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.

Levels of Serum Ferritin and Hepcidin in Patients with Uncomplicated Falciparum Malaria in Hodeidah, Yemen: Considerations for Assessing Iron Status.

Understanding the key regulator of iron homeostasis is critical to the improvement of iron supplementation practices in malaria-endemic areas. This study aimed to determine iron indices and hepcidin (HEPC) level in patients infected with Plasmodium falciparum compared to apparently healthy, malaria-negative subjects in Hodeidah, Yemen. The study included 70 Plasmodium falciparum-infected and 20 malaria-negative adults. Blood films were examined for detection and estimation of parasitemia. Hemoglobin (Hb) level was measured using an automated hematology analyzer. Serum iron and total iron binding capacity (TIBC) were determined by spectrophotometric methods. Levels of serum ferritin (FER) and HEPC were measured by enzyme-linked immunosorbent assays. Data were stratified by sex and age. Comparable Hb levels were found in P. falciparum-infected patients and malaria-negative subjects in each sex and age group (p > 0.05). Compared to their malaria-negative counterparts, disturbed iron homeostasis in patients was evidenced by the significantly lower serum iron levels in females (p = 0.007) and those aged <25 years (p = 0.02) and the significantly higher TIBC in males (p = 0.008). Levels of serum FER and HEPC were significantly elevated in P. falciparum-infected patients compared to the corresponding malaria-negative participants (p < 0.001). Serum FER correlated positively with parasite density (p = 0.004). In conclusion, patients with uncomplicated P. falciparum in Hodeidah display elevated levels of serum HEPC and FER. Hemoglobin level may not reflect the disturbed iron homeostasis in these patients. The combined measurement of iron indices and HEPC provides comprehensive information on the iron status so that the right intervention can be chosen.

Study the relationship of endothelial damage / dysfunction due to occupational exposure to low dose ionizing radiation versus high dose exposure during radiotherapy.

BACKGROUND: Vascular injuries caused by irradiation include acute vasculitis with neutrophil invasion, endothelial cell (EC) swelling, capillary loss, and activation of coagulator mechanisms, along with local ischemia and fibrosis. The circulating endothelial cells (CECs), increase dramatically in diseases with vascular damage. AIM: The aim of this study is to provide data on the endothelial dysfunction due to occupational exposure to low dose ionizing radiation versus high dose exposure during radiotherapy (RT). PATIENTS AND METHODS: This study included 100 subjects divided into three main groups: Group I: High dose exposure group: 50 breast cancer patients treated with post-operative radiotherapy. Group II: Low dose exposure group: 25 hospital radiation workers. Group III: 25 healthy volunteers' age and sex matched as control group who had never worked in radiation-related jobs. TM levels measured by enzyme linked immunosorbent assay (ELISA). Circulating endothelial cells (CEC) enumerated in peripheral blood by flow cytometric analysis of their signature receptor CD146. RESULTS: % CD146+ cells and plasma TM were significantly increased in radiation workers and after exposure to radiotherapy treatment in breast cancer patients. When comparing patients group with radiation workers group, we found significant elevation in plasma TM in radiation workers while insignificant difference was found in % CD146+ cells. CONCLUSION: CECs and plasma TM both are increased in radiation workers and patients treated with radiotherapy. They may constitute valuable markers of endothelial injury. Workers exposed to low doses of ionizing radiation may develop significant endothelial dysfunction predisposes them to cardiovascular complications namely thrombosis, mostly due to oxidative stress among other causes.

ß-Globin Mutations in Egyptian Patients With ß-Thalassemia.

ß-thalassemia is a common hereditary disorder, particularly in Middle Eastern countries. More than 200 mutations in the ß globin gene have been reported; most are point mutations in functionally important regions (HBB; OMIM #141900)). The spectrum of mutations varies significantly between different geographical regions; only a few common mutations of ß-globin cause ß-thalassemia in each population. The aim of this study was to determine the spectrum of mutations that cause ß-thalassemia in the North Coast of Egypt and to investigate their correlation with the phenotypic severity of ß-thalassemia. We carried out our study with a total of 47 Egyptian patients (25 male and 22 female) confirmed to have ß-thalassemia. Evaluation of ß-thalassemia mutations revealed the presence of 10 ß-globin mutations. The most frequently encountered mutations were intronic: IVS 1.6 [T>C] (27.66%) and IVS 1.110 [G>A] (22.35%), followed by IVS 2.848 [C>A], IVS 1.1 (G>A), and IVS 2.745 [C>G]. We observed the exonic and promoter mutations less frequently. A homozygous mutation was found in 24 patients (51%) and compound heterozygous mutations were found in 13 patients (28%). However, in 9 patients (19%), we identified only 1 mutation. In 1 patient (2%), we detected no mutation. The detection rate of the method that we used in our population was 88% (83 of the tested 94 alleles). The results we obtained did not reveal any correlation between genotype and phenotype among patients with ß-thalassemia.

Fungal Infection among Patients with Some Hematopoietic Disorders.

With the increasing number of immune compromised patients suffering from hematological disorders, invasive fungal infections have emerged as a major cause of morbidity and mortality among these patients. This study evaluated the use of conventional blood culture and PCR techniques in the isolation and identification of fungi from patients with different hematopoietic disorders. Ninety blood samples were tested by both techniques, conventional blood culture detected fungal infections in only five (5.6%) samples, which were further identified to be of Candida spp. While PCR technique detected fungal infections in 56 (62.2%) samples, which were further subjected to nested PCR technique giving final identification of Candida spp. infections in 36 (40%) samples and Aspergillus spp. in 16 (17.8) samples. The sensitivity of PCR technique was 100% and the specificity ranged from 40% to 100%. Thus, the use of nested PCR technique was an efficient and sensitive method for detection of invasive fungal infections among patients with hematopoietic disorders.