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  • Author or Editor: Ira K. Gordon x
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Abstract

Objective—To investigate activation of the mammalian target of rapamycin (mTOR) pathway and the antitumor effect of rapamycin in canine osteosarcoma cells.

Sample Population—3 established primary canine osteosarcoma cell lines generated from naturally developing tumors.

Procedures—Expression of total and phosphorylated mTOR and p70S6 kinase was assessed by use of western blot analysis in canine osteosarcoma cells with and without the addition of rapamycin. A clonogenic assay was performed to determine the surviving fraction of osteosarcoma cells at various concentrations of rapamycin.

Results—Total and phosphorylated mTOR and p70S6 kinase expression was evident in all 3 cell lines evaluated, which was indicative of activation of this pathway. Treatment with rapamycin resulted in a time-dependent decrease in phosphorylated mTOR expression and a lack of detectable phosphorylated p70S6 kinase. No detectable change in expression of total mTOR and total p70S6 kinase was identified after rapamycin treatment. The clonogenic assay revealed a significant dose-dependent decrease in the surviving fraction for all 3 cell lines when treated with rapamycin.

Conclusions and Clinical Relevance—These data indicated that mTOR and its downstream product are present and active in canine osteosarcoma cells. The pathway can be inhibited by rapamycin, and treatment of cells with rapamycin decreased the surviving tumor cell fraction. These data support the molecular basis for further investigation into the use of mTOR inhibitors as an antineoplastic approach for dogs with osteosarcoma.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine progression-free and overall survival times of cats with squamous cell carcinoma (SCC) of the nasal planum following treatment with a single fraction of strontium Sr 90 (90Sr).

Design—Retrospective case series.

Animals—49 cats with SCC of the nasal planum.

Procedures—Information including FIV infection status, diagnosis of SCC vs SCC in situ (ie, evidence that the tumor did or did not penetrate the epidermal basement membrane, respectively), 90Sr dose and number of probe applications, treatment-related response and complications, and recurrence of SCC and new lesion development was obtained from medical records. The relationships of these variables with calculated progression-free and overall survival times were assessed.

Results—Of 49 cats that underwent 90Sr plesiotherapy (median dose, 128 Gy), 48 (98%) had a response to treatment and 43 (88%) had a complete response. Median progression-free and overall survival times were 1,710 and 3,076 days, respectively. Treatment complications were infrequent (4 [8%] cats) and mild. Following treatment, the SCC recurrence rate was 20% (10/49 cats); 16 (33%) cats developed new lesions in other locations. Overall survival time was significantly longer for cats with a complete response to treatment than for those with a partial response. None of the other variables evaluated had a significant effect on progression-free or overall survival time.

Conclusions and Clinical Relevance—Treatment of cats with SCC of the nasal planum with a single fraction of 90Sr appeared to be effective and well tolerated. Initial response to treatment was predictive of overall survival time.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate changes in characteristics of feline injection-site sarcomas (ISSs) from 1990 through 2006.

Design—Retrospective case series.

Animals—392 cats with a histologic diagnosis of soft tissue sarcoma, osteosarcoma, or chondrosarcoma at potential injection sites.

Procedures—Classification and anatomic location of tumors and signalment of affected cats were compared between ISSs diagnosed before and after publication of the Vaccine Associated Feline Sarcoma Task Force vaccination recommendations in 1996.

Results—From before to after publication of the vaccination recommendations, proportions of ISSs significantly decreased in the interscapular (53.4% to 39.5%) and right and left thoracic (10.2% to 3.6% and 9.1% to 1.3%, respectively) regions. On the other hand, proportions of ISSs significantly increased in the right thoracic limb (1.1% to 9.5%) and the combined regions of the right pelvic limb with right lateral aspect of the abdomen (12.5% to 25.0%) and the left pelvic limb with left lateral aspect of the abdomen (11.4% to 13.8%). Patterns of tumor classification and signalment did not change.

Conclusions and Clinical Relevance—Despite publication of the vaccination recommendations, a high proportion of tumors still developed in the interscapular region. There was also an increase in lateral abdominal ISSs, which are more difficult to treat and are likely attributable to aberrant placement of injections intended for the pelvic limbs. Veterinarians are complying with vaccination recommendations to some extent, but they need to focus on administering vaccines as distally as possible on a limb to allow for complete surgical margins if amputation of a limb is required.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To describe the clinical signs, physical examination findings, clinical laboratory abnormalities, etiology, and outcome in cats with spontaneous hemoperitoneum.

Design—Retrospective case series.

Animals—65 client-owned cats with spontaneous hemoperitoneum.

Procedures—Medical records of cats with spontaneous hemoperitoneum at 7 large referral clinics were reviewed. Cats were included if a definitive diagnosis of spontaneous hemoperitoneum could be obtained from review of the medical records.

Results—65 cats met inclusion criteria. The most common historical findings were lethargy, anorexia, and vomiting. Common findings on physical examination included inadequate hydration status and hypothermia. The most common clinicopathologic abnormalities were high serum AST activity, anemia, prolonged prothrombin time, and prolonged partial thromboplastin time. Forty-six percent (30/65) of cats had abdominal neoplasia, and 54% (35/65) had nonneoplastic conditions. Hemangiosarcoma was the most often diagnosed neoplasm (18/30; 60%), and the spleen was the most common location for neoplasia (11/30; 37%). Eight cats survived to be discharged from the hospital. Cats with neoplasia were significantly older and had significantly lower PCVs than cats with non-neoplastic disease.

Conclusions and Clinical Relevance—Spontaneous hemoperitoneum in cats often results in debilitating clinical consequences. In contrast to dogs with hemoperitoneum, the cause of hemoperitoneum in cats is approximately evenly distributed between neoplastic and nonneoplastic diseases. Although only a few cats were treated in this study, the prognosis appears poor.

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in Journal of the American Veterinary Medical Association