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| 1 | 新诊断的慢性髓性白血病患者中尼罗替尼vs伊马替尼的疗效比较显示文摘背景尼罗替尼已证实在新诊断慢性期费城染色体(ph染色体)阳性的慢性髓性白血病(CML)患者中比伊马替尼有更好的疗效。我们在这些患者中比较并评价尼罗替尼与伊马替尼的疗效和安全性。方法在这项随机化、多中心、开放的3期研究中,846名患者来自于过去六个月内被诊断为慢性期ph染色体阳性的CML。我们采用计算机生成的随机数据表、区组分组和以Sokal评分为依据的分层方法将患者按1:1:1比例分别接受尼罗替尼(剂量每天2次,300mg或400mg)、或者伊马替尼(剂量每天1次400mg),以口服的方式予药。主要终点指标是12个月时依据国际评分(BCR-ABLIS)0.1%的BCR-ABL转录水平的重要分子反应率或外周血的实时量化PCR。该项研究在ClinicalTrials.gov注册,项目编号为NCT00471497。结果 24个月时,尼罗替尼组的重要分子反应率显著高于伊马替尼组[201例(71%)尼罗替尼300mg组,187例(67%)尼罗替尼400mg组,124例(44%)伊马替尼组;两种比较P<0.0001]。尼罗替尼组任意时刻完全细胞遗传学反应的比例(定义为BCR-ABLIS水平减少值≤0.0032%)也显著高于伊马替尼组[74例(26%)尼罗替尼300mg组,59例(21%)尼罗替尼400mg组,29例(10%)伊马替尼组;分别P<0.0001和P=0.0004]。加速期或爆发期时,伊马替尼组比尼罗替尼组在克隆进化方面进展更显著(尼罗替尼300mg组2例,尼罗替尼400mg组5例,伊马替尼组17例;分别P=0.0003和P=0.0089)。24个月时,所有组的生存率基本一致,但是两尼罗替尼组的CML相关死亡数比伊马替尼组更少(尼罗替尼300mg组5例,尼罗替尼400mg组3例,伊马替尼组10例)。总的来说,仅有3或4级的非血液病性不良反应在至少2.5%的患者身上表现,分别为头痛[8例(3%)尼罗替尼300mg组,4例(1%)尼罗替尼400mg组,2例(<1%)伊马替尼组]和皮疹[2例(<1%)尼罗替尼300mg组,7例(3%)尼罗替尼400mg组,5例(2%)伊马替尼组]。伊马替尼组的3或4级粒细胞减少症比任意尼罗替尼组更普遍[33例(12%)尼罗替尼300mg组,30例(11%)尼罗替尼400mg组,59例(21%)伊马替尼组]。在研究开展的第二年中报告了另外8例严重不良反应事件(尼罗替尼300mg组4例,尼罗替尼400mg组3例,伊马替尼组1例)。讨论尼罗替尼继续在新诊断慢性期CML患者中表现出更好的疗效。这些结果支持尼罗替尼可作为新诊断患者临床治疗的一线药物。 | 贺洁宇 Kantarjian HM Hochhaus A Saglio G 柳叶刀 | 2012 | 肿瘤药学2012，2，1： | 2 |
| 2 | Bone marrow microenvironment: The guardian of leukemia stem cells显示文摘Bone marrow microenvironment (BMM) is the main sanctuary of leukemic stem cells (LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the close connection between LSCs and the BMM. The elimination of LSCs is of high importance, since they follow cancer stem cell theory as a part of this population. Based on cancer stem cell theory, a cell with stem cell-like features stands at the apex of the hierarchy and produces a heterogeneous population and governs the disease. Secretion of cytokines, chemokines, and extracellular vesicles, whether through autocrine or paracrine mechanisms by activation of downstream signaling pathways in LSCs, favors their persistence and makes the BMM less hospitable for normal stem cells. While all details about the interactions of the BMM and LSCs remain to be elucidated, some clinical trials have been designed to limit these reciprocal interactions to cure leukemia more effectively. In this review, we focus on chronic myeloid leukemia and acute myeloid leukemia LSCs and their milieu in the bone marrow, how to segregate them from the normal compartment, and finally the possible ways to eliminate these cells. | Mohammad Houshmand Teresa Mortera Blanco Paola Circosta Narjes Yazdi Alireza Kazemi Giuseppe Saglio Mahin Nikougoftar Zarif | 2019 | World Journal of Stem Cells2019，11，8： | 2 |
| 3 | Feeding behaviour of fast- and slow-growing stains of rainbow trout,Oncorhynchus mykiss (Walbaum) during first feeding 显示文摘 | Valente L M P Saglio P Cunha L M | 2001 | Aquaculture Research2001，32，： | 1 |
| 4 | Orientation of carp,Cyprinus capio L,to free amino acids from Tu- bifex extract in an olfactometer 显示文摘 | Saglio P H Fauconneau B Blanc J M | 1990 | Journal of Fish Biology1990，37，6： | 1 |
| 5 | WT1 overexpression in acute myeloid leukemia and myelodysplastic syndromes 显示文摘 | Cilloni D Gottardi E Saglio G | 2006 | Methods Mol Med2006，125，： | 1 |
| 6 | Feeding behaviour of fast-and slow-growing stains of rainbow trout, Oncorhynchus mykiss ( Walbaum ) during first feeding 显示文摘 | Valente L M P Saglio P Cunha L M | 2001 | Aquaculture Research2001，32，6： | 1 |
| 7 | Nilotinib ver- sus imatinib in patients (pts) with newly diagnosed philadelphia chromosome-positive ( Ph + ) chronic myeloid leukemla in ehron- ic phase (CML-CP) : ENESTnd 36-month (too) follow-up显示文摘 | SAGLIO G LECOUTRE PD PASQUINI R | 2011 | Blood2011，118，： | 1 |
| 8 | ENESTnd up- date : continued superiority of nilotinib versus imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) 显示文摘 | HUGHES TP HOCHHAUS A SAGLIO G | 2010 | Blood2010，116，： | 1 |
| 9 | Molecular pathways: BCR-ABL显示文摘 | Cilloni D Saglio G | 2012 | Clin Cancer Res2012，18，4： | 1 |
| 10 | Nilotinib versus imatinib for newly diagnosed chronic myeloid leukernia显示文摘 | SAGLIO G KIM D W ISSARAGRISIL 5 | 2010 | N Engl J Med2010，362，24： | 1 |
| 11 | Lxr - activating oxysterols induce the expression of inflammatory markers in endothelial cells through lxr - independent mechanisms 显示文摘 | Morello F Saglio E Noghero A | 2009 | Atherosclerosis2009，207，： | 1 |
| 12 | Nilo-tinib versus imatinib for newly diagnosed chronic mye-loid leukemia 显示文摘 | SAGLIO G KIM D W JSSARAGRISIL S | 2010 | N Engl J Med2010，362，22： | 1 |
| 13 | Glycolytic flux and hexokinase activities in anoxic maize root tips acclimated by hypoxic pretreatment显示文摘 | BOUNY J M SAGLIO P H | 1996 | Plant Physiology1996，111，18： | 1 |
| 14 | Innovative approaches to treat steroid- resistant or steroid refractory GVHD 显示文摘 | Berger M Biasin E Saglio F | 2008 | Bone Marrow Transplant2008，42，2： | 1 |
| 15 | Adherence to BCR-ABLinhibitors: issues for CML therapy 显示文摘 | Jabbour E Saglio G Radich J | 2012 | Clin Lymphoma MyelomaLeuk2012，12，4： | 1 |
| 16 | High hexokinase activity in tomato fruit perturbs carbon and energy metabolism and reduces fruit and seed size显示文摘 | Menu T Saglio P Granot D | 2004 | Plant Cell Environ2004，27，： | 1 |
| 17 | Innovative approaches to treat ster- oid-resistant or steroid refractory GVHD 显示文摘 | Berger M Biasin E Saglio F | 2008 | Bone Marrow Transplant2008，42，2： | 1 |
| 18 | Early response with dasatinib or imatinib in chronic myeloid leukemia:3-year follow-up from a rando- mized phase 3 trial (DASISION) 显示文摘 | Jabbour E Kantarjian HM Saglio G | 2014 | Blood2014，123，4： | 1 |
| 19 | Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia 显示文摘 | Saglio G Kim DW Issaragrisil S et a/ | 2010 | NEnglJMed2010，362，5： | 1 |
| 20 | Nilotinib versus imatinib for the treatment of patients with newly di- agnosed chronic phase, Philadelphia chromosome-posi- tive, chronic myeloid leukaemia: 24-month minimum fol- low-up of the phase 3 randomised ENESTnd trial显示文摘 | Kantarjian HM Hochhaus A Saglio G | 2011 | Lan- cet 0ncol2011，12，9： | 1 |
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