In the current study, we aimed to identify the cytotoxic and apoptotic effects of bortezomib (BOR) on human K562 chronic myelogenous leukemia cells and to evaluate the potential roles of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway members STAT3, STAT5, and JAK2 on BOR-induced cell death of leukemic cells. Cell viability was assessed via trypan blue dye exclusion test, and cytotoxicity of the BOR-treated cells was conducted by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay. The relative messenger RNA (mRNA) expression levels of STAT3, STAT5A, STAT5B, and JAK2 were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). On the other hand, their protein expression levels were detected by western blot method. The obtained results indicated that BOR treatment reduced cell viability and induced leukemic cell apoptosis in a dose- and time-dependent manner as compared to untreated control cells. While mRNA expression levels of STAT5A, STAT5B, and STAT3 were significantly reduced following BOR treatment when compared to untreated controls, it had no effect upon JAK2 mRNA expression. As for protein levels, STAT expressions were downregulated after BOR treatment especially at 72nd and 96th hours. Our results pointed out that BOR treatment had a significant potential of being an anticancer agent for chronic myelogenous leukemia therapy, and this effect could be due to the expressional downregulations of JAK/STAT pathway members.
Introduction Platelet dysfunction is not uncommon in patients with end-stage renal disease (ESRD). Type of renal replacement therapy may have an effect on platelet functions, which has not been well investigated. We evaluated in vitro closure time (CT) differences between peritoneal dialysis (PD) and hemodialysis (HD) patients using platelet function analyzer (PFA-100)and observed a significant difference between these renal replacement therapies.
Methods Patients with ESRD undergoing PD (n = 24) or HD (n = 23) for more than 6 months were included. Blood samples for collagen/epinephrine (Col/EPI) and collagen/adenosine diphosphate (Col/ADP) measurements were obtained before HD at a mid-week session for HD patients and at an outpatient control time for PD patients.
Results Three of 24 (12.5%) PD patients and 16 of 23 (69.5%) HD patients had prolonged PFA-100 Col/EPI, p< 0.001. Likewise, 4.2% of PD patients and 87.0% of HD patients had prolonged PFA-100 Col/ADP, p< 0.001. Moreover, the median times of PFA-Col/EPI and PFA-100 Col/ADP were significantly lower in PD patients compared with those of HD patients (p< 0.001). Multivariate analysis showed that the type of renal replacement was a risk factor for both elevated PFA-100 Col/ADP and PFA-100 Col/EPI after adjusted for platelets, hematocrit, and urea (p< 0.001).
Conclusions The type of renal replacement therapy may have an effect on in vitro CTs; therefore, studies including more patients with long-term follow-up are needed to investigate if the difference has any impact on clinical outcomes.
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