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Abstract

OBJECTIVE To assess the in vitro effects of doxorubicin and tetrathiomolybdate (TM) on cells from a canine hemangiosarcoma cell line.

SAMPLE Cultured cells from the canine hemangiosarcoma–derived cell line DEN-HSA.

PROCEDURES Cells were treated with TM (0 to 1.5μM), doxorubicin (0 to 5μM), or both with or without 24 hours of pretreatment with ascorbic acid (750μM). Degree of cellular cytotoxicity was measured with a colorimetric assay. Long-term growth inhibition was assessed with a 10-day colony-formation assay. Induction of apoptosis was quantitated by fluorometric assessment of caspase-3 and −7 activation. Formation of reactive oxygen species (ROS) was also detected fluorometrically.

RESULTS Exposure of cells to the combination of TM and doxorubicin resulted in a greater decrease in proliferation and clonogenic survival rates than exposure to each drug alone. This treatment combination increased ROS formation and apoptosis to a greater extent than did doxorubicin or TM alone. Ascorbic acid inhibited both TM-induced ROS formation and apoptosis.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the enhancement in cytotoxic effects observed with DEN-HSA cell exposure to the combination of doxorubicin and TM was achieved through an increase in ROS production. These findings provide a rationale for a clinical trial of this treatment combination in dogs with hemangiosarcoma.

Full access
in American Journal of Veterinary Research

Objective

To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival.

Design

Prospective clinical trial.

Animals

105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis.

Procedure

Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed.

Results

Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure.

Clinical Implications

Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy. (J Am Vet Med Assoc 1997;210:778–784

Free access
in Journal of the American Veterinary Medical Association

Objective

To determine quality and duration of progression-free survival (PFS) time in dogs with periodontal tumors after definitive megavoltage irradiation and to analyze prognostic factors for PFS time and patterns of treatment failure.

Design

Prospective clinical trial.

Animals

47 dogs with acanthomatous, fibromatous, or ossifying epulis.

Procedure

Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's proportional hazards regression model to determine prognostic factors for PFS time.

Results

The only independent prognostic factor for PFS time was tumor T stage. Pattern of local tumor recurrence (marginal vs infield regrowth) was independent of clinical stage, tumor location, and site. In 4% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 6.4% of the dogs, chronic radiation reactions included bone necrosis.

Clinical Implications

Irradiation was a safe and effective treatment of small (T1 and T2 stage) periodontal tumors. The usefulness of the radiation protocol in this study is limited in dogs with large (T3) tumors, particularly those located in the caudal half of the oral cavity, because of poor results and high risk of acute radiation toxicoses. (J Am Vet Med Assoc 1997;210:785–788

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS).

Animals—27 cats with a nonresectable, recurrent, or metastatic VAS.

Procedure—Each cat received ifosfamide (900 mg/m2 of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifos-famide-associated toxic effects were graded in accordance with predetermined criteria.

Results—61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treat-ments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/μL (range, 200 to 5,382 cells/μL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis.

Conclusions and Clinical Relevance—Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To develop a simple extractionless method for detection of rosiglitazone in canine plasma and test the method in a pharmacokinetic study after oral administration of rosiglitazone in dogs.

Animals—3 client-owned dogs with cancer.

Procedures—High-performance liquid chromatography-tandem mass spectrometry was performed on canine plasma. The 3 dogs with cancer in the pharmacokinetic study were assessed via physical examination and clinicopathologic evaluation and considered otherwise healthy. Food was withheld for 12 hours, and dogs were administered a single dose (4 mg/m2) of rosiglitazone. Plasma was collected at various times, processed, and analyzed for rosiglitazone.

Results—The developed method was robust and detected a minimum of 0.3 ng of rosiglitazone/mL. Mean ± SD maximum plasma concentration was 205.2 ± 79.1 ng/mL, which occurred at 3 ± 1 hours, and mean ± SD elimination half-life was 1.4 ± 0.4 hours. The area under the plasma rosiglitazone concentration-versus-time curve varied widely among the 3 dogs (mean ± SD, 652.2 ± 351.3 ng/h/mL).

Conclusions and Clinical Relevance—A simple extractionless method for detection of rosiglitazone in canine plasma was developed and was validated with excellent sensitivity, accuracy, precision, and recovery. The method enabled unambiguous evaluation and quantitation of rosiglitazone in canine plasma. This method will be useful for pharmacokinetic, bioavailability, or drug-drug interaction studies. Oral rosiglitazone administration was well tolerated in the dogs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs.

DESIGN Retrospective case series.

ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only.

PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates.

RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

The anti-GnRH immunotherapeutic product Improvest was administered to intact male large flying foxes (Pteropus vampyrus) under managed care for androgen mitigation, leading to a decrease in agonistic behaviors, falls, and injuries from conspecific attention.

ANIMALS

12 males were included in this study.

PROCEDURES

Eleven bats received subcutaneous (SC) Improvest interscapular, and 1 animal received Improvest SC in its leg. Assessments included clinical presentation, treatment, behavior, and urine and fecal glucocorticoid metabolites and testosterone (T5) concentrations.

RESULTS

Eleven of the 12 bats developed reactions, which included facial edema, localized irritation, swelling of the head and neck, and pruritus with varying degrees of skin ulceration and subsequent necrosis. Three of the animals required extensive treatments, and the 1 animal who received the injection in its leg was unaffected. Posttreatment, fecal glucocorticoid metabolite and/or T5 values were at or below the nonbreeding season baseline for 3 successive breeding seasons, and there was a reduction in agonistic interactions, falls, and injuries.

CLINICAL RELEVANCE

A behavioral characteristic of this species is to focus on areas of irritation that exacerbated the extent of the skin wounds. Some cases required medical, surgical, and behavioral intervention. Large flying foxes may be particularly sensitive to this immunotherapeutic when given subcutaneously in the interscapular region. Despite this reaction, the positive long-term effects on behavior and multiyear reduction of hormones suggest that the use of this immunotherapeutic warrants further investigation, although the results should be taken into consideration with other factors such as handling, treatments, chronicity of lesions.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate effects of substituting mitoxantrone for doxorubicin in a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapeutic protocol for first-line treatment of dogs with multicentric intermediate- to large-cell lymphoma.

DESIGN Retrospective cohort study.

ANIMALS 44 dogs treated with cyclophosphamide, mitoxantrone, vincristine, and prednisone (CMOP) and 51 dogs treated with CHOP at 12 referral institutions.

PROCEDURES Medical records were reviewed to determine response to treatment, progression-free survival time, and overall survival time. For dogs treated with CMOP, adverse events were also recorded.

RESULTS All 44 (100%) dogs treated with CMOP and 37 of 38 (97.4%) dogs treated with CHOP had a complete or partial response. Median progression-free survival time for dogs treated with CMOP was 165 days (95% confidence interval [CI], 143 to 187 days), and median overall survival time was 234 days (95% CI, 165 to 303 days). For dogs treated with CHOP, median progression-free survival time was 208 days (95% CI, 122 to 294 days), and median overall survival time was 348 days (95% CI, 287 to 409 days). Progression-free and overall survival times were not significantly different between groups. Overall, 9 of the 44 (20%) dogs treated with CMOP had adverse events likely or probably related to mitoxantrone, but all of these adverse events were mild.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that mitoxantrone may be a reasonable substitution in a CHOP protocol for treatment of dogs with multicentric intermediate- to large-cell lymphoma when doxorubicin is contraindicated.

Full access
in Journal of the American Veterinary Medical Association

Abstract

CASE DESCRIPTION

3 dogs with retroperitoneal masses (2 renal and 1 located near the diaphragm) were treated by percutaneous microwave ablation (MWA).

CLINICAL FINDINGS

Dogs between 11 and 13 years of age weighing between 13.7 and 43.8 kg had either a renal mass (n = 2) or a mass located in the caudodorsal aspect of the retroperitoneal space near the right side of the diaphragm (1). Cytology revealed that one of the renal masses and the mass located near the diaphragm were malignant neoplasias. Findings on cytologic evaluation of a sample of the other renal mass was nondiagnostic. Maximum mass diameters ranged between 1.4 and 2.5 cm.

TREATMENT AND OUTCOME

All dogs were treated by percutaneous MWA. Probes were directed into tumors by use of ultrasound and CT guidance, and microwave energy was applied to each mass. Findings on imaging of each mass following MWA was consistent with successful treatment. No intraprocedural or major postprocedural complications occurred, and all dogs were discharged from the hospital within 3 days of treatment. Two dogs died at 3 and 21 months after MWA with no known local recurrence; 1 dog was still alive 64 months after treatment.

CLINICAL RELEVANCE

Although the indications for MWA in the treatment of neoplasia in companion animals are limited, the outcomes of dogs in the present report provided preliminary evidence that percutaneous MWA can be safely used to effectively treat retroperitoneal neoplasia. This procedure was successfully performed with image guidance in all 3 dogs.

Full access
in Journal of the American Veterinary Medical Association