The Three Rs…
Although contentious, common marmosets are used as a nonhuman primate animal model in various fields, including physiology, drug metabolism, preclinical toxicology, and reproductive biology. Recently, transgenic marmosets have been created (Sasaki et al, Nature, 2009;28:523–527). Nonhuman primates may be the only species considered suitable for testing certain biotechnology-derived pharmaceuticals (“humanized” medicines), and this is driving the worldwide increase in nonhuman primate use. Veterinary pathologists will thus welcome the report on glomerular and tubulointerstitial lesions in common marmosets in this issue of Veterinary Pathology (Isobe et al, “Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus),” 2012;49:839–845). Ethically, it is important to have detailed information on the background lesions in these species to ensure the most efficient and reductive use of these animals. Isobe and colleagues provide a detailed description of the spontaneous renal disease as well as a grading system and a list of reagents used to aid in the diagnosis of the disease.
Seeing Is Believing
Accurate interpretation of immunohistochemical reactions in neoplastic and nonneoplastic lesions requires the knowledge of normal tissue’s immunohistochemical properties. Featured in this issue is a report on the immunohistochemistry of canine eyes (Labelle et al, “Immunohistochemical Characteristics of Normal Canine Eyes,” Vet Pathol, 2012;49:860–869). Interestingly, the canine retinal pigment epithelium is immunoreactive for both cytokeratins and vimentin. This finding and others may have major implications in the use of animal models of human ocular disease as reviewed by Zeiss and coworkers in a previous edition of Veterinary Pathology (2010;47:396–413).
The Marvelously Adaptable Cancer Genome
As demonstrated by 2 papers in this issue, identifying discrete genetic features of cancer can elucidate its comparative or prognostic aspects (York et al, “TP53 Mutations in Canine Brain Tumors,” Vet Pathol, 2012;49:796–801, and Newman et al, “C-kit Expression in Canine Mucosal Melanomas,” Vet Pathol, 2012;49:760–765). In the former paper, p53 mutations in canine brain tumors occur at much lower rates than in comparable human tumors; in the latter, C-kit expression is associated with longer survival.
But cancer is a slippery customer. Chemotherapeutic failure results in part from continued evolution of resistant clones within a tumor. The recent advent of single-cell sequencing is able to characterize the evolution of clonal subpopulations in the native tumor, and how the genome of surviving clones can adapt to each round of chemotherapy (Science, May 25, 2012;336:976–977). As suspected, it’s never one thing. The inherent genomic instability of tumor cells drives progressive heterogeneity and tremendous behavioral plasticity (Saunders et al, “Role of Intratumoural Heterogeneity in Cancer Drug Resistance: Molecular and Clinical Perspectives,” EMBO Mol Med, June 25, 2012). And detailed single-cell sequencing reveals a far greater number of inciting mutations than initially suspected. These are early days, but as the technology becomes automated, features of the adaptive landscape that characterizes chemotherapy resistance will emerge.
