Annual Meeting Program - Society of Toxicology

Society of Toxicology 2012
Program Description (Continued)
Abstract #
Tuesday Afternoon, March 13
1:30 PM to 4:15 PM
Room 103
​Aberrant Gene Expression in Toxicity and Disease—
Epigenetics and microRNAs
Symposium Session: Circulating microRNAs: A New Class of
Biomarkers for Tissue-Specific Toxicity
Chairperson(s): Wenyue Hu, Pfizer, Inc., San Diego, CA, and Greg Falls,
GlaxoSmithKline, Research Triangle Park, NC.
Sponsor:
Drug Discovery Toxicology Specialty Section
Endorsed by:
Cardiovascular Toxicology Specialty Section
In Vitro Alternatives Specialty Section
Molecular Biology Specialty Section
Regulatory and Safety Evaluation Specialty Section
MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that downregulate
gene expression. Some miRNAs are produced at high concentrations
within cells in a tissue-specific manner, and such miRNAs have recently
been reported to be remarkably stable in plasma or other accessible body
fluids. More importantly, differential increases in circulating miRNA populations
have been shown by numerous studies to be associated with different
disease or toxicity phenotypes. For example, tumor-derived miRNAs have
been shown to distinguish patients with cancer from healthy individuals.
Plasma concentrations of miR-122, miR-133a, and miR-124 have recently
been shown to correspond to injuries in liver, muscle, and brain, respectively.
Elevation in cardiac-specific miR-208a in plasma has been implicated as a
potential biomarker for early diagnosis of acute myocardial infarction in
humans. Taken together, because of their size, abundance, tissue specificity,
and relative stability in body fluids, miRNAs hold promise as a new class
of accessible biomarkers to monitor tissue-specific injuries. Our panel will
explore the importance of this topic by providing perspectives from both
industry and government sectors on the application of miRNAs as potential
tissue injury biomarkers, the promises and pitfalls of miRNAs, and technical
issues related to miRNA profiling in tissue and biofluids. Finally, our discussion
will end with the impact of miRNA biomarkers on drug development in
nonclinical studies, and the potential translatability to safety assessment in
clinical settings.
#1655 1:30 CIRCULATING MICRORNAS: A NEW CLASS
OF BIOMARKERS FOR TISSUE-SPECIFIC
TOXICITY. ​W. Hu 1 , and G. J. Falls 2 . 1 Drug Safety
R&D, Pfizer, San Diego, CA, and 2 Safety Assessment,
GlaxoSmithKline, Research Triangle Park, NC.
1:30 INTRODUCTION. ​Wenyue Hu
#1656 1:35 MICRORNACHANGES IN RAT MESENTERY
AND SERUM ASSOCIATED WITH DRUG-
INDUCED VASCULAR INJURY. ​M. Scicchitano,
and R. Thomas. Safety Assessment, GlaxoSmithKline,
King of Prussia, PA.
#1657 2:07 URINE MICRORNAS AS KIDNEY INJURY
BIOMARKERS: THE CASE FOR EXOSOMES. ​
P. Yuen. National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health,
Bethesda, MD. Sponsor: G. Falls.
#1658 2:39 MICRORNA BIOMARKERS OF
GASTROINTESTINAL TOXICITY IN TISSUES
AND BIOFLUIDS. ​A. Yang, D. Kalabat, A. Vitsky,
W. Scott, and W. Huang. Drug Safety R&D, Pfizer, San
Diego, CA.
Abstract #
#1659 3:11 EXTRACELLULAR MICRORNAS: A NEW
SOURCE OF BIOMARKERS FOR LIVER
INJURY. ​K. Wang. Institute for Systems Biology,
Seattle, WA. Sponsor: G. Falls.
#1660 3:43 CIRCULATING MICRORNAS AS POTENTIAL
BIOMARKERS OF DRUG-INDUCED
TESTICULAR TOXICITY. ​J. Kelsall 2 , and H. Lin 1 .
1
Drug Safety R&D, Pfizer, Andover, MA, and 2 Safety
Assessment UK, AstraZeneca, Macclesfield, Cheshire,
United Kingdom.
Tuesday Afternoon, March 13
1:30 PM to 4:15 PM
Room 303
Symposium Session: In Vitro and In Vivo Alternative Models of
Developmental Toxicity of Pharmaceutical Compounds
Chairperson(s): Claudia McGinnis, Hoffmann-La Roche, Basel,
Switzerland, and Aldert Piersma, National Institute for Public Health and
the Environment RIVM, Bilthoven, Netherlands.
Sponsor:
Reproductive and Developmental Toxicology Specialty Section
Endorsed by:
In Vitro and Alternative Methods Specialty Section
Regulatory and Safety Evaluation Specialty Section
In vitro methods for testing of developmental toxicity effects of chemicals
have been in use since ECVAM validated the EST (Embryonic Stem Cell Test
for Embryotoxicity) assay as an alternative to in vivo developmental toxicology
studies. The EST assay has been slow accept in the pharmaceutical
industry, mostly due to the perceived complexity and uncertain applicability
domain associated with in vitro differentiation from stem cells to cardiomyocytes,
the classical EST endpoint. In recent years, considerable efforts have
been undertaken to define new endpoints using genomic, proteomic, and
metabolomic markers. In addition, a human stem cell-derived EST approach
has been initiated as well as the validation of other alternative models such as
zebrafish for embryotoxicity prediction. There are many new developments
in this field such as comparing in vitro and in vivo alternative approaches
and the use of models to identify primary targets of known teratogens. In
addition, novel automation and culturing approaches will be reviewed that
have considerably aided in the reduction of variability and work load of the
EST assay. Advances in using transcriptomics for identification of predictive
biomarkers will also be covered, along with the current status of development
of a human EST assay. Finally, bottlenecks in the implementation of
these assays in regulatory toxicology will be discussed.
#1661 1:30 IN VITRO AND IN VIVO ALTERNATIVE
MODELS OF DEVELOPMENTAL TOXICITY
OF PHARMACEUTICAL COMPOUNDS. ​C.
McGinnis 1 , A. H. Piersma 2 , H. Handa 3 , T. B. Knudsen 4 ,
and J. Hescheler 5 . 1 Nonclinical Safety, Hoffmann-La
Roche, Basel, Switzerland, 2 Laboratory for Health
Protection Research, National Institute for Public
Health and the Environment RIVM, Bilthoven,
Netherlands, 3 Solutions Research Laboratory,
Tokyo Institute of Technology, Yokohama, Japan,
4
National Center for Computational Toxicology, US
EPA, Research Triangle Park, NC, and 5 Institute of
Neurophysiology, University of Cologne, Cologne,
Germany.
1:30 Introduction. ​Claudia Mcginnis
#1662 1:35 THE ROCHE EXPERIENCE WITH THE EST
ASSAY AND DEVELOPMENT OF A NOVEL,
FULLY AUTOMATED APPROACH. ​C.
McGinnis. Nonclinical Safety, Hoffmann-La Roche,
Basel, Switzerland.
Tuesday
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