Browsing by Author "Abdelaziz Ibrahim, Sherif"

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Adipocyte of Obese Breast Cancer Patients Is Characterized by The Overexpression of Caveolin-1 Protein/Mediator the Main Constituent of the Plasma Membrane Vesicles Caveolae That Contain Proteins Contribute to Breast Cancer Progression
(Egyptian Society of Biological Sciences, 2019) Saber, Aya; Abdelaziz Ibrahim, Sherif; Hosney, Mohamed; Taha Mohamed, Hossam; Fares, Mohamed; Sabet, Salwa; El-Shinawi, Mohamed; Mostafa Mohamed, Mona
Breast cancer (BC) is the second leading mortality cause due to poor survival rates compared to lung cancer all over the world. Recently, lifestyle increased obesity among the population globally. Since, the adipose tissues (AT) are the major contributor to the volume of the breast and adipocytes cells, which constitute AT are one of the major prominent cells play an effective role in cancer progression via releasing different mediators and adipokines. Thus, AT may display a crucial role in BC progression, especially in obese patients compared to non-obese patients, which characterized by increased AT. Interestingly, adipocytes are characterized by expressing caveolin-1 (Cav-1) protein. Cav-1 constitutes the lipid raft of caveola which contains different proteolytic enzymes inducing cancer metastasis. In this regard, the aim of the present study was to explore the level of expression of Cav-1 protein in the tissue specimen of 5 non-obese vs. 15 obese patients using immunohistochemistry (IHC) and immunoblotting techniques. Our finding demonstrates that the level of Cav-1expression was statistically significantly low in non-obese compared to obese BC patients (p < 0.05). Herein, our results revealed that the highest expression of Cav-1 in obese patients compared to non-obese (control) patients can be considered as a biomarker for BC patients.
Characterization of inflammatory breast cancer: a vibrational microspectroscopy and imaging approach at the cellular and tissue level
(Royal Society of Chemistry, 2018) Taha Mohamed, Hossam; Untereiner, Valérie; Proult, Isabelle; Abdelaziz Ibrahim, Sherif; Götte, Martin; El-Shinawi, Mohamed; Mostafa Mohamed, Mona; D. Sockalingum, Ganesh; Brézillon, Stéphane
Inflammatory breast cancer (IBC) has a poor prognosis because of the lack of specific biomarkers and its late diagnosis. An accurate and rapid diagnosis implemented early enough can significantly improve the disease outcome. Vibrational spectroscopy has proven to be useful for cell and tissue characterization based on the intrinsic molecular information. Here, we have applied infrared and Raman microspectroscopy and imaging to differentiate between non-IBC and IBC at both cell and tissue levels. Two human breast cancer cell lines (MDA-MB-231 and SUM-149), 20 breast cancer patients (10 non-IBC and 10 IBC), and 4 healthy volunteer biopsies were investigated. Fixed cells and tissues were analyzed by FTIR microspectroscopy and imaging, while live cells were studied by Raman microspectroscopy. Spectra were analyzed by hierarchical cluster analysis (HCA) and images by common k-means clustering algorithms. For both cell suspensions and single cells, FTIR spectroscopy showed sufficient high inter-group variability to delineate MDA-MB-231 and SUM-149 cell lines. Most significant differences were observed in the spectral regions of 1096–1108 and 1672–1692 cm−1. Analysis of live cells by Raman microspectroscopy gave also a good discrimination of these cell types. The most discriminant regions were 688–992, 1019–1114, 1217–1375 and 1516–1625 cm−1. Finally, k-means cluster analysis of FTIR images allowed delineating non-IBC from IBC tissues. This study demonstrates the potential of vibrational spectroscopy and imaging to discriminate between non-IBC and IBC at both cell and tissue levels.
IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: the potential role of tumor infiltrated macrophages
(Mosby, 2018) Taha Mohamed, Hossam; El-Husseiny, Noura; A. El-Ghonaimy, Eslam; Abdelaziz Ibrahim, Sherif; A. Bazzi, Zainab; Cavallo-Medved, Dora; B. Boffa, Michael; El-Shinawi, Mohamed; Mostafa Mohamed, Mona
Background: Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM), encoded by THBD, is important for TAFI activation. CPB2 gene expression is influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10). Our previous results showed that tumor infiltrating monocytes/macrophages (CD14+ /CD16+ ) isolated from inflammatory breast cancer (IBC) patients’ secrete high levels of IL-10. The aim of the present study is to test genetic polymorphism and expression of CPB2 in healthy breast tissues and carcinoma tissues of 2 non-IBC and IBC patients. Furthermore, to investigate whether IL-10 modulates the expression of CPB2 and THBD in vivo and in-vitro. Materials and methods We tested CPB2 Thr325Ile polymorphism using restriction fragment length polymorphism, (RFLP) technique in healthy and carcinoma breast tissues. The mRNA expression of CPB2, THBD and IL10 were assessed by RT-qPCR. Infiltration of CD14+ cells was assessed by immunohistochemistry. We investigated the correlation between infiltration of CD14+ cells and expression of IL10 and CPB2. Furthermore, we correlated IL10 expression with the expression of both CPB2 and THBD in breast carcinoma tissues. Finally, we validated the role of recombinant IL-10 in regulating the expression of CPB2 and THBD using different breast cancer cell lines. Results: Our data showed that CPB2 genotypes carrying the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were more frequent in both IBC and non-IBC patients compared to control group. CPB2 genotypes did not show any statistical correlation with CPB2 mRNA expression levels or patients’ clinical pathological properties. Interestingly, CPB2 and IL10 expression were significantly higher and positively correlated with the incidence of CD14+ cells in carcinoma tissues of IBC as compared to non-IBC. On the other hand, THBD expression was significantly lower in IBC carcinoma versus non-IBC tissues. Based on molecular subtypes, CPB2 and IL10 expression were significantly higher in triple negative (TN) as compared to hormonal positive (HP) carcinoma tissues of IBC. Moreover, CPB2 expression was positively correlated with presence of lymphovascular invasion and the expression of IL10 in carcinoma tissues of IBC patients. Furthermore, recombinant human IL-10 stimulated CPB2 expression in SUM-149 (IBC cell line) but not in MDA-MB-231 (non-IBC cell line), while there was no significant effect THBD expression. 3 Conclusion: Carcinoma tissues of IBC patients are characterized by higher expression of CPB2 and lower expression of THBD. Moreover, CPB2 positively correlates with IL10 mRNA expression, incidence of CD14+ cells and lymphovascular invasion in IBC patients. IL-10 stimulated CPB2 expression in TN-IBC cell line suggests a relevant role of CPB2 in the aggressive phenotype of IBC.
Incidence of Human Cytomegalovirus in Breast Carcinoma Tissues is Associated with A Higher Expression of Growth Factor Receptor-Bound Protein 2
(The Egyptian Journal of Hospital Medicine, 2019) Fares, Mohamed; Taha Mohamed, Hossam; Abdelaziz Ibrahim, Sherif; Hosney, Mohamed; I. Rady, Mohamed; El-Shinawi, Mohamed; Mostafa Mohamed, Mona
Background: female mammary carcinoma is the second most common cancer incidence among women and the fifth most common leading cause of cancer death worldwide. Premenopausal young women are more frequently targeted by inflammatory breast cancer (IBC), which is the most lethal form of breast cancer. The human cytomegalovirus (HCMV) has been identified as one of the viral infection with a higher frequency in carcinoma tissues of IBC than in non-IBC. The adaptor protein growth factor receptor-bound protein 2 (Grb2), was found to be upregulated in HCMV-infected cells and play as crucial role in cancer progression. Objective: this study aimed to assess the expression level of Grb2 in carcinoma tissues of IBC and non-IBC with HCMV infection. Patients and Methods: overall, 135 female diagnosed with breast carcinoma were enrolled in this study. Using conventional and real time polymerase chain reaction (PCR), we determined the incidence of HCMV and assessed the expression level of Grb2 mRNA in the breast cancer tissue samples. Results: Grb2 mRNA was significantly upregulated in HCMV+ IBC higher than in HCMV+ non-IBC. According to the molecular subtype, Grb2 mRNA was significantly higher upregulated in breast carcinoma tissues of HCMV+ hormonal positive (HP) than in triple negative (TN) counterparts. Conclusion: HCMV infection is associated with a high expression of Grb2 mRNA in IBC and that HP HCMV+ mammary carcinoma tissues confer upregulated Grb2 mRNA, suggesting a potential role of HCMV infection in enhancing of Grb2 mRNA expression in breast cancer with HP.
Inflammatory breast cancer: Mixed viral infections within carcinoma tissues and the expression of Ki-67 proliferation marker.
(American Society of Clinical Oncology, 2017) taha Mohamed, Hossam; Hesham Abdel Fattah, Hadeer; El-Shinawi, Mohamed; Abdelaziz Ibrahim, Sherif; S. El-Halawany, Medhat; El Ghazaly, Hesham; Schneider, Robert; Mohamed, Mona
Background: Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. Our previous results showed that IBC carcinoma tissues possess mixed human cytomegalovirus genotypes than non-IBC carcinoma tissues. However, the role of viral infection in breast cancer is poorly understood. Methods: We enrolled 135 women diagnosed breast cancer (91 Non-IBC and 44 IBC). The incidence of different viral DNA (Herpes viruses and HPV) was performed using nested and multiplex PCR and DNA sequencing. The expression of Ki-67 proliferation index was assessed by immunohistochemistry. Results: DNA of HCMV and HPV-16 were the most detected in breast tissues of both IBC and non-IBC patients. However, as a single infection the incidence of HCMV-DNA and HHV-8 DNA were significantly higher in carcinoma tissues of IBC in comparison with non-IBC (p = 0.035, p= 0.039, respectively). Moreover, the prevalence of mixed infection of different viral DNA was higher in IBC than non-IBC carcinoma tissues (P= 0.003). HCMV and HPV-16 were the dominant mixed infection in both non-IBC and IBC tissues. Interestingly, although no significant difference in expression of Ki67 has been detected in tissues of IBC and non-IBC, we found that Ki-67 was significantly higher in mixed than single viral infected tissues of both non-IBC and IBC (p = 0.04 and p = 0.03 respectively). Conclusions: The incidence of mixed viral DNA detected in carcinoma tissues of IBC is higher than non-IBC. Moreover, mixed viral DNA is positively correlated with upregulation of Ki67 expression in breast carcinoma tissues.
Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways
(BioMed Central, 2017) Abdelaziz Ibrahim, Sherif; Gadalla, Ramy; A. El-Ghonaimy, Eslam; Samir, Omnia; Taha Mohamed, Hossam; Hassan, Hebatallah; Greve, Burkhard; El-Shinawi, Mohamed; Mostafa Mohamed, Mona; Götte, Martin
Background Inflammatory breast cancer (IBC), a particularly aggressive form of breast cancer, is characterized by cancer stem cell (CSC) phenotype. Due to a lack of targeted therapies, the identification of molecular markers of IBC is of major importance. The heparan sulfate proteoglycan Syndecan-1 acts as a coreceptor for growth factors and chemokines, modulating inflammation, tumor progression, and cancer stemness, thus it may emerge as a molecular marker for IBC. Methods We characterized expression of Syndecan-1 and the CSC marker CD44, Notch-1 & -3 and EGFR in carcinoma tissues of triple negative IBC (n = 13) and non-IBC (n = 17) patients using qPCR and immunohistochemistry. Impact of siRNA-mediated Syndecan-1 knockdown on the CSC phenotype of the human triple negative IBC cell line SUM-149 and HER-2-overexpressing non-IBC SKBR3 cells employing qPCR, flow cytometry, Western blotting, secretome profiling and Notch pharmacological inhibition experiments. Data were statistically analyzed using Student’s t-test/Mann-Whitney U-test or one-way ANOVA followed by Tukey’s multiple comparison tests. Results Our data indicate upregulation and a significant positive correlation of Syndecan-1 with CD44 protein, and Notch-1 & -3 and EGFR mRNA in IBC vs non-IBC. ALDH1 activity and the CD44(+)CD24(-/low) subset as readout of a CSC phenotype were reduced upon Syndecan-1 knockdown. Functionally, Syndecan-1 silencing significantly reduced 3D spheroid and colony formation. Intriguingly, qPCR results indicate downregulation of the IL-6, IL-8, CCL20, gp130 and EGFR mRNA upon Syndecan-1 suppression in both cell lines. Moreover, Syndecan-1 silencing significantly downregulated Notch-1, -3, -4 and Hey-1 in SUM-149 cells, and downregulated only Notch-3 and Gli-1 mRNA in SKBR3 cells. Secretome profiling unveiled reduced IL-6, IL-8, GRO-alpha and GRO a/b/g cytokines in conditioned media of Syndecan-1 knockdown SUM-149 cells compared to controls. The constitutively activated STAT3 and NFκB, and expression of gp130, Notch-1 & -2, and EGFR proteins were suppressed upon Syndecan-1 ablation. Mechanistically, gamma-secretase inhibition experiments suggested that Syndecan-1 may regulate the expression of IL-6, IL-8, gp130, Hey-1, EGFR and p-Akt via Notch signaling. Conclusions Syndecan-1 acts as a novel tissue biomarker and a modulator of CSC phenotype of triple negative IBC via the IL-6/STAT3, Notch and EGFR signaling pathways, thus emerging as a promising therapeutic target for IBC.