Disruption of chromosome 11 in canine fibrosarcomas highlights an unusual variability of CDKN2B in dogs.

BACKGROUND: In dogs in the western world neoplasia constitutes the most frequently diagnosed cause of death. Although there appear to be similarities between canine and human cancers, rather little is known about the cytogenetic and molecular alterations in canine tumours. Different dog breeds are susceptible to different types of cancer, but the genetic basis of the great majority of these predispositions has yet to be discovered. In some retriever breeds there is a high incidence of soft tissue sarcomas and we have previously reported alterations of chromosomes 11 and 30 in two poorly differentiated fibrosarcomas. Here we extend our observations and present a case report on detail rearrangements on chromosome 11 as well as genetic variations in a tumour suppressor gene in normal dogs. RESULTS: BAC hybridisations on metaphases of two fibrosarcomas showed complex rearrangements on chromosome 11, and loss of parts of this chromosome. Microsatellite markers on a paired tumour and blood DNA pointed to loss of heterozygosity on chromosome 11 in the CDKN2B-CDKN2A tumour suppressor gene cluster region. PCR and sequencing revealed the homozygous loss of coding sequences for these genes, except for exon 1beta of CDKN2A, which codes for the N-terminus of p14ARF. For CDKN2B exon 1, two alleles were observed in DNA from blood; one of them identical to the sequence in the dog reference genome and containing 4 copies of a 12 bp repeat found only in the canine gene amongst all species so far sequenced; the other allele was shorter due to a missing copy of the repeat. Sequencing of this exon in 141 dogs from 18 different breeds revealed a polymorphic region involving a GGC triplet repeat and a GGGGACGGCGGC repeat. Seven alleles were recorded and sixteen of the eighteen breeds showed heterozygosity. CONCLUSION: Complex chromosome rearrangements were observed on chromosome 11 in two Labrador retriever fibrosarcomas. The chromosome alterations were reflected in the loss of sequences corresponding to two tumour suppressor genes involved in cell-cycle progression. Sequencing of CDKN2B across many different breeds revealed a widespread polymorphism within the first exon of the gene, immediately before the ankyrin coding sequences.

Dexamethasone modulates Salmonella enterica serovar Typhimurium infection in vivo independently of the glucocorticoid-inducible protein annexin-A1.

Salmonella enterica serovar Typhimurium (S. Typhimurium) infection causes an inflammatory response through activation of Toll-like receptor 4 by lipopolysaccharide. Dexamethasone, a glucocorticoid analogue, suppresses inflammatory responses by many mechanisms including inhibition of the lipopolysaccharide-induced production of proinflammatory mediators. There is little information on the effect of glucocorticoids on murine salmonellosis. In this study, we treated susceptible BALB/c mice by subcutaneous implantation of slow-release dexamethasone pellets before infection with S. Typhimurium. Dexamethasone promotes bacterial growth early in infection and induces a dose-dependent increase in bacterial growth within mouse livers and spleens. The bacterial load in organs from infected placebo-treated mice was lower than that in dexamethasone-treated mice. Glucocorticoids inhibit lipopolysaccharide-induced inflammation partially through the steroid-inducible protein annexin-A1 (ANXA1). Infection of wild-type and ANXA1 knock-out mice with S. Typhimurium led to similar organ bacterial loads. ANXA1 also did not affect the bacterial load in organs from infected dexamethasone-treated mice. This suggests that glucocorticoids, independently of ANXA1, accelerate S. Typhimurium growth in vivo in susceptible BALB/c mice.

Mortalities, amyloidosis and other diseases in free-living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands.

Between 2007 and 2014, 337 free-living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands, were examined post mortem as part of a mortality and disease surveillance scheme. Road traffic accidents (RTAs) were attributable for 50.7 per cent (171/337) of the casualties, 34.4 per cent (116/337) succumbed to diseases including fatal exudative dermatitis (FED), 7.1 per cent (24/337) to predation, 6.5 per cent (22/337) to other trauma and 1.2 per cent (4/337) to suspected poisoning. Cat predation accounted for 5 per cent (17/337) of mortalities. Pathologies were diverse and individual animals were often identified with more than one disease process. Squirrelpox virus (SQPV) particles were not detected in selected cases examined by transmission electron microscopy (TEM). Amyloid was identified in 19.3 per cent (65/337) of squirrels, often in conjunction with inflammatory lesions like hepatic capillariasis. A consistent cause of amyloid accumulation was not identified, although there was a significant association of amyloidosis with hepatic capillariasis and FED. In addition to RTAs, amyloidosis and FED have been identified as important causes of squirrel morbidity and mortality on Jersey, while the underlying aetiology and predisposing factors for these two disease complexes are presently unclear. Disease, fragmented woodlands, an increasingly suburban habitat, along with various anthropogenic factors, may jeopardise the long-term viability of this island red squirrel population.

Solitary plasmacytoma of bone in two successfully treated cats.

This is the first report of feline solitary plasmacytoma of bone. We describe the clinical, clinico-pathological, radiographic and pathological findings of two successfully treated cats with long-term follow-up. The first case presented with spinal pain and neurological deficits. Radiographs demonstrated sclerosis of lumbar vertebra L6 and a myelogram confirmed interference to flow of contrast in the L4-7 region. A biopsy of L6 revealed neoplastic plasma cell infiltration. There was no evidence of paraproteinaemia on serum protein electrophoresis. The cat underwent hypofractionated megavoltage radiotherapy. Clinical signs resolved completely and 4 years after diagnosis the cat remains well and has no electrophoretically detectable paraproteinaemia. The second case presented with neurological deficits of the tail and spinal radiographs revealed extensive osteolysis of the sacrum. A biopsy of sacral bone demonstrated neoplastic plasma cell infiltration. The animal was normoglobulinaemic. The cat improved clinically with induction chemotherapy (melphalan and methylprednisolone). The same chemotherapeutics were continued at maintenance doses for 4.3 years, at which time there was recurrence of neurological deficits and a palpable sacral mass. Cytological examination of a fine needle aspirate confirmed recurrence of plasma cell neoplasia. A low concentration monoclonal paraproteinaemia was detected. Vincristine was administered resulting in resolution of neurological deficits and a palpably smaller sacral mass. Eighteen months into vincristine therapy, there was recurrence of clinical signs and the cat was euthanased, more than 6 years after the initial diagnosis.

Myeloma-related disorders in cats commonly present as extramedullary neoplasms in contrast to myeloma in human patients: 24 cases with clinical follow-up.

BACKGROUND: Myeloma-related disorders (MRD) are rare neoplasms of plasma cells. Published case reports describe a diversity of clinical presentations with confusing terminology and diagnostic criteria as a consequence of the assumption that MRD in cats are analogous to those in dogs or humans. OBJECTIVE: The aim of the study was to describe clinical, clinicopathologic and imaging findings, response to treatment, survival and possible associations with other diseases or vaccination in a large case series. A priori hypotheses were that cats with MRD commonly present with extramedullary involvement and uncommonly have radiographic bone lesions, in contrast to human patients. ANIMALS: Twenty-four cats with MRD confirmed by cytology or histopathology and immunohistochemistry. METHOD: A multicenter retrospective study was performed. RESULTS: Two types of clinical presentation were observed. The first group (n = 17) had neoplasia involving abdominal organs, bone marrow, or both. All developed systemic clinical signs and paraproteinemia. Five of 7 cats that received chemotherapy improved clinically or had decreased serum globulin concentration (median survival, 12.3 months; range, 8.5-22 months). The second group comprised 7 cats with skin masses, 2 of which were paraproteinemic and developed rapidly worsening systemic signs. In cats without systemic signs, excision of the skin masses appeared to be associated with prolonged survival (up to 2.4 years). Cats with MRD commonly presented with extramedullary involvement (67%), versus humans with MRD (5%) (P < .001), and uncommonly presented with radiographic bone lesions (8%) versus humans with MRD (80%) (P < .001). CONCLUSIONS: Radiographic bone lesions are uncommon in cats with MRD and extramedullary presentation is common, relative to human myeloma.

Extra-nodal subcutaneous Hodgkin's-like lymphoma and subsequent regression in a cat.

Hodgkin's-like lymphoma is a slow growing neoplasm, usually affecting the lymph nodes of the head and neck, which has been sporadically described in veterinary patients. This report describes the clinical and histopathological features in a 9-year-old male neutered Siamese cat that presented with a 6 week history of mid-dorsocranial swelling. Immunohistochemistry demonstrated positive staining for CD79a, paired box protein and B lymphocyte antigen-36, with variable, weak-to-moderate cytoplasmic staining for human leukocyte antigen-DR and CD18, and negative staining for antimacrophage antibody. The diagnosis based on incisional biopsy was Hodgkin's-like lymphoma; however, no evidence of neoplasia was found following wide surgical excision. This case report demonstrates two unreported items of note: the novel extranodal site of Hodgkin's-like lymphoma in a cat and tumour regression following initial biopsy. It is hypothesised that the surgical trauma of biopsying the lesion or the introduction of foreign material may have caused the regression of the neoplastic cells through induction of an anti-tumour immune or inflammatory response.