Browsing by Author "Aref, Ahmed"

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Clinico-pathological relationship between androgen receptor (AR) and tumor infiltrating lymphocytes (TILs) in triple negative breast cancer (TNBC)
(Springer, 2021-01) Helal, Thanaa; Bakkach, Joaira; Elghazawy, Hagar; Aref, Ahmed; Kelany, Mohamed; Abdallah, Lamiaa; Abdelbakey, Fatma; Ali, Dalia; Ali, Doaa; Ahmed, Mai; Abd El-Hafeez, Amer; Ghosh, Pradipta; Alorabi, Mohamed
Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-dened therapeutic targets. Androgen receptor (AR) and tumor-inltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behavior is still not fully understood. Methods Thirty-six TNBC patients were evaluated for AR (positive if ≥ 1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantied following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was dened as having stromal TILs ≥ 50%, whereas lymphocyte-decient breast cancer (LDBC) was dened as < 50%. Results The mean age was 52.5 years and 27.8% were ≥ 60 years. Seven patients (21.2%) were AR+. All AR + cases were postmenopausal (≥ 50 years old). No statistical difference was found in median overall survival (OS) between AR- and AR + groups (31.5 vs. 25 months, p = 0.77). LPBC was 32.2%. Median TILs was 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p = 0.41) in ARand AR + respectively. All patients who were ≥ 60 years old expressed CD20. LDBC was found to be signicantly higher in N + vs. N- patients (p = 0.03) with median TILs of 20% vs. 50% in N + vs. N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node involvement (OR = 6, 95% CI = 1.05–34.21, p = 0.04). Conclusions AR expression was evident in older age (≥ 50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR + tumors. LDBC was associated with higher risk of lymph node involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.
Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study
(01/06/2022) Helal, Thanaa Elsayed; Aref, Ahmed; Gomaa, Asmaa Ibrahim; Nada, Ola; Abd-Elghaffar, Mohamed; Farouk, Khaled; Ehsan, Nermine Ahmed
Objective: Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC. Methods: This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR). Results: EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively. EMT mRNA in HCC tissues correlated with protein expression by 50-70%. Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis. Reduced E-cadherin was a predictor of HRR (P=0.002). Conclusion: Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.
Stem cells derived exosomes as biological nano carriers forVCR sulfate for treating breast cancer stem cells
(Nature Publishing Group, 2024-05) Farouk, Ahmed H; Aref, Ahmed; Fathy, Belal A; Abdallah, Ahmed N
Due to vincristine sulfate’s (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24−) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo’s in vivo effectiveness and safety and improve the loading and delivery strategies.