Browsing by Author "El-Khazragy, Nashwa"

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DUAL REPLACEMENT OF LNC-MEG3 AND MIR-155 TRIGGER TUMOR SUPPRESSIVE ACTIVITY IN MULTIPLE MYELOMA
(Elsevier, 08/01/2020) El-Khazragy, Nashwa; Safwat, Gehan; Emad, Passant
an urgent need. Recent evidence demonstrated a definitive tumor suppressor role of Long non-coding RNA maternally expressed gene 3 (MEG3) and miR-155 in Multiple Myeloma (MM), however, their biological role remains unclear. It has been demonstrated that both markers are downregulated in MM patients compared to healthy. Objectives: We aimed to investigate the biological effect of double hit replacement for both lnc-MEG3 and miR-155 in MM cells, and compare it with the effect of each biomarker separately. Methods: MM cells were transfected by MEG3 overexpression plasmid and miR-155 mimic, the miR-155 and lnc-MEG3 expression levels were measured by qRT-PCR. MTT assay was performed to assess the cell proliferation, cell cycle, and apoptosis were monitored by Flow cytometry analysis. Results: lnc-MEG3 and miR-155 were downregulated in MM cells. In- vitro overexpression of lnc-MEG3 and miR-155 suppresses cell proliferation, induce cell cycle arrest, and promote apoptosis, the effect was more prominent with upregulation of both markers than with each individual biomarker. Conclusion: the present data demonstrate that dual overexpression of lnc-MEG3 and miR-155 elicits a powerful dual tumor suppressor effect in MM cells, in spite they have different signaling pathways, thus providing a promising therapeutic strategy in MM patients.
Knockdown of WEE1 Gene Induces Cytotoxic Effects in Hairy Cell Leukemia
(Elsevier, 2021-09) El-Khazragy, Nashwa; Bakkar, Ashraf; Elnakib, Mostafa
Clinical Lymphoma Myeloma and Leukemia Volume 21, Supplement 1, September 2021, Page S325 Acute Myeloid Leukemia CLL-393: Knockdown of WEE1 Gene Induces Cytotoxic Effects in Hairy Cell Leukemia Author links open overlay panelNashwaEl-Khazragy12AshrafBakkar3MostafaElnakib4 1 Department of Clinical Pathology-Hematology and Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, Egypt 2 Global Research Labs, Cairo, Egypt 3 Faculty of Biotechnology, October University for Modern Sciences and Arts, Giza, Egypt 4 Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt Available online 30 August 2021. https://doi.org/10.1016/S2152-2650(21)01763-8 Get rights and content Background: Hairy cell leukemia (HCL) is a rare B-cell lymphoid neoplasm with morphological variations that can be difficult to distinguish. A BRAFV600E mutation is found in 80% of patients. Despite the fact that purine analogs (PNA) with or without anti-CD20 antibodies remain the first-line treatment, resistance is still a major issue that has a severe impact on patient outcomes. The successful therapeutic application of short interfering RNA (siRNA) in tumor suppression is being paved by gene silencing. In the cell cycle, the WEE1 gene is the master inhibitor of cyclin-dependent kinase 1. Cumulative data suggests that the WEE1 gene plays a definite function in cell biological processes and that silencing the WEE1 gene could have a variety of implications in cancer cells. Objectives: The purpose of this study was to examine how ex vivo knockdown of the WEE1 gene affects the viability of hairy cell leukemia (HCL) cells in order to see if it has therapeutic potential. Methods: The HCL cell line [Mo T] was used in an experimental in vi’ro investigation. To silence the WEE1 gene ex vivo, cells were transfected using siRNA. Furthermore, the effect of gene knockdown on cell viability was assessed using the MTT test, as well as cell cycle and apoptosis assays performed by flow cytometry. Furthermore, the WEE1 gene expression level in silenced cells was measured and correlated with cellular protein expression. Results: Silencing the WEE1 gene resulted in a significant decrease in cell viability, increased cell apoptosis, and arrested the cell cycle transition from the G1 to the S phase of the cell cycle. In addition, transfected cells showed a significant reduction in WEE1 gene expression, demonstrating the efficiency of gene silencing. Conclusion: In primary hairy cells, silencing the WEE1 gene resulted in significant cytotoxic effects, suggesting that knockdown of the WEE1 gene could be a promising therapeutic target in HCL.
miRNAs: novel noninvasive biomarkers as diagnostic and prognostic tools in neonatal sepsis
(Elsevier Inc, 2023-08) El-Khazragy, Nashwa; Mostafa, Mohamed Fathalla; Elnakib, Mostafa; Hemida, Eman H.A; Salah, Amira; Fawzy, Nesma Mohamed; Safwat, Gehan; Emam, Mennatallah M; Mahran, Nievin Ahmed; Rabie, Dina; Mohamed, Noura Mostafa
Neonatal sepsis is known as a clinical syndrome that is character- ized by signs or symptoms of infection within the first 28 days fol- lowing delivery, and it can be confirmed by the isolation of the causative pathogen from the blood [1,2]. It is divided into 2 catego- ries: early-onset (within the first 72 hours from presentation) and late-onset (>72 hours) [3,4]. Based on a recent global estimate from over 14 countries, neonatal sepsis occurred in 29,608 cases out of 2,797,879 live births over a 10-year period (2009−2018), with an incidence of 3930 cases per 100,000 live births. It is also associated with a considerably high mortality rate of 17.6% (ranging from 10.3%−28.6%) worldwide [5]. Many risk factors are contributed to high mortality in neonates with sepsis, including lower Apgar scores, septic shock, mechanical ventilation, umbilical catheterization, neu- tropenia, severe thrombocytopenia, and carbapenem-resistant microorganisms [6] Due to the presentation of nonspecific signs and symptoms of infection, the diagnosis of neonatal sepsis poses a challenge to health- care practitioners [7,8], which further affects how quickly the treat- ment plan is initiated and the prognosis in this patient population [9]. Therefore, to minimize the risk of negative outcomes (namely progression or mortality), researchers have suggested the use of “bio- markers” that would help in the diagnosis of sepsis [9,10]. Based on the definition provided by the National Institute of Health (NIH), bio- markers are considered “indicators” that can be objectively measured to either indicate the presence of a disease or identify the response to a certain therapeutic drug. In the case of neonatal sepsis, both procal- citonin and C-reactive protein (CRP) are frequently investigated bio- markers; however, they are associated with limited diagnostic value [11]. To overcome those limitations, the introduction of novel
PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival
(Elsevier, 2023-01) El-Khazragy, Nashwa; Gaballah, Ahmed; Bakkar, Ashraf; Hemida, Eman H.A; Samir, Nehal; Tarek, Marwa; Adly, Heba M; Saleh, Saleh A.K; Hanna, Demiana H
The high mortality rate of HER-2+ve breast cancer (BC) is linked to Trastuzumab resistance, which is linked to PTEN rs701848 variants. In 160 patients with metastatic HER2+ve BC who were treated with trastuzumab, the PTEN genotypes were determined. Obtained results revealed that the PTEN locus is a major predictor of Trastuzumab resistance, and the C allele is linked to a higher risk. Background: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predict- ing drug resistance. Objective: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes. Materials and Methods: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response. Results: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype. Conclusion: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended Clinical Breast Cancer, Vol. 000, No.xxx, 1–9 © 2022 Elsevier Inc. All rights reserved.
Tissue-based long non-coding RNAs “PVT1, TUG1 and MEG3” signature predicts Cisplatin resistance in ovarian Cancer
(Elsevier Inc.Mansy, 2020-08) El-Khazragy, Nashwa; Mohammed, Hayam Fathy; Yassin, Mohamed; Elghoneimy, K.K.; Bayoumy, Walid; Hewety, Amr; EL Magdoub, Hekmat M.; Elayat, Wael; Zaki, Walid; Safwat, Gehan; Mosa, Mai; Zedan, Khouloud; Salem, Salema; Bannunah, Azzah M.; Mansy, Azza
Objectives: The current study aimed to investigate the potentiality of three lncRNAs “Plasmacytoma variant translocation 1(lnc-PVT1), Taurine upregulated gene type 1(lnc- TUG1) and Maternally expressed gene 3 (lnc-MEG-3)”, to predict Cisplatin resistance in ovarian cancer (OC), in addition, to access their prognostic significance. Methods: The expression level of lncRNAs were measured in 100 formalin-fixed paraffin- embedded tissue (FFET) samples of OC patients who were treated by Cisplatin-based chemotherapy using qPCR.Results: The results showed that lnc_PVT1 was significantly higher by 2.3 folds in Cisplatin resistant tissues, while, lnc-TUG1 and lnc-MEG3 were downregulated by 1.2 and 3 folds, respectively. In addition, the three lncRNAs exhibited high sensitivity and specificity in predicting chemo-resistance and they were negatively associated with OS and progression- free survival (p<0.001). Conclusion: The lnc-PVT1, lnc-TUG1, and lnc-MEG3 transcriptome signatures could be used for predicting resistance to Cisplatin in OC patients.