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Abdel-azim, N., L. F. Alkilany, Z. K. Hassan, and N. Gaber, "Investigating causes and risk factors of pre-chemotherapy viremia in acute lymphoblastic leukemia pediatric patients", Infection. , vol. 2022 Jul 25 , issue 2022 Jul 25 , pp. 1–9., 2022.
Amira Salah El-Din Youssef, Mohamed A. Abdel-Fattah, M. L. A. N. M. A. M. 3, M. M. E. A. B. H. K. 1 5 A. 6 7 Ahmed O. Touny, 4 Zeinab K. Hassan, H. Khaled, and A. R. N. Zekri, "Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience", Curr Issues Mol Biol., vol. 2022 Mar; 44(3), issue 44(3), pp. 1332–1352., 2022.
Zekri, A. - R. N., M. Mohanad, M. M. Hafez, H. K. Soliman, Z. K. Hassan, M. Abouelhoda, K. E. Amer, M. G. Seadawy, and O. S. Ahmed, "Genome sequencing of SARS-CoV-2 in a cohort of Egyptian patients revealed mutation hotspots that are related to clinical outcomes.", Biochimica et biophysica acta. Molecular basis of disease, vol. 1867, issue 8, pp. 166154, 2021. Abstract

BACKGROUND: Severe acute respiratory syndrome-2 (SARS-CoV-2) exhibits a broad spectrum of clinical manifestations. Despite the fact that SARS-CoV-2 has slower evolutionary rate than other coronaviruses, different mutational hotspots have been identified along the SARS-CoV-2 genome.

METHODS: We performed whole-genome high throughput sequencing on isolates from 50 Egyptian patients to see if the variation in clinical symptoms was related to mutations in the SARS-CoV-2 genome. Then, we investigated the relationship between the observed mutations and the clinical characteristics of the patients.

RESULTS: Among the 36 most common mutations, we found two frameshift deletions linked to an increased risk of shortness of breath, a V6 deletion in the spike glycoprotein's signal peptide region linked to an increased risk of fever, longer fever duration and nasal congestion, and L3606-nsp6 deletion linked to a higher prevalence of cough and conjunctival congestion. S5398L nsp13-helicase was linked to an increased risk of fever duration and progression. The most common mutations (241, 3037, 14,408, and 23,403) were not linked to clinical variability. However, the E3909G-nsp7 variant was more common in children (2-13 years old) and was associated with a shorter duration of symptoms. The duration of fever was significantly reduced with E1363D-nsp3 and E3073A-nsp4.

CONCLUSIONS: The most common mutations, D614G/spike-glycoprotein and P4715L/RNA-dependent-RNA-polymerase, were linked to transmissibility regardless of symptom variability. E3909G-nsp7 could explain why children recover so quickly. Nsp6-L3606fs, spike-glycoprotein-V6fs, and nsp13-S5398L variants may be linked to clinical symptom worsening. These variations related to host-virus interactions might open new therapeutic avenues for symptom relief and disease containment.

Zekri, A. - R. N., K. Easa Amer, M. M. Hafez, Z. K. Hassan, O. S. Ahmed, H. K. Soliman, A. A. Bahnasy, W. Abdel Hamid, A. Gad, M. Ali, et al., "Genomic characterization of SARS-CoV-2 in Egypt.", Journal of advanced research, vol. 30, pp. 123-132, 2021. Abstract

Introduction: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe, causing a pandemic. In Egypt over 115,000 individuals were infected so far.

Objective: In the present study, the objective is to perform a complete genome sequence of SAR-CoV2 isolated from Egyptian coronavirus disease (COVID-19) patients.

Methods: Nasopharyngeal swabs were collected from 61 COVID-19 patients who attended at National Cancer Institute, Kasr Al-Aini Hospital and the army hospital. Viral RNA was extracted and whole genomic sequencing was conducted using Next Generation Sequencing.

Results: In all cases, the sequenced virus has at least 99% identity to the reference Wuhan 1. The sequence analysis showed 204 distinct genome variations including 114 missense mutations, 72 synonymous mutations, 1 disruptive in-frame deletion, 7 downstream gene mutations, 6 upstream gene mutations, 3 frame-shift deletions, and 1 in-frame deletion. The most dominant clades were G/GH/GR/O and the dominant type is B.

Conclusion: The whole genomic sequence of SARS-CoV2 showed 204 variations in the genomes of the Egyptian isolates, where the Asp614Gly (D614G) substitution is the most common among the samples (60/61). So far, there were no strikingly variations specific to the Egyptian population, at least for this set of samples.

Aljahani, A. H., K. M. Alarjani, Z. K. Hassan, M. F. Elkhadragy, E. A. Ismail, A. H. Al-Masoud, and H. M. Yehia, "Molecular detection of methicillin heat-resistant Staphylococcus aureus strains in pasteurized camel milk in Saudi Arabia.", Bioscience reports, vol. 40, issue 4, 2020. Abstract

Antibiotic- and heat-resistant bacteria in camel milk is a potential public health problem. Staphylococcus aureus (S. aureus) is an opportunistic pathogen in humans, dairy cattle and camels. We characterized the phenotype and genotype of methicillin-resistant staphylococcal strains recovered from pasteurized and raw camel milk (as control) distributed in the retail markets of Saudi Arabia. Of the 100 samples assessed between March and May 2016, 20 S. aureus isolates were recovered from pasteurized milk, 10 of which were resistant to cefoxitin, and as such, were methicillin-resistant. However, raw camel milk did not contain methicillin-resistant S. aureus (MRSA). Antimicrobial susceptibility tests showed that the resistance ratio for other antibiotics was 60%. We performed a polymerase chain reaction (PCR) assay using primers for the methicillin-resistant gene mecA and nucleotide sequencing to detect and verify the methicillin-resistant strains. Basic local alignment search tool (BLAST) analysis of the gene sequences showed a 96-100% similarity between the resistant isolates and the S. aureus CS100 strain's mecA gene. Ten of the methicillin-resistant isolates were heat-resistant and were stable at temperatures up to 85°C for 60 s, and three of these were resistant at 90°C for 60 or 90 s. The mean decimal reduction time (D85-value) was 111 s for the ten isolates. Sodium dodecyl sulfate (SDS)/polyacrylamide gel electrophoresis (PAGE) showed that there was no difference in the total protein profiles for the ten methicillin heat-resistant S. aureus (MHRSA) isolates and for S. aureus ATCC 29737. In conclusion, a relatively high percentage of the tested pasteurized camel milk samples contained S. aureus (20%) and MHRSA (10%).

Daghestani, M., H. H. Hakami, Z. K. Hassan, G. Badr, and M. A. R. S. B. H. & Maysoor H. Amin, "The anti-cancer effect of Echis coloratus and Walterinnesia aegyptia venoms on colon cancer cells", Toxin Reviews, 2019.
Soliman, H. K., M. Abouelhoda, M. N. El Rouby, O. S. Ahmed, G. Esmat, Z. K. Hassan, M. M. Hafez, D. A. Mehaney, M. Selvaraju, R. K. Darwish, et al., "Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report.", Virology journal, vol. 16, issue 1, pp. 132, 2019. Abstract

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-antiviral treatment (DAA). At the end of the treatment, the patient showed a good response to the HCV treatment (i.e., no HCV-RNA was detected in the plasma), while the HPgV-RNA was still detected. Sequence alignment and phylogenetic analyses demonstrated that the detected HPgV was a novel isolate and was not previously published.

CONCLUSION: We report a new variant of HPgV in a patient suffering from hepatitis C viral infection.

Daghestani, M., M. Daghestani, M. Daghistani, A. Eldali, Z. K. Hassan, M. H. Elamin, and A. Warsy, "ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1.", Lipids in health and disease, vol. 17, issue 1, pp. 58, 2018. Abstract

BACKGROUND: In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders.

METHODS: We studied 329 non-related adults (33.1% men and 66.9% women), aged 18-36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m), overweight (BMI ≥25.1-29.9 kg/m) subjects, and obese (≥30 kg/m).

RESULTS: In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele.

CONCLUSION: The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.

Alotaibi, M. R., Z. K. Hassan, S. S. Al-Rejaie, M. A. Alshammari, M. M. Almutairi, A. R. Alhoshani, W. A. Alanazi, M. M. Hafez, and O. A. Al-Shabanah, "Characterization of Apoptosis in a Breast Cancer Cell Line after IL-10 Silencing", Asian Pacific journal of cancer prevention : APJCP, vol. 19, issue 3, pp. 777-783, 2018. Abstract

Background: Breast cancer is affected by the immune system in that different cytokines play roles in its initiation
and progression. Interleukin-10 (IL-10), an anti-inflammatory cytokine, is an immunosuppressive factor involved in
tumorigenesis. The present study was conducted to investigate the gene silencing effect of a small interference RNA
(siRNA) targeting IL-10 on the apoptotic pathway in breast cancer cell line. Methods: The siRNA targeting IL-10 and
a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) clone were introduced into MDA-MB-231 cells. Real-time
PCR assays were used to determine IL-10 and GAPDH gene expression levels, in addition to those for protein kinase
B (AKT), phosphoinositide 3-kinase (PI3K), B-cell lymphoma 2 (Bcl2), caspase-3 and caspase-9 genes related to
apoptosis. Results: Inhibition of IL-10 by the siRNA accelerated apoptosis and was accompanied by significant
increase in caspase-3 and caspase-9 and a significant decrease in PI3K, AKT and Bcl2 expression levels compared to
the non-transfected case. Conclusions: In conclusion, the production of IL-10 may represent a new escape mechanism
by breast cancer cells to evade destruction by the immune system. IL-10 gene silencing causes down regulation of both
PI3K/AKT and Bcl2 gene expression and also increases the Bbc3, BAX caspase3, and caspase 3 cleavage expression
levels. IL–10 might represent a promising new target for therapeutic strategies.

MM, H., H. SS, E. - K. MF, H. ZK, and A. - H. N. O. 1 A. - H. K. A. 1 A. - H. M. M. Al Rejaie SS1, Sayed-Ahmed MM1, "Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats.", BMC Complement Altern Med. , vol. 13;17(1):45., 2017.
Hassan, Z. K., M. M. Hafez, M. M. Kamel, and A. R. N. Zekri, "Human Papillomavirus Genotypes and Methylation of CADM1, PAX1, MAL and ADCYAP1 Genes in Epithelial Ovarian Cancer Patients", Asian Pacific journal of cancer prevention : APJCP, vol. 18, issue 1, pp. 169-176, 2017. Abstract

Background: High-risk types of human papillomavirus (HR-HPV) may play a role in the development of epithelial
ovarian cancer (EOC). The aim of this study was to determine any HPV genotypes and correlations to CADM1,
PAX1, MAL and ADCYAP1 gene methylation in Egyptian EOC patients. Materials and methods: The prevalence
of HR-HPV in 100 formalin fixed paraffin embedded EOC tissues was determined using nested polymerase chain
reaction (PCR) with MY09/MY11 and GP5+/GP6 + primers to amplify a broad spectrum of HPV genotypes in a single
reaction. DNA sequencing was applied to identify HPV genotypes for the positive samples. All samples negative for
HPV were re-analyzed for HR-HPV and low-risk HPV subtypes using type specific primers. Results: The prevalence
of HPV was 10% in our EOC cases. HPV-16 and HPV-18 were the predominant genotypes followed by HPV−33, all
being associated with advanced stages. Other HR-HPV and low risk HPV genotypes were not found. CADM1 was
hypermethylated in 100% of patients infected with HPV-16 and HPV-33 and in 75% of patients infected with HPV-18.
Hypermethylation of PAX1 was evident in 80% and in 75% of patients infected with HPV-16 and HPV-18 while MAL
was hypermethylated in 100% and ADCYAP1 was hypermethylated in 60% and in 75%, respectively. Conclusion:
The presence of high risk HPV genotypes among epithelial ovarian carcinoma may reflect an importance of infection
in the pathogenesis of EOC. In HR-HPV infected cancers, DNA methylation may be one of the mechanisms triggering
the alteration in CADM1, PAX1, MAL and ADCYAP1 gene expression levels.

Zekri, A. R. N., H. Salama, E. medhat, S. Hamdy, Z. K. Hassan, Y. M. Bakr, A. S. E. D. - Youssef, D. Saleh, R. Saeed, and D. Omran, "Potential Diagnostic and Prognostic Value of Lymphocytic Mitochondrial DNA Deletion in Relation to Folic Acid Status in HCV-Related Hepatocellular Carcinoma", Asian Pacific journal of cancer prevention : APJCP, vol. 18, issue 9, pp. 2451-2457, 2017. Abstract

Objective: We assessed the possibility of using mitochondrial (mt) DNA deletion as a molecular biomarker for
disease progression in HCV-related hepatocellular carcinoma (HCC) and to identify its association with folic acid status.
Methods: Serum folic acid and lymphocytic mtDNA deletions were assessed in 90 patients; 50 with HCC, 20 with
liver cirrhosis (LC), and 20 with chronic hepatitis C (CHC) compared to 10 healthy control subjects. The diagnostic
accuracy of mtDNA deletions frequency was evaluated using receiver-operating characteristic (ROC) curve analysis
Survival analysis was performed using the Kaplan-Meier method. Differences in the survival rates were compared
using log-rank test. Result: Our data revealed a significant elevation of mtDNA deletions frequency in the HCC
group compared to the other groups (P-value <0.01). Also, our data showed a significant correlation between folate
deficiency and high frequency of mtDNA deletions in patients with HCV-related HCC when compared to the other
groups (r= -0.094 and P-value <0.05). Moreover, the size of the hepatic focal lesion in the HCC patients was positively
correlated with mtDNA deletions (r= 0.09 and P-value <0.01). The median survival time for the HCC patients with
high frequency of mtDNA deletions (ΔCt ≥3.9; 5.7+ 0.6 months) was significantly shorter than those with low mtDNA
deletions frequency (ΔCt < 3.9; 11.9+ 0.04 months, P-value <0.01). Conclusion: Our data provided an evidence that
lymphocytic mtDNA deletion could be used as non-invasive biomarker for disease progression and patients’ survival in
HCV-related HCC. Also, our findings implied a causal relationship between the folate deficiency and the high mtDNA
deletions frequency among Egyptian patients with HCV related HCC.

SS, H., Al-Yhya NA, E. - K. MF, Al-Olayan EM, Alajmi RA, H. ZK, and A. M. A. E. 7 Hassan SB6, "The Protective Properties of the Strawberry (Fragaria ananassa) against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Mediated by Anti-Apoptotic and Upregulation of Antioxidant Genes Expression Effects.", Frontiers in Physiology, vol. Aug 5;7:325. , 2016.
Murugan, A. K., E. A. Humudh, E. Qasem, H. Al-Hindi, M. Almohanna, Z. K. Hassan, and A. S. Alzahrani, "Absence of somatic mutations of the mTOR gene in differentiated thyroid cancer.", Meta gene, vol. 6, pp. 69-71, 2015. Abstract

Thyroid cancer is the most common endocrine malignancy with increasing incidence. Mammalian target of rapamycin (mTOR) is an important downstream mediator of phosphatidylinositol 3-kinase (PI3K/Akt) signaling and regulates cell growth, apoptosis and metabolism. The mTOR gene is frequently mutated in human cancers. Although PI3K/Akt pathway and its component genes were extensively studied in thyroid cancer, it is not known whether mTOR gene is somatically mutated and play a role in differentiated thyroid cancer (DTC). To determine the status of mTOR mutations in 53 DTC, we extensively examined 19 selected exons of mTOR gene which were reported to be frequently mutated in other human cancers. Unlike in other human cancers, we did not find common somatic mutations in the mTOR gene in differentiated thyroid cancer, except for some synonymous single nucleotide polymorphisms. Our results suggest that mTOR mutation is very rare and may not play a significant role in DTC.

Zekri, A. - R. N., Z. K. Hassan, A. A. Bahnassy, H. M. Khaled, M. N. El-Rouby, R. M. Haggag, and F. O. U. A. D. M. ABU-TALEB, "Differentially expressed genes in metastatic advanced Egyptian bladder cancer.", Asian Pacific journal of cancer prevention : APJCP, vol. 16, issue 8, pp. 3543-9, 2015. Abstract

BACKGROUND: 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.

MATERIALS AND METHODS: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis.

RESULTS: 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 differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta.

CONCLUSIONS: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

Hafez, M. M., O. A. Al-Shabanah, S. S. Al-Rejaie, N. O. Al-Harbi, Z. K. Hassan, A. Alsheikh, A. I. Al Theyab, M. L. Aldelemy, and M. M. Sayed-Ahmed, "Increased hypermethylation of glutathione S-transferase P1, DNA-binding protein inhibitor, death associated protein kinase and paired box protein-5 genes in triple-negative breast cancer Saudi females.", Asian Pacific journal of cancer prevention : APJCP, vol. 16, issue 2, pp. 541-9, 2015. Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-β (RARβ1) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin- fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

El-Amin, M., P. Virk, M. A. R. Elobeid, Z. M. Almarhoon, Z. K. Hassan, S. A. Omer, N. M. Merghani, M. H. Daghestani, and E. M. Al-Olayan, "Anti-diabetic effect of Murraya koenigii (L) and Olea europaea (L) leaf extracts on streptozotocin induced diabetic rats.", Pakistan journal of pharmaceutical sciences, vol. 26, issue 2, pp. 359-65, 2013. Abstract

Phytotherapy has a promising future in the management of diabetes, considered to be less toxic and free from side effects as compared to the use of synthetic drugs. The aim of the present study was to assess the antidiabetic possible of orally administered aqueous extracts of Murraya koenigii (ML) and Olea europaea (OL) leaves (100 and 200 mg/kg doses), in streptozotocin (70 mg/kg) induced diabetic rats. Metformin was used as a standard drug. Blood glucose, cholesterol, triglycerides, creatinine levels and body weight were estimated. ML and OL administration showed significant decrease (p>0.05) in cholesterol, triglyceride, and serum glucose levels (range 55.6%-64.6%) compared to the metformin (62.7%); however, there was no significant effect on body weight and serum creatinine. Our results suggest that both the ML and OL possess a potent antihyperglycemic and hypolipidemic effect, which may be due to the presence of antioxidants such as carbazole alkaloids and polyphenols.

Zekri, A. - R. N., Z. K. Hassan, A. A. Bahnassy, D. H. Eldahshan, M. N. E. El-Rouby, M. M. Kamel, and M. M. Hafez, "Gene expression profiling of non-hodgkin lymphomas.", Asian Pacific journal of cancer prevention : APJCP, vol. 14, issue 7, pp. 4393-8, 2013. Abstract

BACKGROUND: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach.

MATERIALS AND METHODS: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer.

RESULTS: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3.

CONCLUSIONS: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.

Al-Shabanah, O. A., M. M. Hafez, Z. K. Hassan, M. M. Sayed-Ahmed, W. N. Abozeed, S. S. Al-Rejaie, and A. A. Alsheikh, "Human papillomavirus genotyping and integration in ovarian cancer Saudi patients.", Virology journal, vol. 10, pp. 343, 2013. Abstract

BACKGROUND: Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients.

METHODS: Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18.

RESULTS: High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal.

CONCLUSION: The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer.

Elamin, M. H., M. H. Daghestani, S. A. Omer, M. A. Elobeid, P. Virk, E. M. Al-Olayan, Z. K. Hassan, O. B. Mohammed, and A. Aboussekhra, "Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells.", Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, vol. 53, pp. 310-6, 2013. Abstract

Breast cancer constitutes a major health problem for women worldwide. However, its incidence varies between populations and geographical locations. These variations could be diet-related, since there are several carcinogenic compounds in the modern diet, while natural products contain various anti-cancer elements. Several lines of evidence indicate that, in addition to their clear preventive effect, these compounds could also be used as therapeutic agents. In the present report we have shown that oleuropein, a pharmacologically safe natural product of olive leaf, has potent anti-breast cancer properties. Indeed, oleuropein exhibits specific cytotoxicity against breast cancer cells, with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells. This effect is mediated through the induction of apoptosis via the mitochondrial pathway. Moreover, oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21. Furthermore, oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-κB and its main oncogenic target cyclin D1. This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells. Therefore, oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer, especially the less-responsive basal-like type.

Daghestani, M. H., A. Warsy, M. H. Daghestani, A. N. Al-Odaib, A. Eldali, N. A. Al-Eisa, S. A. Omer, and Z. K. Hassan, "Arginine 16 Glycine Polymorphism in β2-Adrenergic Receptor Gene is Associated with Obesity, Hyperlipidemia, Hyperleptinemia, and Insulin Resistance in Saudis.", International journal of endocrinology, vol. 2012, pp. 945608, 2012. Abstract

Background. Several studies have shown an association between codon 16 polymorphism of the β2AR gene and obesity. Methods. We studied the association between Arg16Gly polymorphism and obesity and its influence on anthropometric parameters, lipids, insulin resistance and leptin in Saudi individuals. The study group included 329 individuals (males: 109 and females: 220). Metabolic parameters, including glucose, lipids, insulin, and leptin were analyzed and anthropometric parameters including waist and hip circumference, waist/hip (W/H) ratio, and body mass index (BMI) were measured and HOMA-IR was calculated. Genotyping was conducted by DNA sequencing of 353 bp fragments, carrying the Arg16Gly polymorphic site. Results and Conclusion. Overweight and obese subjects had a significantly higher frequency of Gly16 (0.375 and 0.38, resp.) compared with normal-weight subjects (0.200). In addition, subjects carrying Gly16 allele regardless of their BMI had greater waist and hip circumference, W/H ratio, plasma lipids, leptin, glucose level, and insulin resistance as judged from the HOMA-IR, compared to those with the wild-type allele. The findings of this study show a significant association between the Arg16Gly polymorphism in β2AR gene and the development of insulin resistance, overweight, and obesity in Saudi populations with an influence on the levels of lipid and leptin.

Zekri, A. - R. N., A. A. Bahnassy, W. S. Mohamed, F. A. El-Kassem, S. J. El-Khalidi, M. M. Hafez, and Z. K. Hassan, "Epstein-Barr virus and breast cancer: epidemiological and molecular study on Egyptian and Iraqi women.", Journal of the Egyptian National Cancer Institute, vol. 24, issue 3, pp. 123-31, 2012. Abstract

BACKGROUND AND PURPOSE: The role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is potentially important for better understanding of breast cancer etiology, early detection and possibly prevention of breast cancer. The aim of the current study is to unravel the association between EBV and primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women).

PATIENTS AND METHODS: The study was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC), in situ hybridization (ISH) and PCR techniques.

RESULTS: Our gold standard for EBV reactivity in breast cancer cases was positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50 (28%) of Egyptian and Iraqi women; respectively where p=0.073, compared to 0/20 (0%) of their control groups (p<0.05). Regarding the association between EBV positivity and tumor grade, there was not any statistical significant difference between EBV presence and tumor grade in both populations where p=0.860 and p=0.976 and the calculated rank biserial correlation coefficient was 0.114 and 0.269 for Egyptian and Iraqi women respectively.

CONCLUSION: Our findings show that EBV might act as a promoter for the development of PIBC and it might contribute to increased tumor aggressiveness in Egyptian and Iraqi patients.

Zekri, A. - R. N., Z. K. Hassan, A. A. Bahnassy, G. M. Sherif, D. ELdahshan, M. Abouelhoda, A. Ali, and M. M. Hafez, "Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus.", Asian Pacific journal of cancer prevention : APJCP, vol. 13, issue 11, pp. 5433-8, 2012. Abstract

BACKGROUND: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures.

PATIENTS AND METHODS: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis.

RESULT: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein (AFP≥600 IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets.

CONCLUSION: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.