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Article ; Online: The role of mouse tumour models in the discovery and development of anticancer drugs.

Ireson, Christopher R / Alavijeh, Mo S / Palmer, Alan M / Fowler, Emily R / Jones, Hazel J

2019 Volume 121, Issue 2, Page(s) 101–108

Abstract: Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of novel oncology drugs during the past decade continues ... ...

Abstract	Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of novel oncology drugs during the past decade continues to be modest. In addition, the attrition of agents during clinical development remains high. This attrition can be attributed, at least in part, to the clinical development being underpinned by the demonstration of predictable efficacy in experimental models of human tumours. This review will focus on the range of models available for the discovery and development of anticancer drugs, from traditional subcutaneous injection of tumour cell lines to mice genetically engineered to spontaneously give rise to tumours. It will consider the best time to use the models, along with practical applications and shortcomings. Finally, and most importantly, it will describe how these models reflect the underlying cancer biology and how well they predict efficacy in the clinic. Developing a line of sight to the clinic early in a drug discovery project provides clear benefit, as it helps to guide the selection of appropriate preclinical models and facilitates the investigation of relevant biomarkers.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Disease Models, Animal ; Drug Development ; Drug Discovery ; Humans ; Mice ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2019-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-019-0495-5
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Article: Discovery and development of anticancer aptamers.

Ireson, Christopher R / Kelland, Lloyd R

Molecular cancer therapeutics

2006 Volume 5, Issue 12, Page(s) 2957–2962

Abstract: Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific ... ...

Abstract	Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation. The first aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib) that is administered locally (intravitreally) to treat age-related macular degeneration by targeting vascular endothelial growth factor. The most advanced aptamer in the cancer setting is AS1411, formerly known as AGRO100, which is being administered systemically in clinical trials. AS1411 is a 26-mer unmodified guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has shown activity against human tumor xenografts in vivo. The mechanism underlying its antiproliferative effects in cancer cells seems to involve initial binding to cell surface nucleolin and internalization, leading to an inhibition of DNA replication. In contrast to other unmodified oligonucleotides, AS1411 is relatively stable in serum-containing medium, probably as a result of the formation of dimers and a quartet structure. In a dose escalation phase I study in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or seven continuous infusion regime) have been studied. Promising signs of activity have been reported (multiple cases of stable disease and one near complete response in a patient with renal cancer) in the absence of any significant adverse effects. Further trials are ongoing in renal and non-small cell lung cancers. In preclinical studies, additional aptamers have been described against several cancer targets, such as tenascin-C, the transcription factor signal transducer and activator of transcription 3, and antiapoptotic and Ku proteins.
MeSH term(s)	Animals ; Aptamers, Nucleotide/pharmacology ; Aptamers, Nucleotide/therapeutic use ; Aptamers, Peptide/pharmacology ; Aptamers, Peptide/therapeutic use ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Oligodeoxyribonucleotides/pharmacokinetics ; Oligodeoxyribonucleotides/pharmacology ; Oligodeoxyribonucleotides/therapeutic use
Chemical Substances	AGRO 100 ; Aptamers, Nucleotide ; Aptamers, Peptide ; Oligodeoxyribonucleotides
Language	English
Publishing date	2006-12-15
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Review
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-06-0172
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Article: Influence of shallow groundwater–surface water interactions on the hydrological connectivity and water budget of a wetland complex

Brannen, Rosa / Spence, Christopher / Ireson, Andrew

Hydrological processes. 2015 Aug. 30, v. 29, no. 18

2015

Abstract: Linkages between the controls on surface storage and catchment streamflow response were examined in a wetland‐dominated basin in the Canadian Prairie Pothole region. Snowmelt, surface storage, water table elevation, atmospheric fluxes, and streamflow ... ...

Abstract	Linkages between the controls on surface storage and catchment streamflow response were examined in a wetland‐dominated basin in the Canadian Prairie Pothole region. Snowmelt, surface storage, water table elevation, atmospheric fluxes, and streamflow were monitored during spring snowmelt and summer in a 1 km² sub‐catchment containing a semi‐permanent pond complex connected via an intermittent stream. Snow accumulation in the basin in the spring of the 2013 study year was the largest in the 24‐year record. Rainfall totals in 2013 were close to the long term average, although June was an anomalously wet month. The water budget of the pond complex indicates that there was a significant subsurface contribution to surface storage. Activation of an effective transmission zone occurred between uplands and the stream network where the water table was located near the ground surface, which allowed significant lateral movement of subsurface water into the stream network. This was also important for maintaining and re‐establishing surface connectivity and streamflow during rainfall events. The observed period of surface‐water connectivity was one of the longest on record in the catchment due to unusually wet conditions; nevertheless, the results of this study have implications for how contributing area and runoff should be considered in monitoring and modelling studies in the region, as inclusion of more frequent and varied runoff processes will be essential to understanding changing streamflow regimes. © 2015 Her Majesty the Queen in Right of Canada. Hydrological Processes. © 2015 John Wiley & Sons, Ltd.
Keywords	basins ; ephemeral streams ; highlands ; models ; monitoring ; rain ; runoff ; snowmelt ; spring ; stream flow ; subwatersheds ; summer ; surface storage ; surface water ; water balance ; water table ; wetlands ; Prairie Pothole region
Language	English
Dates of publication	2015-0830
Size	p. 3862-3877.
Publishing place	Wiley
Document type	Article
ZDB-ID	1479953-4
ISSN	1099-1085 ; 0885-6087
ISSN (online)	1099-1085
ISSN	0885-6087
DOI	10.1002/hyp.10563
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Measuring In-Cabin School Bus Tailpipe and Crankcase PM

Ireson, Robert G / Ondov, John M / Zielinska, Barbara / Weaver, Christopher S / Easter, Michael D / Lawson, Douglas R / Hesterberg, Thomas W / Davey, Mark E / Liu, L-J Sally

Journal of the Air & Waste Management Association (1995)

2011 Volume 61, Issue 5, Page(s) 494–503

Abstract: Exposures of occupants in school buses to on-road vehicle emissions, including emissions from the bus itself, can be substantially greater than those in outdoor settings. A dual tracer method was developed and applied to two school buses in Seattle in ... ...

Abstract	Exposures of occupants in school buses to on-road vehicle emissions, including emissions from the bus itself, can be substantially greater than those in outdoor settings. A dual tracer method was developed and applied to two school buses in Seattle in 2005 to quantify in-cabin fine particulate matter (PM
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1003064-5
ISSN	2162-2906 ; 0894-0630 ; 1047-3289 ; 1096-2247
ISSN (online)	2162-2906
ISSN	0894-0630 ; 1047-3289 ; 1096-2247
DOI	10.3155/1047-3289.61.5.494
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Article ; Online: Silencing of protein kinase D2 induces glioma cell senescence via p53-dependent and -independent pathways.

Bernhart, Eva / Damm, Sabine / Heffeter, Petra / Wintersperger, Andrea / Asslaber, Martin / Frank, Saša / Hammer, Astrid / Strohmaier, Heimo / DeVaney, Trevor / Mrfka, Manuel / Eder, Hans / Windpassinger, Christian / Ireson, Christopher R / Mischel, Paul S / Berger, Walter / Sattler, Wolfgang

Neuro-oncology

2014 Volume 16, Issue 7, Page(s) 933–945

Abstract: Background: Glioblastoma multiforme (GBM) is a highly aggressive tumor of the central nervous system with a dismal prognosis for affected patients. Aberrant protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a member of the PKC- ... ...

Abstract	Background: Glioblastoma multiforme (GBM) is a highly aggressive tumor of the central nervous system with a dismal prognosis for affected patients. Aberrant protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a member of the PKC-activated protein kinase D (PRKD) family, PRKD2, was identified as mediator of GBM growth in vitro and in vivo. Methods: The outcome of PRKD2 silencing and pharmacological inhibition on glioma cell proliferation was established with different glioma cell lines. Western blotting, senescence assays, co-immunoprecipitation, fluorescence activated cell sorting, quantitative PCR, and immunofluorescence microscopy were utilized to analyze downstream signaling. Results: RNA-interference (21-mer siRNA) and pharmacological inhibition (CRT0066101) of PRKD2 profoundly inhibited proliferation of p53(wt) (U87MG, A172, and primary GBM2), and p53(mut) (GM133, T98G, U251, and primary Gli25) glioma cells. In a xenograft experiment, PRKD2 silencing significantly delayed tumor growth of U87MG cells. PRKD2 silencing in p53(wt) and p53(mut) cells was associated with typical hallmarks of senescence and cell cycle arrest in G1. Attenuated AKT/PKB phosphorylation in response to PRKD2 silencing was a common observation made in p53(wt) and p53(mut) GBM cells. PRKD2 knockdown in p53(wt) cells induced upregulation of p53, p21, and p27 expression, decreased phosphorylation of CDK2 and/or CDK4, hypophosphorylation of retinoblastoma protein (pRb), and reduced transcription of E2F1. In p53(mut) GM133 and primary Gli25 cells, PRKD2 silencing increased p27 and p15 and reduced E2F1 transcription but did not affect pRb phosphorylation. Conclusions: PRKD2 silencing induces glioma cell senescence via p53-dependent and -independent pathways.
MeSH term(s)	Animals ; Blotting, Western ; Brain Neoplasms/metabolism ; Cell Line, Tumor ; Cellular Senescence/physiology ; Flow Cytometry ; Gene Silencing ; Glioma/metabolism ; Heterografts ; Humans ; Immunoprecipitation ; Mice ; Microscopy, Fluorescence ; Protein Kinase D2 ; Protein Kinases/metabolism ; RNA Interference ; Real-Time Polymerase Chain Reaction ; Signal Transduction/physiology ; Transfection ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Protein Kinase D2 ; Tumor Suppressor Protein p53 ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2014-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/not303
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Article: Measuring in-cabin school bus tailpipe and crankcase PM

Ireson, Robert G / Ondov, John M / Zielinska, Barbara / Weaver, Christopher S / Easter, Michael D / Lawson, Douglas R / Hesterberg, Thomas W / Davey, Mark E / Liu, L-J Sally

Journal of the Air & Waste Management Association (1995)

2011 Volume 61, Issue 5, Page(s) 494–503

Abstract	Exposures of occupants in school buses to on-road vehicle emissions, including emissions from the bus itself, can be substantially greater than those in outdoor settings. A dual tracer method was developed and applied to two school buses in Seattle in 2005 to quantify in-cabin fine particulate matter (PM2.5) concentrations attributable to the buses' diesel engine tailpipe (DPMtp) and crankcase vent (PMck) emissions. The new method avoids the problem of differentiating bus emissions from chemically identical emissions of other vehicles by using a fuel-based organometallic iridium tracer for engine exhaust and by adding deuterated hexatriacontane to engine oil. Source testing results showed consistent PM:tracer ratios for the primary tracer for each type of emissions. Comparisons of the PM:tracer ratios indicated that there was a small amount of unburned lubricating oil emitted from the tailpipe; however, virtually no diesel fuel combustion products were found in the crankcase emissions. For the limited testing conducted here, although PMck emission rates (averages of 0.028 and 0.099 g/km for the two buses) were lower than those from the tailpipe (0.18 and 0.14 g/km), in-cabin PMck concentrations averaging 6.8 microg/m3 were higher than DPMtp (0.91 microg/m3 average). In-cabin DPMtp and PMck concentrations were significantly higher with bus windows closed (1.4 and 12 microg/m3, respectively) as compared with open (0.44 and 1.3 microg/m3, respectively). For comparison, average closed- and open-window in-cabin total PM2.5 concentrations were 26 and 12 microg/m3, respectively. Despite the relatively short in-cabin sampling times, very high sensitivities were achieved, with detection limits of 0.002 microg/m3 for DPMtp and 0.05 microg/m3 for PMck.
MeSH term(s)	Air Pollutants/analysis ; Air Pollutants/toxicity ; Environmental Exposure/prevention & control ; Environmental Monitoring/methods ; Environmental Monitoring/standards ; Gasoline/analysis ; Gasoline/toxicity ; Humans ; Motor Vehicles/standards ; Particle Size ; Particulate Matter/analysis ; Particulate Matter/toxicity ; Schools ; Urban Health/standards ; Vehicle Emissions/prevention & control ; Vehicle Emissions/toxicity ; Weights and Measures/instrumentation ; Weights and Measures/standards
Chemical Substances	Air Pollutants ; Gasoline ; Particulate Matter ; Vehicle Emissions
Language	English
Publishing date	2011-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1003064-5
ISSN	1096-2247 ; 0894-0630 ; 1047-3289
ISSN	1096-2247 ; 0894-0630 ; 1047-3289
DOI	10.3155/1047-3289.61.5.494
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Article: Quantification of Self Pollution from Two Diesel School Buses using Three Independent Methods.

Liu, L-J Sally / Phuleria, Harish C / Webber, Whitney / Davey, Mark / Lawson, Douglas R / Ireson, Robert G / Zielinska, Barbara / Ondov, John M / Weaver, Christopher S / Lapin, Charles A / Easter, Michael / Hesterberg, Thomas W / Larson, Timothy

Atmospheric environment (Oxford, England : 1994)

2010 Volume 44, Issue 28, Page(s) 3422–3431

Abstract: We monitored two Seattle school buses to quantify the buses' self pollution using the dual tracers (DT), lead vehicle (LV), and chemical mass balance (CMB) methods. Each bus drove along a residential route simulating stops, with windows closed or open. ... ...

Abstract	We monitored two Seattle school buses to quantify the buses' self pollution using the dual tracers (DT), lead vehicle (LV), and chemical mass balance (CMB) methods. Each bus drove along a residential route simulating stops, with windows closed or open. Particulate matter (PM) and its constituents were monitored in the bus and from a LV. We collected source samples from the tailpipe and crankcase emissions using an on-board dilution tunnel. Concentrations of PM(1), ultrafine particle counts, elemental and organic carbon (EC/OC) were higher on the bus than the LV. The DT method estimated that the tailpipe and the crankcase emissions contributed 1.1 and 6.8 mug/m(3) of PM(2.5) inside the bus, respectively, with significantly higher crankcase self pollution (SP) when windows were closed. Approximately two-thirds of in-cabin PM(2.5) originated from background sources. Using the LV approach, SP estimates from the EC and the active personal DataRAM (pDR) measurements correlated well with the DT estimates for tailpipe and crankcase emissions, respectively, although both measurements need further calibration for accurate quantification. CMB results overestimated SP from the DT method but confirmed crankcase emissions as the major SP source. We confirmed buses' SP using three independent methods and quantified crankcase emissions as the dominant contributor.
Language	English
Publishing date	2010-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	216368-8
ISSN	1352-2310 ; 0004-6981
ISSN	1352-2310 ; 0004-6981
DOI	10.1016/j.atmosenv.2010.06.005
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Article: Detailed characterization and profiles of crankcase and diesel particulate matter exhaust emissions using speciated organics.

Zielinska, Barbara / Campbell, David / Lawson, Douglas R / Ireson, Robert G / Weaver, Christopher S / Hesterberg, Thomas W / Larson, Timothy / Davey, Mark / Liu, L J Sally

Environmental science & technology

2008 Volume 42, Issue 15, Page(s) 5661–5666

Abstract: A monitoring campaign was conducted in August-September 2005 to compare different experimental approaches quantifying school bus self-pollution. As part of this monitoring campaign, a detailed characterization of PM2.5 diesel engine emissions from the ... ...

Abstract	A monitoring campaign was conducted in August-September 2005 to compare different experimental approaches quantifying school bus self-pollution. As part of this monitoring campaign, a detailed characterization of PM2.5 diesel engine emissions from the tailpipe and crankcase emissions from the road draft tubes was performed. To distinguish between tailpipe and crankcase vent emissions, a deuterated alkane, n-hexatriacontane-d74 (n-C36D74) was added to the engine oil to serve as an intentional quantitative tracer for lubricating oil PM emissions. This paper focuses on the detailed chemical speciation of crankcase and tailpipe PM emissions from two school buses used in this study. We found that organic carbon emission rates were generally higher from the crankcase than from the tailpipe for these two school buses, while elemental carbon contributed significantly only in the tailpipe emissions. The n-C36D74 that was added to the engine oil was emitted at higher rates from the crankcase than the tailpipe. Tracers of engine oil (hopanes and steranes) were present in much higher proportion in crankcase emissions. Particle-associated PAH emission rates were generally very low (< 1 microg/km), but more PAH species were present in crankcase than in tailpipe emissions. The speciation of samples collected in the bus cabins was consistent with most of the bus self-pollution originating from crankcase emissions.
MeSH term(s)	Air Pollutants/analysis ; Air Pollutants/chemistry ; Air Pollutants/toxicity ; Deuterium/chemistry ; Environmental Monitoring ; Hydrocarbons/chemistry ; Motor Vehicles ; Particle Size ; Particulate Matter/analysis ; Particulate Matter/chemistry ; Polycyclic Aromatic Hydrocarbons/chemistry ; Risk Assessment ; Time Factors ; Vehicle Emissions/analysis ; Vehicle Emissions/toxicity
Chemical Substances	Air Pollutants ; Hydrocarbons ; Particulate Matter ; Polycyclic Aromatic Hydrocarbons ; Vehicle Emissions ; Deuterium (AR09D82C7G)
Language	English
Publishing date	2008-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	0013-936X
ISSN	0013-936X
DOI	10.1021/es703065h
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Article: Development of a sensitive high-performance liquid chromatography method for the detection of 667 COUMATE in vivo.

Ireson, Christopher R / Parish, David / Purohit, Atul / Woo, Lawrence W L / Potter, Barry V L / Chander, Surinder K / Reed, Michael J

The Journal of steroid biochemistry and molecular biology

2003 Volume 84, Issue 2-3, Page(s) 337–342

Abstract: Steroid sulphatase inhibitors which decrease or prevent the biosynthesis of oestrogens, potentially have an important role in the treatment of breast cancer in postmenopausal women. The non-steroidal sulphatase inhibitor 667 COUMATE has been shown to be ... ...

Abstract	Steroid sulphatase inhibitors which decrease or prevent the biosynthesis of oestrogens, potentially have an important role in the treatment of breast cancer in postmenopausal women. The non-steroidal sulphatase inhibitor 667 COUMATE has been shown to be active both in vitro and in vivo. The pharmacokinetics of this drug have not been investigated. In preparation for the clinical evaluation of this agent, a sensitive and robust reversed phase high-performance liquid chromatography (HPLC) method was developed for the detection of 667 COUMATE in biological fluids. The sulphatase inhibitor was extracted from plasma with diethyl ether and separated from putative metabolites and endogenous plasma components with a C3-phenyl column. Using this method an extraction efficiency of 76+/-5% and a limit of detection of less than 0.1 ng/ml was achieved. The stability of this agent was investigated under different pH conditions and during storage in plasma at room temperature or -20 degrees C. 667 COUMATE was found to be stable when stored in acidified plasma (pH 4.5) at -20 degrees C. In conclusion, the HPLC method developed is a reproducible and sensitive assay that will enable quantitation of the potent non-steroidal sulphatase inhibitor 667 COUMATE in biological fluids in the forthcoming Phase I clinical trial.
MeSH term(s)	Chemistry, Clinical/methods ; Chromatography, High Pressure Liquid ; Coumarins/analysis ; Ether/analysis ; Humans ; Hydrogen-Ion Concentration ; Models, Chemical ; Sulfonamides/analysis ; Sulfonic Acids ; Temperature ; Time Factors
Chemical Substances	Coumarins ; Sulfonamides ; Sulfonic Acids ; Ether (0F5N573A2Y) ; irosustat (366037O6O7) ; coumarin (A4VZ22K1WT)
Language	English
Publishing date	2003-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/s0960-0760(03)00047-5
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Article: The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells.

Newman, Simon P / Ireson, Christopher R / Tutill, Helena J / Day, Joanna M / Parsons, Michael F C / Leese, Mathew P / Potter, Barry V L / Reed, Michael J / Purohit, Atul

Cancer research

2006 Volume 66, Issue 1, Page(s) 324–330

Abstract: The bis-sulfamoylated derivative of 2-methoxyestradiol (2-MeOE2), 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2-MeOE2bisMATE), has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo. 2-MeOE2bisMATE is ... ...

Abstract	The bis-sulfamoylated derivative of 2-methoxyestradiol (2-MeOE2), 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2-MeOE2bisMATE), has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo. 2-MeOE2bisMATE is bioavailable, in contrast to 2-MeOE2 that has poor bioavailability. In this study, we have examined the role of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 in the metabolism of 2-MeOE2. In MDA-MB-231 cells, which express high levels of 17beta-HSD type 2, and in MCF-7 cells transfected with 17beta-HSD type 2, high-performance liquid chromatography analysis showed that a significant proportion of 2-MeOE2 was metabolized to inactive 2-methoxyestrone. Furthermore, MCF-7 cells transfected with 17beta-HSD type 2 were protected from the cytotoxic effects of 2-MeOE2. In contrast, no significant metabolism of 2-MeOE2bisMATE was detected in transfected cells and 17beta-HSD type 2 transfection did not offer protection against 2-MeOE2bisMATE cytotoxicity. This study may go some way to explaining the poor bioavailability of 2-MeOE2, as the gastrointestinal mucosa expresses high levels of 17beta-HSD type 2. In addition, this study shows the value of synthesizing sulfamoylated derivatives of 2-MeOE2 with C17-position modifications as these compounds have improved bioavailability and potency both in vitro and in vivo.
MeSH term(s)	17-Hydroxysteroid Dehydrogenases/metabolism ; Biotransformation ; Breast Neoplasms/enzymology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Growth Processes/drug effects ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Estradiol/analogs & derivatives ; Estradiol/metabolism ; Estradiol/pharmacokinetics ; Humans ; Stereoisomerism ; Transfection
Chemical Substances	2-methoxyestradiol-3,17-bis-O,O-sulfamate ; Estradiol (4TI98Z838E) ; 2-methoxyestradiol (6I2QW73SR5) ; 17-Hydroxysteroid Dehydrogenases (EC 1.1.-)
Language	English
Publishing date	2006-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-05-2391
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

Order via subito