Triple-negative breast cancer (TNBC) subtype is one of the most aggressive tumors with no definite receptor and so with a limited number of effective chemotherapeutics. Doxorubicin (Dox) is the first-line...

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CD40 plays a substantial role in inflammation and has been linked to pathogenic processes of chronic inflammatory diseases such as asthma as well as chronic obstructive pulmonary disease (COPD). Aim:The study was to investigate the association of CD40 gene (-1C/T) single nucleotide polymorphism (SNP) with the susceptibility to asthma and COPD in the Egyptian population, and its functional effect on the expression of CD40. Methods:We analyzed -1C/T SNP of the CD40 gene in 40 patients with COPD, 50 patients with asthma, and 60 normal subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CD40 expression was measured using flow cytometry. Immunoglobulin E was also determined in asthmatics. Results:The CT genotype was prevailing in the COPD patients and control group, while in the asthmatics it was the CC. Independent of the smoking status; being CC homozygous still conferred a 4-fold increase in the risk of asthma and a 2.5-fold increase in the risk of COPD. Carrying T allele showed a significantly lower risk for asthma. Furthermore, in both asthma and COPD, the least expression of CD40 protein was found with the TT genotype, which seems to have a protective effect. Despite the significant upregulation of total serum IgE in asthmatics it was not significantly associated with CD40 genotyping or the protein expression. Conclusion:Our study demonstrated that CD40 − 1C/T polymorphism significantly contribute to the susceptibility to asthma and COPD in the Egyptian population. Reduced CD40 expression with the TT genotypes might imply that the − 1C/T polymorphism is linked to inflammation in addition to the initiation and development of both. The genetic predisposition to certain pathways may further help to define the development of either asthma or COPD. This may lead to stratification of patients by their genetic make-up and open new therapeutic prospects.

Background: Given the potential adverse effects of asthma and Chronic Obstructive Pulmonary Disease (COPD), this study was undertaken to explore Alpha-1 Antitrypsin (AAT) polymorphism in the Egyptian population and its role in the development and/ or progression of asthma and COPD. The identification of IL-10 as a potential modifier gene for COPD susceptibility provided insight into additional inflammatory pathways to consider in AAT deficiency. Methods: This study was carried on 90 unrelated Egyptians; 37 asthmatics, 33 COPD patients and 20 controls. Patients were evaluated clinically and with spirometry. The frequency of AAT gene polymorphism was assessed by real-time PCR. Serum levels of AAT protein, IL-10 and IgE were estimated. Results: PiZ allele was found in COPD and asthma patients as well as controls. While PiS allele was never shown up in all the groups. The prevalence of PiZ was higher in asthma and COPD than in controls (75.75%, 72.7% and 50% respectively). Serum AAT was significantly decreased in patients with asthma and COPD. Patients with the PiZ allele, despite having lower values of the serum AAT, this difference was not significant. Serum AAT was significantly correlated with severity of airflow obstruction in both asthma and COPD. There was a significant elevation of serum IgE in COPD patients carrying PiZ allele. Serum IL-10 was significantly higher in asthma and COPD patients than the controls. There was a positive significant correlation between IL-10 and IgE in COPD patients. Conclusion: The z allele frequency in the Egyptian population is higher among asthmatic and COPD patients, suggesting that it could in fact be an underlying hidden risk factor for the development of these diseases. Asthmatics carrying this deficient allele have a genetic predisposition for progressing to COPD. Genetic counselling of patients having obstructive airway diseases is very important for diagnosis, prognosis and treatment.