MicroRNA signature refine response prediction in CML

microRNAs (miRs) dysregulation have emerged as a crucial step in tumorigenesis, being related with cancer development, progression and response to treatment. In chronic myeloid leukaemia (CML), the resistance to tyrosine kinase inhibitors (TKI) is responsible for treatment failure and could be linked to changes in miRs expression. This work aimed to correlate the expression levels of 3 miRs, miR-21, miR-26b and miR-451, with response to TKI treatment in CML patients. miR-451 levels at diagnosis were significantly higher in patients with optimal response after 6 and 12 months of therapy. Conversely, patients without optimal response had highest levels of miR-21. miR-21 and miR-451 appear to be good biomarkers of response, able to predict optimal TKI responders (p < 0.05). Using the combined profile of both miRs, we create a predictive model of optimal response after one year of treatment. This study highlights the role of miR-21 and miR-451 expression levels at diagnosis in predicting which patients achieve the optimal response.info:eu-repo/semantics/publishedVersio

Effects of Resistance Exercise on Endothelial Progenitor Cell Mobilization in Women

This study aimed to determine the effect of a single bout of resistance exercise at different intensities on the mobilization of circulating EPCs over 24 hours in women. In addition, the angiogenic factors stromal cell-derived factor 1 (SDF-1α), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-alpha (HIF-1α) and erythropoietin (EPO) were measured as potential mechanisms for exercise-induced EPCs mobilization. Thirty-eight women performed a resistance exercise session at an intensity of 60% (n = 13), 70% (n = 12) or 80% (n = 13) of one repetition maximum. Each session was comprised of three sets of 12 repetitions of four exercises: bench press, dumbbell curl, dumbbell squat, and standing dumbbell upright row. Blood was sampled at baseline and immediately, 6 hours, and 24 hours post-exercise. Circulating EPC and levels of VEGF, HIF-1α and EPO were significantly higher after exercise (P \u3c 0.05). The change in EPCs from baseline was greatest in the 80% group (P \u3c 0.05), reaching the highest at 6 hours post-exercise. The change in EPCs from baseline to 6 hours post-exercise was correlated with the change in VEGF (r = 0.492, P = 0.002) and HIF-1α (r = 0.388, P = 0.016). In general, a dose-response relationship was observed, with the highest exercise intensities promoting the highest increases in EPCs and angiogenic factors

Genetic variants of ABC and SLC transporter genes and chronic myeloid leukaemia: impact on susceptibility and prognosis

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.info:eu-repo/semantics/publishedVersio

Beyond the limits of oxygen: effects of hypoxia in a hormone-independent prostate cancer cell line

Prostate cancer (PCa) has a high incidence worldwide. One of the major causes of PCa resistance is intratumoral hypoxia. In solid tumors, hypoxia is strongly associated with malignant progression and resistance to therapy, which is an indicator of poor prognosis. The antiproliferative effect and induced death caused by doxorubicin, epirubicin, cisplatin, and flutamide in a hormone-independent PCa cell line will be evaluated. The hypoxia effect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All drugs induced an antiproliferative effect and also cell death in the cell line under study. Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia decreases cellular proliferation and migration. Hypoxia can influence cellular resistance, proliferation, and migration. This study shows that hypoxia may be a key factor in the regulation of PCa.info:eu-repo/semantics/publishedVersio