Abstract：
:Resistance to imatinib can occur in patients with chronic myelogenous leukemia (CML). In this study, we report mechanisms of action of histone deacetylase (HDAC) inhibitor, depsipeptide (FK228) in BCR/ABL-expressing cell lines and its effectiveness in imatinib-resistant cells from patients with blast crisis of CML. FK228 potently induced apoptosis of TF-1 BCR/ABL, K562, and H7 BCR/ABL cells. We found that histone H4, BCR/ABL, heat shock protein 90 (HSP-90), p53, focal adhesion kinase (FAK), paxillin, and retinoblastoma protein (Rb) were acetylated in the treated cells. Cells were also blocked in G(2)/M phase of the cell cycle and activity of mitogen-activated protein kinase (MAPK) was blocked, but p38MAPK (p38) was activated. Inhibitor of apoptosis proteins (IAPs) were suppressed, and common results of apoptotic induction were observed, such as caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) activation. Although p38 was phosphorylated after FK228 treatment, histone H4 acetylation, caspase-3 activation, and apoptosis were not inhibited by treatment with the p38 inhibitor SB203580. We also found that human telomerase reverse transcriptase (hTERT) ShRNA-transfected cells demonstrated decreased FK228-induced apoptosis. Of clinical relevance, FK228-induced apoptosis of imatinib-resistant primary cells from patients with CML, who had progressed to blast crisis (BC) while receiving therapy with imatinib. In conclusion, FK228 potently induces apoptosis of CML cells by acetylation and degradation of BCR/ABL protein. Our study suggests how FK228 may mediate its effects on imatinib-resistant CML cells.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Okabe S,Tauchi T,Nakajima A,Sashida G,Gotoh A,Broxmeyer HE,Ohyashiki JH,Ohyashiki Kdoi
10.1089/scd.2007.9994subject
Has Abstractpub_date
2007-06-01 00:00:00pages
503-14issue
3eissn
1547-3287issn
1557-8534journal_volume
16pub_type
杂志文章abstract：:Umbilical cord blood (CB) CD34(+) cells, on the basis of flow cytometry analysis, are comprised of multiple populations. In in vitro assays, only CD34(regular) FSC(high) cells are functional and low percentages of nonfunctional CD34(regular) FSC(low) cells were determined to be present in liquid-stored CB. Liquid-stor...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2006.15.124
更新日期：2006-02-01 00:00:00
abstract：:Since human mesenchymal stem cells (MSCs) are therapeutically attractive for tissue regeneration and repair, we examined the physiological responses of human umbilical cord blood-derived MSCs (hUCB-MSCs) to genotoxic stress. We found that that sublethal doses of reactive oxygen species (ROS) and ionizing radiation cau...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2011.0284
更新日期：2012-07-20 00:00:00
abstract：:A long-term goal of mesenchymal progenitor cell (MPC) research is to identify cell-surface markers to facilitate MPC isolation. One reported MPC feature in humans and other species is lack of CD14 (lipopolysaccharide receptor) expression. The aim of this study was to evaluate CD14 as an MPC sorting marker. Our hypothe...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2010.0175
更新日期：2011-04-01 00:00:00
abstract：:One of the challenges in stem cell research is to avoid transformation during cultivation. We studied high passage subventricular zone derived neural stem cells (NSCs) cultures of adult rats in the absence of growth factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). We termed this culture...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2009.0416
更新日期：2010-07-01 00:00:00
abstract：:Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The "Bonghan System (BHS)" was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initi...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2015.0024
更新日期：2015-10-01 00:00:00
abstract：:Mesenchymal stromal cells (MSCs) are multipotent stem cells with immunosuppressive and trophic support functions. While MSCs from different sources frequently display a similar appearance in culture, they often show differences in their surface marker and gene expression profiles. Although bone marrow is considered th...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2017.0029
更新日期：2018-01-15 00:00:00
abstract：:After intra-articular injection, synovium-derived mesenchymal stem cells (SMSCs) can adhere to damaged cartilage (a process called homing) and then repair the cartilage defect. Nonetheless, the main obstacle of the current method is the insufficient homing ratio of SMSCs, which fails to meet the requirements for carti...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2019.0137
更新日期：2020-04-01 00:00:00
abstract：:With the recent advances in regenerative medicine, nanotechnology has created a niche for itself as a promising avenue in this field. Innumerable studies have been carried out by researchers using virus-based methodologies for the purpose of epigenetic reprogramming. Although this method is ostensibly safe, nonetheles...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2014.0309
更新日期：2015-03-01 00:00:00
abstract：:Aneurysm refers to the dilation of the vessel wall for more than 50%. Abdominal aortic aneurysm (AAA) refers to the dilation and weakening of all three layers of the abdominal aorta, which mostly occur infrarenally. The population aged above 50 years is at risk of AAA development, while a familiar history doubles the ...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2014.0517
更新日期：2015-07-01 00:00:00
abstract：:Transplantation of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the diseased/injured central nervous system (CNS); however, controlling their differentiation remains a significant hurdle. This study is aimed at controlling differentiation and specifically at screening exogenous factors to...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2008.0412
更新日期：2009-12-01 00:00:00
abstract：:A common observation in metabolic disorders and aging is the elevation of free fatty acids, which can form ectopic fat deposition and result in lipotoxicity. Ectopic fat deposition of skeletal muscle has been recognized as an important component of aging, frailty and sarcopenia. Previous studies have suggested that li...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2020.0168
更新日期：2021-01-11 00:00:00
abstract：:The aim of this study was to clarify the mechanisms that regulate hematopoietic cell expansion in vitro by identifying defined culture conditions. We report the results of experiments with CD34(+) cells from cord blood (CB, n = 13), bone marrow (BM, n = 4), and mobilized peripheral blood stem cells (PBSC, n = 5) using...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2004.13.362
更新日期：2004-08-01 00:00:00
abstract：:Small molecules (SM) can greatly enhance the efficiency of induced pluripotent stem (iPS) cell generation, but the mechanisms by which they act have not been fully explored. We show here that an SM cocktail (NaB, PD03259, and SB431542) significantly promotes iPS cell generation from human fibroblasts, and NaB is more ...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2012.0650
更新日期：2013-08-15 00:00:00
abstract：:Death ligands and their tumor necrosis factor receptor (TNFR) family receptors are the best-characterized and most efficient inducers of apoptotic signaling in somatic cells. In this study, we analyzed whether these prototypic activators of apoptosis are also expressed and able to be activated in human pluripotent ste...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2013.0057
更新日期：2013-11-15 00:00:00
abstract：:Human mesenchymal stromal cells (hMSCs) show great potential for clinical and experimental use due to their capacity to self-renew and differentiate into multiple mesenchymal lineages. However, disadvantages of primary cultures of hMSCs are the limited in vitro lifespan, and the variable properties of cells from diffe...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2013.0599
更新日期：2014-10-01 00:00:00
abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In ...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2012.0529
更新日期：2013-07-01 00:00:00
abstract：:Multipotent stem/progenitor cells from bone marrow stroma (mesenchymal stromal cells or MSCs) were previously shown to enhance proliferation and differentiation of neural stem cells (NSCs) in vivo, but the molecular basis of the effect was not defined. Here coculturing human MSCs (hMSCs) with rat NSCs (rNSCs) was foun...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2009.0444
更新日期：2011-02-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) have attracted much attention as potential platforms for transgene delivery and cell-based therapy for human disease. MSCs have the capability to self-renew and retain multipotency after extensive expansion in vitro, making them attractive targets for ex vivo modification and autologous t...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2007.0194
更新日期：2008-06-01 00:00:00
abstract：:Recent studies have focused on transcriptional regulation and gene expression profiling of human embryonic stem cells (hESCs). However, little information is available regarding the relationship between RNA expression and transcriptional regulation, which is critical in the complete understanding of pluripotency and d...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2006.15.315
更新日期：2006-06-01 00:00:00
abstract：:The development of the heart is essential for embryogenesis and precedes development of other organs. However, the mechanisms involved in embryonic cardiac development are ill-defined. Recent evidence suggests that Smad and Wnt signaling pathways are important in stem cell fate determination and their commitment to ca...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2006.15.29
更新日期：2006-02-01 00:00:00
abstract：:Pluripotent human embryonic stem cells (hESCs) provide appropriate systems for developmental studies and prospective donor cell sources for regenerative medicine. Identification of surface markers specific to hESCs is a prerequisite for studying hESC biology and can be used to generate clinical-level donor cell prepar...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2010.0265
更新日期：2011-04-01 00:00:00
abstract：:Lymphedema is a medically irreversible condition for which currently conservative and surgical therapies are either ineffective or impractical. The potential use of progenitor and stem cell-based therapies has offered a paradigm that may provide alternative treatment options for lymphatic disorders. Moreover, basic re...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2014.0390
更新日期：2015-02-01 00:00:00
abstract：:Little is known about the effects of ionizing radiation on the earliest stages of embryonic development although it is well recognized that ionizing radiation is a natural part of our environment and further exposure may occur due to medical applications. The current study addresses this issue using D3 mouse embryonic...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2015.0260
更新日期：2016-01-15 00:00:00
abstract：:Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic OPLL. To date, the specific molecular pathogenesis of OPLL has not been clearly elucidated. In this study, bone marrow-derived mesenchymal stem cells obtained from healthy donors (HD-MSCs) and patients with OPLL (OPLL-MSCs) were cul...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2020.0117
更新日期：2020-12-01 00:00:00
abstract：:Red blood cell (RBC) differentiation from human induced pluripotent stem cells (hiPSCs) offers great potential for developmental studies and innovative therapies. However, ex vivo erythropoiesis from hiPSCs is currently limited by low efficiency and unphysiological conditions of common culture systems. Especially, the...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2019.0132
更新日期：2019-12-01 00:00:00
abstract：:Progenitor expansion during development is a highly regulated process dictating the final organ size, while expansion of specific progenitor populators can adjust the final cellular composition of the organ. Understanding factors involved in these pathways is required to develop cell-based therapies such as β-cell tra...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2013.0106
更新日期：2013-11-15 00:00:00
abstract：:Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key ...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2020.0133
更新日期：2020-12-01 00:00:00
abstract：:N-methyl-d-aspartate receptors (NMDARs) are expressed abundantly in the brain and play an important role in the regulation of neuronal development, learning, memory, neurodegenerative diseases, and neurogenesis, all of which are extensively discussed in reviews published elsewhere. While the number of research article...
journal_title：Stem cells and development
pub_type： 杂志文章,评审
doi：10.1089/scd.2016.0325
更新日期：2017-06-01 00:00:00
abstract：:The induction and detection of chemotactic migration in mesenchymal stem cells (MSC) are complicated by their adherent nature. We describe here the experimental details for inducing the transmigration of MSC seeded in microchemotaxis chambers and reliably identifying the translocated cells. A combination of 8-microm p...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2005.14.231
更新日期：2005-04-01 00:00:00
abstract：:Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and s...
journal_title：Stem cells and development
pub_type： 杂志文章
doi：10.1089/scd.2013.0448
更新日期：2013-12-01 00:00:00
