الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer (BC) is the most common cancer and the leading cause of death in
females worldwide.
The tumor microenvironment (TME) is now recognized as an important factor in tumor
development and progression, as well as a measurable parameter of treatment response.
In TME, IL-6 that is essential for tumor cell proliferation and differentiation released by
cancerous cells as well as other stromal cells. The elevated levels of this cytokine is typically
associated with a poor prognosis and lower survival in breast cancer patients.
The current study aimed at investigating the autophagic activities and level of cancer
stem cells in breast cancer tumor microenvironment supplemented with anti-IL-6 monoclonal
antibodies. This study was designed to investigate the immunotherapeutic effect of
neutralizing the overexpressed IL-6 secreted within the breast cancer TME.
The study was conducted on 20 patients with pathologically proved breast carcinoma
who endue at modified radical mastectomy for histologically proved breast cancer from the
department of experimental and clinical Surgery, Medical Research Institute, Alexandria
University. Fresh sterile tissue from primary breast tumor as well as normal breast tissue
from the same excised breast were obtained as surgical specimens from each patient
immediately after surgical resection. Each tissue sample was cultured without and with
appropriate concentration of anti-IL-6 mAb. Paraffin embedded cultured breast tumor and
normal tissues were then evaluated for LC3B levels as a specific marker of autophagy. Levels
of CD44 and CD24 expression were also measured as markers of CSCs in tumor and normal
breast tissue samples using immunofluorescence technique.
Results: The levels of autophagy as well as both CD44 and CD24 in our own designed
breast tumor tissue culture system are significantly higher than that of the corresponding
breast normal ones. These levels significantly decreased by neutralizing the IL-6 activities
using anti-IL-6 mAbs.
No significant correlations were found between CD44 and CD24 levels in all tissue
culture systems except in the anti-IL-6 mAb treated tumor / normal one. While negative
correlations between CD44 and CD24 levels in the anti-IL-6 mAb supplemented tissue
culture systems may be due to shift in the dynamic equilibrium between CSCs and NSCCs
No significant correlations were found between the autophagy level and either CD44 or
CD24 levels in almost all tissue culture systems except the anti-IL-6 mAb tumor tissue culture ones.
Accordingly, neutralization of IL-6 within breast cancer TME may represent a potential
promising immunotherapeutic strategy of the disease through reduction of both autophagic
activity and stemness of the tumor tissue.