Abstract:
:The majority of acute myeloid leukemia (AML) patients will respond to standard chemotherapy, however, resistance is a prevalent problem contributing to incomplete responses, refractory disease, and ultimately patient death. Therefore, choosing more sensitive and effective chemotherapy regimens is of key clinical importance. In order to explore this issue, we investigated and optimized PharmaFlow, an automated flow cytometry method for evaluating the sensitivity of leukemia cells to multiple chemotherapeutic drugs ex vivo. We examined bone marrow samples from 38 Chinese AML patients and incubated them for 48 or 72 h with a panel of 7 single drugs and 6 combinations with cytarabine at different concentrations. Leukemic cell depletion was assessed by PharmaFlow and drug response parameter, called PharmaFlow score, was estimated using population pharmacodynamic models. We identified that most chemotherapeutic drugs and combinations could effectively eliminate pathological cells ex vivo. Estimated drug activities strongly correlated with the patients' duration to achieve clinical remission and PharmaFlow chemosensitivity measured ex vivo was highly predictive of the clinical outcome after chemotherapy. Applying a classification model, we determined a PharmaFlow score of 89.4 as the threshold to predict response to chemotherapy. Using this threshold, we found that in 84.2% of cases patient's cell response ex vivo predicted the observed clinical response and performed similarly or better than prognostic subgroups determined by cytogenetic characteristics. PharmaFlow has the potential to predict chemosensitivity for de novo, secondary and relapsed AML patients prior to treatment and may guide clinicians to tailor treatments and improve patient outcome.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Lin L,Tong Y,Straube J,Zhao J,Gao Y,Bai P,Li J,Wang J,Wang H,Wang X,Huang S,Xu W,Song X,Li Ldoi
10.1002/JLB.5A0220-676RRsubject
Has Abstractpub_date
2020-05-01 00:00:00pages
859-870issue
5eissn
0741-5400issn
1938-3673journal_volume
107pub_type
杂志文章abstract::In the presence of adenosine, formyl-Met-Leu-Phe-stimulated human neutrophils show a greatly diminished production of superoxide anion. Analysis of changes in levels of intracellular calcium revealed that the immediate increase (occurring within seconds) in intracellular calcium following addition of formyl-Met-Leu-Ph...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.48.3.281
更新日期:1990-09-01 00:00:00
abstract::NK cells are members of the innate immunity and play a central role in the defense against viral infections and cancer development, but also contribute to triggering and shaping adaptive immune responses. Human NK cells may express MHC II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which allows...
journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
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doi:10.1002/jlb.51.3.282
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journal_title:Journal of leukocyte biology
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abstract::As part of a study to identify novel genes associated with macrophage activation, we have cloned a new member of the transforming growth factor beta (TGF-beta) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleavage by a furin like ...
journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.54.2.105
更新日期:1993-08-01 00:00:00
abstract::Several members of the cytokine network play an important role in controlling the replication of the human immunodeficiency virus (HIV) in several experimental systems. Their effects can be categorized in the following three functional groups: (1) HIV-inductive cytokines; (2) HIV-suppressive cytokines; (3) cytokines w...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.62.1.34
更新日期:1997-07-01 00:00:00
abstract::Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation. It has been shown to be synthesized and secreted in vitro by epithelial cells and has been localized in tracheal glands and bronchiolar epithelial cells by immunocyt...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.61.6.695
更新日期:1997-06-01 00:00:00
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journal_title:Journal of leukocyte biology
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doi:10.1002/jlb.62.1.100
更新日期:1997-07-01 00:00:00
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0703356
更新日期:2004-06-01 00:00:00
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1106695
更新日期:2007-04-01 00:00:00
abstract::During highly active antiretroviral therapy (HAART), HIV-1 can still persist in circulating, resting CD4+ T lymphocytes, lymph node mononuclear cells, and seminal cells of patients despite sustained suppression of plasma viremia to undetectable levels. Sanctuary sites where antiretroviral drug penetration is not optim...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:2000-09-01 00:00:00
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1202613
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abstract::The oxidative metabolic burst of stimulated human polymorphonuclear leukocytes (PMNs) has been evaluated by the measurement of oxygen consumption, chemiluminescence, and oxygen radicals (O2-, H2O2, OH-) derived from activation of the hexose monophosphate shunt (HMPS). PMNs from patients with chronic granulomatous dise...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.43.4.317
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.3.356
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.52.5.495
更新日期:1992-11-01 00:00:00
abstract::The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet-activating factor (PAF, 10(-8) M) or N-formyl-methio...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.62.2.163
更新日期:1997-08-01 00:00:00
abstract::C1qR(P) is a type I cell surface glycoprotein that has been shown to enhance ingestion of suboptimally opsonized targets by phagocytes in vitro. In this study, we developed and characterized polyclonal antibodies to study the tissue distribution of this receptor targeted to either the N- or C-terminal portion of the m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::The objective of this study was to find the role of LncRNA SNHG12 in the regulation of hypertensive vascular endothelial injury. LncRNA SNHG12 and miR-25-3p expression were detected by quantitative RT-PCR. Protein levels of Sirtuin 6 (SIRT6), endothelial cell (EC) senescence markers p16 and p21, and EC marker CD31 wer...
journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
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更新日期:1990-08-01 00:00:00
abstract::In RAW 264.7 cells, PKC-ε regulates FcγR-mediated phagocytosis. BMDM behave similarly; PKC-ε concentrates at phagosomes and internalization are reduced in PKC-ε⁻/⁻ cells. Two questions were asked: what is the role of PKC-ε? and what domains are necessary for PKC-ε concentration? Function was studied using BMDM and fru...
journal_title:Journal of leukocyte biology
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abstract::To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluores...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00
abstract::Inflammation-limiting nonsteroidal pain relievers magnify myocardial infarction (MI) incidences and increase re-admission events in heart failure (HF) patients. However, the molecular and cellular mechanism of this provocative adverse effect is unclear. Our goal was to determine whether carprofen (CAP) impedes splenic...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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abstract::During the neoplastic progression, macrophages as well as dendritic and NK cells are attracted into the tumor site and initiate the immune response against transformed cells. They activate and present tumor antigens to T cells, which are then activated to kill tumor cells. However, tumor cells are often capable of esc...
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journal_title:Journal of leukocyte biology
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journal_title:Journal of leukocyte biology
pub_type: 杂志文章
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更新日期:2019-12-01 00:00:00
abstract::We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of this study was to dete...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.6.847
更新日期:1996-06-01 00:00:00