Abdel-rahman Zekri - Academia.edu (original) (raw)

Papers by Abdel-rahman Zekri

Research paper thumbnail of Differentially expressed genes in metastatic advanced Egyptian bladder cancer

Asian Pacific journal of cancer prevention : APJCP, 2015

Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using micro... more Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant diff...

Research paper thumbnail of Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

World journal of gastroenterology : WJG, Jan 28, 2014

To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C ... more To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease. Blood and/or tissue samples were obtained from HCV (genotype 4)-associated hepatocellular carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and 33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP), alkaline phosphatase, and alanine and aspartate aminotransferases were measured. Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133 and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real-time polymerase chain reactions. The number of CTCs and/or the expression levels of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard clinicopathologic prognostic factors and disease progression...

Research paper thumbnail of Cairo University Fibrosis Index (CUFI): A MicroRNA Based Score for Accurate Prediction of Hepatic Fibrosis: A Biopsy Controlled Study

Background: The exact identification of liver fibrosis is mandatory for customizing therapy and c... more Background: The exact identification of liver fibrosis is mandatory for customizing therapy and controlling complications. The aim of the current study is to measure the ability to circulate miRNAs; in the diagnosis of hepatic fibrosis.Methods: Routine laboratory, liver biopsy, and histopathological investigations were done on seventy HCV patients. In addition, estimation of HCV-RNA, serum micro RNA (miRNA)-122, 221, 192, 224, 375, and 885 were done by PCR. To assess the ability of each miRNA, the area under the receiver operating characteristics (AUC) curves were plotted. Significant miRNA were analyzed by linear regression analysis in a stepwise pattern to develop a score for pointing out significant fibrosis. Moreover, the following scores were calculated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), aspartate to platelet ratio index (APRI), FIB-4 score, Hui index, Fibrosis Index (FI), Fibro-Q, Fibro-Alfa Biotechnology Research Center (BRC) score, ...

Research paper thumbnail of MOESM2 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 2: The best alignment of our sequence with ref. seq. JN127373.1.

Research paper thumbnail of MOESM1 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 1: The most significant hits of HPgV sequence.

Research paper thumbnail of MOESM5 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 5: Alignments of the NS5B protein structure of HCV and HPgV.

Research paper thumbnail of MOESM3 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 3: Identification of 808 SNPs.

Research paper thumbnail of The Prognostic Significance of 5-Fluorouracil Induced Inflammation and Immuno-Modulation in Colorectal Cancer Patients

Journal of Inflammation Research, 2020

Aim The change in the levels of peripheral inflammatory markers together with EGFR in relation to... more Aim The change in the levels of peripheral inflammatory markers together with EGFR in relation to 5- fluorouracil (5-FU) therapy was evaluated for their prognostic significance in colorectal cancer (CRC) patients. Patients and Methods Expression levels of COX2, IL6, IL1β, EGFR, IL10, and TNFα were determined with quantitative real-time PCR (qPCR) in the peripheral blood of 90 CRC patients. The inflammatory response was correlated with patients’ clinical features, disease-free survival (DFS), and overall survival (OS). Results After 6 months of 5-FU therapy, increased inflammatory response was found to be associated with smoking, T3 or T4 tumors, performance status (PS) III, positive lymph nodes, distant metastasis, and gastrointestinal (GIT) toxicity. The combination of COX2 with interleukins in a predictive equation for DFS was significant in patients with over-expression of EGFR. DFS and OS rates were reduced in patients with increased COX2, IL6, IL10, and TNFα expression with 5-F...

Research paper thumbnail of The Antiviral Efficacy of Withania somnifera (Ashwagandha) against Hepatitis C Virus Activity: In Vitro and in Silico Study

Advances in Microbiology

Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against ... more Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against HCV. Methods: cell proliferation was assessed using MTT assay after isolation of lymphocyte cells and treated with Ashwagandha water extract (ASH-WX) (6.25 mg/ml-100 mg/ml). Assessment of quantitative Real-time PCR, Colony forming assay, TNF-α and molecular docking studies after infection of normal lymphocyte cells with 1 ml (1.5 × 10 6 HCV) serum then incubated with ASH-WX at concentration 25 mg/ml & 50 mg/ml. Results: MTT assay revealed a significant increase (p < 0.001) in normal lymphocyte proliferation at all concentration's particularity at 25 mg/ml with SI (6.06) and at 50 mg/ml with (5.8). While TNF-α significantly decreased following ASH-WX treatment compared with control untreated infected cells (p < 0.05). PCR results showed a marked viral load reduction after treatment by ASH-WX at concentration 25 mg/ml to 6.241 × 10 3 IU/mL. Colony formation assay test revealed colony formation reduction compared to positive untreated control. Molecular docking analysis revealed good prediction of binding between Ashwagandha and NS5B and PKN2 compared to Sovaldi. Conclusion: ASH-WX may be a powerful antiviral against HCV infection.

Research paper thumbnail of MicroRNA Signatures for circulating CD133-positive cells in hepatocellular carcinoma with HCV infection

PloS one, 2018

Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through id... more Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs). We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array. The differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and...

Research paper thumbnail of Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer

PLOS ONE, 2016

The study was designed to assess the possibility of using circulating miRNAs (serum miR-NAs) as d... more The study was designed to assess the possibility of using circulating miRNAs (serum miR-NAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. Methods The study involved two sample sets: 1-a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2-a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR-135b and miR-92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. Results Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.

Research paper thumbnail of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Virology Journal

Background Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was disc... more Background Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV. Case presentation The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient’s plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5′ untranslated region. The patient was then subjected to direct-acting-antivi...

Research paper thumbnail of Serum cytokine profile during disease progression stages in male and female hepatitis C patients

Journal of Bioscience and Applied Research

BioBacta

Research paper thumbnail of Prognostic Impact of BRCA1 and BRCA2 Mutations on Long-Term Survival Outcomes in Egyptian Female Breast Cancer Patients

Biology

Evidence on the prognostic relevance of BRCA1/2 mutations on breast cancer survival is still deba... more Evidence on the prognostic relevance of BRCA1/2 mutations on breast cancer survival is still debatable. To address this ambiguity, we sought to elucidate the impact of BRCA1/2 mutation carriership on long-term clinical outcomes for the first time in Egyptian female breast cancer patients. This study comprised 103 Egyptian female breast cancer patients previously tested for BRCA1/2 mutations. Clinicopathological characteristics and long-term follow-up data were retrieved from clinical records until death or loss to follow-up. Overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and metastasis-free survival (MFS) were compared in BRCA1/2 mutation carriers and non-carriers. Pathogenic variants (Class 5 according to ACMG/AMP guidelines) were observed in 29 cases. The profile of the detected variants was previously reported. After median follow-up time of 6.9 years (range, 4.2–24.4 years), BRCA1/2 carriers exhibited significantly worse RFS compared to non-c...

Research paper thumbnail of Kasr Alainy Fibrosis Index (KAFI) - A Novel Score Based on Micro RNAs for Diagnosis of Significant Fibrosis: A Biopsy Controlled Study

American Journal of Gastroenterology

Research paper thumbnail of Assessment of the diagnostic value of microsatellite instability in the urine of bladder cancer patients

Journal of Clinical Oncology

384 Background: Microsatellite alterations in urine sediments have proved to be a promising tool ... more 384 Background: Microsatellite alterations in urine sediments have proved to be a promising tool for detection of bladder cancer (BC) due to its high sensitivity and specificity. Methods: We assessed the possible prognostic and predictive values of microsatellite alterations in tissue samples and urine sediments obtained from Egyptian patients with BC, and their utility as diagnostic, prognostic and predictive value. Microsatellite instability (MSI) and loss of heterozygosity (LOH) were assessed using 13 microsatellite markers in tumor tissue and urine sediments of 30 patients with BC. The concordance between MSI in tissue and urine samples was determined. Results: We found that MSI was more frequent than LOH (100% and 46.7%; respectively). D16S310, MBP and IFN-α showed the highest MSI frequency in urine samples (70%, 70% and 66.67%; respectively), while MBP, ACTBP2 and D9S171 (66.67%, 63.33%, and 60%; respectively) were the most frequently detected in tumor tissue. All markers corr...

Research paper thumbnail of Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line

The Journal of international medical research, 2018

Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashw... more Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line. Methods After treating HepG2cells with Ashwagandha water extract (ASH-WX; 6.25 mg/ml-100 mg/ml), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase and glutathione reductase), Fas-ligand level, tumour necrosis factor-α (TNF-α) level and caspase-3, -8, and -9 activities were measured. Molecular modelling assessed the binding-free energies of Ashwagandha in the cyclin D1 receptor. Results The MTT assay demonstrated increased cytotoxicity following treatment of HepG2 cells with ASH-WX compared with control untreated cells and theICwas 5% (approximately 5.0 mg/ml). Antioxidant activities, Fas-ligand levels and caspase-3, -8 and -9 activities significantly increased, while TNF-α level significant...

Research paper thumbnail of Differentially expressed genes in metastatic advanced Egyptian bladder cancer

Asian Pacific journal of cancer prevention : APJCP, 2015

Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using micro... more Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant diff...

Research paper thumbnail of Ambovex® as a novel immunological modulator drug for the treatment of hepatocellular carcinoma (HCC) in the liver: a Phase II clinical trial

Journal of Hepatocellular Carcinoma, 2015

Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth mos... more Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth most common cancer and third leading cause of cancer-related mortality worldwide. The approved conventional treatment methods for HCC have shown life-threatening side effects with limited or negligible success, especially in multifocal HCC. As a consequence, new therapeutic approaches are being explored, including immunoregulatory molecules that may have the potential to treat or delay the progression of HCC. A novel pharmaceutical botanical drug-Ambovex ® , an immune-modulator molecule-was tested to treat or delay the progress of HCC. We conducted a 6-month randomized clinical trial with an additional 3-month washing period (no treatment) to evaluate the safety and efficacy of low-dose Ambovex oral spray in treating patients with HCC. The clinical study involved a total of 40 patients, with 33 in the treatment group and seven in the control group. The α-fetoprotein (AFP) levels were measured every month and ultrasound scans were performed at time zero and every 2 months thereafter. Computed tomography (CT) scans were performed for patients in the treatment group. Ambovex proved to be safe, as there were no significant side effects although some patients found that the drug has unpleasant taste. AFP analysis showed a significant decrease in its level (α=0.05; 95% confidence interval) in the treatment group when compared to the control group at 3 months (P=0.0031) and at 6 months (P=0.007). The ultrasound results showed improvement in the treated group, as evidenced by a significant decrease in the lesion numbers and sizes. The lesions in 38% of treated patients decreased from multiple to single with major improvements; 35% of patients exhibited a decrease from multiple lesions to multiple lesions with minor improvements, whereas 27% had stabilized lesions. CT scans in the treated group showed significant improvement, as there was complete disappearance of the lesions after 6 months of treatment with Ambovex in two patients. This clinical study showed the effective and promising results of Ambovex as an immunological modulator in treating HCC. Further exploration of Ambovex is recommended.

Research paper thumbnail of The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma

Journal of the Egyptian National Cancer Institute, 2006

Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is p... more Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. We investigated 110 subjects (43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CIN II, 18 CIN I) confirmed to be positive for HPV16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E, CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential PCR techniques. There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16 (INK4A) (p=0.003, 0.001, 0.001) and a significant decrease in p27 (Kip1) from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27 (KIP1) and p16(INK4A) (p<0.001), cyclin D1 and CDK4 (p=0.001), cyclin E and p27 (Kip1) (p=0....

Research paper thumbnail of Differentially expressed genes in metastatic advanced Egyptian bladder cancer

Asian Pacific journal of cancer prevention : APJCP, 2015

Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using micro... more Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant diff...

Research paper thumbnail of Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

World journal of gastroenterology : WJG, Jan 28, 2014

To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C ... more To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease. Blood and/or tissue samples were obtained from HCV (genotype 4)-associated hepatocellular carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and 33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP), alkaline phosphatase, and alanine and aspartate aminotransferases were measured. Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133 and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real-time polymerase chain reactions. The number of CTCs and/or the expression levels of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard clinicopathologic prognostic factors and disease progression...

Research paper thumbnail of Cairo University Fibrosis Index (CUFI): A MicroRNA Based Score for Accurate Prediction of Hepatic Fibrosis: A Biopsy Controlled Study

Background: The exact identification of liver fibrosis is mandatory for customizing therapy and c... more Background: The exact identification of liver fibrosis is mandatory for customizing therapy and controlling complications. The aim of the current study is to measure the ability to circulate miRNAs; in the diagnosis of hepatic fibrosis.Methods: Routine laboratory, liver biopsy, and histopathological investigations were done on seventy HCV patients. In addition, estimation of HCV-RNA, serum micro RNA (miRNA)-122, 221, 192, 224, 375, and 885 were done by PCR. To assess the ability of each miRNA, the area under the receiver operating characteristics (AUC) curves were plotted. Significant miRNA were analyzed by linear regression analysis in a stepwise pattern to develop a score for pointing out significant fibrosis. Moreover, the following scores were calculated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), aspartate to platelet ratio index (APRI), FIB-4 score, Hui index, Fibrosis Index (FI), Fibro-Q, Fibro-Alfa Biotechnology Research Center (BRC) score, ...

Research paper thumbnail of MOESM2 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 2: The best alignment of our sequence with ref. seq. JN127373.1.

Research paper thumbnail of MOESM1 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 1: The most significant hits of HPgV sequence.

Research paper thumbnail of MOESM5 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 5: Alignments of the NS5B protein structure of HCV and HPgV.

Research paper thumbnail of MOESM3 of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Additional file 3: Identification of 808 SNPs.

Research paper thumbnail of The Prognostic Significance of 5-Fluorouracil Induced Inflammation and Immuno-Modulation in Colorectal Cancer Patients

Journal of Inflammation Research, 2020

Aim The change in the levels of peripheral inflammatory markers together with EGFR in relation to... more Aim The change in the levels of peripheral inflammatory markers together with EGFR in relation to 5- fluorouracil (5-FU) therapy was evaluated for their prognostic significance in colorectal cancer (CRC) patients. Patients and Methods Expression levels of COX2, IL6, IL1β, EGFR, IL10, and TNFα were determined with quantitative real-time PCR (qPCR) in the peripheral blood of 90 CRC patients. The inflammatory response was correlated with patients’ clinical features, disease-free survival (DFS), and overall survival (OS). Results After 6 months of 5-FU therapy, increased inflammatory response was found to be associated with smoking, T3 or T4 tumors, performance status (PS) III, positive lymph nodes, distant metastasis, and gastrointestinal (GIT) toxicity. The combination of COX2 with interleukins in a predictive equation for DFS was significant in patients with over-expression of EGFR. DFS and OS rates were reduced in patients with increased COX2, IL6, IL10, and TNFα expression with 5-F...

Research paper thumbnail of The Antiviral Efficacy of Withania somnifera (Ashwagandha) against Hepatitis C Virus Activity: In Vitro and in Silico Study

Advances in Microbiology

Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against ... more Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against HCV. Methods: cell proliferation was assessed using MTT assay after isolation of lymphocyte cells and treated with Ashwagandha water extract (ASH-WX) (6.25 mg/ml-100 mg/ml). Assessment of quantitative Real-time PCR, Colony forming assay, TNF-α and molecular docking studies after infection of normal lymphocyte cells with 1 ml (1.5 × 10 6 HCV) serum then incubated with ASH-WX at concentration 25 mg/ml & 50 mg/ml. Results: MTT assay revealed a significant increase (p < 0.001) in normal lymphocyte proliferation at all concentration's particularity at 25 mg/ml with SI (6.06) and at 50 mg/ml with (5.8). While TNF-α significantly decreased following ASH-WX treatment compared with control untreated infected cells (p < 0.05). PCR results showed a marked viral load reduction after treatment by ASH-WX at concentration 25 mg/ml to 6.241 × 10 3 IU/mL. Colony formation assay test revealed colony formation reduction compared to positive untreated control. Molecular docking analysis revealed good prediction of binding between Ashwagandha and NS5B and PKN2 compared to Sovaldi. Conclusion: ASH-WX may be a powerful antiviral against HCV infection.

Research paper thumbnail of MicroRNA Signatures for circulating CD133-positive cells in hepatocellular carcinoma with HCV infection

PloS one, 2018

Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through id... more Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs). We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array. The differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and...

Research paper thumbnail of Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer

PLOS ONE, 2016

The study was designed to assess the possibility of using circulating miRNAs (serum miR-NAs) as d... more The study was designed to assess the possibility of using circulating miRNAs (serum miR-NAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. Methods The study involved two sample sets: 1-a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2-a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR-135b and miR-92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. Results Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.

Research paper thumbnail of Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report

Virology Journal

Background Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was disc... more Background Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV. Case presentation The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient’s plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5′ untranslated region. The patient was then subjected to direct-acting-antivi...

Research paper thumbnail of Serum cytokine profile during disease progression stages in male and female hepatitis C patients

Journal of Bioscience and Applied Research

BioBacta

Research paper thumbnail of Prognostic Impact of BRCA1 and BRCA2 Mutations on Long-Term Survival Outcomes in Egyptian Female Breast Cancer Patients

Biology

Evidence on the prognostic relevance of BRCA1/2 mutations on breast cancer survival is still deba... more Evidence on the prognostic relevance of BRCA1/2 mutations on breast cancer survival is still debatable. To address this ambiguity, we sought to elucidate the impact of BRCA1/2 mutation carriership on long-term clinical outcomes for the first time in Egyptian female breast cancer patients. This study comprised 103 Egyptian female breast cancer patients previously tested for BRCA1/2 mutations. Clinicopathological characteristics and long-term follow-up data were retrieved from clinical records until death or loss to follow-up. Overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and metastasis-free survival (MFS) were compared in BRCA1/2 mutation carriers and non-carriers. Pathogenic variants (Class 5 according to ACMG/AMP guidelines) were observed in 29 cases. The profile of the detected variants was previously reported. After median follow-up time of 6.9 years (range, 4.2–24.4 years), BRCA1/2 carriers exhibited significantly worse RFS compared to non-c...

Research paper thumbnail of Kasr Alainy Fibrosis Index (KAFI) - A Novel Score Based on Micro RNAs for Diagnosis of Significant Fibrosis: A Biopsy Controlled Study

American Journal of Gastroenterology

Research paper thumbnail of Assessment of the diagnostic value of microsatellite instability in the urine of bladder cancer patients

Journal of Clinical Oncology

384 Background: Microsatellite alterations in urine sediments have proved to be a promising tool ... more 384 Background: Microsatellite alterations in urine sediments have proved to be a promising tool for detection of bladder cancer (BC) due to its high sensitivity and specificity. Methods: We assessed the possible prognostic and predictive values of microsatellite alterations in tissue samples and urine sediments obtained from Egyptian patients with BC, and their utility as diagnostic, prognostic and predictive value. Microsatellite instability (MSI) and loss of heterozygosity (LOH) were assessed using 13 microsatellite markers in tumor tissue and urine sediments of 30 patients with BC. The concordance between MSI in tissue and urine samples was determined. Results: We found that MSI was more frequent than LOH (100% and 46.7%; respectively). D16S310, MBP and IFN-α showed the highest MSI frequency in urine samples (70%, 70% and 66.67%; respectively), while MBP, ACTBP2 and D9S171 (66.67%, 63.33%, and 60%; respectively) were the most frequently detected in tumor tissue. All markers corr...

Research paper thumbnail of Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line

The Journal of international medical research, 2018

Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashw... more Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line. Methods After treating HepG2cells with Ashwagandha water extract (ASH-WX; 6.25 mg/ml-100 mg/ml), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase and glutathione reductase), Fas-ligand level, tumour necrosis factor-α (TNF-α) level and caspase-3, -8, and -9 activities were measured. Molecular modelling assessed the binding-free energies of Ashwagandha in the cyclin D1 receptor. Results The MTT assay demonstrated increased cytotoxicity following treatment of HepG2 cells with ASH-WX compared with control untreated cells and theICwas 5% (approximately 5.0 mg/ml). Antioxidant activities, Fas-ligand levels and caspase-3, -8 and -9 activities significantly increased, while TNF-α level significant...

Research paper thumbnail of Differentially expressed genes in metastatic advanced Egyptian bladder cancer

Asian Pacific journal of cancer prevention : APJCP, 2015

Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using micro... more Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant diff...

Research paper thumbnail of Ambovex® as a novel immunological modulator drug for the treatment of hepatocellular carcinoma (HCC) in the liver: a Phase II clinical trial

Journal of Hepatocellular Carcinoma, 2015

Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth mos... more Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth most common cancer and third leading cause of cancer-related mortality worldwide. The approved conventional treatment methods for HCC have shown life-threatening side effects with limited or negligible success, especially in multifocal HCC. As a consequence, new therapeutic approaches are being explored, including immunoregulatory molecules that may have the potential to treat or delay the progression of HCC. A novel pharmaceutical botanical drug-Ambovex ® , an immune-modulator molecule-was tested to treat or delay the progress of HCC. We conducted a 6-month randomized clinical trial with an additional 3-month washing period (no treatment) to evaluate the safety and efficacy of low-dose Ambovex oral spray in treating patients with HCC. The clinical study involved a total of 40 patients, with 33 in the treatment group and seven in the control group. The α-fetoprotein (AFP) levels were measured every month and ultrasound scans were performed at time zero and every 2 months thereafter. Computed tomography (CT) scans were performed for patients in the treatment group. Ambovex proved to be safe, as there were no significant side effects although some patients found that the drug has unpleasant taste. AFP analysis showed a significant decrease in its level (α=0.05; 95% confidence interval) in the treatment group when compared to the control group at 3 months (P=0.0031) and at 6 months (P=0.007). The ultrasound results showed improvement in the treated group, as evidenced by a significant decrease in the lesion numbers and sizes. The lesions in 38% of treated patients decreased from multiple to single with major improvements; 35% of patients exhibited a decrease from multiple lesions to multiple lesions with minor improvements, whereas 27% had stabilized lesions. CT scans in the treated group showed significant improvement, as there was complete disappearance of the lesions after 6 months of treatment with Ambovex in two patients. This clinical study showed the effective and promising results of Ambovex as an immunological modulator in treating HCC. Further exploration of Ambovex is recommended.

Research paper thumbnail of The role of cyclins and cyclins inhibitors in the multistep process of HPV-associated cervical carcinoma

Journal of the Egyptian National Cancer Institute, 2006

Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is p... more Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. We investigated 110 subjects (43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CIN II, 18 CIN I) confirmed to be positive for HPV16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E, CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential PCR techniques. There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16 (INK4A) (p=0.003, 0.001, 0.001) and a significant decrease in p27 (Kip1) from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27 (KIP1) and p16(INK4A) (p<0.001), cyclin D1 and CDK4 (p=0.001), cyclin E and p27 (Kip1) (p=0....