Effects of a high-protein, increased-fibre, dry diet supplemented with omega-3 fatty acids on quality of life in dogs undergoing chemotherapy.

Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.

An Analysis of Transcriptomic Burden Identifies Biological Progression Roadmaps for Hematological Malignancies and Solid Tumors.

Biological paths of tumor progression are difficult to predict without time-series data. Using median shift and abacus transformation in the analysis of RNA sequencing data sets, natural patient stratifications were found based on their transcriptomic burden (TcB). Using gene-behavior analysis, TcB groups were evaluated further to discover biological courses of tumor progression. We found that solid tumors and hematological malignancies (n = 4179) share conserved biological patterns, and biological network complexity decreases at increasing TcB levels. An analysis of gene expression datasets including pediatric leukemia patients revealed TcB patterns with biological directionality and survival implications. A prospective interventional study with PI3K targeted therapy in canine lymphomas proved that directional biological responses are dynamic. To conclude, TcB-enriched biological mechanisms detected the existence of biological trajectories within tumors. Using this prognostic informative novel informatics method, which can be applied to tumor transcriptomes and progressive diseases inspires the design of progression-specific therapeutic approaches.

Use of a canine melanoma vaccine in the management of malignant melanoma in an African penguin (Spheniscus demersus).

CASE DESCRIPTION: A 25-year-old 4.4-kg male aquarium-hatched African penguin (Spheniscus demersus) was evaluated because of a raised 1.5 × 0.5-cm pigmented mass extending from within the right naris noted 2 days earlier. CLINICAL FINDINGS: The penguin had a raised pigmented mass extending out from the right naris and onto the upper beak. Histologic examination of excisional biopsy specimens confirmed a diagnosis of malignant melanoma. A treatment plan including administration of meloxicam, radiation therapy, and immunotherapy was initiated. TREATMENT AND OUTCOME: Treatment with meloxicam (0.2 mg/kg, PO, q 24 h) was initiated and continued for a total of 45 weeks; however, the medication was discontinued for a period of 6 weeks because of the risk of toxic effects in the chick that the penguin was feeding at that time. The penguin underwent local hypofractionated radiation therapy and received 4 once weekly 8-Gy fractions of radiation (total radiation dose, 32 Gy). The penguin was administered a canine melanoma vaccine transdermally every other week for 4 doses, with a booster injection given 7 months after the first dose. Treatment with the vaccine appeared to have no adverse effects. The penguin's pre- and postvaccination tyrosinase-specific antibody titers were measured with an anti-human tyrosinase-specific ELISA, and a 3-fold titer increase indicated a positive humoral immune response to the canine melanoma vaccination. The penguin died of unrelated causes 54 weeks after initial diagnosis, and there was no evidence of metastasis on necropsy. CLINICAL RELEVANCE: These case findings suggested that vaccination with a canine melanoma vaccine may be a safe and useful adjunct treatment for management of malignant melanoma in penguins.

Development and validation of a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs.

OBJECTIVE: To develop a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs. ANIMALS: 522 dogs that underwent splenectomy because of splenic masses. PROCEDURES: A multivariable model was developed with preoperative clinical data obtained retrospectively from the records of 422 dogs that underwent splenectomy. Inclusion criteria were the availability of complete abdominal ultrasonographic examination images and splenic histologic slides or histology reports for review. Variables considered potentially predictive of splenic malignancy were analyzed. A receiver operating characteristic curve was created for the final multivariable model, and area under the curve was calculated. The model was externally validated with data from 100 dogs that underwent splenectomy subsequent to model development and was used to create an online calculator to estimate probability of splenic malignancy in individual dogs. RESULTS: The final multivariable model contained 8 clinical variables used to estimate splenic malignancy probability: serum total protein concentration, presence (vs absence) of ≥ 2 nRBCs/100 WBCs, ultrasonographically assessed splenic mass diameter, number of liver nodules (0, 1, or ≥ 2), presence (vs absence) of multiple splenic masses or nodules, moderate to marked splenic mass inhomogeneity, moderate to marked abdominal effusion, and mesenteric, omental, or peritoneal nodules. Areas under the receiver operating characteristic curves for the development and validation populations were 0.80 and 0.78, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The online calculator (T-STAT.net or T-STAT.org) developed in this study can be used as an aid to estimate the probability of malignancy in dogs with splenic masses and has potential to facilitate owners' decisions regarding splenectomy.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials.

While current lymphoma therapies induce remission in most dogs, drug-resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9-(2-phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty-three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T-cell immunophenotype and corticosteroid pre-treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG-CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.

Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011-2018.

Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of toceranib phosphate for dogs with HBT. Twenty-eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty-seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis. Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68-1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77-679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that toceranib phosphate is a well-tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease.

Urologic Oncology.

Primary renal tumors are an uncommon diagnosis in small animals. Presentation, treatment, and prognosis depend on tumor type. Surgery with or without chemotherapy are the mainstays of treatment. Transitional cell carcinoma is the most common tumor of the urinary system. Clinical signs include hematuria, stranguria, and pollakiuria. Metastatic disease can develop over time within medial iliac lymph nodes, lungs, and vertebrae. Treatment of transitional cell carcinoma centers on chemotherapy with mitoxantrone, vinblastine, or carboplatin. Other agents used with success, include toceranib phosphate and chlorambucil. Interventional surgery, such as stenting and laser ablation, is used in a palliative setting addressing urinary obstruction.

Correction: Comparative oncology DNA sequencing of canine T cell lymphoma via human hotspot panel.

[This corrects the article DOI: 10.18632/oncotarget.25209.].

Comparative oncology DNA sequencing of canine T cell lymphoma via human hotspot panel.

T-cell lymphoma (TCL) is an uncommon and aggressive form of human cancer. Lymphoma is the most common hematopoietic tumor in canines (companion animals), with TCL representing approximately 30% of diagnoses. Collectively, the canine is an appealing model for cancer research given the spontaneous occurrence of cancer, intact immune system, and phytogenetic proximity to humans. We sought to establish mutational congruence of the canine with known human TCL mutations in order to identify potential actionable oncogenic pathways. Following pathologic confirmation, DNA was sequenced in 16 canine TCL (cTCL) cases using a custom Human Cancer Hotspot Panel of 68 genes commonly mutated in human TCL. Sequencing identified 4,527,638 total reads with average length of 229 bases containing 346 unique variants and 1,474 total variants; each sample had an average of 92 variants. Among these, there were 258 germline and 32 somatic variants. Among the 32 somatic variants there were 8 missense variants, 1 splice junction variant and the remaining were intron or synonymous variants. A frequency of 4 somatic mutations per sample were noted with >7 mutations detected in MET, KDR, STK11 and BRAF. Expression of these associated proteins were also detected via Western blot analyses. In addition, Sanger sequencing confirmed three variants of high quality (MYC, MET, and TP53 missense mutation). Taken together, the mutational spectrum and protein analyses showed mutations in signaling pathways similar to human TCL and also identified novel mutations that may serve as drug targets as well as potential biomarkers.

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.

Safety and efficacy of intralesional triamcinolone administration for treatment of mast cell tumors in dogs: 23 cases (2005-2011).

OBJECTIVE To evaluate the safety and efficacy of intralesional triamcinolone administration, as a sole or adjuvant treatment, in dogs with mast cell tumors. DESIGN Retrospective case series ANIMALS 23 dogs with mast cell tumors. PROCEDURES Medical records of dogs treated for a confirmed diagnosis of a mast cell tumor between 2005 and 2011 were reviewed. Patients with a confirmed diagnosis and measurable disease (tumor longest dimension ≥ 0.5 cm) that had received ≥ 1 intralesional treatment with triamcinolone, regardless of prior, concurrent, or adjuvant treatments, were eligible for inclusion. Data collected included patient characteristics, results of cytologic and histologic testing and tumor staging, triamcinolone dosage, treatment response, and adverse events. RESULTS 23 dogs with 24 tumors were included. Tumors were treated by means of intralesional triamcinolone administration alone (n = 5), intralesional triamcinolone administration with concurrent oral administration of glucocorticoids (6), and intralesional triamcinolone administration with concurrent cytotoxic chemotherapy, with or without oral administration of corticosteroids and radiation therapy (13). Of 5 dogs treated with intralesional triamcinolone administration alone, 1 achieved a complete response, 3 achieved a partial response, and 1 maintained stable disease. The response rate for all 24 tumors (23 dogs) was 67% (16/24), including 4 with a complete response and 12 with a partial response. The median time to progression was 63 days (range, 6 to 447 days). Three dogs experienced adverse events (local hemorrhage [n = 1]; suspected gastrointestinal ulceration [2]). CONCLUSIONS AND CLINICAL RELEVANCE Intralesional triamcinolone administration may be well tolerated and effective for treatment of nonresectable mast cell tumors in dogs.

A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.

Survival time of dogs with splenic hemangiosarcoma treated by splenectomy with or without adjuvant chemotherapy: 208 cases (2001-2012).

OBJECTIVE: To determine survival time for dogs with splenic hemangiosarcoma treated with splenectomy alone, identify potential prognostic factors, and evaluate the efficacy of adjuvant chemotherapy. DESIGN: Retrospective case series. ANIMALS: 208 dogs. PROCEDURES: Medical records were reviewed, long-term follow-up information was obtained, and survival data were analyzed statistically. RESULTS: 154 dogs were treated with surgery alone, and 54 were treated with surgery and chemotherapy. Twenty-eight dogs received conventional chemotherapy, 13 received cyclophosphamide-based metronomic chemotherapy, and 13 received both conventional and metronomic chemotherapy. Median survival time of dogs treated with splenectomy alone was 1.6 months. Clinical stage was the only prognostic factor significantly associated with survival time. When the entire follow-up period was considered, there was no significant difference in survival time between dogs treated with surgery alone and dogs treated with surgery and chemotherapy. However, during the first 4 months of follow-up, after adjusting for the effects of clinical stage, survival time was significantly prolonged among dogs receiving any type of chemotherapy (hazard ratio, 0.6) and among dogs receiving both conventional and metronomic chemotherapy (hazard ratio, 0.4). CONCLUSIONS AND CLINICAL RELEVANCE: Clinical stage was strongly associated with prognosis for dogs with splenic hemangiosarcoma. Chemotherapy was effective in prolonging survival time during the early portion of the follow-up period. Combinations of doxorubicin-based conventional protocols and cyclophosphamide-based metronomic protocols appeared to be more effective than either type of chemotherapy alone, but prolongations in survival time resulting from current protocols were modest.

Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

Cutaneous lymphoma of the tarsus in cats: 23 cases (2000-2012).

OBJECTIVE: To determine features of lymphoma of the tarsus in cats. DESIGN: Multi-institutional retrospective study. ANIMALS: 23 cats with cutaneous lymphoma of the tarsus. PROCEDURES: Veterinary oncologists were requested to submit cases fitting the following criteria: histologically or cytologically confirmed lymphoma with a location at or near the tarsus and described as subcutaneous or mass-like. Data regarding breed, sex, age, FeLV and FIV status, and reason for evaluation were collected. Results of staging tests, location of the tumor, immunophenotype, and histopathologic description were recorded. Type of treatments, outcome, survival time, presence or absence of progressive disease, and cause of death or reason for euthanasia were also recorded. RESULTS: Most cats were older, with a median age of 12 years (range, 7 to 18 years). No association with positive retroviral status was found. Popliteal lymph node involvement at diagnosis was reported in 5 cats, and a suspicion of lymphoma at a different site on the basis of results of abdominal ultrasonography was reported in 4 cats. Treatments were variable and included corticosteroids alone (n = 2), chemotherapy (9), radiation and chemotherapy (7), or surgery with or without chemotherapy (5). Thirteen cats were reported to have lymphoma at a different site at the time of last follow-up, death, or euthanasia. Median survival time for all cats in the study was 190 days (range, 17 to 1,011 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that tarsal lymphoma is an uncommon manifestation of lymphoma in cats, and in this study was most commonly nonepitheliotropic and of high grade as determined on histologic evaluation. Systemic involvement was identified; therefore, thorough staging is recommended prior to initiating treatment. Future studies are warranted to evaluate effective treatment protocols.

Mast cell tumor invading the cornea in a horse.

A 3-year-old Marwari mare was presented for evaluation of an irregular, reddish mass protruding from behind the right third eyelid. The mass appeared to arise at the ventral limbal area, involved the perilimbal bulbar conjunctiva and widely extended into corneal tissue. No other ocular or systemic abnormalities were detected at the time of presentation. The mass was surgically removed by lamellar keratectomy, with defocused CO(2) laser used as adjunctive therapy to treat the surgical exposed area and its surroundings. Histopathologic evaluation showed sheets of densely packed, well-differentiated neoplastic mast cells separated by fibrovascular connective tissue. Nuclear staining for Ki-67 was performed, and an average of 370 cells were positive per 1000 counted cells. Two months postoperatively, the surgical site was filled with flat fibrovascular and pigmented tissue, while the surrounding cornea was transparent with no superficial vascularization around the fibrotic scar. Thirty-two months after treatment, no recurrence of the neoplasia was reported.

Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study.

Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

Traitement adjuvant à la doxorubicine et au déracoxib pour l'angiosarcome splénique canin : étude pilote. L'angiosarcome canin est une tumeur hautement maligne pour laquelle la chimiothérapie standard a peu fait pour améliorer substantiellement la survie. La cyclooxygénase-2 (Cox-2) joue un rôle dans la formation, la croissance et la métastase des tumeurs et des inhibiteurs ont démontré des bienfaits thérapeutiques pour certains cancers canins. Dans cette étude prospective, 21 chiens ont reçu un traitement adjuvant combinant l'inhibiteur de la Cox-2 sélectif déracoxib avec la doxorubicine, après la splénectomie pour l'angiosarcome. La combinaison a été bien tolérée et seulement des toxicités gastro-intestinales et hématologiques de faible intensité ont été signalées. Une survie médiane globale de 150 jours (écart de 21 à 1506 jours) a été signalée. Même s'il n'y a pas eu de différence significative dans la survie si l'on se base sur le stade de la maladie, les chiens avec un angiosarcome de stade III (n = 11) ont eu une survie médiane de 149 jours, ce qui semble plus long que ce qui avait déjà été signalé. De nouvelles études sont justifiées afin d'évaluer le bienfait potentiel des inhibiteurs de la Cox-2 pour le traitement de l'angiosarcome canin.(Traduit par Isabelle Vallières).

Imaging characteristics of intrathoracic histiocytic sarcoma in dogs.

In this retrospective study, two observers independently reviewed thoracic imaging studies of 39 dogs with confirmed histiocytic sarcoma. The most common findings were intrathoracic lymphadenopathy, identified by the first and second observers in 82.1% and 87.2% of dogs, respectively, and pulmonary masses (74.4% and 82.1%). Right middle lung lobe masses were significantly more common than masses in any other lung lobe (P < 0.0013), with the majority having a ventral distribution. Sternal and tracheobronchial lymphadenopathy were significantly more common than cranial mediastinal lymphadenopathy (P-values of 0.0002 and 0.012, respectively). Interobserver agreement regarding distribution of lymphadenopathy and pulmonary masses was good (kappa = 0.64 and 0.75, respectively). Other findings included pulmonary nodules, pleural effusion, and abnormal pulmonary patterns. In patients with CT examinations, the majority of masses were mildly to moderately enhancing and heterogeneous, poorly marginated, and bronchocentric. Lymphadenopathy and pulmonary masses are the most common intrathoracic findings in dogs with histiocytic sarcoma, and the strong predilection for the ventral aspect of the right middle lung lube may help to differentiate it from other types of neoplasia.

Refining tumor-associated aneuploidy through 'genomic recoding' of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas.

Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. 'Genomic recoding' of canine NHL data into a 'virtual human' chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.