Abstract:
:Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize compositions that we applied in a novel manner to design combinations of chemotherapeutics. Conventional chemotherapeutics (mitoxantrone, cabazitaxel, and docetaxel) and natural bioactive compounds (resveratrol, piperlongumine, and flavopiridol) were used in 12 different combinations containing three drugs at varying concentrations. Cell viability and cell cycle data were collected and used to plot response surfaces in MDRSM that identified the most effective concentrations of each drug in combination. MDRSM allows for extrapolation of data from three or more compounds in variable ratio combinations, unlike the Chou-Talalay method. MDRSM combinations were compared with combination index data from the Chou-Talalay method and were found to coincide. We propose MDRSM as an effective tool in devising combination treatments that can improve treatment effectiveness and increase treatment personalization, because MDRSM measures effectiveness rather than synergism, potentiation, or antagonism.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Oblad R,Doughty H,Lawson J,Christensen M,Kenealey Jdoi
10.1124/mol.117.111450subject
Has Abstractpub_date
2018-08-01 00:00:00pages
907-916issue
2eissn
0026-895Xissn
1521-0111pii
mol.117.111450journal_volume
94pub_type
杂志文章abstract::A number of different agonists activate G protein-coupled receptors to stimulate adenylyl cyclase (AC), increase cAMP formation, and promote relaxation in vascular smooth muscle. To more fully understand this stimulation of AC, we assessed the expression, regulation, and compartmentation of AC isoforms in rat aortic s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.5.983
更新日期:2002-11-01 00:00:00
abstract::Sulfation, catalyzed by members of the sulfotransferase (SULT) superfamily, exerts considerable influence over the biological activity of numerous endogenous and xenobiotic chemicals. In humans, catecholamines such as dopamine are extensively sulfated, and a SULT isoform (SULT1A3 or the monoamine-sulfating form of phe...
journal_title:Molecular pharmacology
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doi:10.1124/mol.54.6.942
更新日期:1998-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.043273
更新日期:2008-06-01 00:00:00
abstract::In isolated perfused rat livers, infusion of the sulfonylureas, glyburide (2.5 microM) and tolbutamide (0.5 mM), stimulated by 2-fold the rate of biliary glutathione secretion. This increase was mainly the result of an apparent increase in the rate of reduced glutathione release by the liver since oxidized glutathione...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::In ND8-47 cells, a neuroblastoma x dorsal root ganglion hybrid cell line, activation of delta-opioid receptors induced an increase in the intracellular free calcium concentration ([Ca2+]i) through dihydropyridine-sensitive calcium channels. This effect was mediated by pertussis toxin-sensitive G proteins. The G protei...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment. An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2013-03-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.115.098509
更新日期:2015-10-01 00:00:00
abstract::The role of protein kinase C (PKC) in the human aryl hydrocarbon receptor (hAhR) signal transduction pathway was examined in cell lines stably transfected with pGUDLUC6.1, in which luc+ is solely controlled by four dioxin-responsive elements (DREs). These cell lines, P5A11 and HG40/6, were derived from HeLa and HepG2 ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.4.691
更新日期:1998-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.077966
更新日期:2012-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.5.1120
更新日期:2004-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::The gene encoding a human 5-hydroxytryptamine (5-HT)1 receptor subtype was isolated from a human placental genomic library by using oligonucleotide probes derived from transmembrane regions of the cloned human 5-HT1D beta receptor. The deduced amino acid sequence of the genomic clone hp75d is identical to that of the ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::We examined the role of putative trafficking sequences in two GABA(A) receptor subunits: α4 and δ. These subunits assemble with a β subunit to form a subtype of GABA(A) receptor involved in generating the "tonic" outward current. Both α4 and δ subunits contain dibasic retention motifs in homologous positions. When bas...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.114.092791
更新日期:2014-07-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.5.721
更新日期:1997-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.1.89
更新日期:2003-01-01 00:00:00
abstract::Systematic series of monoamines, diamines, and triamines were used to define the structural requirements for interaction at the polyamine recognition site of the N-methyl-D-aspartate receptor complex. Effects of amines on binding of [3H]MK-801 to washed synaptic plasma membranes were measured in the presence of L-glut...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::The effect of endocytosis inhibitors on 5-hydroxytryptamine(2A) (5-HT(2A)) receptor desensitization and resensitization was examined in transiently transfected human embryonic kidney (HEK) 293 cells and in C6 glioma cells that endogenously express 5-HT(2A) receptors. In HEK-293 cells, 5-HT(2A) receptor desensitization...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.5.1020
更新日期:2001-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2003-07-01 00:00:00
abstract::Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). HL-60 cells selected in 0.05 micrograms/ml doxorubicin (DOX) are 10-fold and > 20-fold resistant to DOX and etoposide (VP-16), respectively. The accu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Angiotensin II (AII) stimulates rapid increases in cytosolic Ca2+ concentrations in Xenopus laevis oocytes after binding to specific receptors located in the surrounding follicular cells. In follicular oocytes, the peptide AII receptor antagonists saralasin (IC50 = 25 nM) and CGP 42112A (IC50 = 400 nM) were orders of ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Regulation of beta2-adrenergic receptor (beta2AR) levels by glucocorticoids is a physiologically important mechanism for altering beta2AR responsiveness. Glucocorticoids increase beta2AR density by increasing the rate of beta2AR gene transcription, but the cis-elements involved have not been well characterized. We now...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1998-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are ubiquitously expressed in the mammalian central nervous system, where they exert trophic actions on both neuronal and glial cells. However, the acute actions of PDGF on synaptic transmission are unknown. We report a novel regulatory action of PDGF/P...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2000-04-01 00:00:00
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journal_title:Molecular pharmacology
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