Intestinal lymphoma in dogs: 84 cases (1997-2012).

OBJECTIVE To describe signalment, clinicopathologic features, and outcomes of dogs with confirmed primary intestinal lymphoma and assess factors associated with survival times in these patients. DESIGN Retrospective case series. ANIMALS 84 client-owned dogs. PROCEDURES Medical records from 7 veterinary institutions were retrospectively reviewed to identify dogs with primary intestinal lymphoma. Data collected included signalment, clinical signs, anatomic location of tumors, diagnostic procedures, treatment, outcome, and dates of diagnosis and death. RESULTS Overall median survival time (MST) was 62 days (range, 1 to 537 days). Factors associated with shorter survival time on univariate analysis included anorexia or septic peritonitis at the time of diagnosis and tumor location (intestinal tract only, intestinal tract and abdominal lymph nodes, or intestinal tract and extraintestinal organs). The most commonly noted changes in the intestinal tract were altered wall thickening with loss of layering (41 dogs) and presence of ≥ 1 discrete mass (24 dogs). Protocols based on cyclophosphamide, doxorubicin, vincristine, and prednisone with or without l-asparaginase (48 dogs) or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (14 dogs) were most commonly used as first-line treatment; the MSTs of dogs receiving these treatments (60 and 144 days, respectively) did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE The MST of dogs with primary intestinal lymphoma was poor, regardless of first-line treatment used. Anorexia and septic peritonitis were associated with poor prognosis.

Drosophila p53 preserves genomic stability by regulating cell death.

When animal cells are exposed to stressful conditions, the tumor suppressor protein p53 restrains growth by promoting an arrested cell cycle or initiating a cell death program. How these distinct fates are specified through the action of a single protein is not known. To study its functions in vivo we produced a targeted mutation at the Drosophila p53 (Dmp53) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest. Dmp53 function is also required for damage-induced transcription of two tightly linked cell death activators, reaper and sickle. When challenged by ionizing radiation, Dmp53 mutants exhibit radiosensitivity and genomic instability. Hence, elevated mutant loads were not caused by defective checkpoint functions but instead correlated with failures in p53-associated cell death. Our studies support the notion that core ancestral functions of the p53 gene family are intimately coupled to cell death as an adaptive response to maintain genomic stability.

The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid.

In flies and mammals, critical regulators of cell death function by antagonizing Inhibitor of Apoptosis Proteins (IAPs), which themselves directly block caspase action. The three currently known IAP antagonists in Drosophila map to the H99 genomic interval required for all programmed cell death. Here we describe a fourth member of this genetic group, sickle (skl), which maps just outside of the H99 deletion. At its N terminus, Skl shares residues in common with other IAP antagonists in flies (Rpr, Grim, and Hid) and in mammals (Smac/DIABLO and Omi/Htra2). Like other activators of apoptosis mapping in the Reaper region, full-length skl induced apoptosis when overexpressed, and the N terminus of this protein specifically bound to the BIR2 domain of DIAP1. However, unlike the N termini of Grim, Hid, and Rpr, the N terminus of Skl did not induce apoptosis. skl transcripts accumulate in cells that are fated to die in some but not all regions of the embryo. Genotoxic stimuli induced skl expression, but skl was not responsive to all signals that trigger premature apoptosis. skl is potentially a fourth IAP antagonist in the "Reaper region" and a new candidate transducer of apoptotic damage signaling in Drosophila.