Cytogenetic profile of adult acute myeloid leukemia in Egypt: a single-center experience.

BACKGROUND: Acute myeloid leukemia (AML) is a diverse disease characterized by the expansion of blasts of myeloid lineage. Cytogenetic testing is the cornerstone for risk stratification of AML patients. Geographical and environmental factors may play a very important role in the development of leukemia and several differences in genetic profile may be seen among different ethnicities. In our study, we evaluated cytogenetic findings of adult AML patients in South Egypt. METHODS: Cytogenetic testing (karyotyping and M-FISH) was performed for 120 adult patients with AML. Twenty metaphases were analyzed for each patient. RESULTS: In our study, the median age of AML patients was 36.5 years, with an age range between 18 and 86 years. 56.7% of patients had normal karyotypes and 43.3% of patients had clonal cytogenetic abnormalities. t (15;17) was the most detected structural abnormality, and + 8 was the most detected numerical abnormality. Regarding cytogenetic risk stratification, 65% of patients were in the intermediate-risk category. CONCLUSION: The cytogenetic profile of AML patients in our locality showed some differences and some similarities with cytogenetic profiles in different Arab, Asian and Western countries. Further studies are needed using advanced techniques such as next-generation sequencing and optical genome mapping to elucidate more ethnic and geographic genetic heterogeneity among different countries.

sVCAM-1, and TGFß1 in chronic phase, chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

The outcome for chronic phase (CP) chronic myelogenous leukemia (CML) patients has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. We examined the characteristics of CML patients during TKI therapy by determining the plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), and transforming growth factor (TGFß1) biomarkers. The plasma levels of sVCAM-1 and TGFß1 were measured by ELISA at baseline and after 3 months of TKI treatment. The levels of sVCAM-1, and TGFß1 were significantly elevated in patients with CML (P< 0.01). Dasatinib treatment was associated with a significant reduction in the levels of these biomarkers (P< 0.01). In conclusion, plasma levels of sVCAM-1 and TGFß1 could have a role in the pathogenesis of CML and may be used as predictors of hematological and molecular responses to TKIs. A favorable outcome for Dasatinib therapy was observed.

Combinatorial Therapy of Letrozole- and Quercetin-Loaded Spanlastics for Enhanced Cytotoxicity against MCF-7 Breast Cancer Cells.

Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor-positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators-Tween 80, Brij 35, and Cremophor RH40-with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129-310 nm and 240-560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3-97.2% and 97.9-99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.