Abstract：
:DNA-targeted chemotherapies remain fundamental in clinical management of both common solid tumours and hematologic malignancies. Recent studies indicate that novel combinations of cytotoxic chemotherapy may have significant activity even in tumours regarded as being resistant to conventional chemotherapy. In addition, the search for more selective and efficacious drugs that can deliver critical DNA damage with minimal side effects continues. Trabectedin, bendamustine and the pyrrolobenzodiazepine dimer SG2000 exemplify three different classes of DNA targeted agent undergoing clinical evaluation. Increasingly, DNA damaging drugs are being used in combination with novel agents such as small molecule inhibitors or antibodies targeting receptor tyrosine kinases. Understanding the mechanistic basis for interactions of these novel targeted agents with DNA-interactive drugs will inform design of optimal combinations for future studies and is critical to maximize benefit in the clinic.
journal_name
Curr Opin Pharmacoljournal_title
Current opinion in pharmacologyauthors
Hartley JA,Hochhauser Ddoi
10.1016/j.coph.2012.03.008subject
Has Abstractpub_date
2012-08-01 00:00:00pages
398-402issue
4eissn
1471-4892issn
1471-4973pii
S1471-4892(12)00050-1journal_volume
12pub_type
杂志文章,评审abstract：:Diabetes-induced hyperglycemia is a causal factor for cardiovascular disease (CVD) and, specifically, peripheral artery disease (PAD). Metformin is the cornerstone drug therapy for glucose-lowering that exerts beneficial effects beyond glycemic control. New glucose-lowering drugs have recently been shown cardiovascula...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2018.03.001
更新日期：2018-04-01 00:00:00
abstract：:About one third of people in the world suffer from metabolic syndrome (MetS), with symptoms such as hypertension and elevated blood cholesterol, and with increased risk of developing additional diseases such as diabetes mellitus and heart disease. The progression of this multifactorial pathology, which targets various...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2011.09.012
更新日期：2011-12-01 00:00:00
abstract：:Among the methods based on molecular imaging, the measure of the tracer uptake variation between a baseline and follow-up scan with the SUV and [(18)F]FDG-PET/CT is a very powerful tool for assessing response to treatment in oncology. However, the development of new targeted therapeutics and tissue pharmacokinetic eva...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2012.07.016
更新日期：2012-10-01 00:00:00
abstract：:Stroke and multiple sclerosis (MS) illustrate how clinical imaging can facilitate early phase drug development and most effective medicine use in the clinic. Imaging has enhanced understanding of the dynamics of evolution of disease pathophysiology, better defining treatment targets. Imaging measures can enable strati...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2013.10.006
更新日期：2014-02-01 00:00:00
abstract：:Activation of P2Y(1) and P2Y(12) receptors, through secreted ADP that is stimulated by agonists such as thrombin, thromboxane and collagen, is a major mechanism of platelet activation. P2X(1) receptors also participate in platelet shape change and potentiation of calcium mobilization. The cloning of the P2Y(12) recept...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4892(03)00007-9
更新日期：2003-04-01 00:00:00
abstract：:Biomarker profiling is utilized to identify diagnostic and prognostic candidates for stroke. Clinical and preclinical biomarker data suggest altered circulating immune responses may illuminate the mechanisms of stroke recovery. However, the relationship between peripheral blood biomarker profile(s) and brain profiles ...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2015.10.004
更新日期：2016-02-01 00:00:00
abstract：:Sulfonylurea receptor 1 (SUR1) is a molecule with more diverse and critically important functions than previously recognized. Long viewed simply as a subunit involved in formation of a subset of K(ATP) channels, accumulating evidence indicates that SUR1 is newly upregulated in CNS ischemia and injury and is surprising...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章
doi：10.1016/j.coph.2007.10.004
更新日期：2008-02-01 00:00:00
abstract：:Platelets are known to play a pivotal role not only in the formation of arterial thrombosis but also in the progression of atherosclerotic disease. Recent data suggest that these activities of platelets have become enhanced in patients with type 2 diabetes, accounting for many of the cardiovascular complications. Alth...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2005.01.005
更新日期：2005-04-01 00:00:00
abstract：:An increasing number of genetic diseases are found to result from mutations that lead to retention of the affected proteins in the endoplasmic reticulum, where they are recognized as misfolded by the quality control system. Several of these conformational diseases involve mutations in G-protein-coupled receptors. Rece...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2004.08.001
更新日期：2004-10-01 00:00:00
abstract：:Irritable bowel syndrome, which affects 5-10% of the population includes around 25% with predominantly diarrhoea (IBS-D). Several lines of evidence suggest an increase in mucosal 5-HT availability in IBS-D including a decrease in the serotonin transporter (SERT) which is also seen following acute diverticulitis. 5-HT(...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2011.02.005
更新日期：2011-02-01 00:00:00
abstract：:The use and utility of computational models in drug development has significantly grown in the last decades, fostered by the availability of high throughput datasets and new data analysis strategies. These in silico approaches are demonstrating their ability to generate reliable predictions as well as new knowledge on...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2018.08.007
更新日期：2018-10-01 00:00:00
abstract：:Osteoporosis is characterized by low bone mass and increased susceptibility to fracture. Recent in vitro studies showed that strontium ranelate, a novel agent containing two strontium atoms, acts as an effective anti-osteoporotic drug by inhibiting bone resorption by osteoclasts and promoting osteoblast replication an...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2005.05.005
更新日期：2005-12-01 00:00:00
abstract：:Glucocorticoid excess induces hypertension, in which abnormal renal sodium homeostasis is implicated. It is common in industrialised nations where hypertension remains the major risk-factor for cardiovascular disease. Aldosterone is the dominant chronic regulator in sodium homeostasis, but glucocorticoids influence re...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2015.01.005
更新日期：2015-04-01 00:00:00
abstract：:Metabotropic glutamate receptors (mGluRs) are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release and long term synaptic plasticity. Therefore, targeting specific mGluR subtypes by means of selective drugs could be a possible strategy for restoring normal...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2018.03.004
更新日期：2018-02-01 00:00:00
abstract：:Somatostatin (SOM) is a regulatory peptide produced throughout the central nervous system and in most major peripheral organs. In humans, the SOM stable analogue octreotide (OCT) is used to treat opioid-resistant pain. In animal models, SOM and OCT are analgesics and SOM released from the peripheral endings of sensory...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4892(02)00007-3
更新日期：2003-02-01 00:00:00
abstract：:The first therapeutic aptamer was approved for human use in 2004, and a range of chemical substitutions that improve the drug-like properties of aptamers has recently been shown to increase the utility of this modality. Currently there are both anticoagulant and antithrombotic aptamers in the clinic, and additionally ...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2007.12.005
更新日期：2008-04-01 00:00:00
abstract：:Understanding the mechanisms of cell-cell interaction is a key unanswered question in modern pharmacology, given crosstalk defects are at the basis of many pathologies. Microfluidics represents a valuable tool for analyzing intercellular communication mediated by transmission of soluble signals, as occurring for examp...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2013.07.005
更新日期：2013-10-01 00:00:00
abstract：:The second messenger, cAMP, is one of the most important regulatory signals for control of steroidogenesis. This review focuses on current knowledge about regulation of cyclic nucleotides by phosphodiesterases (PDEs) in steroidogenic tissues. The first PDE known to directly regulate steroidogenesis was PDE2, the cGMP-...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2011.09.003
更新日期：2011-12-01 00:00:00
abstract：:Skeletal lesions contribute substantially to morbidity and mortality in patients with cancer. Emerging treatments for metastatic bone disease have arisen from our understanding of the biology of bone metastases. Tumour cells alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, prom...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2015.04.004
更新日期：2015-06-01 00:00:00
abstract：:Multiple myeloma is a tumour with a remarkably destructive effect on its host organ, the bone marrow. Through expression or secretion of adhesion molecules, growth factors, exosomes, miRNAs, chemokines and inhibitors, the tumour substantially alters its microenvironment, promoting both tumour survival and osteolytic b...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2016.02.013
更新日期：2016-06-01 00:00:00
abstract：:Toll-like receptors (TLRs) play a crucial role in host defence and inflammation. Given that a significant amount of evidence implicates TLRs in the pathogenesis of immune diseases and cancer, and their activation occurs early in the inflammatory cascade, they are attractive targets for novel therapeutic agents. Potent...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2012.06.002
更新日期：2012-08-01 00:00:00
abstract：:Inverse agonism has gone from an initial curiosity to a now well-recognized phenomenon. This has demanded expansion of receptor theory models to account for multiple receptor states and a re-definition of ligand efficacy. However, after several decades of discovery, the clinical importance of inverse agonist ligands i...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2006.10.005
更新日期：2007-04-01 00:00:00
abstract：:The repertoire of signal transduction pathways activated by dopamine in brain includes the increase of intracellular calcium. However the mechanism(s) by which dopamine activated this important second messenger system was/were unknown. Although we showed that activation of the D5 dopamine receptor increased calcium co...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2009.09.011
更新日期：2010-02-01 00:00:00
abstract：:The development of HIV protease inhibitors (HIV PIs) has been one of the most significant advances of the past two decades in controlling HIV infection. HIV PIs have been used successfully in highly active anti-retroviral therapy (HAART) for HIV infection, which is currently the most effective treatment available. Inc...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2014.07.008
更新日期：2014-12-01 00:00:00
abstract：:The molecular genetics of Barrett's esophagus (BE) and its evolution to esophageal adenocarcinoma (EAC) have been widely studied; however, the molecular mechanism of BE-EAC carcinogenesis has not been completely understood. MicroRNA (miRNA) is now essential to understand the molecular mechanism of cancer progression. ...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2009.08.009
更新日期：2009-12-01 00:00:00
abstract：:Gasotransmitters fulfill important roles in cellular homeostasis having been linked to various pathologies, including inflammation and cardiovascular diseases. In addition to the known pathways mediating the actions of gasotransmitters, their effects in regulating mitochondrial function are emerging. Given that mitoch...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2019.07.001
更新日期：2019-04-01 00:00:00
abstract：:Women have coronary heart disease (CHD) later than men. This review describes studies of CHD risk factors or outcomes based on studies of premenopausal women followed through the menopause transition, and prospective cohort studies of younger or older women with CHD risk markers or disease outcomes in the context of t...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2013.01.005
更新日期：2013-04-01 00:00:00
abstract：:Lysophosphatidic acid (LPA), a bioactive phospholipid, and its family of cognate G protein-coupled receptors have demonstrated roles in many biological functions in the nervous system. To date, five LPA receptors have been identified, and additional receptors may exist. Most of these receptors have been genetically de...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2008.11.010
更新日期：2009-02-01 00:00:00
abstract：:The past decade has witnessed a growing interest in the trophic effects of antidepressant drugs. Antidepressants stimulate the production and signaling of plasticity-related proteins such as neurotrophins and cAMP response element binding protein, and neurotrophin signaling appears to be both sufficient and necessary ...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.coph.2003.10.004
更新日期：2004-02-01 00:00:00
abstract：:Reporter-gene assays offer an alternative to biochemical assays for following signal transduction pathways from receptors at the cell surface to nuclear gene transcription in living cells. Specific reporter-gene systems are now available for the study of ligand activity at G alpha(i/o), G alpha(s) and G alpha(q) G-pro...
journal_title：Current opinion in pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s1471-4892(01)00091-1
更新日期：2001-10-01 00:00:00
