Ebtsam Zaher - Academia.edu (original) (raw)
Papers by Ebtsam Zaher
Shiraz University of Medical Sciences, Oct 1, 2018
Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring hepatitis... more Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring hepatitis C-infected patients for hepatocellular carcinoma development is an important clinical issue to diagnose these patients during the potentially curable early-stage of disease. This study aims to evaluate the role of N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests as predictors of hepatocellular carcinoma development upon long-term followup of non-responding hepatitis C virus patients. Methods: The study included 850 treatment-naïve hepatitis C virus genotype 4a adult patients; after treatment, 360 achieved sustained viral response while 490 did not. Nonresponding patients had a 5-year rate for hepatocarcinogenesis of 8.4% and a 10-year rate of 27.5%. N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests were evaluated in all patients before and after treatment, and after hepatocellular carcinoma development. The study also included a group of 50 hepatocellular carcinoma patients who were negative for hepatitis C and hepatitis B viruses, and a group of 50 healthy subjects as controls. Results: The non-responders had significantly higher age, stage, grade, viral load, alanine aminotransferase, and aspartate aminotransferase than responders. Also N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, and alphafetoprotein were significantly higher in non-responders; after treatment they decreased in responders. In non-responders they remained higher than the control. The most significant risk factors for hepatocellular carcinoma development in non-responding hepatitis C virus patients were male gender and increased age, stage, grade, aspartate aminotransferase, Nterminal procollagen III, and tissue inhibitor of matrix metalloproteinase-1. Patients with viral-hepatocellular carcinoma were of significantly lower age, higher grade, stage, γ-glutamyltransferase, N-terminal procollagen III, and matrix metalloproteinase-2 than non-viral hepatocellular carcinoma patients. Percent positive N-terminal procollagen III, tissue inhibitor of matrix metalloproteinase-1, and alpha-fetoprotein were significantly higher in viral hepatocellular carcinoma patients. Conclusion: Data suggest that high N-terminal procollagen III and tissue inhibitor of matrix metalloproteinase-1levels after treatment might be particularly important as markers of hepatitis C virus-non-responding patients who are at higher risk of developing hepatocellular carcinoma, especially in older males with high stage and grade liver disease. However, studies of larger scale are needed to verify this suggestion.
The Journal of Cancer Research, 2018
Purpose: The current work aimed to evaluate the diagnostic and prognostic role of a panel of heat... more Purpose: The current work aimed to evaluate the diagnostic and prognostic role of a panel of heat shock proteins; HSP27, HSP60, HSP70 and HSP90, in sera of breast cancer patients, in comparison with CA 15.3 as the standard marker in breast cancer management. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were managed by modified radical mastectomy or breast conservative surgery then received adjuvant therapy and clinically followed up for 5 years. In sera of all patients and controls; HSP27, HSP60, HSP70 and HSP90 were measured by ELISA while CA 15.3 was measured by IRMA. Findings: Pre-treatment serum levels of HSP27, HSP60, HSP70 and HSP90 were significantly elevated in breast cancer patients than in controls, furthermore, they were significant as diagnostic markers, especially when using a panel of HSP70≥9.2 ng/ml and HSP60≥7.5 ng/ml with AUC, sensitivity and specificity of 0.995, 98% and 95%; respectively....
This work aimed to set-up and evaluate a lab-made immunoradiometric assay for the detection of pl... more This work aimed to set-up and evaluate a lab-made immunoradiometric assay for the detection of plasma glypican-3 (GPC3) in comparison with a commercial ELISA kit and to use them to evaluate the diagnostic potential of GPC3 in HCC patients. Anti-GPC3 monoclonal antibodies were radioiodinated and used with a second antibody in the IRMA assay. The study included 450 subjects in 3 groups, 150 HCC patients, 150 hepatitis-C-virus (HCV) patients and 150 normal healthy subjects. Plasma GPC3 was assayed by our lab-made IRMA and by a commercial ELISA kit, along with alpha-fetoprotein (AFP). We were able to set-up an IRMA assay to measure plasma GPC3 and applied it to diagnose HCC patients. When compared to a ELISA kit, our IRMA assay showed much better performance characteristics on ROC curves with much higher area under the curves, sensitivities and specificities when diagnosing HCC patients from normal controls or HCV patients. Using our IRMA assay, showed that GPC3 is a good diagnostic ind...
Experimental and Therapeutic Medicine, 2021
Alexandria Journal of Medicine, 2018
Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of le... more Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of left-sided and right-sided breast cancer (BC) patients, correlate the dose and laterality of radiotherapy to the possible cardiac damage and evaluate whether Left-ventricular Ejection Fraction (LVEF), Troponin-I (TnI), Creatinine Kinase (CK), Creatine Kinase-MB Relative Index (CK-MBRI) or Lactic Dehydrogenase (LDH) could be used to detect the possible onset of radiotherapy-related cardiotoxicity. Subjects and methods: 80 females were assigned as; 30 left-sided BC patients, 30 right-sided BC patients and 20 healthy females. Patients were treated by radical mastectomy followed by FAC-based chemotherapy and radiotherapy. CT-based 3D-planning was used to generate cardiac dose-volume histograms to assess mean dose received by the heart. Echocardiography was done to all patients before and 1 year after completing radiotherapy. In serum, TnI and CK-MB concentration and CK and LDH activities were determined before and 1 year after radiotherapy. Results: In left-sided patients, mean dose delivered to the heart was significantly higher in left-sided patients with significant association with total radiotherapy dose in left-but not right-sided patients. LVEF before and after radiotherapy were statistically different only in left-sided patients. LVEF one year after radiotherapy dropped 20% or more (DLVEF) in 6 patients, all were left-sided. Using cutoff values 0.08 ng/mL for TnI and 1.4 for CK-MBRI; 11 left-sided patients had abnormal TnI and CK-MBRI vs 5 right-sided patients, the 6 patients identified with DLVEF ! 20 were all among them. Conclusion: the mean dose delivered to the heart is significantly higher in left-sided patients, and it was correlated to the total radiotherapy dose. One year after radiotherapy, DLVEF is possibly good marker of cardiotoxicity onset, however, the persistent elevation of both TnI and CK-MBRI could identify both patients with cardiotoxicity and patients that are thought to be in subclinical phase of cardiac damage.
Alexandria Journal of Medicine, 2012
Background: Cell-free DNA (CFDNA) is extracellular nucleic acids found in cell-free plasma/serum ... more Background: Cell-free DNA (CFDNA) is extracellular nucleic acids found in cell-free plasma/serum of humans. This study aims to quantitatively measure CFDNA concentration and integrity in patients with malignant and non-malignant diseases and in healthy controls to investigate their value as a screening test for cancer, and then to correlate them with the clinicopathological parameters of cancer patients. Aim: This study included 145 subjects divided into three groups; group I: 83 patients with different types of cancer, group II: 30 patients with benign diseases and group III: 30 normal healthy volunteers as control. One plasma sample was collected from each subject. CFDNA was extracted from plasma and its concentration was measured using Quant-iTä PicoGreen dsDNA Assay Kit, then CFDNA integrity was detected by conventional PCR for 100, 200, 400 and 800 bp. Results: Results revealed that there was a highly significant difference in the mean level of CFDNA between the cancer group and each of the benign and control groups. AUC of ROC curve for cancer group versus normal and benign groups were 0.968 and 0.928, which indicated the efficiency of CFDNA as a marker for cancer. As for CFDNA integrity, normal and benign subjects showed only two bands at 100 and 200 bp, while all cancer patients demonstrated the 100, 200 and 400 bp bands and 78% of cancer patients had the 800 bp whose presence was statistically correlated with vascular invasion.
Indian Journal of Cancer, 2013
This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with ma... more This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with malignant and nonmalignant diseases and in controls to investigate their value as a screening test for cancer, and to correlate them with clinicopathological parameters of cancer patients. The study included three groups; group I: 120 cancer patients, group II: 120 patients with benign diseases and group III: 120 normal healthy volunteers as control. One plasma sample was collected from each subject. CFDNA was purified from the plasma then its concentration was measured and integrity was assessed by PCR amplification of 100, 200, 400, and 800 bp bands. There was a highly significant difference in CFDNA levels between cancer group and each of benign and control groups. AUC of ROC curve for cancer group versus normal and benign groups were 0.962 and 0.895, which indicated the efficiency of CFDNA as a marker of cancer. As for integrity, normal and benign subjects showed only two bands at 100 and 200 bp, while all cancer patients demonstrated the 400 bp band and 78% of them had the 800 bp whose presence correlated with vascular invasion. The combined use of CFDNA concentration and integrity is a candidate for a universal screening test of cancer. Upon setting suitable boundaries for the test it might be applied to identify cancer patients, particularly among subjects with predisposing factors. Being less expensive, CFDNA concentration could be applied for mass screening and for patients with values overlapping those of normal and benign subjects, the use of the more expensive, yet more specific, integrity test is suggested.
Alexandria Journal of Medicine, 2017
The Journal of Cancer Research, 2017
Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes const... more Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast...
Journal of High Institute of Public Health
Background: Body mass index (BMI) is an independent prognostic factor for survival in breast canc... more Background: Body mass index (BMI) is an independent prognostic factor for survival in breast cancer patients. Patients with higher BMI were found to have poorer cancer prognosis and lower survival rates. Many factors as ghrelin, adiponectin and leptin, have been implicated in obesity but their correlation with breast carcinogenesis and treatment outcome is still a debate. Objective: To identify the relation of ghrelin, adiponectin and leptin with BMI in breast cancer patients and their possible role in carcinogenesis and treatment outcome. Subjects and Methods: Sera from 80 breast cancer patients were analyzed. Ghrelin, adiponectin and leptin were assayed by commercial RIA kits, and their levels were correlated with BMI, clinicopathological parameters and relapse-free survival. The median duration of patients' follow-up was 32 months. Results: 73.7% of the cohort was overweight/ obese. Compared to breast cancer patients with normal BMI, overweight/obese patients had a significantly higher tumor size and higher histological grade. Overweight/obese patients had higher leptin and lower ghrelin and adiponectin levels. Adiponectin was lower in patients with higher tumor grade and lymph node involvement, while ghrelin decreased with increasing tumor size and histological grade. Only serum ghrelin levels were significantly correlated to better disease-free survival. Conclusion: Ghrelin, adiponectin and leptin are significant factors in controlling BMI in breast cancer patients but only ghrelin is a significant predictor of better outcome and recurrence-free survival.
Shiraz University of Medical Sciences, Oct 1, 2018
Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring hepatitis... more Background: Egypt has the highest prevalence of hepatitis C virus worldwide. Monitoring hepatitis C-infected patients for hepatocellular carcinoma development is an important clinical issue to diagnose these patients during the potentially curable early-stage of disease. This study aims to evaluate the role of N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests as predictors of hepatocellular carcinoma development upon long-term followup of non-responding hepatitis C virus patients. Methods: The study included 850 treatment-naïve hepatitis C virus genotype 4a adult patients; after treatment, 360 achieved sustained viral response while 490 did not. Nonresponding patients had a 5-year rate for hepatocarcinogenesis of 8.4% and a 10-year rate of 27.5%. N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, alpha-fetoprotein, and conventional liver function tests were evaluated in all patients before and after treatment, and after hepatocellular carcinoma development. The study also included a group of 50 hepatocellular carcinoma patients who were negative for hepatitis C and hepatitis B viruses, and a group of 50 healthy subjects as controls. Results: The non-responders had significantly higher age, stage, grade, viral load, alanine aminotransferase, and aspartate aminotransferase than responders. Also N-terminal procollagen III, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, and alphafetoprotein were significantly higher in non-responders; after treatment they decreased in responders. In non-responders they remained higher than the control. The most significant risk factors for hepatocellular carcinoma development in non-responding hepatitis C virus patients were male gender and increased age, stage, grade, aspartate aminotransferase, Nterminal procollagen III, and tissue inhibitor of matrix metalloproteinase-1. Patients with viral-hepatocellular carcinoma were of significantly lower age, higher grade, stage, γ-glutamyltransferase, N-terminal procollagen III, and matrix metalloproteinase-2 than non-viral hepatocellular carcinoma patients. Percent positive N-terminal procollagen III, tissue inhibitor of matrix metalloproteinase-1, and alpha-fetoprotein were significantly higher in viral hepatocellular carcinoma patients. Conclusion: Data suggest that high N-terminal procollagen III and tissue inhibitor of matrix metalloproteinase-1levels after treatment might be particularly important as markers of hepatitis C virus-non-responding patients who are at higher risk of developing hepatocellular carcinoma, especially in older males with high stage and grade liver disease. However, studies of larger scale are needed to verify this suggestion.
The Journal of Cancer Research, 2018
Purpose: The current work aimed to evaluate the diagnostic and prognostic role of a panel of heat... more Purpose: The current work aimed to evaluate the diagnostic and prognostic role of a panel of heat shock proteins; HSP27, HSP60, HSP70 and HSP90, in sera of breast cancer patients, in comparison with CA 15.3 as the standard marker in breast cancer management. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were managed by modified radical mastectomy or breast conservative surgery then received adjuvant therapy and clinically followed up for 5 years. In sera of all patients and controls; HSP27, HSP60, HSP70 and HSP90 were measured by ELISA while CA 15.3 was measured by IRMA. Findings: Pre-treatment serum levels of HSP27, HSP60, HSP70 and HSP90 were significantly elevated in breast cancer patients than in controls, furthermore, they were significant as diagnostic markers, especially when using a panel of HSP70≥9.2 ng/ml and HSP60≥7.5 ng/ml with AUC, sensitivity and specificity of 0.995, 98% and 95%; respectively....
This work aimed to set-up and evaluate a lab-made immunoradiometric assay for the detection of pl... more This work aimed to set-up and evaluate a lab-made immunoradiometric assay for the detection of plasma glypican-3 (GPC3) in comparison with a commercial ELISA kit and to use them to evaluate the diagnostic potential of GPC3 in HCC patients. Anti-GPC3 monoclonal antibodies were radioiodinated and used with a second antibody in the IRMA assay. The study included 450 subjects in 3 groups, 150 HCC patients, 150 hepatitis-C-virus (HCV) patients and 150 normal healthy subjects. Plasma GPC3 was assayed by our lab-made IRMA and by a commercial ELISA kit, along with alpha-fetoprotein (AFP). We were able to set-up an IRMA assay to measure plasma GPC3 and applied it to diagnose HCC patients. When compared to a ELISA kit, our IRMA assay showed much better performance characteristics on ROC curves with much higher area under the curves, sensitivities and specificities when diagnosing HCC patients from normal controls or HCV patients. Using our IRMA assay, showed that GPC3 is a good diagnostic ind...
Experimental and Therapeutic Medicine, 2021
Alexandria Journal of Medicine, 2018
Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of le... more Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of left-sided and right-sided breast cancer (BC) patients, correlate the dose and laterality of radiotherapy to the possible cardiac damage and evaluate whether Left-ventricular Ejection Fraction (LVEF), Troponin-I (TnI), Creatinine Kinase (CK), Creatine Kinase-MB Relative Index (CK-MBRI) or Lactic Dehydrogenase (LDH) could be used to detect the possible onset of radiotherapy-related cardiotoxicity. Subjects and methods: 80 females were assigned as; 30 left-sided BC patients, 30 right-sided BC patients and 20 healthy females. Patients were treated by radical mastectomy followed by FAC-based chemotherapy and radiotherapy. CT-based 3D-planning was used to generate cardiac dose-volume histograms to assess mean dose received by the heart. Echocardiography was done to all patients before and 1 year after completing radiotherapy. In serum, TnI and CK-MB concentration and CK and LDH activities were determined before and 1 year after radiotherapy. Results: In left-sided patients, mean dose delivered to the heart was significantly higher in left-sided patients with significant association with total radiotherapy dose in left-but not right-sided patients. LVEF before and after radiotherapy were statistically different only in left-sided patients. LVEF one year after radiotherapy dropped 20% or more (DLVEF) in 6 patients, all were left-sided. Using cutoff values 0.08 ng/mL for TnI and 1.4 for CK-MBRI; 11 left-sided patients had abnormal TnI and CK-MBRI vs 5 right-sided patients, the 6 patients identified with DLVEF ! 20 were all among them. Conclusion: the mean dose delivered to the heart is significantly higher in left-sided patients, and it was correlated to the total radiotherapy dose. One year after radiotherapy, DLVEF is possibly good marker of cardiotoxicity onset, however, the persistent elevation of both TnI and CK-MBRI could identify both patients with cardiotoxicity and patients that are thought to be in subclinical phase of cardiac damage.
Alexandria Journal of Medicine, 2012
Background: Cell-free DNA (CFDNA) is extracellular nucleic acids found in cell-free plasma/serum ... more Background: Cell-free DNA (CFDNA) is extracellular nucleic acids found in cell-free plasma/serum of humans. This study aims to quantitatively measure CFDNA concentration and integrity in patients with malignant and non-malignant diseases and in healthy controls to investigate their value as a screening test for cancer, and then to correlate them with the clinicopathological parameters of cancer patients. Aim: This study included 145 subjects divided into three groups; group I: 83 patients with different types of cancer, group II: 30 patients with benign diseases and group III: 30 normal healthy volunteers as control. One plasma sample was collected from each subject. CFDNA was extracted from plasma and its concentration was measured using Quant-iTä PicoGreen dsDNA Assay Kit, then CFDNA integrity was detected by conventional PCR for 100, 200, 400 and 800 bp. Results: Results revealed that there was a highly significant difference in the mean level of CFDNA between the cancer group and each of the benign and control groups. AUC of ROC curve for cancer group versus normal and benign groups were 0.968 and 0.928, which indicated the efficiency of CFDNA as a marker for cancer. As for CFDNA integrity, normal and benign subjects showed only two bands at 100 and 200 bp, while all cancer patients demonstrated the 100, 200 and 400 bp bands and 78% of cancer patients had the 800 bp whose presence was statistically correlated with vascular invasion.
Indian Journal of Cancer, 2013
This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with ma... more This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with malignant and nonmalignant diseases and in controls to investigate their value as a screening test for cancer, and to correlate them with clinicopathological parameters of cancer patients. The study included three groups; group I: 120 cancer patients, group II: 120 patients with benign diseases and group III: 120 normal healthy volunteers as control. One plasma sample was collected from each subject. CFDNA was purified from the plasma then its concentration was measured and integrity was assessed by PCR amplification of 100, 200, 400, and 800 bp bands. There was a highly significant difference in CFDNA levels between cancer group and each of benign and control groups. AUC of ROC curve for cancer group versus normal and benign groups were 0.962 and 0.895, which indicated the efficiency of CFDNA as a marker of cancer. As for integrity, normal and benign subjects showed only two bands at 100 and 200 bp, while all cancer patients demonstrated the 400 bp band and 78% of them had the 800 bp whose presence correlated with vascular invasion. The combined use of CFDNA concentration and integrity is a candidate for a universal screening test of cancer. Upon setting suitable boundaries for the test it might be applied to identify cancer patients, particularly among subjects with predisposing factors. Being less expensive, CFDNA concentration could be applied for mass screening and for patients with values overlapping those of normal and benign subjects, the use of the more expensive, yet more specific, integrity test is suggested.
Alexandria Journal of Medicine, 2017
The Journal of Cancer Research, 2017
Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes const... more Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast...
Journal of High Institute of Public Health
Background: Body mass index (BMI) is an independent prognostic factor for survival in breast canc... more Background: Body mass index (BMI) is an independent prognostic factor for survival in breast cancer patients. Patients with higher BMI were found to have poorer cancer prognosis and lower survival rates. Many factors as ghrelin, adiponectin and leptin, have been implicated in obesity but their correlation with breast carcinogenesis and treatment outcome is still a debate. Objective: To identify the relation of ghrelin, adiponectin and leptin with BMI in breast cancer patients and their possible role in carcinogenesis and treatment outcome. Subjects and Methods: Sera from 80 breast cancer patients were analyzed. Ghrelin, adiponectin and leptin were assayed by commercial RIA kits, and their levels were correlated with BMI, clinicopathological parameters and relapse-free survival. The median duration of patients' follow-up was 32 months. Results: 73.7% of the cohort was overweight/ obese. Compared to breast cancer patients with normal BMI, overweight/obese patients had a significantly higher tumor size and higher histological grade. Overweight/obese patients had higher leptin and lower ghrelin and adiponectin levels. Adiponectin was lower in patients with higher tumor grade and lymph node involvement, while ghrelin decreased with increasing tumor size and histological grade. Only serum ghrelin levels were significantly correlated to better disease-free survival. Conclusion: Ghrelin, adiponectin and leptin are significant factors in controlling BMI in breast cancer patients but only ghrelin is a significant predictor of better outcome and recurrence-free survival.