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Objective-To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision. Study Design-Retrospective study. Animals-Dogs (n ¼ 35) with soft tissue low-grade spindle cell sarcoma. Methods-Medical records were reviewed and dogs that had marginal surgical resection of lowgrade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included. Results-Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Followup after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because o50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7-836 days) and 703.5 days (95% CI: 566.6-840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins. Conclusion-Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate. Clinical Relevance-Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery. r

Findings indicated that in dogs with cutaneous MCTs, prognostication should not rely on histologic grade alone, regardless of grading system used, but should take into account results of clinical staging.

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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In cancer gene therapy there are basic elements that need to be accomplished in order to produce an effective therapy. These are specifi c targeting of cancer cells, high expression of trans-genes and low toxicity.We have used the telomerase promoter which is shown to be active in 85-90% of canine cancers and combined this with a two-step amplifi cation mechanism. In this system the telomerase promoter drives the transcription of a transcriptional activator protein which in turn activates a strong minimal promoter to transcribe the trans-gene of interest. We have tested this system in cell culture using telomerase positive and negative cell lines and have shown the ability of this system to be very active in telomerase positive cells. We have also compared our system with the GAL4-VP16 system which is commonly used in gene therapy.Results: Our system shows a high level of specifi city and sensitivity and it is superior to the GAL4-VP16 system. Conclusion:We have developed a system with a unique potential to target cancer cells and express trans-genes at a high level and believe that this system will be able to improve gene therapy mechanisms. Prospect:We are working on developing a conditionally replicative adenovirus using CAV-1 making it capable of replicating and inducing lysis in telomerase positive cells. Simultaneously we are on using the TRAIL gene for cancer cell killing.