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  • Author or Editor: Tsuyoshi Kadosawa x
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Objective—To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells.

Sample Population—3 osteosarcoma cell lines established from osteosarcomas in dogs.

Procedure—Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted.

Results—In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies.

Conclusion and Clinical Relevance—Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs. (Am J Vet Res 2000;61:69–73)

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in American Journal of Veterinary Research


Objective—To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice.

Animals—Forty-five 5-week-old female BALB/c nude mice.

Procedure—1 × 107 POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 µg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined.

Results—Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group.

Conclusions and Clinical Relevance—9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs. (Am J Vet Res 2000; 61:1241–1244)

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in American Journal of Veterinary Research


Objective—To characterize the clinical features of visceral mast cell tumors (MCT) without associated cutaneous involvement in dogs.

Design—Retrospective study.

Animals—10 dogs with histologically confirmed MCT without associated cutaneous lesions.

Procedure—Information on signalment, clinical signs, laboratory examinations, and time from first admission to death was obtained from the medical record of each dog.

Results—Purebred male dogs of miniature breeds appeared to have a higher prevalence of visceral MCT. Clinical signs included anorexia, lethargy, vomiting, and diarrhea. Anemia (n = 7), hypoproteinemia (5), and mastocythemia (5) were detected. Treatments, including glucocorticoids, were not successful. Primary sites of tumors were the gastrointestinal tract (n = 6) and the spleen or liver (1); the primary site was not confirmed in the remaining 3 dogs. In 7 dogs, tumors were categorized as grade II or III, on the basis of histologic findings. The prognoses were poor, and all dogs died within 2 months after first admission.

Conclusions and Clinical Relevance—Visceral MCT is uncommon in dogs, and the prognosis is extremely poor. Biological behavior and drug susceptibility of visceral MCT may be different from cutaneous MCT. The lack of specific clinical signs may result in delay of a definitive diagnosis. The rapid progression of clinical signs and difficulty in diagnosis contributes to a short survival time. ( J Am Vet Med Assoc 2000;216: 222–226)

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in Journal of the American Veterinary Medical Association