Annual Meeting Program - Society of Toxicology

Society of Toxicology 2008
Program Description (Continued)
Abstract #
#645 10:45 THE ONCOGENIC MICRORNA-27A
TARGETS GENES THAT REGULATE
SPECIFICITY PROTEIN (SP)
TRANSCRIPTION FACTORS AND
ESTROGEN RECEPTOR a IN BREAST
CANCER CELLS. S. Safe 1,2 , S. U. Mertens-
Talcott 1 , S. Chintharlapalli 2 and X. Li 1 . 1 Veterinary
Physiology & Pharmacology, Texas A&M University,
College Station, TX and 2 Institute of Biosciences
& Technology, Texas A&M Health Science Center,
Houston, TX.
#646 11:15 NETWORKS OF PROTEIN-PROTEIN
INTERACTIONS NECESSARY FOR
UBIQUITINATION OF ESTROGEN
RECEPTOR ALPHA BY BRCA1/BARD1. C. M.
Eakin 1 , M. J. MacCoss 2 , D. E. Christensen 1 and R.
E. Klevit 1 . 1 Biochemistry, University of Washington,
Seattle, WA and 2 Genome Sciences, University of
Washington, Seattle, WA. Sponsor: D. Eakin.
Tuesday Morning, March 18
9:00 AM to 11:45 AM
Room 611
WORKSHOP SESSION: DRUG-RELATED TORSADES DE
POINTES: ADVANCEMENTS IN PRECLINICAL MODELING OF
POTENTIAL CARDIAC TOXICITY
Chairperson(s): Alan Bass, Schering-Plough Research Institute,
Kenilworth, NJ and Jean-Pierre Valentin, AstraZeneca, Macclesfield,
United Kingdom.
Endorsed by:
Regulatory and Safety Evaluation Specialty Section*
Risk Assessment Specialty Section
Safety Pharmacology Society
Drug-induced delay in cardiac ventricular repolarization (QT/QTc prolongation)
serves as a sensitive surrogate of the potential life-threatening
cardiac arrhythmia, torsades des pointes (TdP), but importantly lacks the
specificity to know if, when & under what circumstances TdP may be elicited
in the clinical population. Identification of better preclinical models
of drug-related TdP is a significant challenge for the scientific community,
and was thoroughly debated at an ILSI/HESI workshop convened in
November 2005 at which recommendations for further study were proposed
(www.hesiglobal.org/Events/TdPWorkshop.htm). Advancements in three
key areas of investigation will be judged in terms of progress in each of
these areas of model development. They include: cellular and molecular
biology of drug-induced TdP, attempts to directly link drug exposure to
TdP; understanding the dynamics of periodicity (beat to beat variability in
the electrocardiogram) from preclinical and clinical investigations; and in
vitro and in vivo modeling of drug-induced TdP. The timing of the 2008
SOT workshop is important as 2009/2010 was selected for a followup two
day ILSI/HESI meeting at which those areas of scientific pursuit holding
the greatest promise of providing better predictors of TdP arrhythmia will be
considered and possibly prioritized. The 2008 workshop will be an important
interim assessment of advancements in each of the three areas of study
since the 2005 program and also serve to advocate further investigation by
toxicology scientists in preparation for the important debate in 2009/2010.
Drug-induced TdP remains a serious public health issue in rapidly bringing
safe new pharmaceutical agents to the marketplace for diseases for which
there are no acceptable alternative therapies. As a result, accurate identification
of those drugs posing a risk of cardiac toxicity using the best preclinical
models is of paramount importance. This workshop is being co-sponsored
by Society of Toxicology and Safety Pharmacology Society.
Abstract #
#647 9:00 DRUG-RELATED TORSADES DES POINTES:
ADVANCEMENTS IN PRECLINICAL
MODELING OF POTENTIAL CARDIAC
TOXICITY. A. S. Bass 1 and J. Valentin 2 .
1
Investigational & Regulatory Safety Pharmacology,
Schering-Plough, Kenilworth, NJ and 2 Drug
Safety, AstraZeneca, Macclesfield, Chesire, United
Kingdom.
#648 9:17 CELLULAR AND MOLECULAR BIOLOGY
OF DRUG-INDUCED TDP: THE ROLE
OF POTASSIUM CHANNELS, OTHER
PROTEINS, AND DOWNSTREAM EVENTS.
D. Roden. Oates Institute for Experimental
Therapeutics, Vanderbilt University School of
Medicine, Nashville, TN. Sponsor: A. Bass.
#649 9:54 CELLULAR AND MOLECULAR BIOLOGY
OF DRUG-INDUCED TORSADE DE POINTES
(TDP) IN THE LONG QT SYNDROME: ROLE
OF CALCIUM CHANNEL MODULATION IN
TRIGGERING TDP. G. Salama. Cell Biology and
Physiology, University of Pittsburgh, Pittsburgh, PA.
Sponsor: A. Bass.
#650 10:31 DYNAMICS OF PERIODICITY:
PRECLINICAL AND CLINICAL EVIDENCE
OF PROARRHYTHMIA POTENTIAL. A. A.
Fossa. Translational and Molecular Medicine, Pfizer
Global Research and Development, Groton, CT.
Sponsor: A. Bass.
#651 11:08 ADVANCES IN NON-CLINICAL MODELS
FOR DETECTING DRUG-INDUCED
TORSADES DE POINTES (TdP). J. Valentin 1 ,
C. Lawrence 1 , C. E. Pollard 1 , G. Duker 2 and T. G.
Hammond 1 . 1 Safety Assessment UK, AstraZeneca
R&D, Alderley Park, Macclesfield, United Kingdom
and 2 Integrative Pharmacology, AstraZeneca R&D,
Molndal, Sweden.
Tuesday Morning, March 18
9:00 AM to 11:45 AM
Room 6A
WORKSHOP SESSION: THE ALLERGIC MARCH: THE ROLE
OF CHEMICALS IN THE INCREASING PREVALENCE OF
ALLERGY AND ASTHMA
Chairperson(s): Ian Kimber, The University of Manchester, Manchester,
United Kingdom and Ian Gilmour, U.S. EPA, Research Triangle Park, NC.
Endorsed by:
Immunotoxicology Specialty Section*
It is now well-established that during the last four decades there has been in
industrialized western societies a substantial increase in the prevalence of
asthma and atopic allergic disesae. These changes are acknowledged to have
been too rapid to be accounted for by alterations in the gene pool, and for
this reason there has been considerable interest in the roles played by environmental
influences and acquired host factors on susceptibility to allergy
and asthma. In this context there has been speculation that increased exposure
to certain specific chemicals and/or chemical pollution more generally,
may impact on the development of allergy and asthma. We will here explore
whether and to what extent chemical exposure is implicated in susceptibility
to allergic disease, and in addition what other environmental factors may be
influential
Tuesday
up-to-date information at www.toxicology.org 147