Publications by authors named "Noura El-Husseiny"

4 Publications

  • Page 1 of 1

IL-8 secreted by tumor associated macrophages contribute to lapatinib resistance in HER2-positive locally advanced breast cancer via activation of Src/STAT3/ERK1/2-mediated EGFR signaling.

Biochim Biophys Acta Mol Cell Res 2021 May 2;1868(6):118995. Epub 2021 Mar 2.

Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt; Director of Biotechnology program, Faculty of Science, Galala University, 43511 Suez, Egypt. Electronic address:

Locally advanced breast cancer (LABC) is an aggressive disease characterized by late clinical presentation, large tumor size, treatment resistance and low survival rate. Expression of EGFR/HER2 and activation of intracellular tyrosine kinase domains in LABC are associated with poor prognosis. Thus, target therapies such as the anti-receptor tyrosine kinases lapatinib drug have been more developed in the past decade. The response to lapatinib involves the inhibition of RTKs and subsequently signaling molecules such as Src/STAT3/Erk1/2 known also to be activated by the cytokines in the tumor microenvironment (TME). The aim of the present study is to identify the major cytokine that might contribute to lapatinib resistance in EGFR+/HER2+ LABC patients. Indeed, tumor associated macrophages (TAMs) are the main source of cytokines in the TME. Herein, we isolated TAMs from LABC during modified radical mastectomy (MRM). Cytokine profile of TAMs revealed that IL-8 is the most prominent highly secreted cytokine by TAMs of LABC patients. Using in-vitro cell culture model we showed that recombinant IL-8 (50 and 100 ng/mL) at different time intervals interfere with lapatinib action via activation of Src/EGFR and signaling molecules known to be inhibited during treatment. We proposed that to improve LABC patients' response to lapatinib treatment it is preferred to use combined therapy that neutralize or block the action of IL-8.
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http://dx.doi.org/10.1016/j.bbamcr.2021.118995DOI Listing
May 2021

Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-β-catenin signalling, the stem cell phenotype and disease progression.

J Adv Res 2019 Mar 8;16:75-86. Epub 2018 Dec 8.

Department of Zoology, Faculty of Science, Cairo University, Cairo University, Giza 12613, Egypt.

The aim of the present study was to evaluate the expression levels of the aryl hydrocarbon receptor (AHR) and its target gene and to correlate their expression with Wnt5a/b-β-catenin, the CD44/CD24 cancer stem cell (CSC) subset and factors associated with poor prognosis in inflammatory breast cancer (IBC) and non-IBC patients. The methods of analysis used were quantitative real-time PCR, western blotting, immunohistochemistry and flow cytometry. Compared to non-IBC tissues, IBC tissues exhibited the overexpression of AHR and its target gene/protein CYP1B1. and mRNA levels were associated with the poor clinical prognosis markers tumour grade, lymphovascular invasion, cell proliferation and lymph node metastasis. Furthermore, AHR expression correlated with the expression of Wnt5a/b and β-catenin signalling molecules, and mRNA expression was downregulated in the SUM149 human IBC cell line and the MDA-MB-231 non-IBC cell line upon inhibition of AHR. gene knockout (CRISPR-Cas9) inhibits and expression in the IBC cell line. The CD44/CD24 subset was significantly correlated with the expression of AHR, CYP1B1, Wnt5a/b and β-catenin in IBC tissues. The overexpression of AHR and its target CYP1B1 correlated with the expression of Wnt5a/b and β-catenin, CSCs, and poor clinical prognostic factors of IBC. Thus, targeting AHR and/or its downstream target molecules CYP1B1 and Wnt5a/b may represent a therapeutic approach for IBC.
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http://dx.doi.org/10.1016/j.jare.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413307PMC
March 2019

Anti-proliferative effect of chitosan nanoparticles (extracted from crayfish Procambarus clarkii, Crustacea: Cambaridae) against MDA-MB-231 and SK-BR-3 human breast cancer cell lines.

Int J Biol Macromol 2019 Apr 17;126:478-487. Epub 2018 Dec 17.

Cancer Cell Biology, Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.

Actually, the most common cancer in women is the breast cancer which is the second most widespread cancer overall. In 2018, there were over two million new cases of women breast cancer. Particularly, we tried to extract chitosan from crayfish Procambarus clarkii, Crustacea: Cambaridae, by N-deacetylation of chitin. The chemical structure of chitosan was characterized by Fourier transform infrared (FT-IR) spectroscopy. Also DDA was calculated from FT-IR and ultraviolet spectrophotometry data. Chitosan nanoparticles were prepared using a ball-milling technique. The as-prepared chitosan nanoparticles were characterized by transmission electron microscopy, dynamic light scattering as well as zeta potential. The cytotoxicity of chitosan and its nanoparticles (50 and 100 μg/mL) against human breast cancer (SK BR3 and MDA-MB-231 cell lines) was evaluated. MTT assay asserts the significant inhibitory action of both chitosan and its nanoparticles on the proliferation of human breast cancer cells in vitro. Chitosan nanoparticles had more anti-proliferative effects on MDA-MB-231 and SK-BR-3 cell lines than its corresponding chitosan. Although, chitosan nanoparticles, that has higher DDA, had a higher cytotoxic activity against human breast cancer MDA-MB-231 and SK-BR-3 cell lines in vitro. Eventually, chitosan and its nanoparticles can be considered as a promising natural compounds in human breast cancer treatment.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.12.151DOI Listing
April 2019

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages.

Curr Probl Cancer 2018 Mar - Apr;42(2):215-230. Epub 2018 Jan 10.

Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Breast-Gynecological International Cancer Society, Cairo, Egypt. Electronic address:

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 non-IBC and IBC patients. Furthermore, to investigate whether IL-10 modulates the expression of CPB2 and THBD in vivo and in-vitro. 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. In addition, 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. Our results 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. In 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.
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http://dx.doi.org/10.1016/j.currproblcancer.2018.01.009DOI Listing
April 2019