) infection and to point out the effect of HHV 6 -HCV co-infection on Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) liver enzymes. Nested polymerase chain reaction was carried out on extracted DNA from sera of both groups with hepatitis C and control group. Serological investigations were carried out as well. Fifty-three serum samples with HCV-RNA were examined, (25%) were positive HHV-6 DNA, (82%) were positive for HHV-6 IgG antibodies and (22%) were positive for HHV-6 IgM antibodies; among control specimens (18.5%) were positive f...
Egyptian Journal of Medical Human Genetics, 2010
Objective Monocyte chemoattractant protein-1 (MCP-1) is a member of CC chemokine that plays an im... more Objective Monocyte chemoattractant protein-1 (MCP-1) is a member of CC chemokine that plays an important role in the recruitment of monocytes/macrophages into renal tubulointerstitium. A biallelic A/G polymorphism at position 2518 in the MCP-1 gene was found to regulate MCP-1 expression. MCP-1 and its A/G gene polymorphism have been implicated in the pathogenesis of some renal diseases. The aim of this study was to evaluate the role of circulating MCP-1 level and the relevance of functional genetic variations of MCP-1 as early predictors of the development of glomerulonephropathy (GN) in Egyptian patients. Methods This is a case control study that was conducted in 50 GN patients, 20 non-GN cases and 20 ethnically matched healthy controls. MCP-1 serum level was detected by ELISA technique, while genotyping of polymorphisms in the MCP-1 genes was performed using a polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) detection. Results High MCP-1 circulating levels and subsequently MCP-1 2518G polymorphism are associated with the developing of nephropathy irrespective to the underlying etiology. MCP-1 serum level was significantly high when compared with healthy controls (P = 0.0007) and non-GN cases (P = 0.01). There was predominance of A allele at 2518 of MCP-1 gene in healthy controls (87.5%) and non-GN cases (77.5%). The frequency of the 2518G MCP-1 polymorphism was significantly higher in GN patients than in healthy controls (P < 0.0001; OR = 15.6) and non-GN cases (P < 0.0001; OR = 7.7). Interestingly, homozygosity for G allele plays the main role in such association. Conclusion A/G polymorphism in MCP-1 gene and subsequently high circulating MCP-1 level confer a relevant role in the susceptibility to the development of nephropathy in the Egyptian population denoting that MCP-1 system could be an early predictor of such renal complication.
Transplant …, 2004
To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-B... more To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV),
Leukemia & …, 2007
SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV4... more SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV40 and NHL is biologically plausible since SV40 causes hematological malignancies in laboratory rodents. We investigated 266 Egyptian cases of hematological malignancies (158 NHL, ...
Experimental and Molecular Pathology, 2011
Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We so... more Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC.Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined
Abstract: Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threa... more Abstract: Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening infection in immunocompromised patients. Therefore, sensitive and reliable diagnostic test is essential for choice line of antiviral therapy and patients ’ management. Methods. HCMV detection was investigated by serological assay, PCR assay in both WBC’s and plasma samples, antigenemia assay in PMBLs in 32 leukemia patients, 20 bladder cancer patients and 20 apparently healthy controls. Results. HCMV IgG was detected in 100 % of our cancer patients. High HCMV IgG Ab titer was found to be less frequent in leukemia patients than solid tumor patients. In other words, low HCMV Ab titer was most common in leukemia patients. Antigenemia assay was positive in 8/32 (25%) of leukemia patients but viremia was positive in only 2/32 (6%) of leukemia patients. High level of antigenemia was associated with development of severe HCMV disease in leukemia patients. Conclusion. Antigenemia test is ...
International journal of health sciences, 2008
BACKGROUND Chronic HBV and HCV infections are the major risk factors for the development of HCC t... more BACKGROUND Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. METHODS Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II. RESULTS Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC c...
International Journal of …, 2007
Your browser version may not work well with NCBI's web applications. More information here..... more Your browser version may not work well with NCBI's web applications. More information here... ...
Evaluation of SV-40 as a biological prognostic factor in Egyptian patients with malignant pleural... more Evaluation of SV-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma Bahnassy, Abeer A.1 Gaafar, Rabab M.2 Zekri, Abdel-Rahman N.3 Hassan, Nelly A.4 Aboulkassem, Fatma2 Abdel-Rahman, Mohamed5 Mohammad, Waleed S.6 1 Pathology, NCI, Cairo, Egypt 2 Medical Oncology, NCI, Cairo, Egypt 3 Cancer Biology Dpt., NCI, Cairo, Egypt 4 Epidemiology & Biostatistics, NCI, Cairo, Egypt 5 Surgery, NCI, Cairo, Egypt 6 Virology & Immunology, NCI, Cairo, Egypt Background: Malignant Mesothelioma is a highly aggressive primary neoplasm of the pleural, peritoneal, and pericardial surfaces. It is a challenging disease in all aspects, from presentation and diagnosis to staging and treatment. In the past 50 years, the incidence of malignant pleural mesothelioma (MPM) has been increasing especially in developing countries, along with industrial development. The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological rol...
Background/aim Infection with hepatitis C virus (HCV) frequently results in a persistent infectio... more Background/aim Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus infection results in activation or direct induction of the interferon regulatory factors (IRFs), which are a family of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been shown to play an essential role in virus-dependent signaling, whereas IRF-1 is critical for proper IFN-dependent gene expression. This study has been performed to show the expression profile of IRF-1, IRF-3, and IRF-7 in Egyptian patients with HCV-related liver diseases and hepatocellular carcinoma (HCC). Materials and methods This study included 90 patients, who were positive for HCV infection by reverse transcription PCR, divided into three groups: group I (Gr I) included 30 patients with chronic hepatitis C, group II (G...
Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening inf... more Background. Human cytomegalovirus (HCMV) is a persistent pathogen, can cause life threatening infection in immunocompromised patients. Therefore, sensitive and reliable diagnostic test is essential for choice line of antiviral therapy and patients’ management. Methods. HCMV detection was investigated by serological assay, PCR assay in both WBC’s and plasma samples, antigenemia assay in PMBLs in 32 leukemia patients, 20 bladder cancer patients and 20 apparently healthy controls. Results. HCMV IgG was detected in 100% of our cancer patients. High HCMV IgG Ab titer was found to be less frequent in leukemia patients than solid tumor patients. In other words, low HCMV Ab titer was most common in leukemia patients. Antigenemia assay was positive in 8/32 (25%) of leukemia patients but viremia was positive in only 2/32 (6%) of leukemia patients. High level of antigenemia was associated with development of severe HCMV disease in leukemia patients. Conclusion. Antigenemia test is a reliable d...
Pathology …, 2007
The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an ... more The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.
Journal of Biosciences and Medicines
The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a ... more The prevalence of Hepatitis C viral infection in Egypt is the highest rate in the world. It is a major public health problem in Egypt. The objective of this study was to detect the clearance of HCV-RNA in Egyptian patients who were recommended for combination therapy of pyglated interferon α 2a and ribavirin (PEG-interferon/Ribavirin). Ninety-five positive HCV-IgG cases were tested for HCV-RNA at baseline and at weeks 4, 12, 24, 48 and 72 of treatment with PEG-interferon α 2a/Ribavirin. The correlations between the viral parameters during and after treatment were evaluated. Patients recommended receiving PEG-interferon 2a/ribavirin combination therapy showed high response rate determined as 71.9% achieved Sustained Virological Response (SVR) from total patients, and 71.4% from patients who received 48 weeks therapy. In general, the employment of TMA provided us the accuracy of results with confidence in our work. There was a significant relation (p < 0.001) between results of Transcription mediated amplification (TMA) and response to therapy that indicate to positive correlation. The development of sensitive accurate assays for HCV-RNA detection and quantification is necessary to improve not only the assessment of the response to antiviral therapy but also our understanding of the mechanism underlying antiviral resistance.
Asian Journal of Medical Sciences, 2011
Objective: This work is designed to study the possible role of chronic inflammation induced by E.... more Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis. Material & Methods: This study was done on one hundred and fifty adult male albino rats (50 - 60 gm) that divided into five groups; a) Normal control group, b) Dibutyl amine and sodium nitrate treated group, c)E.Coli treated group, d) Dibutyl amine and sodium nitrate treated group plus E. coli, and e) Dibutyl amine and sodium nitrate treated group plus soy bean flour. Survival rate and histopatholgical changes during the period of treatment were recorded. Level of malondialdhyde, glutathione, catalase, hydrogen peroxide, Total anti-oxidant capacity and nitric oxide were measured. RNA extracted from bladder tissues was determined in addition to P16 level and caspase-3 expression. Results: Survival analysis showed a signifi...
Asian Journal of …, 2011
Objective: This work is designed to study the possible role of chronic inflammation induced by E.... more Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis. Material & Methods: This study was done on one hundred and fifty adult male albino rats (50-60 gm) that divided into five groups; a) Normal control group, b) Dibutyl amine and sodium nitrate treated group, c)E.Coli treated group, d) Dibutyl amine and sodium nitrate treated group plus E. coli, and e) Dibutyl amine and sodium nitrate treated group plus soy bean flour. Survival rate and histopatholgical changes during the period of treatment were recorded. Level of malondialdhyde, glutathione, catalase, hydrogen peroxide, Total anti-oxidant capacity and nitric oxide were measured. RNA extracted from bladder tissues was determined in addition to P16 level and caspase-3 expression. Results: Survival analysis showed a significant decrease (p< 0.001) in E.Coli and dibutyl amine plus sodium nitrate treated groups in comparing with the normal and other treated groups. Also, E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors, and enhances oxidative and nitrosative stresses via increasing levels of nitric acid, hydrogen peroxide and malondialdhyde. Regarding the molecular changes, extra bands have been found in E. coli and E. coli + carcinogen treated groups approximately at 16-18KD which are not present in the other groups. Conclusion: Bacterial infection of the urinary bladder may play a major additive and synergistic role in bladder carcinogenesis. Our results have also shown that soy bean flour may have a protective action during induction of urinary tumors.