13 research outputs found
The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway
Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques
Low vitamin D status is associated with systemic and gastrointestinal inflammation in dogs with a chronic enteropathy
Vitamin D is traditionally known for its role in calcium homeostasis and bone metabolism.
However, it has been demonstrated that numerous types of cells express the vitamin D
receptor and it is now clear that the physiological roles of vitamin D extend beyond the
maintenance of skeletal health. Vitamin D insufficiency, which is typically assessed by
measuring the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has
been associated with a number of disorders in people including hypertension, diabetes,
cardiovascular diseases, cancer, autoimmune conditions and infectious diseases. Meta-analyses
have demonstrated that serum 25(OH)D concentrations are an important predictor
of survival in people with a wide variety of illnesses and have been linked to all-cause
mortality in the general human population.
The role of vitamin D in non-skeletal disorders in cats and dogs is poorly understood. This is
surprising since cats and dogs could act as excellent models for probing the biology of
vitamin D. Vitamin D status in people is largely dependent on cutaneous production of
vitamin D. This is influenced by many factors such as season, latitude and exposure to
ultraviolet (UV) radiation. The interpretation of human studies investigating the effects
vitamin D status on disease outcomes are therefore influenced by a number of confounding
variables. Unlike humans, domesticated cats and dogs do not produce vitamin D cutaneously
and obtain vitamin D only from their diet. The physiological functions and regulation of
vitamin D are otherwise similar to humans. Most pets are fed commercial diets containing a
relatively standard amount of vitamin D. Consequently, companion animals are attractive
model systems in which to examine the relationship vitamin D status and health outcomes.
Furthermore, spontaneously occurring model systems which did not require disease to be
induced in healthy animals would allow the numbers of animals used in scientist research to
be reduced.
This thesis aimed to define vitamin D homeostasis in companion animals in three disease
settings; in cats with feline immunodeficiency virus (FIV) infection, dogs with chronic
enteropathies (CE) and in hospitalised ill cats. Additional aims were to assess the prognostic
significance of serum 25(OH)D concentrations in companion animals and the relationship
between serum 25(OH)D concentrations and markers of inflammation. The hypothesis of
this thesis was that vitamin status D would negatively correlate with presence of disease,
markers of inflammation and disease outcomes. As similar findings have been demonstrated
in human medicine, the hypothesis was that cats and dogs would be suitable models to
investigate the role of vitamin D in human disease.
This thesis demonstrates that in dogs with a CE serum 25(OH)D concentrations are
negatively correlated with inflammation and are predictive of clinical outcomes. Vitamin D
status was also lower in cats with FIV and importantly vitamin D status was predictive of
short term mortality in hospitalised ill cats. This research will be of interest to veterinary
surgeons and opens the possibility for clinical trials which examine if low vitamin D status is
causally associated with ill health and whether vitamin D supplementation results in superior
treatment outcomes in companion animals. This thesis also demonstrates the potential of cats
and dogs as model systems in which to examine the role of vitamin D in human health
Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
Sandra M Axiak1, Kim A Selting1, Charles J Decedue2, Carolyn J Henry1,3, Deborah Tate1, Jahna Howell2, K James Bilof1, Dae Y Kim4 1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; 2CritiTech Inc, Lawrence, KS, USA; 3Department of Internal Medicine, Division of Hematology and Oncology; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Background: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Methods: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m2, and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m2. Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. Results: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m2. Grade 1–2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. Conclusion: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m2. Keywords: paclitaxel, nanoparticle, canin
Feline infectious peritonitis: still an enigma?
Feline infectious peritonitis (FIP) is one of the most important fatal infectious diseases of cats, the pathogenesis of which has not yet been fully revealed. The present review focuses on the biology of feline coronavirus (FCoV) infection and the pathogenesis and pathological features of FIP. Recent studies have revealed functions of many viral proteins, differing receptor specificity for type I and type II FCoV, and genomic differences between feline enteric coronaviruses (FECVs) and FIP viruses (FIPVs). FECV and FIP also exhibit functional differences, since FECVs replicate mainly in intestinal epithelium and are shed in feces, and FIPVs replicate efficiently in monocytes and induce systemic disease. Thus, key events in the pathogenesis of FIP are systemic infection with FIPV, effective and sustainable viral replication in monocytes, and activation of infected monocytes. The host's genetics and immune system also play important roles. It is the activation of monocytes and macrophages that directly leads to the pathologic features of FIP, including vasculitis, body cavity effusions, and fibrinous and granulomatous inflammatory lesions. Advances have been made in the clinical diagnosis of FIP, based on the clinical pathologic findings, serologic testing, and detection of virus using molecular (polymerase chain reaction) or antibody-based methods. Nevertheless, the clinical diagnosis remains challenging in particular in the dry form of FIP, which is partly due to the incomplete understanding of infection biology and pathogenesis in FIP. So, while much progress has been made, many aspects of FIP pathogenesis still remain an enigma