Owner perceptions of their cat's quality of life when treated with a modified University of Wisconsin-Madison protocol for lymphoma

The objectives of this study were to assess owner perceptions of their cat’s quality of life during treatment for lymphoma with a doxorubicin-containing multi-agent chemotherapy protocol, whether various health-related parameters correlated with quality of life scores, and to assess owner satisfaction with the protocol

Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016

Background There is limited information on the epidemiology of canine mammary tumours. This study aimed to estimate the incidence and risk factors for mammary tumours in UK bitches. Methods A nested case–control study was conducted within VetCompass to estimate the frequency and risk factors for clinically diagnosed mammary tumours during 2016 (VetCompass study). A second case–control study explored further breed associations for cases confirmed histopathologically compared to the VetCompass controls (laboratory study). Multivariable logistic regression was used to evaluate associations between risk factors and mammary tumours. Results The incidence of mammary tumours was 1340.7/100,000 per year (95% confidence interval: 1198.1–1483.3). A total of 222 clinical cases (VetCompass study) and 915 laboratory cases (laboratory study) were compared to 1515 VetCompass controls in the two analyses. In the VetCompass study, Springer and Cocker Spaniels, Boxers, Staffordshire Bull Terriers and Lhasa Apsos had increased odds of developing mammary tumours. Neutering was associated with reduced odds, while odds increased with increasing age and a history of pseudopregnancy. In the laboratory study, increasing age was associated with greater odds of mammary tumours, and the breeds most at risk were similar to those identified in the VetCompass study. Limitations The timing of neutering was not consistently available. Comparing laboratory cases to VetCompass controls provided only exploratory evidence for the breed associations identified. Conclusions The study provides an update on the frequency of canine mammary tumours

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

Prevalence and risk factors for mast cell tumours in dogs in England

Background Mast cell tumour (MCT) appears to be a frequent tumour type in dogs, though there is little published in relation to its frequency in dogs in the UK. The current study aimed to investigate prevalence and risk factors for MCTs in dogs attending English primary-care veterinary practices. Methods Electronic patient records from practices participating in the VetCompass animal surveillance project between July 2007 and June 2013 were searched for MCT diagnosis. Various search terms and standard diagnostic terms (VeNom codes) identified records containing MCT diagnoses, which were evaluated against clinical criteria for inclusion to the study. MCT prevalence for the entire dataset and specific breed types were calculated. Descriptive statistics characterised MCT cases and multivariable logistic regression methods evaluated risk factors for association with MCT (P \u3c 0.05). Results Within a population of 168,636 dogs, 453 had MCT, yielding a prevalence of 0.27% (95% confidence interval (CI) 0.24% - 0.29%). The highest breed type specific prevalences were for the Boxer at 1.95% (95% CI 1.40% - 2.51%), Golden Retriever at 1.39% (0.98% - 1.81%) and Weimaraner at 0.85% (95% CI 0.17% to 1.53%). Age, insurance status, neuter status, weight and breed type were associated with MCT diagnosis. Of dogs of specific breed type, the Boxer, Pug and Staffordshire Bull Terrier showed greater odds of MCT diagnosis compared with crossbred dogs. Conversely, the German Shepherd Dog, Border Collie, West Highland White Terrier, Springer Spaniel and Cocker Spaniel had reduced odds of MCT diagnosis compared with crossbred dogs. No association was found between MCT diagnosis and sex. Clinical significance This study highlights a clinically significant prevalence of MCT and identifies specific breed types with predisposition to MCT, potentially aiding veterinarian awareness and facilitating diagnosis

Canine B cell lymphoma shows no deficit of cytotoxic T cells relative to thymic Tregs.

<p>When expressed as a proportion of all cells aspirated from the lymph node, the frequency of CD8⁺ T cells (A,B) was decreased in BCL (and MCT), again attributed to neoplastic effacement (p = 0.0005). The frequency of CD8⁺ cells within the CD5⁺ T cell population also showed differences between groups (C; p = 0.04). The ratio of CD8⁺:FOXP3⁺ cells (D) was not significantly different between groups (p = 0.06), though dogs with BCL showed the six highest ratios of the cohort, and a trend for higher values in the BCL group was observed. Indeed, the ratio of CD8⁺:FOXP3⁺Helios⁺ cells (E) was higher in the BCL than RH cases (p = 0.04); only two data points for the MCT (3.48; 3.95) were available for this variable and were not therefore represented. Representative dot plots for all the groups are shown alongside their respective isotype controls, followed by box-and-whisker plots summarising the data. (For key to symbols, refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105027#pone-0105027-g002" target="_blank">Figure 2</a>).</p

FOXP3, MHC class II, age at presentation and rescue therapy are independent prognostic factors in canine B cell lymphoma.

<p><u>Abbreviations</u>: TTR, time to remission; PFS, progression-free survival; OS, overall survival; CI, confidence interval; FOXP3⁺ (% CD5⁺CD4⁺), frequency of FOXP3⁺ cells within the sequential CD5⁺ and CD4⁺ gates; FOXP3⁺ (%), frequency of FOXP3⁺ cells within the total harvested population; median ratio =  ratio of median remission or survival time (TTR/PFS/OS) of the sub-group of dogs with a value of the variable greater than the median of the group to that of the sub-group of dogs with a value of the variable less than or equal to the median of the group.</p

Staining antibodies, isotype controls and fluorochromes.

<p><u>Abbreviations</u>: FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.</p

Clinical, cytological and treatment details of dogs in the study.

<p><u>Abbreviations</u>: Me, entire male; Mn, neutered male; Fe, entire female; Fn, neutered female; WHO, World Health Organization; N/A, not applicable; DLBCL, diffuse large B cell lymphoma; PTCL, peripheral T cell lymphoma; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisolone protocol; COP, cyclophosphamide, vincristine, prednisolone protocol; Pred, prednisolone alone; NSAIDS, non-steroidal anti-inflammatory drugs.</p><p><u>Notes</u>: ¹: Age when presenting signs were first observed. ²: Body condition score was assessed by different clinicians on either a 5 or 9 point scale: ‘under-conditioned’ was defined by a score of 1–2/5 or 1–3/9; ‘optimal’ was defined by a score of 2.5–3/5 or 4–5/9; while ‘over-conditioned’ was defined by a score of 3.5–5/5 or 6–9/9. ³: Serum or plasma calcium concentration was not measured in one of the T cell lymphoma cases prior to initiation of therapy. ⁴: The initial treatment protocol is listed. ‘Other’ treatments included cytarabine, L-asparaginase and lomustine (B cell lymphoma) and L-asparaginase, lomustine, prednisolone, masitinib and chlorambucil (T cell lymphoma).</p

FOXP3⁺ Treg frequency is no higher in canine B cell lymphoma than control samples.

<p>The frequency of FOXP3⁺ cells in fine needle aspirates harvested from the lymph nodes of dogs with B cell lymphoma (BCL), T cell lymphoma (TCL), reactive hyperplasia (RH) and mast cell tumors (MCT) is shown, expressed as a proportion of all cells (A, B, showing the effect of neoplastic effacement of normal lymphoid tissue; p = 0.00005), gated CD5⁺ cells (C, showing the resident T cells; p = 0.41), or sequentially gated CD5⁺ and then CD4⁺ T cells (D, showing specifically the resident CD4⁺ T cells; p = 0.74). Representative dot plots are shown for each of the groups, followed by box-and-whisker plots summarising the data. In each of the dot plots, the respective isotype control stain is shown above the specific stain. In this and subsequent figures, red symbols correspond to data from dogs ‘pre-treated’ with corticosteroids or any chemotherapeutic drug within three weeks of sampling. In the case of RH cases, square symbols (□) represent data from dogs with dermatitis; diamonds (◊) represent data from dogs with distant neoplasia; triangles (Δ) represent data from dogs with immune-mediated disease; and inverted triangles (▾) represent data from dogs with systemic infection. The expression of FOXP3 by PBMCs (E; p = 0.21) or by the CD5⁺ (F; p = 0.53) or specific CD5⁺CD4⁺ (G; p = 0.15) T cells within PBMCs similarly showed no differences between groups.</p