Abstract:
:Myelodysplastic syndromes (MDS) are a group of aquired hematopoietic disorders characterized by ineffective hematopoiesis, and increased risk of progression of acute myeloid leukemia. For a long period of time, the standard therapy for MDS was hematopoietic stem cell transplantation, however DNA methyltransferase inhibitors (DNMT inhibitors) including decitabine (DAC) and azacitidine (AZA), and lenalidomide, a derivative of thalidomide have been highlighted as new chemotherapeutic agents for MDS. However, the underlying mechanisms of action of these drugs have not been fully defined yet. Therefore, we investigated the in vitro effects of DNMT inhibitors and lenalidomide on an MDS-derived cell line, MDS92 and its blastic subline MDS-L, both of which carry del(5q). MDS-L cells were found to be quite sensitive to DAC, which induced to cell death through DNA damage-mediated G2 arrest via p53- independent pathways. Gene expression profiling suggested that DAC affects biogroups representing hematological systems, cellular development, cell death and apoptosis. Next, we examined the effects of lenalidomide on MDS-L. Cell growth was inhibited and multinucleated cells were frequently formed prior to cell death by lenalidomide treatment. Time-lapse microscopic observation and DNA ploidy analysis revealed that lenalidomide does not affect DNA synthesis itself but inhibits cytokinesis of MDS-L cells. The gene expression profiling showed decreased expression of M phase-related genes. These data contribute to the understanding of action mechanisms of lenalidomide on MDS with del(5q).
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Tsujioka T,Matsuoka A,Tohyama Y,Tohyama Kdoi
10.2174/1381612811209023204subject
Has Abstractpub_date
2012-01-01 00:00:00pages
3204-14issue
22eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20120507-014journal_volume
18pub_type
杂志文章,评审abstract::A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003401046
更新日期:2000-02-01 00:00:00
abstract::By updating John Littleton's work published 15 years ago this review summarizes recent work on pharmacodynamic aspects of acamprosate and the perspective for future developments. In addition to insights into the role of glutamatergic receptor systems, craving and relapse inspired by acamprosate, clinical research poin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791516341
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The application of an ion selective technique for the determination of analyte concentrations is considered one of the most economical techniques for quality control purposes. OBJECTIVE:To elaborate and investigate the construction and general performance characteristics of potentiometric PVC membrane senso...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666180727112730
更新日期:2018-01-01 00:00:00
abstract::The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potentia...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990434
更新日期:2014-01-01 00:00:00
abstract::The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384772
更新日期:2004-01-01 00:00:00
abstract::Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite hi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180111105201
更新日期:2018-01-01 00:00:00
abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::Histone deacetylases (HDACs) are important enzymes that effect post-translational modifications of proteins by altering the acetylation state of lysine residues. HDACs control epigenetic changes that trigger cell transformation and proliferation of transformed cells associated with many diseases. These enzymes are val...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2012-01-01 00:00:00
abstract::Over the last years a number of reports have described elevated numbers of regulatory T (Treg) cells inside of tumors, in close proximity of the tumor, draining lymph nodes and also in peripheral blood of patients with solid tumors and hematologic malignancies. There is increasing evidence that Treg cells can migrate ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788453211
更新日期:2009-01-01 00:00:00
abstract::Adenosine A(2A)-dopamine D(2) receptor interactions play a very important role in striatal function. A(2A)-D(2) receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagon...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784480108
更新日期:2008-01-01 00:00:00
abstract::Radiolabelled peptides and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation with clinical implications for several chronic inflammatory disorders for diagnosis, therapy decision making and follow up. In the last decades, a number of novel monoclonal antibodies and peptides h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785777414
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160607065917
更新日期:2016-01-01 00:00:00
abstract::Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. Even a moderate degree of hyperglycemia appears detrimental for the outcome of critically ill patients, since maintenance of normoglycemia (blood glucose levels journal_title:Current pharmaceutical design pub_type: 杂志文章,评审 doi:10.2174/138161208784980563 更新日期:2008-01-01 00:00:00
abstract::There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intravenous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including a halogenated anesthetics. The cardiac protective properties of halogenated agents (...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1570161112666140123105536
更新日期:2014-01-01 00:00:00
abstract::Lowering low density lipoprotein (LDL) - cholesterol is one of the key issues in modern preventive cardiology by which we are able to interact with the natural course of atherosclerosis. Diet and healthy life style are mandatory for the treatment of CAD high risk patients. Numerous lipid lowering trials confirmed the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795428849
更新日期:2011-01-01 00:00:00
abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200824104856
更新日期:2020-08-23 00:00:00
abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796904803
更新日期:2011-01-01 00:00:00
abstract::Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactof...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180327155929
更新日期:2018-01-01 00:00:00
abstract::A new controlled delivery system has been developed for ropinirole (RP) for the treatment of Parkinson´s Disease (PD) consisting in PLGA microparticles (MPs) which exhibited in vitro constant release of RP (78.23 µg/day/10 mg MPs) for 19 days. The neuroprotective effects of RP released from MPs were evaluated in SKN-A...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666160928145346
更新日期:2017-01-01 00:00:00
abstract::Recent decades mark a great progress in the treatment of HIV infection. What was once a deadly disease is now a chronic infection. However, HIV-infected patients are prone to develop comorbidities, which severely affect their daily functions. For example, a large population of patients develop a variety of neurologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726113001
更新日期:2016-01-01 00:00:00
abstract::This review describes gene therapy strategies that take advantage of defective signal transduction pathways to selectively kill cancer cells without adversely affecting normal cells. The distinctive features of cancer cells currently exploited by gene therapy include mitosis, cell permissiveness to infection, specific...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393927
更新日期:2002-01-01 00:00:00
abstract::Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802884681
更新日期:2012-01-01 00:00:00
abstract::In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert mult...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582504
更新日期:2012-01-01 00:00:00
abstract::Ischaemic stroke of the brain accounts for about one third of all deaths in industrialized countries. Many of the patients who survive are severily impaired. Thus, there is an enormous need for pharmacotherapy for the treatment of ischaemic stroke. Why is such a treatment not available yet? Are the pathophysiological ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612024607135
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, a leading cause of death and disability in developed countries. Therapeutic options are notably limited. There is no specific pharmacological treatment, and early surgery has few indications that represent only a small clinically relevant s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161221153937
更新日期:2017-01-01 00:00:00
abstract::This review summarizes some of the published attempts to incorporate protein and NMR structures in the design of new antibiotics that specifically target Cell Wall biosynthesis. Most of the steps involved in peptidglycan synthesis have been investigated as potential strategies against cell wall inhibition. Structural ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033455305
更新日期:2003-01-01 00:00:00
abstract::Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease (CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular disease. However, despite the efficacy of statins in reducing c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990298
更新日期:2013-01-01 00:00:00
abstract::Research on Substance P (SP) has, until recently, focused on its role in pain and inflammation. However, a report that NK(1) receptor antagonists have utility in the treatment of depression has stimulated research into the function of SP and the NK(1)receptor in anxiety and depression. The distribution of SP and the N...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053764779
更新日期:2005-01-01 00:00:00
abstract::Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, thereby upregulating gonadotrophin secretion and release from the pituitary. Hence, Tamoxifen is used to upregulate activatio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200213095228
更新日期:2020-02-12 00:00:00
abstract::Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200406081920
更新日期:2020-01-01 00:00:00