Objective—To determine whether exposure of
canine osteosarcoma cells to deracoxib or piroxicam
results in decreased viability, whether the cytotoxic
effects of deracoxib and piroxicam involve induction
of apoptosis, and whether deracoxib is a more
potent inhibitor of osteosarcoma cell growth than
Sample Population—1 fibroblast and 3 osteosarcoma
Procedure—Cell counts and viability assays were
performed using osteosarcoma cells (POS, highly
metastatic POS, and canine osteosarcoma cell 31)
and fibroblasts after 72 hours of incubation with deracoxib
at concentrations of 0.5µM to 500µM or piroxicam
at concentrations of 1µM to 1,000µM.
Percentage viability was determined for each concentration.
A DNA fragmentation analysis was performed
to assess drug-induced apoptosis.
Results—Concentration of deracoxib required for
50% inhibition of cell viability (IC50) was reached in all
3 osteosarcoma cell lines and ranged from 70 to
150µM, whereas the IC50 for piroxicam was only
reached in the POS cell line at 500µM. Neither deracoxib
nor piroxicam induced sufficient toxicity in
fibroblasts to reach an IC50. Exposure of osteosarcoma
cells to cytotoxic concentrations of deracoxib and
piroxicam did not result in DNA fragmentation.
Conclusions and Clinical Relevance—Intermediate
and high concentrations of deracoxib and high concentrations
of piroxicam were cytotoxic to osteosarcoma
cells; neither drug inhibited cell viability at typical
plasma concentrations in dogs. Deracoxib inhibited
viability of cells at concentrations that did not
affect fibroblast viability. There was no evidence of
apoptosis induction for either drug; however, only 1
cell line was evaluated for apoptosis induction and
only for a limited selection of drug concentrations.
(Am J Vet Res 2005;66:1961–1967)
Objective—To determine the effect of pamidronate
disodium on the in vitro viability of osteosarcoma
cells and non-neoplastic cells from dogs.
Sample Population—3 osteosarcoma and 1 fibroblast
cell lines derived from dogs.
Procedure—Cell counts and cell viability assays were
performed in cultures of osteosarcoma cells (POS,
HMPOS, and COS31 cell lines) and fibroblasts after
24, 48, and 72 hours of incubation with pamidronate
at concentrations of 0.001 to 1,000µM or with no
drug (control treatment). Percentage viability was
determined in cell samples for each concentration of
pamidronate and each incubation time. A DNA fragmentation
analysis was performed to assess bisphosphonate-
Results—Osteosarcoma cell viability decreased significantly
in a concentration- and time-dependent
manner at pamidronate concentrations ranging from
100 to 1,000µM, most consistently after 48 and 72
hours' exposure. In treated osteosarcoma cells, the
lowest percentage cell viability was 34% (detected
after 72 hours' exposure to 1,000µM pamidronate).
Conversely, 72 hours' exposure to 1,000µM
pamidronate did not significantly reduce fibroblast viability
(the lowest percentage viability was 76%). After
72 hours of exposure, pamidronate did not cause
DNA fragmentation in POS or HMPOS cells.
Conclusions and Clinical Relevance—Results indicate
that pamidronate may have the potential to inhibit
osteosarcoma growth in dogs, possibly through a
nonapoptotic mechanism. The clinical relevance of
these in vitro findings remains to be determined, but
administration of pamidronate may potentially be indicated
as an adjuvant treatment in chemotherapeutic
protocols used in dogs. (Am J Vet Res 2005;66:
Objective—To determine whether thalidomide
inhibits the growth of primary and pulmonary
metastatic canine osteosarcoma in mice after xenotransplantation.
Animals—Athymic nude mice.
Procedure—Canine osteosarcoma cells were injected
SC in 50 mice. Mice were randomly placed into
the following groups: control group (n = 13; DMSO
[drug vehicle] alone [0.1 mL/d, IP]); low-dose group
(12; thalidomide [100 mg/kg, IP]), mid-dose group (13;
thalidomide [200 mg/kg, IP]); and high-dose group
(12; thalidomide [400 mg/kg, IP]). Starting on day 8,
treatments were administered daily and tumor measurements
were performed for 20 days. On day 28,
mice were euthanatized and primary tumors were
weighed. Lungs were examined histologically to
determine the number of mice with metastasis and
tumor emboli. Mean area of the pulmonary
micrometastatic foci was determined for mice from
Results—Primary tumor size and weight were not
significantly different among groups. The number of
mice in the mid-dose (200 mg/kg) and high-dose (400
mg/kg) groups with micrometastasis was significantly
less than the number of control group mice; however,
the number of mice with tumor emboli was not
affected by thalidomide treatment. Size of
micrometastasis lesions was not affected by thalidomide
Conclusions and Clinical Relevance—Mean area of
micrometastases was not affected by treatment;
however, growth of micrometastases had not yet
reached an angiogenesis-dependent size. Although
thalidomide did not affect growth of primary tumors in
mice after xenotransplantation of canine osteosarcoma
cells, our findings indicate that thalidomide may
interfere with the ability of embolic tumor cells to
complete the metastatic process within the lungs.
( Am J Vet Res 2004;65:659–664)
Objective—To describe a percutaneously controlled
static hydraulic urethral sphincter (SHUS) and evaluate
urodynamic effects of the SHUS in canine cadavers.
Sample Population—Cadavers of 6 adult female
Procedure—Cadavers were obtained immediately
after dogs were euthanatized. Baseline maximal urethral
closure pressure (MUCP) and cystourethral leak
point pressure (CLPP) were measured by use of a
urethral pressure profilometer. An SHUS system was
constructed by use of a silicone vascular occluder and
subcutaneous infusion port. The SHUS system was
then placed around the pelvic urethra in each cadaver.
Measurements of MUCP and CLPP were repeated
after varying occlusion of the SHUS (0%, 25%, and
50% occlusion). Baseline MUCP and CLPP values
were compared with values obtained at 0%, 25%,
and 50% occlusion of the SHUS by use of repeatedmeasures
Results—Mean ± SD MUCP for canine cadavers was
7 ± 1.3 cm H2O at baseline, which increased to 127 ±
53 cm H2O after 50% occlusion of the SHUS. Mean
CLPP was 11 ± 8.6 cm H2O at baseline, which
increased to 73 ± 38 cm H2O after 50% occlusion of
the SHUS. Mean MUCP and CLPP were significantly
associated with the amount of occlusion.
Conclusions and Clinical Relevance—The SHUS
had positive effects on MUCP and CLPP in canine
cadavers. Therefore, additional evaluation of the
SHUS in live dogs is warranted. ( Am J Vet Res 2004;
Procedure—Computed tomography (CT) of the pelvis, including a bone-density phantom, was performed for each dog. Centrally located transverse CT slices and a computer workstation were used to identify 16 regions of interest (ROIs) in the proximal portion of the femur. For each ROI, the mean Hounsfield unit value was recorded; by use of the bone-density phantom and linear regression analysis, those values were converted to equivalent BMD (eBMD). Mean eBMD values for the subchondral and nonsubchondral ROIs in dogs with and without osteoarthritis (determined at necropsy) were compared. A mixed-model ANOVA and post hoc linear contrasts were used to evaluate the effects of osteoarthritis, breed, and sex on the BMD value.
Results—At necropsy, osteoarthritis was detected in 14 hip joints in 9 dogs; all lesions included early cartilage fibrillation. After adjusting for breed and sex, eBMD in subchondral ROIs 8 and 12 (adjacent to the fovea) were 8% and 6% higher, respectively, in osteoarthritis-affected dogs, compared with unaffected dogs; in the nonsubchondral ROIs, eBMD was 10% higher in osteoarthritis-affected dogs.
Conclusions and Clinical Relevance—Compared with findings in unaffected dogs, increased eBMD in hip joints of dogs with early osteoarthritis supports a strong relationship between the subchondral and epiphyseal regions and articular cartilage in the pathogenesis and progression of osteoarthritis.
Objective—To determine whether dorsolateral subluxation
(DLS) scores in young dogs could be used to
reliably predict which dogs would develop evidence of
hip osteoarthritis and whether DLS scores measured
at various ages correlated with each other.
Animals—129 Labrador Retrievers, Greyhounds, and
Labrador Retriever-Greyhound crossbreds.
Procedures—DLS scores were measured on radiographs
taken at 4, 8, and 12 months of age and at
necropsy (8 to 36 months of age). At necropsy, the
hip joints were examined macroscopically and a score
assigned for degree of cartilage degeneration.
Results—DLS scores at 4 (n = 35, rs = –0.62), 8 (n =
106, rs = –0.54), and 12 (n = 15, rs = –0.87) months of
age were significantly correlated with cartilage degeneration
scores, and DLS scores at 8 months of age
were significantly correlated with scores obtained at
the time of necropsy (n = 39, rs = 0.87). The DLS
scores at 4 months of age were significantly different
from scores at 8 months of age, but scores did not differ
significantly thereafter. Likelihood ratios for cartilage
lesions for low (< 45%), intermediate (≥ 45 but ≤
55%), and high (> 55%) DLS scores at 8 months of
age were 8.0, 2.6, and 0.2, respectively.
Conclusions and Clinical Relevance—Results suggest
that DLS score at 8 months of age was a reasonable,
albeit imperfect, predictor of the condition of the
hip joint cartilage at necropsy. Thus, the DLS method
might be useful for early identification of dogs with hip
dysplasia. (Am J Vet Res 2001;62:1711–1715)
Objective—To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice.
Animals—27 athymic nude mice.
Procedures—To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated.
Results—Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group.
Conclusions and Clinical Relevance—Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs.
Impact for Human Medicine—Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.
OBJECTIVE To describe the signalment, clinical signs, biological behavior, and outcome for cats with apocrine gland anal sac adenocarcinoma (AGASACA) that underwent surgical excision.
DESIGN Retrospective case series.
ANIMALS 30 client-owned cats.
PROCEDURES Databases of 13 Veterinary Society of Surgical Oncology member–affiliated institutions were searched for records of cats with a histologic diagnosis of AGASACA that underwent tumor excision. For each cat, information regarding signalment, clinical signs, diagnostic test results, treatment, and outcome was extracted from the medical record. The Kaplan-Meier method was used to determine median time to local recurrence (TLR), disease-free interval (DFI), and survival time. Cox regression was used to identify factors associated with TLR, DFI, and survival time.
RESULTS Perineal ulceration or discharge was the most common clinical sign in affected cats. Eleven cats developed local recurrence at a median of 96 days after AGASACA excision. Incomplete tumor margins and a high nuclear pleomorphic score were risk factors for local recurrence. Nuclear pleomorphic score was negatively associated with DFI. Local recurrence and a high nuclear pleomorphic score were risk factors for death. Median DFI and survival time were 234 and 260 days, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, in cats, perineal ulceration or discharge should raise suspicion of AGASACA and prompt rectal and anal sac examinations. Local recurrence was the most common life-limiting event in cats that underwent surgery for treatment of AGASACA, suggesting that wide margins should be obtained whenever possible during AGASACA excision. Efficacy of chemotherapy and radiation therapy for treatment of cats with AGASACA requires further investigation. (J Am Vet Med Assoc 2019;254:716–722)
Objective—To characterize the radiosensitivity and capacity for sublethal damage repair (SLDR) of radiation-induced injury in 4 canine osteosarcoma cell lines.
Sample Population—4 canine osteosarcoma cell lines (HMPOS, POS, COS 31, and D17).
Procedures—A clonogenic colony-forming assay was used to evaluate the cell lines' intrinsic radiosensitivities and SLDR capacities. Dose-response curves for the cell lines were generated by fitting the surviving fractions after radiation doses of 0 (control cells), 1, 2, 3, 6, and 9 Gy to a linear quadratic model. To evaluate SLDR, cell lines were exposed to 2 doses of 3 Gy (split-dose experiments) at an interval of 0 (single 6-Gy dose), 2, 4, 6, or 24 hours, after which the surviving fractions were assessed.
Results—Mean surviving fraction did not differ significantly among the 4 cell lines at the radiation doses tested. Mean surviving fraction at 2 Gy was high (0.62), and the α/β ratios (predictor of tissue sensitivity to radiation therapy) for the cell lines were low (mean ratio, 3.47). The split-dose experiments revealed a 2.8- to 3.9-fold increase in cell survival when the radiation doses were applied at an interval of 24 hours, compared with cell survival after radiation doses were applied consecutively (0-hour interval).
Conclusions and Clinical Relevance—Results indicated that these canine osteosarcoma cell lines are fairly radioresistant; α/β ratios were similar to those of nonneoplastic, lateresponding tissues. Future clinical investigations should involve increasing the fraction size in a manner that maximizes tumor killing without adverse effects on the nonneoplastic surrounding tissues.