Studies on telomere and telomerase biology are fundamental to the understanding of aging and age-related diseases such as cancer. However, human studies have been hindered by differences in telomere biology between humans and the classical murine animal model system. In this paper, we describe basic studies of telomere length and telomerase activity in canine normal and neoplastic tissues and propose the dog as an alternative model system. Briefly, telomere lengths were measured in normal canine peripheral blood mononuclear cells (PBMCs), a range of normal canine tissues, and in a panel of naturally occurring soft tissue tumours by terminal restriction fragment (TRF) analysis. Further, telomerase activity was measured in canine cell lines and multiple canine tissues using a combined polymerase chain reaction/enzyme-linked immunosorbent assay method. TRF analysis in canine PBMCs and tissues demonstrated mean TRF lengths to range between 12 and 23 kbp with heterogeneity in telomere lengths being observed in a range of normal somatic tissues. In soft tissue sarcomas, two subgroups were identified with mean TRFs of 22.2 and 18.2 kbp. Telomerase activity in canine tissue was present in tumour tissue and testis with little or no activity in normal somatic tissues. These results suggest that the dog telomere biology is similar to that in humans and may represent an alternative model system for studying telomere biology and telomerase-targeted anticancer therapies.
Stereotactic body radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted.
In vitro and in vivo studies of human tissues have demonstrated telomeric attrition with age and have linked this attrition to cellular senescence and aging. Telomere studies in canine subjects have not thus far consistently uncovered the same pattern of telomere attrition that would be expected because of the end replication problem. In this report we describe the investigation of telomere lengths in a broad age range of dogs from three different breeds: the Labrador Retriever, Miniature Schnauzer and Beagle. Peripheral blood mononuclear cell-derived DNA samples were subjected to terminal restriction fragment (TRF) analysis and demonstrated a range of mean TRFs from 9.7 to 22.3 kbp. Telomeric attrition tended to be associated with increasing donor age (P = 0.06). Interbreed differences in mean TRF values were also noted (P = 0.006). These results warrant further investigation of possible interbreed differences, given that shorter telomeres may contribute to differing life expectancy between breeds.
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