Effects of small nucleolar RNA SNORD44 on the proliferation, apoptosis and invasion of glioma cells.

To master the effect of small nucleolar RNA, SNORD44, on the proliferation, apoptosis and invasion of glioma cells and its relevant mechanism. SNORD44 and GAS5 expression in glioma tissues and cells was detected through qRT-PCR. Then, the glioma cell lines (U87 and U251) were divided into different groups with different treatments. Cell proliferation was determined by MTT assay, while the abilities of the cell migration and invasion were measured by wound-healing test and Transwell assay, respectively. Cell apoptosis were detected by flow cytometry and TUNEL assay. The expression of apoptosis proteins was quantified through Western blotting. Finally, the xenograft models were established on nude mice to investigate the effects of SNORD44 on the growth of glioma and the expressions of Ki67, MMP2 and MMP9 in vivo. SNORD44 and GAS5 were down-regulated in glioma tissues and cells in a positive correlation. Either SNORD44 or GAS5 overexpression decreased the proliferation, invasion and migration of U87 and U251 cells with the up-regulation of apoptosis rates, as well as the expressions of cleaved PARP, caspase 3, caspase 8 and caspase 9. Moreover, the in vivo experiment showed that overexpression of SNORD44 blocked the growth of glioma xenograft in nude mice accompanying with the inhibition of Ki67, MMP2 and MMP9 expressions. The combination overexpression of SNORD44 and GAS5 gained better inhibitory effects on glioma cells. Overexpression of SNORD44 and GAS5 activate the caspase-dependent apoptosis pathway to facilitate the apoptosis with the inhibited proliferation, invasion and migration of glioma cells.

BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro.

The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood. Recently, we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants. Here, we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs). We showed that K562-MVs could be integrated into co-cultured normal BM-MSCs and dose-dependently enhanced the proliferation of BM-MSCs. Meanwhile, K562-MVs (400 ng/mL) significantly increased the expression of BCR-ABL1 in these BM-MSCs, accompanied by the enhanced secretion of TGF-ß1. These BM-MSCs in turn could trigger the TGF-ß1-dependent proliferation of K562 cells. Moreover, we confirmed the presence of BCR-ABL1 in circulating MVs from 11 CML patients. Compared to the normal BM-MSCs, the BM-MSCs from CML patients more effectively increased the BCR-ABL1 expression and TGF-ß1 secretion in K562 cells as well as the proliferation of K562 cells. Our findings enrich the mechanisms involved in the interaction between leukemia cells and BM-MSCs and provide novel ways to monitor minimal residual disease and worthwhile approaches to treat CML.

Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study.

To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%) patients achieved overall remission rate (ORR), and 18 (14.8%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 ±â€Š3.9)% and 3-year OS rate of (11.1 ±â€Š3.6)%. No difference of CR (P = .621), ORR (P = .385), and allo-HSCT (P = .537) achievement was observed among different chemotherapy regimens. Interestingly, we observed that the CLAG-based regimen did not affect CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an independent factor for prolonged OS (P = .016). No other regimens were determined to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG-based regimen achieved numerically higher ORR rates and significant favorable OS. Therefore, CLAG-based regimens should be a prioritized treatment option for R/R AML patients.

Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.

Efficacy and Safety of Generic Dasatinib as a Second-line Treatment for Patients with Chronic Myeloid Leukemia: a Multicenter Retrospective Study in Hubei Province, China.

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML). Yinishu, a generic dasatinib made in China, was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL. The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics, rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure. For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABLIS) was maintained very low throughout the course of Yinishu treatment. Drug-related adverse events occurred with the same frequency in these two groups. It was confirmed that Yinishu was effective and safe as a secondline treatment for CML patients. Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.

[The mistakes of E. Dinc's double divisor-ratio spectra derivative method].

Double divisor-ratio spectra derivative method has been developed and applied to determining two ternary mixtures simultaneously by E. Dinc. In fact, E. Dinc's double divisor-ratio spectra derivative method is completely wrong. It can not be applied to determining ternary mixtures simultaneously. This paper proves the Mistake of E. Dinc's method in both theory and practice.

[Expansion of marrow hematopoietic progenitor cells ex vivo supported by culture system from mouse marrow embryonic fibroblasts and leukemia inhibitory factor].

The objective of this study was to explore the effect of culture system from embryonic fibroblasts and leukemia inhibitory factor (LIF) on expansion of mouse bone marrow hematopoietic progenitor cells ex vivo, and to observe its effect on the expression of homing-related cell adhesion molecules among VLA-4 (CD49e), VLA-5 (CD49e), LFA-1 (CD11a), HCAM (CD44) and L-selectin (CD62L). The culture system from the mouse embryonic fibroblasts inactivatd by mitomycin C and contained LIF was used to culture with mouse BMMNC for 7 days. The total number of BMMNC, CFC, Sca-1(+) cells, cell apoptosis rate and the expression of above cell adhesion molecules were counted. The results showed that culture system consisted of embryonic fibroblasts and LIF significantly enhanced the total number of BMMNC, CFC, Sca-1(+) cells, suppressed cell apoptosis (P < 0.05). In control without MEF and LIF, the total number of BMMNC was reduced remarkedly, CFC and Sca-1(+) cells were completely dead, the majority of cells produced apoptosis (P < 0.01). The expression of CD49d, Cd44 and CD61L on Sca-1(+) cells were similar to that befor expression (P < 0.05), but the expression of CD49e and CD11a on Sca-1(+) cells were remarkably increased (P < 0.05). It is concluded that culture system from embryonic fibroblasts and LIF can only significantly expand mouse bone marrow hematopoietic progenitor cells ex vivo, but the expanded hematopoietic progenitor may well sustain the expression of homing-related adhesion molecules. The homing functions of these expanded hematopoietic progenitors kept no change.