Studying ferroptosis and iron metabolism pre- and post-radiotherapy treatment in breast cancer patients.

BACKGROUND: Radiotherapy (RT) is an important part of the treatment of many tumors. Radiotherapy causes oxidative damage in all cellular compartments, including lipid membrane, on a random basis. Toxic lipid peroxidation accumulation has only lately been linked to a regulated type of cell death known as ferroptosis. Iron is required for ferroptosis sensitization in cells. AIM OF THE WORK: This work aimed to study ferroptosis and iron metabolism before and after RT in BC patients. SUBJECTS AND METHODS: Eighty participants were included divided into two main groups: group I: 40 BC patients treated with RT. Group II: 40 healthy volunteers' age and sex matched as control group. Venous blood samples were collected from BC patients (prior to and after RT) and healthy controls. Glutathione (GSH), malondialdehyde (MDA), serum iron levels and % of transferrin saturation were measured by colorimetric technique. Ferritin, ferroportin, and prostaglandin-endoperoxide synthase 2 (PTGS2) levels were assessed by ELISA. RESULTS: Serum ferroportin, reduced glutathione, and ferritin showed significant decrease after radiotherapy in comparison to before radiotherapy. However, there was significant increase in serum PTGS2, MDA, % of transferrin saturation and iron levels after radiotherapy in comparison to before radiotherapy. CONCLUSION: Radiotherapy induced ferroptosis in breast cancer patients as a new cell death mechanism and PTGS2 is a biomarker of ferroptosis. 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.

Assessment of thyroid gland hormones and ultrasonographic abnormalities in medical staff occupationally exposed to ionizing radiation.

BACKGROUND: Ionizing radiation (IR) is high-energy radiation that has the potential to displace electrons from atoms and break chemical bonds. It has the ability to introduce mutations, DNA strand breakage, and cell death. Being a radiosensitive organ, exposure of the thyroid gland to IR can lead to significant changes in its function. AIM OF THE WORK: Was to measure the levels of thyroid hormones panel and ultrasonography abnormalities in medical staff occupationally exposed to IR. SUBJECTS AND METHODS: A total of 120 subjects were divided into three main groups: Group I: radiation-exposed workers occupationally exposed to radioiodine (131I) (n = 40), Group II: radiation-exposed workers occupationally exposed to X-ray (n = 40), and Group III: non-exposed healthy professionals matched in age and sex with the previous groups (n = 40). Thyroid hormones panel including free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), anti-thyroperoxidase antibodies (anti-TPO), and thyroglobulin (Tg) were measured. Thyroid ultrasonography was performed. Oxidative stress markers such as malondialdehyde (MDA), hydrogen peroxide (H2O2), and total antioxidant capacity (TAC) were measured. RESULTS: Group I had significantly higher fT3 levels than the control group. fT3 levels were considerably higher, while TSH was substantially lower in group II participants than in the control group. Tg was markedly lower in radiation-exposed workers. However, anti-TPO levels in radiation-exposed workers were significantly higher than in the control group. MDA and H2O2 were substantially higher; TAC was significantly lower in radiation-exposed workers compared to the control group. According to ultrasonographic examination, thyroid volume and the percentage of thyroid nodules in all radiation workers were significantly higher than in the control group. CONCLUSION: Despite low exposure doses, occupational exposure to IR affects the thyroid hormones and links with a higher likelihood of developing thyroid immune diseases.

Assessment of Serum Hypoxia Biomarkers Pre- and Post-radiotherapy in Patients with Brain Tumors.

Hypoxia is a prevalent hallmark of many malignant neoplasms. The aim was to assess the serum hypoxia biomarkers HIF-1α, VEGF, osteopontin, erythropoietin, caveolin-1, GLUT-1, and LDH pre- and post-radiotherapy in patients with brain tumors. The study was conducted on 120 subjects were divided into two groups: group I: 40 healthy volunteers as control group. Group II: 80 brain tumor patients were subdivided into glioblastoma subgroup: 40 glioblastoma patients, meningioma subgroup: 40 malignant meningioma patients. Two venous blood samples were collected from every patient prior to and following RT and one sample from controls. Biomarkers were assayed by ELISA. In glioblastoma subgroup, HIF-1α, VEGF, and LDH were significantly increased after RT. On the contrary, these biomarkers were significantly decreased after RT in malignant meningioma subgroup. Osteopontin was significantly increased after RT in both subgroups. Regarding erythropoietin, it was significantly decreased in both subgroups when compared to before RT. Caveolin-1 showed a significant increase in glioblastoma subgroup after RT comparing to before RT. GLUT-1 was significantly increased after RT in both subgroups comparing to before RT. Association of significant elevation of hypoxia biomarkers either pre- or post-RT with aggressive tumor such as glioblastoma indicates that, they are markers of malignancy and may have a role in tumor development and progression.

Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3).

AIM OF WORK: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. MATERIAL AND METHODS: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. RESULTS: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. CONCLUSION: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.