Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

References
761
analysis will facilitate future studies ( Thomas et al. , 2003,
2005 ) .
In a small study of canine leukemia, cytogenetic abnormalities
did not correlate with survival ( Grindem and
Buoen, 1986 ). Similarly, a small study of feline leukemia
found no relationship between cytogenetic abnormalities
and prognosis ( Grindem and Buoen, 1989 ). In a study of
the cytogenetics of canine lymphoma, dogs with tumors
having trisomy 13 had a significantly longer median survival
time compared to dogs with tumors having other
chromosomal aberrations ( Hahn et al. , 1994 ). Further studies
are needed to determine the prognostic importance of
chromosomal aberrations in veterinary oncology.
VIII. MOLECULAR ONCOLOGY
The literature detailing the application of molecular biology
techniques in human clinical oncology is vast. Not only
have methods studying alterations in gene expression and
DNA mutations contributed greatly to the understanding of
cancer biology, they also are useful for defining subgroups
of patients with similar histology yet different prognoses,
identifying patients that will benefit from targeted therapy,
and predicting the risk for toxicity from treatment ( Khanna
and Helman, 2006 ). A complete review of molecular biology
applications in oncology is beyond the scope of this chapter,
and they are reviewed elsewhere ( Costa and Lizardi, 2005 ).
Canine mast cell tumors illustrate the potential of molecular
techniques to advance veterinary oncology. Mutations,
notably tandem duplications in exons 11 and 12, have been
discovered in the protooncogene c- kit of malignant canine
mast cells ( London et al. , 1999 ). These changes can lead
to the constitutive activation of Kit, a type 3 receptor tyrosine
kinase, in the absence of its ligand, stem cell factor.
Dysregulation of Kit may play a role in the uncontrolled
growth or inappropriate survival of canine mast cells, potentially
leading to mast cell tumor formation. These observations
led to in vitro studies of tyrosine kinase inhibitors in
canine mast cell tumors, which showed promise as targeted
therapeutic agents for tumors with Kit dysregulation ( Liao
et al. , 2002 ). These targeted inhibitors then entered clinical
trials in veterinary medicine ( London et al. , 2003 ; Pryer et al. ,
2003 ). Although the presence of c- kit mutations does not predict
biological behavior of canine mast cell tumors ( Downing
et al. , 2002 ), cytoplasmic immunoreactivity with anti-Kit
(CD 117) antibodies does appear to predict local recurrence
and survival time ( Preziosi et al. , 2004 ; Webster et al. , 2004 ).
IX. PROTEOMICS, GENOMICS,
METABOLOMICS
The advent of sophisticated methods for protein separation
and rapid identification has provided the ability for
researchers to study global patterns of protein and gene
expression or activity in metabolic pathways, in emerging
disciplines known as proteomics, genomics, and metabolomics.
The applications of proteomics to veterinary medicine
have revealed a series of fucosylated proteins, including
CD44 and E-selectin, that are elevated in dogs with lymphoma
and decrease during the course of chemotherapy
treatment ( Xiong et al. , 2003 ). With the completion of the
sequencing of the canine genome, a microarray is being
developed to study the changes in tumor gene expression
in canine tumors ( Thomas et al. , 2003 ) , which may lead to
improved early diagnosis methods and targeted therapeutic
strategies. These technologies are not yet ready for widespread
clinical use, in part because of the challenges of
analyzing the massive amounts of data generated and the
persistent concerns about reproducibility of results. Despite
these challenges, the “ -omics ” have tremendous potential
to become rapid, high-throughput systems for identifying
candidate tumor markers for more careful study. See
Chapter 5 for more detailed information about proteomics.
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