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目的用等位基因聚合酶链反应(AS-PCR)方法检测Bcr-abl阴性的骨髓增殖性肿瘤(MPN)、骨髓增生异常综合征(MDS)、骨髓增生异常综合征/骨髓增殖性肿瘤(MDS/MPN)、急性髓系白血病(AML)、急性淋巴细胞白血病(ALL)、Bcr-abl阳性的慢性粒细胞白血病(CML)患者和正常健康人对照的外周血白细胞JAK2-V617F基因点突变情况,了解该突变在不同疾病中的表达,并建立敏感特异高效的JAK2-V617F突变的临床检测方法。方法采用AS-PCR方法检测基因组中JAK2-V617F突变,并经基因测序确定。所有MPN患者均行骨髓活检了解其纤维增生度。结果MPN各型中真性红细胞增多症(PV)阳性率为93.8%;原发性血小板增多症(ET)阳性率为60.0%;原发性骨髓纤维化(IMF)阳性率为0;MDS阳性率为4.5%;MDS/MPN阳性率为12.5%;AML、ALL、CML及正常对照均为阴性。MPN各型之间、MPN与其它疾病之间,阳性率差异有显著性(P<0.05)。JAK2-V617F突变阳性的PV及ET患者白细胞数较阴性患者高,差异有显著性(P<0.05)。且阳性患者骨髓纤维组织增生较阴性者明显,差异... 相似文献
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Ralfs Buks Mgane Brusson Sylvie Cochet Tatiana Galochkina Bruno Cassinat Ivan Nemazanyy Thierry Peyrard Jean-Jacques Kiladjian Alexandre G. de Brevern Slim Azouzi Wassim El Nemer 《International journal of molecular sciences》2021,22(7)
Myeloproliferative neoplasms (MPNs) are a group of disorders characterized by clonal expansion of abnormal hematopoietic stem cells leading to hyperproliferation of one or more myeloid lineages. The main complications in MPNs are high risk of thrombosis and progression to myelofibrosis and leukemia. MPN patients with high risk scores are treated by hydroxyurea (HU), interferon-α, or ruxolitinib, a tyrosine kinase inhibitor. Polycythemia vera (PV) is an MPN characterized by overproduction of red blood cells (RBCs). ABCG2 is a member of the ATP-binding cassette superfamily transporters known to play a crucial role in multidrug resistance development. Proteome analysis showed higher ABCG2 levels in PV RBCs compared to RBCs from healthy controls and an additional increase of these levels in PV patients treated with HU, suggesting that ABCG2 might play a role in multidrug resistance in MPNs. In this work, we explored the role of ABCG2 in the transport of ruxolitinib and HU using human cell lines, RBCs, and in vitro differentiated erythroid progenitors. Using stopped-flow analysis, we showed that HU is not a substrate for ABCG2. Using transfected K562 cells expressing three different levels of recombinant ABCG2, MPN RBCs, and cultured erythroblasts, we showed that ABCG2 potentiates ruxolitinib-induced cytotoxicity that was blocked by the ABCG2-specific inhibitor KO143 suggesting ruxolitinib intracellular import by ABCG2. In silico modeling analysis identified possible ruxolitinib-binding site locations within the cavities of ABCG2. Our study opens new perspectives in ruxolitinib efficacy research targeting cell types depending on ABCG2 expression and polymorphisms among patients. 相似文献
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Vincenzo Nasillo Giovanni Riva Ambra Paolini Fabio Forghieri Luca Roncati Beatrice Lusenti Monica Maccaferri Andrea Messerotti Valeria Pioli Andrea Gilioli Francesca Bettelli Davide Giusti Patrizia Barozzi Ivana Lagreca Rossana Maffei Roberto Marasca Leonardo Potenza Patrizia Comoli Rossella Manfredini Antonino Maiorana Enrico Tagliafico Mario Luppi Tommaso Trenti 《International journal of molecular sciences》2021,22(4)
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches. 相似文献
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纳米V_2O_5/TiO_2-SiO_2复合材料的抗菌性能 总被引：2，自引：0，他引：2
以高比表面多孔纳米TiO2-SiO2为载体,用浸渍法制备纳米V2O5/TiO2-SiO2复合材料,考察了其抗菌性能,采用TEM、FTIR、XPS、XRD等手段对产物进行了表征。结果表明,复合材料不需紫外光照射即具有较强的抗菌性能,对大肠杆菌和金黄葡萄球菌产生透明抑菌圈,直径达11~13 mm。复合材料中V以V5+和V4+形式存在,部分V5+已进入TiO2晶格取代Ti4+,发生了氧化还原反应,产生了电子转移,形成了新键;O1s电子结合能和Ti2p结合能增大;掺杂促进TiO2-SiO2从锐钛型向金红石相转化,抑制粒径的长大,使复合材料活性提高。 相似文献
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溶剂热合成纳米孔状V2O3粉末的研究 总被引：1，自引：0，他引：1
采用溶剂热路线合成纳米孔状V2O3粉末,产物用x射线衍射仪和透射电子显微镜进行表征,实验结果显示制备的V2O3粉末呈纳米孔状,颗粒的粒径在几百纳米左右,孔径在5～15nm之间。 相似文献
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Single crystals of V2O5 and Li0.03V2O5 were imaged in ambient conditions by atomic force microscopy (AFM). Atomic-scale resolution images are compared with total electron-density plots of the surface calculated using the ab initio HartreeFock method. The calculated oxygen charge at the V2O5(0 1 0) surface suggests an increased local reactivity of the bridging oxygens with respect to electrophilic attacks by adsorbate molecules. The intercalation of lithium has no consequence on the reactivity of the surface. This is supported by results from electrostatic potentials calculated from the cluster charge distributions. 相似文献
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对于失活的SCR脱硝催化剂,回收再利用技术有着重要的社会、环保和经济价值。目前,燃煤电厂用的最多的商用SCR脱硝催化剂为V_2O_5-WO_3/TiO_2脱硝催化剂。介绍了对废V_2O_5-WO_3/TiO_2脱硝催化剂中的钒元素的回收工艺及原理,并对SCR脱硝催化剂回收再利用进行了展望。 相似文献
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以TiO2载体,采用浸渍法制备了不同V2O5负载量的用于选择性催化还原NOx的V2O5／TiO2催化剂。利用BET,SEM和Ⅺ①,对不同V2O5负载量的催化剂组成、结构、形貌和性能进行了表征,考察不同V2O5负载量对催化剂制备的影响。结果表明制备的催化剂具有较多的中孔和微孔,催化剂中V2O5含量的增加,会降低催化剂的表面积;V2O5含量为2％的V2O5／TiO2催化剂样品比表面积最大,但是其活性非常低;V2O5含量为4％催化剂比表面积较大,NOx脱转化率高;V2O5的负载量小时,V2O5主要以等轴聚合的钒基型式（V3O7和V6O13）存在,这些钒基是催化剂的活性中心;当负载量超过6％,V2O5主要以结晶相存在,占据大量活性位,降低催化效果。 相似文献
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以V2O5为原料,活性炭为还原剂,采用碳热还原法制备了VO_2。探讨了还原剂用量和反应时间对各价态钒氧化物质量分数的影响,采用化学滴定法、XRD、SEM和DSC分析了产品的纯度、物相、形貌和相变温度。结果表明:在V2O5和活性炭的物质的量比为2∶1、反应时间为5 h的条件下,所得产品纯度(以VO_2质量分数计)为99.6%,VO_2转化率达到93.9%。产品为M相VO_2,其颗粒细小(粒径为110μm)且结晶性良好。 相似文献
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Desheng Feng Ming Li Sze Long Yee Yang Jiang Mao Chen Yi Peng Xiaodong Ma 《Journal of the American Ceramic Society》2021,104(9):4843-4853
V2O5-Fe2O3 and V2O5-TiO2 systems represent two important chemical systems with various applications, including energy, catalysts, and high-performance materials. In the present study, high-temperature phase equilibrium experiments were conducted at the temperature range of 670–1000°C in air. Electron probe X-ray micro-analyzer (EPMA) was used to analyze the microstructure and composition of the phases presented in quenched samples. Systematic experiments demonstrated that V2O5-containing systems should not be quenched by water-based quenching media. Phase diagrams in both systems were constructed, and the eutectic and peritectic points of the systems were confirmed and compared with previous studies. The present study improved the previous results and could be used as the base for thermodynamic modelings and further applications of the two systems. 相似文献
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Yunmoon Oh Jin-Sol Lee Ji Sun Lee Jae Hyeon Park Hyung Sik Kim Sungpil Yoon 《International journal of molecular sciences》2022,23(9)
P-glycoprotein (P-gp) overexpression is one of the major mechanisms of multidrug resistance (MDR). Previously, co-treatment with Janus kinase 2 (JAK2) inhibitors sensitized P-gp-overexpressing drug-resistant cancer cells. In this study, we assessed the cytotoxic effects of JAK2 inhibitor, fedratinib, on drug-resistant KBV20C cancer cells. We found that co-treatment with fedratinib at low doses induced cytotoxicity in KBV20C cells treated with vincristine (VIC). However, fedratinib-induced cytotoxicity was little effect on VIC-treated sensitive KB parent cells, suggesting that these effects are specific to resistant cancer cells. Fluorescence-activated cell sorting (FACS), Western blotting, and annexin V analyses were used to further investigate fedratinib’s mechanism of action in VIC-treated KBV20C cells. We found that fedratinib reduced cell viability, increased G2 arrest, and upregulated apoptosis when used as a co-treatment with VIC. G2 phase arrest and apoptosis in VIC–fedratinib-co-treated cells resulted from the upregulation of p21 and the DNA damaging marker pH2AX. Compared with dimethyl sulfoxide (DMSO)-treated cells, fedratinib-treated KBV20C cells showed two-fold higher P-gp-inhibitory activity, indicating that VIC–fedratinib sensitization is dependent on the activity of fedratinib. Similar to VIC, fedratinib co-treatment with other antimitotic drugs (i.e., eribulin, vinorelbine, and vinblastine) showed increased cytotoxicity in KBV20C cells. Furthermore, VIC–fedratinib had similar cytotoxic effects to co-treatment with other JAK2 inhibitors (i.e., VIC–CEP-33779 or VIC–NVP-BSK805) at the same dose; similar cytotoxic mechanisms (i.e., early apoptosis) were observed between treatments, suggesting that co-treatment with JAK2 inhibitors is generally cytotoxic to P-gp-overexpressing resistant cancer cells. Given that fedratinib is FDA-approved, our findings support its application in the co-treatment of P-gp-overexpressing cancer patients showing MDR. 相似文献
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Myeloid malignancy is a broad term encapsulating myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Initial studies into genomic profiles of these diseases have shown 2000 somatic mutations prevalent across the spectrum of myeloid blood disorders. Epigenetic mutations are emerging as critical components of disease progression, with mutations in genes controlling chromatin regulation and methylation/acetylation status. Genes such as DNA methyltransferase 3A (DNMT3A), ten eleven translocation methylcytosine dioxygenase 2 (TET2), additional sex combs-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and isocitrate dehydrogenase 1/2 (IDH1/2) show functional impact in disease pathogenesis. In this review we discuss how current knowledge relating to disease progression, mutational profile and therapeutic potential is progressing and increasing understanding of myeloid malignancies. 相似文献
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Theodoros Karantanos Tania Jain Alison R. Moliterno Richard J. Jones Amy E. DeZern 《International journal of molecular sciences》2021,22(5)
Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. Different groups have highlighted that men have overall worse survival and higher incidence of transformation to acute leukemia compared to women across neoplasms such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap neoplasms, and CML. More recent studies evaluating the genomic profile of patients with these neoplasms demonstrated a male predominance for mutations in high-risk genes including ASXL1, U2AF1, SRSF2 and ZRSR2. The understanding of the underlying biology is limited but a number of hypotheses have been developed and are currently being investigated. This review summarizes the current knowledge about sex-related differences in the clinical outcomes and genomic profile of patients with chronic myeloid neoplasms and discusses the hypothesized biologic mechanisms as an attempt to explain these observations. 相似文献
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Angel Chao Min-Jie Liao Shun-Hua Chen Yun-Shien Lee Chi-Neu Tsai Chiao-Yun Lin Chia-Lung Tsai 《International journal of molecular sciences》2022,23(5)
Stress-induced phosphoprotein-1 (STIP1)—a heat shock protein (HSP)70/HSP90 adaptor protein—is commonly overexpressed in malignant cells, where it controls proliferation via multiple signaling pathways, including JAK2/STAT3. We have previously shown that STIP1 stabilizes the protein tyrosine kinase JAK2 in cancer cells via HSP90 binding. In this study, we demonstrate that STIP1 may act as a substrate for JAK2 and that phosphorylation of tyrosine residues 134 and 152 promoted STIP1 protein stability, induced its nuclear-cytoplasmic shuttling, and promoted its secretion into the extracellular space. We also found that JAK2-mediated STIP1 phosphorylation enhanced cell viability and increased resistance to cisplatin-induced cell death. Conversely, interference STIP1 with JAK2 interaction—attained either through site-directed mutagenesis or the use of cell-penetrating peptides—decreased JAK2 protein levels, ultimately leading to cell death. On analyzing human ovarian cancer specimens, JAK2 and STIP1 expression levels were found to be positively correlated with each other. Collectively, these results indicate that JAK2-mediated phosphorylation of STIP-1 is critical for sustaining the JAK2/STAT3 signaling pathway in cancer cells. 相似文献