Objective—To determine the effects of the antioxidant astaxanthin on growth of canine osteosarcoma cells with and without concurrent chemotherapeutic or irradiation insult.
Sample Population—Cells from 3 established canine osteosarcoma cell lines (D17, OS 2.4, and HMPOS).
Procedures—Growth-curve kinetics and cell cytotoxic effects were assessed by means of various treatment combinations and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was performed to examine previously identified signaling pathways that astaxanthin reportedly affects. Additionally, cell-cycle kinetic evaluations, soft agar colony-forming assays, and antioxidant assays were performed to better understand the effect of astaxanthin on cell growth and function.
Results—Exposure to astaxanthin alone resulted in a mild to pronounced attenuation of cell proliferation in vitro, depending on the cell line, and did not interfere with the cell-death response to doxorubicin, irradiation, or peroxide-mediated insult. In some instances, astaxanthin acted in an additive fashion to augment cell death. Astaxanthin exposure increased the antioxidant potential of cells, whereas peroxide-mediated cell stress increased the antioxidant potential to the same degree as astaxanthin exposure or greater. No dramatic changes in phosphorylation of protein kinase B or upregulation of connexin 43 were detected.
Conclusions and Clinical Relevance—Findings suggested that astaxanthin administration may be beneficial in treatment of dogs for osteosarcoma. Its actions as an antioxidant did not improve osteosarcoma cell survival during chemotherapeutic or irradiation insults, warranting further research into this natural compound as an adjuvant, antiproliferative treatment for osteosarcoma in dogs.
To evaluate potential prognostic indicators for local recurrence, distant metastasis, and survival time in dogs with incompletely excised high-grade soft tissue sarcomas (HGSTSs), as defined by a mitotic index ≥ 9, that underwent definitive-intent radiation treatment (RT; ≥ 48 Gy total dose) with or without adjuvant chemotherapy.
41 client-owned dogs with HGSTSs treated with surgical resection followed by definitive-intent RT between January 1, 2000, and December 31, 2016.
Medical records were reviewed retrospectively, and data were collected. The Kaplan-Meier method was used to evaluate the overall survival time (OST) of dogs and time to progression (TTP) of disease, starting from the first day of RT. The Cox proportional hazards model was used to analyze the impact of results for several variables on OST and TTP.
The median OST was 981 days, with 1-, 3-, and 5-year survival rates of 85%, 43%, and 18%, respectively. The median TTP was not reached; however, the mean TTP was 1,581 days. Ten of the 41 (24%) dogs developed metastasis, and 8 (20%) developed local recurrence. Sixteen of the 41 dogs received chemotherapy. The hazard of disease progression over the study period increased as the mitotic index (hazard ratio [HR], 1.115) or duration of RT (HR, 1.427) increased. The hazard of death over the study period increased as the RT duration (HR, 1.372) or surgical scar length (HR, 1.272) increased.
CONCLUSIONS AND CLINICAL RELEVANCE
Although adjuvant chemotherapy was not associated with improved survival time in dogs of the present study, results indicated that improved OST and TTP could be achieved through strict adherence to the prescribed irradiation schedule and avoidance of unnecessary prolongation of the course of RT.
Objective—To determine outcome for dogs with nonresectable thyroid carcinomas treated with sodium iodide I 131 and identify factors associated with outcome.
Design—Retrospective case series.
Procedures—A definitive or presumptive diagnosis of thyroid tumor was made on the basis of cytologic or histologic examination, abnormal accumulation of sodium pertechnetate Tc 99m during scintigraphy, or both, and dogs were treated with sodium iodide I 131. Dogs with cervical thyroid tumors were evaluated 3 to 6 weeks after 131I therapy, and residual tumor was resected when feasible.
Results—Prior to 131I therapy, 32 dogs had a solitary mass and 7 had metastases; 21 were hyperthyroid, 16 were euthyroid, and 2 were hypothyroid. Median survival time for dogs with local or regional tumors (ie, stage II or III) was significantly longer (839 days) than median survival time for dogs with metastasis (366 days). Tumor site (cervical vs ectopic), dose of sodium iodide I 131, age, body weight, treatment (131I therapy alone vs 131I therapy followed by surgery), and serum T4 concentration prior to 131I therapy were not significantly associated with survival time. Three dogs died of radioiodine-associated myelosuppression within 3 months after treatment, but no specific factor associated with development of toxicosis was identified.
Conclusions and Clinical Relevance—Results suggested that 131I therapy may result in prolonged survival times in dogs with nonresectable thyroid tumors, regardless of serum thyroxine concentration prior to treatment. Dogs undergoing 131I therapy should be monitored for signs of bone marrow suppression.
Objective—To evaluate efficacy of radiation for treatment
of incompletely resected soft-tissue sarcomas
Design—Prospective serial study.
Animals—48 dogs with soft-tissue sarcomas.
Procedure—Tumors were resected to < 3 cm3 prior
to radiation. Tumors were treated on alternate days
(three 3-Gy fractions/wk) until 21 fractions had been
administered. Cobalt 60 radiation was used for all
Results—Five-year survival rate was 76%, and survival
rate was not different among tumor types or
locations. Four (8%) dogs developed metastases.
Eight (17%) dogs had tumor recurrence after radiation.
Development of metastases and local recurrence
were significantly associated with reduced survival
rate. Median survival time in dogs that developed
metastases was 250 days. Median disease-free
interval for all dogs was 1,082 days. Median time to
recurrence was 700 days. Dogs that developed recurrence
after a prolonged period responded well to a
second surgery. Acute radiation toxicosis was minimal;
osteosarcoma developed at the radiation site in
Conclusion and Clinical Relevance—An excellent
long-term survival rate may be achieved by treating
soft-tissue sarcomas in dogs with resection followed
by radiation. Amputation is not necessary for longterm
control of soft-tissue sarcomas in limbs.
Development of metastases and recurrence of local
tumors after radiation treatment are associated with
decreased survival rate. Acute and delayed radiation
toxicosis was minimal with the protocol used in this
study. (J Am Vet Med Assoc 2000;217:205–210)
Objective—To determine the efficacy of strontium 90 β irradiation in the management of cutaneous mast cell tumors (CMCTs) in cats.
Study Design—Retrospective case series.
Animals—35 client-owned cats with CMCTs.
Procedure—Medical records of cats with CMCTs in which tumors were radiated by use of a strontium 90 ophthalmic applicator from 1992 to 2002 were reviewed. Cats were included if CMCT was diagnosed, there were no other sites of MCT involvement at the time of treatment, and records contained adequate follow-up information to permit retrospective assessment of local tumor control.
Results—54 tumors in 35 cats were treated with a median dose of 135 Gy of strontium 90 β irradiation, resulting in local tumor control in 53 of 54 (98%) tumors with a median follow-up time of 783 days after treatment. Median survival time was 1,075 days. Adverse effects of treatment appeared to be infrequent and of mild severity.
Conclusions and Clinical Relevance—Results indicated that strontium 90 β irradiation resulted in long-term tumor control and should be considered an effective alternative to surgical resection in management of CMCTs in cats.
Objective—To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors.
Animals—16 client-owned dogs with metastatic or advanced-stage refractory tumors.
Procedures—An open-label, dose-escalation, singledose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted. Docetaxel (at doses of 1.5, 1.625, or 1.75 mg/kg) and CSA (5 mg/kg) were administered concurrently via gavage twice during a 3-week period. Plasma docetaxel concentrations were quantified by use of high-performance liquid chromatography, and pharmacokinetic disposition was characterized by use of noncompartmental analysis. Dogs' clinical signs and results of hematologic and biochemical analyses were monitored for evidence of toxicosis.
Results—No acute hypersensitivity reactions were observed after oral administration of docetaxel. Disposition of docetaxel was dose independent over the range evaluated, and pharmacokinetic variables were similar to those reported in previous studies involving healthy dogs, with the exception that values for clearance were significantly higher in the dogs reported here. The maximum tolerated dose of docetaxel was 1.625 mg/kg. Gastrointestinal signs of toxicosis were dose limiting.
Conclusions and Clinical Relevance—The absence of myelosuppression suggested that the docetaxelCSA combination may be administered more frequently than the schedule used. Further studies are warranted to evaluate combination treatment administered on a biweekly schedule in dogs with epithelial tumors.
Objective—To evaluate the veterinary version of the
bladder tumor antigen (V-BTA) test as a screening test
for transitional cell carcinoma (TCC) of the lower urinary
tract of dogs.
Animals—229 client-owned dogs.
Procedure—Urine samples from dogs were shipped
overnight to a single laboratory to facilitate testing
within 48 hours of collection by use of the V-BTA rapid
latex agglutination urine dipstick test. Groups of dogs
included the following: 1) dogs with TCC of the lower
urinary tract, 2) healthy control dogs, 3) unhealthy
control dogs with non-TCC urinary tract disease, and
4) unhealthy control dogs without urinary tract disease.
Test sensitivity and specificity were calculated
by use of standard methods. Logistic models were
developed to assess the effect of disease status, test
conditions, urine composition, and signalment on the
performance of the V-BTA test.
Results—A total of 229 urine samples were analyzed,
including 48 from dogs with suspected (n = 3) or confirmed
(45) TCC. Test sensitivities were 88, 87, and
85% for all dogs with (suspected and confirmed) TCC,
dogs with confirmed TCC at any site, and dogs with
confirmed TCC of the urinary bladder, respectively.
Test specificities were 84, 41, and 86% for healthy
control dogs, unhealthy control dogs with non-TCC
urinary tract disease, and unhealthy control dogs
without urinary tract disease, respectively. The test
performed slightly better on centrifuged urine samples
than on uncentrifuged urine samples.
Conclusions and Clinical Relevance—Our results
indicate that the V-BTA test is useful in screening for
urinary tract TCC in dogs. (Am J Vet Res