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  • Author or Editor: Casey D. Cadile x
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Abstract

Objective—To establish the diagnostic significance of the telomeric repeat amplification protocol (TRAP) assay in detecting feline malignancies.

Sample Population—Solid tissue specimens collected from 33 client-owned cats undergoing diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital between July 1997 and September 1999 and an additional 20 tissue samples were collected from 3 clinically normal control cats euthanatized at the conclusion of an unrelated study.

Procedure—The TRAP assay was used for detection of telomerase activity. Each result was compared to its respective histopathologic diagnosis.

Results—Twenty-nine of 31 malignant and 1 of 22 benign or normal tissue samples had telomerase activity, indicating 94% sensitivity and 95% specificity of the TRAP assay in our laboratory.

Conclusion and Clinical Relevance—The diagnostic significance of telomerase activity has been demonstrated in humans and recently in dogs by our laboratory. We tested feline samples to determine whether similar patterns of telomerase activity exist. On the basis of our results, the TRAP assay may be clinically useful in providing a rapid diagnosis of malignancy in cats. The telomerase enzyme may also serve as a therapeutic target in feline tumors. (Am J Vet Res 2001;62:1578–1581)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues.

Sample Population—57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs.

Procedures—Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois.

Results—Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length.

Conclusions and Clinical Relevance—Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human antitelomerase strategies.

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in American Journal of Veterinary Research

Abstract

Objective—To compare results of treatment with temozolomide or dacarbazine, in combination with an anthracycline, in dogs with relapsed or refractory lymphoma.

Design—Nonrandomized, controlled clinical trial.

Animals—63 dogs with relapsed or refractory lymphoma.

Procedures—Chemotherapy was administered in 21-day cycles. A combination of temozolomide and an anthracycline (doxorubicin or dactinomycin) was administered to 21 dogs and a combination of dacarbazine and an anthracycline was administered to 42 dogs. Efficacy and toxicoses were assessed.

Results—Thirteen of the 18 (72%) dogs treated with the temozolomide-anthracycline combination and 25 of the 35 (71%) dogs treated with the dacarbazine-anthracycline combination had a complete or partial response. Median duration of response to rescue chemotherapy was 40 days (range, 0 to 217 days) for dogs in the temozolomide group and 50 days (range, 0 to 587 days) for dogs in the dacarbazine group. The incidence of high-grade hematologic toxicoses was significantly higher among dogs in the dacarbazine group than among dogs in the temozolomide group, but the incidence of gastrointestinal tract toxicoses was not significantly different between groups. There were no significant differences between groups in regard to proportion of dogs with a complete or partial response, duration of response to rescue chemotherapy, survival time following rescue chemotherapy, or overall survival time.

Conclusions and Clinical Relevance—Both combinations had promise in the treatment of dogs with relapsed or refractory lymphoma, although administration of temozolomide was more convenient than administration of dacarbazine and caused fewer hematologic toxicoses.

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in Journal of the American Veterinary Medical Association