👤 Zaynab El-Gammal

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for this type of cancer may be by putting these malignant cells into dormancy. The oocyte's embryonic milieu presents a unique tumor reversion microenvironment by inducing growth arrest and changing cells' phenotypes. We conducted an in-silico study to determine the most likely oocyte extract (OE) proteins involved in inducing dormancy using HDock, CluPro, and molecular dynamic (MD) simulation. Results showed low energy scores for complexes between OE proteins and four surface markers: K1C14, CLD3, CLD4, and ITA6. Apolipoprotein A1 (APOA1) and Apolipoprotein C3 (APOC3) showed the highest stability and affinity with these four surface markers: K1C14, CLD3, CLD4, and ITA6. These proteins are involved in key tumor-related pathways such as angiogenesis, proliferation, apoptosis, and migration. This will pave the way for exploring novel therapeutic options to induce dormancy in TNBC cells. Show less

Early childhood obesity is a real public health problem worldwide. Identifying the etiologies, especially treatable and preventable causes, can direct health professionals toward proper management. Measurement of serum leptin levels is helpful in the diagnosis of congenital leptin and leptin receptor deficiencies which are considered important rare causes of early childhood obesity. The main aim of this study was to investigate the frequency of LEP, LEPR, and MC4R gene variants among a cohort of Egyptian patients with severe early onset obesity. The current cross-sectional study included 30 children who developed obesity during the first year of life with BMI > 2SD (for age and sex). The studied patients were subjected to full medical history taking, anthropometric measurements, serum leptin and insulin assays, and genetic testing of LEP, LEPR and MC4R. Disease causing variants in LEP and LEPR were identified in 10/30 patients with a detection rate of 30%. Eight different homozygous variants (two pathogenic, three likely pathogenic, and three variants of uncertain significant) were identified in the two genes, including six previously unreported LEPR variants. Of them, a new frameshift variant in LEPR gene (c.1045delT, p.S349Lfs*22) was recurrent in two unrelated families and seems to have a founder effect in our population. In conclusion, we reported ten new patients with leptin and leptin receptor deficiencies and identified six novel LEPR variants expanding the mutational spectrum of this rare disorder. Furthermore, the diagnosis of these patients helped us in genetic counseling and patients' managements specially with the availability of drugs for LEP and LEPR deficiencies. Show less