الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
BC is the most frequent cancer among women. It is also the world’s second biggest cause of cancer mortality. According to malignancy statistics 2020, BC accounts for 30% of all female malignancies, with 276,480 new BC and over 42,000 mortality expected in 2020. In Egypt, it accounts for 33% of all female cancer cases, with over 22,000 new cases identified each year. Many cancers are treated with radiotherapy, but radio resistance is still a major factor in radiotherapy failure. Radiotherapy causes oxidative damage in all cellular compartments, including the lipid membrane, on a random basis. Toxic lipid peroxidation accumulation has only lately been linked to the direct cause of ferroptosis, a controlled form of cell death. In cancer cells, IR causes ferroptosis and increased overall ROS levels in cancer cells The buildup of lipid peroxidation is a characteristic of ferroptosis. Free radicals induce lipid peroxidation, which mostly affects UFA in the cell membrane. Initial LOOHs and subsequent reactive aldehydes (e.g., malondialdehyde (MDA)) are the results of lipid peroxidation, and they increase during ferroptosis.
The objective of this study was to study ferroptosis and iron metabolism before and after RT in BC patients.
This research included 70 subjects divided into two main groups: group I: 40 BC patients a treated with RT. group II: The control group consisted of 30 healthy volunteers who were age and sex matched. BC patients were treated with RT, The dose given was a 2 Gray daily irradiation dose, for five weeks, five days a week, 50 Gy total dose. Patients were selected from those admitted to Bahia hospital, Cairo, Egypt.
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Serum was separated and Glutathione, lipid peroxidation biomarker malondialdehyde (MDA) and serum iron levels were measured using commercially available local diagnostic kits. % of transferrin saturation, Ferritin, Ferroportin and PTGS2 levels were assessed by using ELISA test.
Our results showed that:
Statistically significant decrease in serum Ferroportin in BC patients after RT when compared to before radiotherapy and statistically significant difference between BC patients before and after RT treatment when compared to control group.
Statistically significant increase in serum PTGS2 in BC patients after RT when compared to before RT and statistically significant difference between BC patients before and after RT treatment when compared to control group.
Statistically significant increase in MDA levels in BC patients after irradiation when compared to before RT and statistically significant difference between BC patients before and after RT treatment when compared to control group.
Statistically significant decrease in reduced Glutathione in BC patients after irradiation when compared to before RT and statistically significant difference between BC patients before and after RT treatment when compared to control group.
Statistically significant increase in serum Iron in BC patients after RT treatment when compared to before RT.
Statistically significant decrease in Ferritin in BC patients after RT treatment when compared to before RT and statistically significant difference between BC patients before and after RT when compared to control group.
Statistically significant increase in percentage of transferrin saturation in BC patients after irradiation when compared to before RT.
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6.2. Conclusion
The present study investigated ferroptosis and iron metabolic markers in BC patients receiving RT.
The following our conclusions:
- Radiotherapy induced ferroptosis in breast cancer patients as a new cell death mechanism.
- PTGS2 is a biomarker of ferroptosis.
- Serum PTGS2, MDA, % of Transferrin saturation and Iron levels significantly increased post irradiation highlighting enhanced ROS and ferroptosis induction.
- Serum ferroportin, reduced glutathione and serum ferritin significantly declined after irradiation.
- Ferroptosis could be targeted in the therapy of BC patients.
6.3. Recommendations
from the above findings, we may recommend the following:
- Iron profile should be done to patients before and after irradiation.
- PTGS2, MDA and glutathione measuring should be included in the work-up of patients subjected to radiotherapy prior to and after termination of the sessions being a marker of radiotherapy efficacy.
- Iron modulation is a useful approach for the treatment of BC especially if combined with targeted therapy and immune based therapy.
- Further studies are warranted to be translated into clinical compounds.