RESUMO
Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued.
RESUMO
Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued.
RESUMO
Chronic lymphocytic leukemia (CLL) is one of the common lymphoid malignancies. Single agent ibrutinib has 74％ progression-free survival (PFS) rate in RESONATE-2 trial, but ibrutinib-based therapy combined with obinutuzumab or rituximab in recent iLLUMINTE trial and ALLIANCE trail have 79％ and 88％ PFS rate respectively, which brings encouraging results. New inhibitors and chimeric antigen receptor T-cell (CAR-T) immunotherapy provide new treatment regimens for CLL patients who relapsed after receiving ibrutinib. The clinical trials have been done in phase Ⅰ/Ⅱ.
RESUMO
A great progress has been made in the treatment of chronic myeloid leukemia (CML) owing to the first generation tyrosine kinase inhibitor (TKI). Nowadays, more and more hematologists are eager to understand how to rapidly reduce the BCR-ABL transcripts level, and to get the standard therapeutic reactions, which emerges the second generation TKI. However, the first and second generation TKI have the potential of drug resistance, and thus the third and fourth generation TKI may resolve this problem. Imatinib drug discontinuation trial emphasizes the importance of digital polymerase chain reaction (PCR) and the probability of the second treatment-free remission.
RESUMO
The 59th American Society of Hematology (ASH) Annual Meeting is known as the most powerful hematological meeting around the world. The outcomes in the meeting showed the progress of current hematological diseases from the fundamental research to the clinical practice, from the diagnosis to the treatment. The 59th ASH Annual Meeting covered the contents from the improvement of the formal treatment of acute myelogenous leukemia to the strategies of the aggressive B-cell lymphoma, from the prospect on myelodysplastic syndromes to the influence of biological features on the treatment strategies of indolent lymphoma, from the individualized treatment of chronic lymphocytic leukemia to the study on acquired or hereditary bone marrow failure. The inspiring outcomes from the scholars in China have gained good reputations from the international.
RESUMO
The diagnosis and treatment of multiple myeloma (MM) have make remarkable progress, which were reviewed in the 57th American Society of Hematology (ASH) annual meeting. In this annual meeting, the effects of advanced proteasome inhibitor (PI), antibody, checkpoint blockade, immunomodulatory agent (IMiD), histone deacetylase (HDACI) and chimeric antigen receptor T-cell (CAR-T), and new diagnostic technologies were reported. The real point is to apply the best available diagnosis and therapy at this meeting. At present, regardless of advances, all of randomized clinical trials push to combined agents, and combined with hematopoietic stem cell transplantation, efficacy will be improved in further. So some professors also refered to 2015 year as 'the advance year of MM'.
RESUMO
A full-length cDNA sequence encoding for the precursor of a venom peptide (named BmKCT) with homology to chlorotoxin has been isolated from a cDNA library made from the venom glands of the Chinese Scorpion Buthus martensii Karsch. The sequence of BmKCT is similar (68 % identities) to that of chlorotoxin isolated from Leiurus quinquestriatus quinquestriatus. To understand the biological function of BmKCT, this peptide was expressed using pGEX expression system and purified using GST affinity column and gel filtration.Whole cell patch-clamping recording showed that BmKCT could significantly inhibit chloride currents of gliomas cells, and the inhibitory effect was reversible. These results suggested that BmKCT might belong to the class of short chain toxins blocking the chloride ion channels.
RESUMO
<p><b>OBJECTIVE</b>To investigate the effects of BmkTXK(beta), a newly purified 'long chain' peptide inhibitor of K(+) channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes.</p><p><b>METHODS</b>The standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXK(beta) on potassium currents and action potentials.</p><p><b>RESULTS</b>BmkTXK(beta) produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD(20,50,90)) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or V(max) (n = 9). At a dose of 1 micro mol/L, BmkTXK(beta) decreased I(to) by 41.4% (n = 10, P < 0.01) at a membrane potential of +50 mV [from (13.63 +/- 0.87) pA/pF to (7.98 +/- 0.78) pA/pF]. I(to) was reduced significantly with an IC(50) value of 1.82 micromol/L (95% confidence interval: 1.47 - 2.17 micro mol/L), in a clear concentration-dependent manner. BmkTXK(beta) blocked I(Ks) and I(Ks),tail with an IC(50) of 20.15 micromol/L and a 95% confidence interval of 16.93 - 23.37 micromol/L. At a concentration of 10 micromol/L, BmkTXK(beta) blocked both I(Ks) (mean reduction 37.3% +/- 4.2%, P < 0.01, n = 7) and I(Ks), tail (mean reduction 35.8% +/- 4.1%, P < 0.01, n = 7). At 0 mV, 10 micromol/L BmkTXK(beta) inhibited both I(Kr) (mean reduction 40.5% +/- 2.6%, P < 0.01, n = 6) and I(Kr), tail (mean reduction 42.3% +/- 2.9%, P < 0.01, n = 6). Blocking of I(Kr) by BmkTXK(beta) occurred in a concentration-dependent manner, with an IC(50) of 17.21 micromol/L (95% confidence interval: 14.76-19.66 micromol/L). An absence of effects on I(K1) was observed for BmkTXK(beta), with no change in reversal-potential (n = 6, P > 0.05).</p><p><b>CONCLUSIONS</b>BmkTXK(beta) exerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXK(beta) could be a promising class III drug for anti-arrhythmic therapy without the risk of proarrhythmia.</p>