Abstract:
:In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, one stressing populations and the other stressing individuals, and discuss their important and far-reaching consequences to implementation of pharmacogenetics/genomics in practice, especially when dealing with admixed populations. We conclude that a variable mosaic genome paradigm, which envisages the genome of any particular individual as a unique mosaic of variable haplotype blocks--has considerably higher explanation and predictive power for the populations of the Americas. We then move to the more formal pharmacogenomics arena to examine the pharmacogenetic/pharmacogenomic diversity in the Americas and review the challenges and advantages of admixed populations for pharmacogenomic studies. Because interethnic admixture is either common or increasing at a fast pace in many, if not most populations, extrapolation on a global scale of pharmacogenomic data from well-defined ethnic groups is plagued with uncertainty. Intra-ethnic diversity adds complexity to the scientific appraisal, regulatory decisions and, eventually, prescribing of drugs purportedly targeted to a given "race" or ethnicity. Pharmacogenetics/genomics has the potential to benefit people worldwide and to reduce the health disparities between developing and developed nations. This goal is unlikely to be achieved by relinquishing the notion of personalized drug therapy tailored to individual genetic characteristics--the original promise of pharmacogenetics--in favor of a model (pharmacogenomic?) of population-based drug development and prescription, with all its potential pitfalls, especially when extended to admixed populations in developing or developed nations.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Suarez-Kurtz G,Pena SDdoi
10.2174/138945006779025392subject
Has Abstractpub_date
2006-12-01 00:00:00pages
1649-58issue
12eissn
1389-4501issn
1873-5592journal_volume
7pub_type
杂志文章,评审abstract::Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the conversion of arachidonic acid to prostaglandin and other eicosanoids. Molecular pathology studies have revealed that Cox-2 is over-expressed in cancer and stroma cells during tumor progression, and anti-cancer chemo-radiotherapies induce expression of Co...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011795677764
更新日期:2011-06-01 00:00:00
abstract::A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033347190
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:The incidence of inflammatory bowel disease (IBD) continues to rise worldwide and despite the advances on pharmacotherapy, the etiopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) remains underexplained. In this context, the migratory waves of the last decades created a challenging setting to...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666201119142045
更新日期:2020-11-19 00:00:00
abstract::Transport molecules can significantly affect the pharmacodynamics and pharmacokinetics of drugs. An important transport molecule, the 170 kDa P-glycoprotein (Pgp), is constitutively expressed at several organ sites in the human body. Pgp is expressed at the blood-brain barrier, in the kidneys, liver, intestines and in...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778019264
更新日期:2006-08-01 00:00:00
abstract::The genus Zanthoxylum (Rutaceae) comprises about 250 species, of which many are used as food, often as condiments, substituting pepper due to the pungent taste of fruits, seeds, leaves, and bark, and therapeutic remedies especially in Eastern Asian countries and in Central America. The whole plant is also consumed as ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011798184128
更新日期:2011-12-01 00:00:00
abstract::Enzymes are proteins that act as biological catalysts to speed up cellular biochemical processes. According to their main Enzyme Commission (EC) numbers, enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase; EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different enzym...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666181002143355
更新日期:2019-01-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, most cases are on an advanced and inoperable stage, with limited therapeutic options. Existing therapies have shown to be insufficient and novel strategies are urgently necessary. New advances in understanding the disease a...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140528151649
更新日期:2015-01-01 00:00:00
abstract::Natural products represent a rich resource for drug delivery and are currently being exploited to target tumour angiogenesis. A vast array of products of natural origin have been shown to have anti-angiogenic potential in preclinical models, including purified endogenous inhibitors, and exogenous compounds derived fro...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776054951
更新日期:2006-03-01 00:00:00
abstract::Prostaglandins serve as the connecting link between inflammation and cancer. mPGES1, the downstream enzyme in the prostaglandin pathway is considered a better target than COX-2 against the progression of cancer due to the cardiovascular and other complications associated with the inhibition of the latter. Despite the ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160826093137
更新日期:2017-01-01 00:00:00
abstract::Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase inhibitors, such as roflumi...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111314020008
更新日期:2013-02-01 00:00:00
abstract::Fluoroquinolones are one of the world's most valuable and popularly used categories of antimicrobial agents. This paper attempts to review the substantial progress of fluoroquinolones from their discovery to black box warning. Antibiotic drug choice will remain difficult in the presence of increasing resistance, but t...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200621193355
更新日期:2020-01-01 00:00:00
abstract::Proline dehydrogenase/proline oxidase (PRODH/POX) is an enzyme catalyzing the first step of proline degradation, during which ROS and/or ATP is generated. POX is widely distributed in living organisms and is responsible for a number of regulatory processes such as redox homeostasis, osmotic adaptation, cell signaling ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011613151031150637
更新日期:2015-01-01 00:00:00
abstract::It is well documented that elevated levels of PAI-1 in plasma can decrease the fibrinolytic activity in blood with an associated increased risk of thrombus formation. A diverse range of molecules including bacterial lipopolysaccharide (LPS), the inflammatory mediators tumor necrosis factor alpha (TNFalpha) and interle...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007781662382
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Recently, there are scientific attempts to discover new drugs in the biotechnology industry in order to treat various diseases including atherosclerosis. OBJECTIVE:The main objective of the present review was to highlight the cellular, molecular biology and inflammatory process related to the atheromatous p...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160502151600
更新日期:2017-01-01 00:00:00
abstract::The complexity of the central nervous system (CNS) exposes it to a number of different diseases, often caused by only small variations in gene sequence or expression level. Antisense oligonucleotides and RNA interference-mediated therapies hold great promise for the treatment of CNS diseases in which neurodegeneration...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450053344920
更新日期:2005-02-01 00:00:00
abstract::Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. >2 log tumor ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011794815301
更新日期:2011-03-01 00:00:00
abstract::Target discovery using the molecular approach, as opposed to the more traditional systems approach requires the study of the cellular or biological process underlying a condition or disease. The approaches that are employed by the "bench" scientist may be genetic, genomic or proteomic and each has its rightful place i...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450115666141120110323
更新日期:2015-01-01 00:00:00
abstract::The understanding of the neurobiological processes leading to major depressive disorder (MDD) is an active field of research in the scientific community. For years, the alteration of monoamine neurotransmission, in particular serotonin (5-HT), has been considered the most significant pathophysiological mechanism of th...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990154
更新日期:2013-05-01 00:00:00
abstract::The Notch signaling plays a key role in cell differentiation, survival, and proliferation through diverse mechanisms. Thus, alterations of the Notch signaling can lead to a variety of disorders including human malignancies. Of considerable interest, recent evidence indicates that there is a significant cross-talk betw...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990188
更新日期:2013-09-01 00:00:00
abstract::Infiltrating inflammatory cells into the kidney mediate the initiation and progression of damage by direct cytotoxicity, the secretion of soluble factors such as cytokines and proteases, or by the subsequent induction of further immune response. Before leukocytes can exert their effects on renal damage or repair, they...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006775270213
更新日期:2006-01-01 00:00:00
abstract::Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007780058933
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. LITERATURE REVIEW:The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161005145143
更新日期:2017-01-01 00:00:00
abstract::Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160217123042
更新日期:2016-01-01 00:00:00
abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such as Alzheimer's and Parkinson's disease and cerebral ischemia for over 2000 years. OBJECTIVE:In this article we review the neuroprotective effects o...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161227125121
更新日期:2017-01-01 00:00:00
abstract::Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain informati...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009789753246
更新日期:2009-12-01 00:00:00
abstract::The heterogeneity of proteoglycans (PG)s contributes to their functional diversity. Many functions depend on their ability to bind and modulate the activity of components of the extracellular matrix (ECM). The ability of PGs to interact with other molecules, such as growth factors, is largely determined by the fine st...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2005-09-01 00:00:00
abstract::Despite the success of combined antiretroviral therapy, more than half of HIV-1-infected patients in the USA show HIV-associated neurological and neuropsychiatric deficits. This is accompanied by anatomical and functional alterations in vulnerable brain regions of the mesocorticolimbic and nigrostriatal systems that r...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::The use of imatinib, second and third generation ABL tyrosine kinase inhibitors (TKI) (i.e. dasatinib, nilotinib, bosutinib and ponatinib) made CML a clinically manageable and, in a small percentage of cases, a cured disease. TKI therapy also turned CML blastic transformation into a rare event; however, disease progre...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160615074120
更新日期:2017-01-01 00:00:00
abstract::Breast cancer remains the leading cause of cancer death among females worldwide. It signifies a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Current treatment modalities, including surgery, radiotherapy, and adjuvant chemotherapy or hormone therapy, have not be...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012804545632
更新日期:2012-12-01 00:00:00