Objective—To identify matrix metalloproteinases
(MMP) 2 and 9 in canine tumor tissue and to compare
the amount of activity to that in unaffected stromal
Animals—30 dogs with spontaneously developing,
Procedure—Tumor and nearby stromal tissue (muscle)
were obtained at the time of surgery. Specimens were
homogenized, and supernatants were assayed, using
gelatin zymography. Human derived standards were
run concurrently. Densitometry was done to obtain a
semiquantitative arbitrary unit value for each specimen.
The amount of activity in tumor tissue was compared
with the amount in stromal tissue.
Results—Gelatinolytic bands were observed from
the analysis of all tumor tissues and in most stromal
tissues. These bands migrated in the same molecular
weight area as the human MMP 2 and 9 standards.
Gelatinolytic activity could be quenched by the addition
of 50 mM EDTA and 1 µg of synthetic tissue
inhibitor of metalloproteinase (TIMP) 2 per 100 ml.
There was significantly more gelatinolytic activity in
tumor tissue than in stromal tissue.
Conclusions and Clinical Relevance—MMP 2 and 9
are detectable in canine neoplastic tissue. matrix metalloproteinases
activity in tumor tissue is higher than in
unaffected stromal tissue, indicating that canine MMP
may be involved in the pathogenesis of tumor growth
and metastasis. (Am J Vet Res 2000;61:111–114)
OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide.
ANIMALS 6 healthy adult cats.
PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m2) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments. Plasma samples were obtained at various time points for up to 8 hours after administration. Samples were treated with semicarbazide hydrochloride to trap the 4-OHCP in stable form, which allowed for cyclophosphamide and trapped 4-OHCP to be simultaneously measured by use of tandem mass spectrometry. Pharmacokinetic parameters were determined from drug concentration-versus-time data for both cyclophosphamide and 4-OHCP.
RESULTS Cyclophosphamide was tolerated well regardless of route of administration. Pharmacokinetic parameters for 4-OHCP were similar after oral, IV, and IP administration. Area under the concentration-time curve for cyclophosphamide was lower after oral administration than after IV or IP administration.
CONCLUSIONS AND CLINICAL RELEVANCE Cyclophosphamide can be administered interchangeably to cats as oral, IV, and IP formulations, which should provide benefits with regard to cost and ease of administration to certain feline patients.
Objective—To determine the incidence of regional
lymph node metastasis in dogs with appendicular
osteosarcoma and determine whether regional lymph
node metastasis was associated with shortened disease-free interval or survival time.
Animals—228 dogs with appendicular osteosarcoma
in which regional lymph nodes were examined histologically
at the time of limb amputation.
Procedure—Information collected from the medical
records included signalment; affected site; initial
serum alkaline phosphatase activity; whether treatment
involved adjuvant chemotherapy and, if so,
chemotherapeutic agents administered and number of
treatments; disease-free interval; and survival time.
Results—10 (4.4%) dogs had histologic evidence of
regional lymph node metastasis at the time of amputation.
Median disease-free interval for dogs without
regional lymph node metastasis (238 days; range, 0 to
1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median
survival time for dogs without lymph node metastasis
(318 days; range, 20 to 1,711 days) was significantly
longer than median survival time for dogs with lymph
node metastasis (59 days; range, 19 to 365 days).
Conclusions and Clinical Relevance—Results suggest
that regional lymph node metastasis is rare in dogs with
appendicular osteosarcoma but that dogs with lymph
node metastasis have a poorer prognosis than do dogs
without. (J Am Vet Med Assoc 2005;226:1364–1367)
Objective—To describe the biological behavior, clinical outcome, and prognostic factors of osteosarcoma of the maxilla, mandible, or calvarium in dogs.
Design—Retrospective case series.
Animals—183 client-owned dogs with osteosarcoma of the maxilla, mandible, or calvarium.
Procedures—Medical records for dogs treated for osteosarcoma of the maxilla, mandible, or calvarium from 1986 through 2012 were reviewed. Dogs with a histopathologic diagnosis of osteosarcoma and treated for a primary tumor arising from these bones of the head were included.
Results—Mean age was 9.3 years, and body weight was 31.8 kg (70.0 lb). Most dogs (124/183 [67.8%]) were purebred, and the most common primary tumor site was the maxilla (80 [43.7%]). Treatments included palliative medical treatment only (11/183 [6.0%]), coarsely fractionated radiation therapy (RT; 12 [6.6%]), fractionated or stereotactic RT (18 [9.8%]), surgery (135 [73.8%]), and both surgery and fractionated RT (7 [3.8%]). Eighty-three (45.4%) dogs received adjuvant chemotherapy. Local recurrence or progression occurred in 80 of 156 (51.3%) dogs, and 60 of 156 (38.5%) dogs developed distant metastases. Median survival time for all dogs was 239 days. Dogs that underwent surgery had a median survival time of 329 days. Histologically tumor-free surgical margins were associated with significantly decreased hazards of progression or recurrence (hazard ratio [HR], 0.4) and death (HR, 0.5). Dogs with osteosarcoma of the calvarium had a significantly greater hazard of local recurrence or progression (HR, 2.0).
Conclusions and Clinical Relevance—In this study, tumor excision in dogs with histologically tumor-free margins resulted in better local control and longer survival time than did other treatment types.
Objective—To identify biomarker proteins for B-cell lymphoma in canine serum by use of surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry and build classification trees with multiple biomarkers that have high sensitivity and specificity for that tumor type.
Sample Population—Sera from 29 dogs with B-cell lymphoma and 87 control dogs (approx equal numbers of healthy dogs, dogs with malignant cancers other than B-cell lymphoma, and dogs with various nonneoplastic diseases or conditions).
Procedures—Serum samples were fractionated chromatographically and analyzed via SELDI-TOF mass spectrometry. Peak amplitudes of the spectra from the 2 sample groups were compared to identify potential biomarker peaks, and classification trees were built by use of computer software to detect patterns formed by multiple biomarkers among SELDI data sets.
Results—Several biomarker protein peaks in canine serum were identified, and a classification tree was built on the basis of 3 biomarker protein peaks. With 10-fold cross-validation of the sample set, the best individual serum biomarker peak had 75% sensitivity and 86% specificity and the classification tree had 97% sensitivity and 91% specificity for the classification of B-cell lymphoma.
Conclusions and Clinical Relevance—On the basis of biomarker proteins identified in canine serum, classification trees were constructed, which may be useful for the development of a diagnostic test for B-cell lymphoma in dogs. Further investigation is needed to determine whether these biomarkers are useful for screening susceptible dog populations or for monitoring disease status during treatment and remission of B-cell lymphoma in dogs.
Objective—To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment.
Design—Retrospective case series.
Animals—54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data.
Procedure—Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment.
Results—Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis.
Conclusions and Clinical Relevance—Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.
Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.
Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.
Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.
Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.
Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.
Objective—To characterize the signalment, clinical
signs, biological behavior, and response to treatment
of carcinoma of the apocrine glands of the anal sac in
Animals—113 dogs with histologically confirmed carcinoma
of the apocrine glands of the anal sac.
Procedure—Data on signalment, clinical signs, and
staging were reviewed and analyzed along with treatment
modality for potential association with survival
Results—Sex distribution was approximately equal
(54% female, 46% male). One hundred four dogs
underwent treatment consisting of surgery, radiation
therapy, chemotherapy, or multimodal treatment.
Median survival for treated dogs was 544 days (range,
0 to 1,873 days). Dogs treated with chemotherapy
alone had significantly shorter survival (median, 212
days) than those receiving other treatments (median,
584 days). Dogs not treated with surgery had significantly
shorter survival (median, 402 days) than those
that underwent surgery as part of their treatment
(median, 548 days). Dogs with tumors ≥ 10 cm2 had
significantly shorter survival (median, 292 days) than
dogs with tumors ≥ 10 cm2 (median, 584 days).
Hypercalcemia was identified in 27% (n = 29) of dogs,
and those dogs had significantly shorter survival (median,
256 days), compared with those that were normocalcemic
(median, 584 days). Dogs with pulmonary
metastasis had significantly shorter survival (median,
219 days) than dogs without evidence of pulmonary
metastasis (median, 548 days).
Conclusions and Clinical Relevance—Unlike most
previous reports, this study revealed an approximately
equal sex distribution, and results suggest a more
favorable prognosis. (J Am Vet Med Assoc 2003;223: