Browsing by Author "Elghazawy, Hagar"

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    Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway
    (Korean Society for Biotechnology and Bioengineering, 2022-11) Abd El-Hafeez, Amer Ali; Marzouk, Hala Mohamed M; Abdelhamid, Mohamed A. A; Khalifa, Hazim O; Hasanin, Tamer H. A; Habib, Ahmed G. K; Abdelwahed, Fatma Mahmoud; Barakat, Fatma M; Bastawy, Eslam M; Abdelghani, Eman M. B; Ozawa, Toru Hosoi, Koichiro; Aref, Ahmed M; Fujimura, Takashi; Ibrahim, Ahmed R. N; Abdelmoniem, Aalaa S. O; Elghazawy, Hagar; Ghosh, Pradipta; Kawamoto, Seiji; Pil Pack, Seung
    flow cytometric analysis, knockdown of ASK1, and reactive oxygen species (ROS) production were evaluated to clarify the mechanism of action. Phytochemical screening confirmed the presence of wide range of phytoconstituents. Hyoscyamus muticus methanolic extracts (HMME) showed the highest anti-cancer activities against leukemia, breast, renal, and prostate cancers as compared to ethanol and aqueous extracts. Specifically, HMME exerted cytotoxic effect against the MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines with IC50 values of 8.75 and 7.25 μg/mL, respectively. Mechanistically, DAPI staining and flow cytometric analysis revealed that HMME induces apoptosis via the death receptor, FAS, but not the mitochondrial pathway. Moreover, ASK1 and p38 were rapidly activated in response to HMME, and knockdown of ASK1 by a small interference of RNA specific to Ask1 attenuated p38 and caspase-3 activation and suppressed apoptosis, implying that HMME-induced apoptosis relies on the ASK1-p38-caspase-3 pathway. Furthermore, we confirmed that cellular ROS generation was a critical mediator in HMME-induced apoptosis because the ROS- scavenger N-acetyl cysteine significantly decreased the phosphorylation of ASK1 and HMME-induced apoptosis. Our results confirmed HMME cytotoxic effects in TNBCs via ROS-dependent activation of the Fas/FasL-ASK1-p38 axis.
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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.