Abstract：
:Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of non-histone proteins. Some well-recognized mechanisms of HDACI lethality include, in addition to relaxation of DNA and de-repression of gene transcription, interference with chaperone protein function, free radical generation, induction of DNA damage, up-regulation of endogenous inhibitors of cell cycle progression, e.g., p21, and promotion of apoptosis. Intriguingly, this class of agents is relatively selective for transformed cells, at least in pre-clinical studies. In recent years, additional mechanisms of action of these agents have been uncovered. For example, HDACIs interfere with multiple DNA repair processes, as well as disrupt cell cycle checkpoints, critical to the maintenance of genomic integrity in the face of diverse genotoxic insults. Despite their pre-clinical potential, the clinical use of HDACIs remains restricted to certain subsets of T-cell lymphoma. Currently, it appears likely that the ultimate role of these agents will lie in rational combinations, only a few of which have been pursued in the clinic to date. This review focuses on relatively recently identified mechanisms of action of HDACIs, with particular emphasis on those that relate to the DNA damage response (DDR), and discusses synergistic strategies combining HDACIs with several novel targeted agents that disrupt the DDR or antagonize anti-apoptotic proteins that could have implications for the future use of HDACIs in patients with cancer.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Bose P,Dai Y,Grant Sdoi
10.1016/j.pharmthera.2014.04.004subject
Has Abstractpub_date
2014-09-01 00:00:00pages
323-36issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(14)00092-8journal_volume
143pub_type
杂志文章,评审abstract：:Ross River virus (RRV) is a mosquito-borne alphavirus indigenous to Australia and the Western Pacific region and is responsible for several thousand cases of human RRV disease (RRVD) per annum. The disease primarily involves polyarthritis/arthralgia, with many patients also presenting with rash, myalgia, fever, and/or...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.006
更新日期：2005-09-01 00:00:00
abstract：:Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists s...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.09.003
更新日期：2012-01-01 00:00:00
abstract：:Natriuretic peptides play a critical role in coordination of fluid/electrolyte balance and vascular tone. The renal effects of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are distinct from the paracrine effects of vascular C-type natriuretic peptide (CNP). CNP is widely expressed t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.08.011
更新日期：2005-02-01 00:00:00
abstract：:Polymorphisms have been detected in a variety of xenobiotic-metabolizing enzymes at both the phenotypic and genotypic level. In the case of four enzymes, the cytochrome P450 CYP2D6, glutathione S-transferase mu, N-acetyltransferase 2 and serum cholinesterase, the majority of mutations which give rise to a defective ph...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90053-g
更新日期：1993-02-01 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with a high mortality rate. Genetic and biochemical studies have shown that RAS signaling mediated by KRAS plays a pivotal role in disease initiation, progression and drug resistance. RAS signaling affects several cellular processes in PDAC, includ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.09.003
更新日期：2016-12-01 00:00:00
abstract：:Long noncoding RNAs (lncRNAs) have multiple functions in the regulation of cellular homeostasis. In recent years, numerous studies have shown that tumor-associated lncRNAs play key roles in promoting and maintaining tumor initiation and progression by shaping the tumor microenvironment through changing tumor cell intr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107591
更新日期：2020-09-01 00:00:00
abstract：:Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structur...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00236-x
更新日期：2002-07-01 00:00:00
abstract：:Cyclooxygenase (COX) enzymes, or prostaglandin-endoperoxide synthases (PTGS), are heme-containing bis-oxygenases that catalyze the first committed reaction in metabolism of arachidonic acid (AA) to the potent lipid mediators, prostanoids and thromboxanes. Two isozymes of COX enzymes (COX-1 and COX-2) have been identif...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.04.011
更新日期：2006-11-01 00:00:00
abstract：:Hepatic methionine adenosyltransferase (MAT) deficiency is caused by mutations in the human MAT1A gene that abolish or reduce hepatic MAT activity that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. This genetic disorder is characterized by isolated persistent hypermethioninemia in the absenc...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00047-9
更新日期：2000-01-01 00:00:00
abstract：:Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.007
更新日期：2018-06-01 00:00:00
abstract：:This article reviews the experimental data that points to formation of reactive oxygen species (ROS) and oxidative DNA base damage as being important contributors to cancer development. Particular emphasis is placed on the role they play in genetic changes occurring during tumor promotion. A number of structurally dif...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90047-4
更新日期：1992-01-01 00:00:00
abstract：:Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.11.006
更新日期：2018-05-01 00:00:00
abstract：:Injury to peripheral or spinal nerves following either trauma or disease has several consequences including the development of neuropathic pain. This syndrome is often refractory against conventional analgesics; and thus, novel medicaments are desired for its treatment. Recent studies have emphasized that dysfunction ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
doi：10.1016/j.pharmthera.2009.03.018
更新日期：2009-07-01 00:00:00
abstract：:Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted anticancer therapies. Targeting the DNA damage response has recently attracted research interest, as these processes are enhanced in tumour cells. The major replicatio...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107518
更新日期：2020-06-01 00:00:00
abstract：:Adipocyte hyperplasia occurs by the proliferation and differentiation of adipocyte precursor cells or preadipocytes. Although the process of commitment to the adipocyte lineage is poorly understood, a great deal of information has accumulated about the processes and regulatory mechanisms involved in preadipocyte diffe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90018-3
更新日期：1994-01-01 00:00:00
abstract：:Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.pharmthera.2009.05.006
更新日期：2009-09-01 00:00:00
abstract：:The neurobiological processes by which ethanol seeking and consumption are established and maintained are thought to involve areas of the brain that mediate motivated behavior, such as the mesolimbic dopamine system. The mesolimbic dopamine system is comprised of cells that originate in the ventral tegmental area (VTA...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.06.002
更新日期：2004-08-01 00:00:00
abstract：:During the last 20 years, an expanding body of research has elucidated the central role of amyloid precursor protein (APP) processing and amyloid beta peptide (Abeta) production in the risk, onset, and progression of the neurodegenerative disorder Alzheimer's disease (AD), the most common form of dementia. Ongoing res...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.06.006
更新日期：2007-11-01 00:00:00
abstract：:Microsomal P450-mediated monooxygenase activity supported by NADPH requires an interaction between flavoprotein NADPH-cytochrome P450 reductase and cytochrome P450. These proteins have been identified as the simplest system (with the inclusion of a phospholipid (PL) component) that possesses monooxygenase function; ho...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00031-7
更新日期：2003-05-01 00:00:00
abstract：:Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues. Many antivirals with an opposite (L) configuration were reported, with lamivudine being the most notable example. In contrast, carbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00062-5
更新日期：2000-03-01 00:00:00
abstract：:There is substantial molecular evidence for the involvement of beta1 integrin in tissue organisation and remodelling, which confers a key role in cell growth, differentiation, migration, and survival. This role has been, in part, highlighted using the transgenic approach which does little to define the more subtle fun...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.07.002
更新日期：2008-11-01 00:00:00
abstract：:Portal hypertension (PHT) is a common clinical syndrome associated with chronic liver diseases; it is characterized by a pathological increase in portal pressure. Pharmacotherapy for PHT is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow. Due to the altered hemodynamic profile in P...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00128-0
更新日期：2001-03-01 00:00:00
abstract：:Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great pro...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.03.003
更新日期：2018-08-01 00:00:00
abstract：:Fish oil supplementation has been reported to be generally beneficial in autoimmune, inflammatory and cardiovascular disorders. Most researchers have attributed these beneficial effects to the high content of omega-3 fatty acids in fish oil (FO). The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.01.004
更新日期：2009-04-01 00:00:00
abstract：:Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.03.005
更新日期：2012-07-01 00:00:00
abstract：:Protein kinases recognize and bind to specific amino acid sequences on their protein substrates. These sequences can be readily identified using combinatorial peptide libraries. Unfortunately, conventional peptide libraries are not designed to identify subtle structural factors that can dramatically enhance enzyme aff...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00187-0
更新日期：2002-02-01 00:00:00
abstract：:Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90055-5
更新日期：1992-01-01 00:00:00
abstract：:Metabolic syndrome has been described as the association of insulin resistance, hypertension, hyperlipidemia and obesity. Its prevalence increased dramatically, mainly in developed countries. Animal models are essential to understand the pathophysiology of this syndrome. This review presents the murine models of metab...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.11.004
更新日期：2013-03-01 00:00:00
abstract：:The pulmonary endothelium plays a crucial role in lung development and function during the perinatal period. Its 2 most important functions at this time are to help reduce pulmonary vascular resistance (PVR) in order to permit the entire cardiac output to pass through the lungs for the first time and to facilitate the...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.06.016
更新日期：2006-01-01 00:00:00
abstract：:There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids. However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous syste...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.12.004
更新日期：2013-03-01 00:00:00
