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Immunophenotyping of neoplastic cells in canine lympho-proliferative disease (LPD) can provide useful prognostic information. However, the underlying cause(s) for development of disease from B-cells or T-cells is not well understood. Modiano and colleagues performed a large scale study comparing the prevalence of T- or B-cell LPD among 1,236 dogs of 87 different breeds. They found that 15 of the 87 breeds showed significantly higher prevalence of either Tor B-cell disease compared to a reference population. For example, Shih Tzu dogs were much more likely to have T-cell LPD than B-cell LPD, while Cocker Spaniels were much more likely to have B-cell LPD than T-cell LPD. Cytogenetic analyses revealed specific recurrent chromosomal abnormalities that were associated with non-Hodgkin's lymphoma in Golden Retrievers. Furthermore, the authors demonstrated that the risk factors for development of T-cell and B-cell disease are different and can be related to ancestry in some breeds. This study provides important insight into the pathogenesis of canine LPD.
Modiano JF, Breen M, Burnett RC, Parker HG, Inusah S, Thomas R, Avery PR, Lindblad-Toh K, Ostrander EA, Cutter GC, Avery AC: Distinct B-cell and T-cell lymphoproliferative disease prevalence among dog breeds indicates heritable risk. Cancer Res 65(13):5654–61, 2005
Humans with inflammatory bowel disease (IBD) have an increased risk of colonic dysplasia and colorectal cancer. Mice deficient for the p-glycoprotein membrane efflux pump (mdr1–/– mice) spontaneously develop IBD are a useful model for the human disease. Previously it was shown that infection with Helicobacter bilis accelerates development of colitis in mdr1–/– mice, while infection with H. hepaticus delays development of colitis. In the present study, the investigators co-infected mdr1–/– mice with both H. bilis and H. hepaticus. By 39 weeks, some mice developed high grade colonic crypt dysplasia and invasive colonic carcinoma. Over-expression of the c-myc oncogene and proinflammatory interleukins 1
and 1ß were demonstrated in the colonic epithelial cells of co-infected mice. These findings may contribute to our understanding of the role of inflammation in cancer development.
Maggio-Price L, Bielefeldt-Ohmann H, Treuting P, Iritani BM, Zeng W, Nicks A, Tsang M, Shows D, Morrissey P, Viney JL: Dual infection with Helicobacter bilis and Helicobacter hepaticus in p-glycoprotein-deficient mdr1a–/– mice results in colitis that progresses to dysplasia. Am J Pathol 166(6):1793–806, 2005
Two new isolates of swine-origin Helicobacter pylori-like bacteria have recently been isolated. To characterize the gastric disease induced by these organisms, gnotobiotic pigs were infected with the new isolates (2662 and 1268), H. pylori (the human pathogen), and H. heilmannii. One of the new isolates, 2662, was highly pathogenic. Infected pigs developed ulcers of the gastroesophageal and gastric glandular regions. The 2662 isolate also induced lympho-plasmacytic inflammation and lymphoid follicle formation. This study suggests that swine-origin H. pylori-like organisms may play a role in the development of gastric diseases of swine.
Krakowka S, Rings DM, Ellis JA: Experimental induction of bacterial gastritis and gastric ulcer disease in gnotobiotic swine inoculated with porcine Helicobacter-like species. AJVR 66(6):945–952, 2005
Gastrointestinal nematodes are ubiquitous in nature. AKR mice are susceptible to infection with Trichuris muris, while BALB/c mice are resistant. Until now, the mechanism by which BALB/c mice are able to expel the parasites was unknown. Cliffe et al. hypothesized that the rate of colonic epithelial cell turnover may be a factor in the success of nematode expulsion. They found that BALB/c mice infected with T. muris have a higher rate of colonic epithelial cell proliferation and migration than AKR mice, resulting in an "epithelial escalator" that effectively escorts the worms to the intestinal lumen where they are expelled. The rate of epithelial turnover is regulated, at least in part, by the interleukin-13 cytokine and the CXCL10 chemokine.
Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C, Grencis RK: Accelerated intestinal epithelial cell turnover: A new mechanism of parasite expulsion. Science 308(5727):1463–5, 2005
The investigation of organ-specific stem cells for the regeneration of diseased or damaged tissues is an area of intense research. A recent report describes the characterization of self-renewing, clonogenic cardiac stem cells in the dog. Canine cardiac stem cells were positive for c-kit, MDR1 and Sca-1-like antigens, and one stem cell was present for every 18,000 myocytes. Investigators induced myocardial infarction in dogs, followed by administration of hepatocyte growth factor and insulin-like growth factor-1 to stimulate the stem and progenitor cells. Administration of these growth factors was associated with myocardial regeneration, neovascularization and improved contractility.
Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P: Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci 102(25):8966–71, 2005
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