Comparative genomics of canine hemoglobin genes reveals primacy of beta subunit delta in adult carnivores

Sequences of primers used for PCR and sequencing studies. (XLSX 45 kb

Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B

Background: Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible. Results: Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors. Conclusions: Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease

Dexamethasone, Melphalan, Actinomycin D, Cytosine Arabinoside (DMAC) Protocol for Dogs With Relapsed Lymphoma

Background: In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma. Hypothesis: That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma. Animals: Fifty-four dogs. Results: Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2–467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog). Conclusions and Clinical Importance: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated

Dexamethasone, Melphalan, Actinomycin D, Cytosine Arabinoside (DMAC) Protocol for Dogs With Relapsed Lymphoma

Background: In general, treatment of relapsed lymphoma is associated with a lower probability of response and shorter duration of remission. The purpose of this study was to evaluate the efficacy of the combination chemotherapy protocol DMAC (dexamethasone, melphalan, actinomycin D, and cytosine arabinoside) for reinduction of remission in dogs with relapsed lymphoma. Hypothesis: That DMAC would be an effective reinduction protocol for dogs with relapsed lymphoma. Animals: Fifty-four dogs. Results: Seventy-two percent of the dogs achieved remission (44% complete remission [CR] and 28% partial remission [PR]), 11% had stable disease (SD), and 17% had progressive disease (PD). The median remission duration was 61 days (range, 2–467+ days). The median remission durations for dogs with CR, PR, and SD were 112, 44, and 27 days, respectively. Factors that affected the response rate were previous treatment with doxorubicin and an inability to achieve remission with the previous protocol. Thrombocytopenia occurred in 56% of the dogs (grade 1 in 3 dogs, grade 2 in 6 dogs, grade 3 in 7 dogs, and grade 4 in 7 dogs) and neutropenia in 17% of the dogs (grade 2 in 1 dog, grade 3 in 2 dogs, and grade 4 in 4 dogs). Gastrointestinal toxicosis occurred in 22% of the dogs (grades 1 in 5 dogs, grade 2 in 3 dogs, and grade 3 in 1 dog). Conclusions and Clinical Importance: The DMAC protocol is an effective rescue protocol for dogs with relapsed multicentric lymphoma. Although thrombocytopenia is a common manifestation of toxicity, in general, the protocol is well tolerated

Clinical pathology of Greyhounds and other sighthounds

Abstract: Owing to the development of Greyhounds as racing sighthounds, these dogs have acquired unique physiologic adaptations that distinguish them from other breeds. Reference intervals for many analytes in retired racing Greyhounds (RRGs) differ from those of other breeds; most of the hematologic differences have also been described in other sighthounds. In this review, we provide a survey of the literature on clinical pathology of Greyhounds and other sighthounds and results of laboratory testing, including analysis of CBCs, biochemical profiles, coagulation tests, and blood gases, in RRGs at The Ohio State University. Major clinicopathologic differences in this breed include higher RBC mass, creatinine concentration, glomerular filtration rate, activities of hepatic enzymes, and concentration of cardiac troponin, as well as lower WBC, neutrophil, and platelet counts, thromboelastographic values, and concentrations of serum haptoglobin, total globulins, and T4

Vertebral heart size in retired racing greyhounds

The vertebral heart size (VHS) is used to objectively assess cardiac dimensions on thoracic radiographs. A high VHS suggest the presence of cardiac pathology, such as dilated cardiomyopathy, degenerative atrioventricular valvular disease, pericardial effusion, pericardioperitoneal diaphragmatic hernia, tricuspid dysplasia, ventricular septal defect, or patent ductus arteriosus, among others. However, breed or body conformation can influence the VHS. Because Greyhounds have a high prevalence of physiologic systolic murmurs associated with high aortic velocity, and large cardiac dimensions when compared with dogs of similar size, they are frequently suspected of having heart disease. The purpose of this study was to compare the VHS in normal Greyhounds with those in Rottweilers, and a group of dogs from various other breeds using both analog and digital radiology. The VHS was significantly higher in Greyhounds (P\u3c0.0001), when compared with Rottweilers and to other dog breeds. The mean VHS on lateral radiographs for Greyhounds was 10.5±0.1, for Rottweilers it was 9.8±0.1, and for mixed breed dogs it was 10.1±0.2. This study confirms that the relative cardiomegaly reported in necropsy and echocardiographic studies in Greyhounds is easily detected using plain radiography and the VHS. © Copyright 2007 by the American College of Veterinary Radiology

Adjuvant CCNU (Lomustine) and Prednisone Chemotherapy for Dogs With Incompletely Excised Grade 2 Mast Cell Tumors

The use of adjuvant 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; lomustine) to treat incompletely excised canine mast cell tumors (MCTs) has not been evaluated. Medical records of 12 dogs with grade 2 MCT treated with incomplete surgical excision and adjuvant CCNU and prednisone chemotherapy were reviewed. Local recurrence rate, metastasis rate, and survival time were evaluated. None of the dogs developed local recurrence or regional/ distant metastases. Two dogs developed fatal liver failure. The 1- and 2-year progression-free rates of surviving dogs were 100% and 77%, respectively. Postoperative adjuvant CCNU appears to be a useful alternative to radiation therapy for incompletely excised canine cutaneous MCTs