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1.
BMC Genomics ; 20(1): 226, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890123

RESUMO

BACKGROUND: Despite the tremendous therapeutic advances that have stemmed from somatic oncogenetics, survival of some cancers has not improved in 50 years. Osteosarcoma still has a 5-year survival rate of 66%. We propose the natural canine osteosarcoma model can change that: it is extremely similar to the human condition, except for being highly heritable and having a dramatically higher incidence. Here we reanalyze published genome scans of osteosarcoma in three frequently-affected dog breeds and report entirely new understandings with immediate translational indications. RESULTS: First, meta-analysis revealed association near FGF9, which has strong biological and therapeutic relevance. Secondly, risk-modeling by multiple logistic regression shows 22 of the 34 associated loci contribute to risk and eight have large effect sizes. We validated the Greyhound stepwise model in our own, independent, case-control cohort. Lastly, we updated the gene annotation from approximately 50 genes to 175, and prioritized those using cross-species genomics data. Mostly positional evidence suggests 13 genes are likely to be associated with mapped risk (including MTMR9, EWSR1 retrogene, TANGO2 and FGF9). Previous annotation included seven of those 13 and prioritized four by pathway enrichment. Ten of our 13 priority genes are in loci that contribute to risk modeling and thus can be studied epidemiologically and translationally in pet dogs. Other new candidates include MYCN, SVIL and MIR100HG. CONCLUSIONS: Polygenic osteosarcoma-risk commonly rises to Mendelian-levels in some dog breeds. This justifies caninized animal models and targeted clinical trials in pet dogs (e.g., using CDK4/6 and FGFR1/2 inhibitors).


Assuntos
Neoplasias Ósseas/veterinária , Doenças do Cão/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Modelos Estatísticos , Herança Multifatorial , Osteossarcoma/veterinária , Animais , Neoplasias Ósseas/genética , Cruzamento , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Doenças do Cão/patologia , Cães , Predisposição Genética para Doença , Genoma , Osteossarcoma/genética , Medição de Risco/métodos
2.
BMC Genomics ; 18(1): 141, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28178945

RESUMO

BACKGROUND: The main function of hemoglobin (Hb) is to transport oxygen in the circulation. It is among the most highly studied proteins due to its roles in physiology and disease, and most of our understanding derives from comparative research. There is great diversity in Hb gene evolution in placental mammals, mostly in the repertoire and regulation of the ß-globin subunits. Dogs are an ideal model in which to study Hb genes because: 1) they are members of Laurasiatheria, our closest relatives outside of Euarchontoglires (including primates, rodents and rabbits), 2) dog breeds are isolated populations with their own Hb-associated genetics and diseases, and 3) their high level of health care allows for development of biomedical investigation and translation. RESULTS: We established that dogs have a complement of five α and five ß-globin genes, all of which can be detected as spliced mRNA in adults. Strikingly, HBD, the allegedly-unnecessary adult ß-globin protein in humans, is the primary adult ß-globin in dogs and other carnivores; moreover, dogs have two active copies of the HBD gene. In contrast, the dominant adult ß-globin of humans, HBB, has high sequence divergence and is expressed at markedly lower levels in dogs. We also showed that canine HBD and HBB genes are complex chimeras that resulted from multiple gene conversion events between them. Lastly, we showed that the strongest signal of evolutionary selection in a high-altitude breed, the Bernese Mountain Dog, lies in a haplotype block that spans the ß-globin locus. CONCLUSIONS: We report the first molecular genetic characterization of Hb genes in dogs. We found important distinctions between adult ß-globin expression in carnivores compared to other members of Laurasiatheria. Our findings are also likely to raise new questions about the significance of human HBD. The comparative genomics of dog hemoglobin genes sets the stage for diverse research and translation.


Assuntos
Hibridização Genômica Comparativa , Hemoglobinas/genética , Animais , Sequência de Bases , Quimerismo/veterinária , Cães , Evolução Molecular , Loci Gênicos , Haplótipos , Hemoglobinas/química , Hemoglobinas/classificação , Humanos , Família Multigênica , Filogenia , Regiões Promotoras Genéticas , Estrutura Quaternária de Proteína , alfa-Globinas/química , alfa-Globinas/classificação , alfa-Globinas/genética , Globinas beta/química , Globinas beta/classificação , Globinas beta/genética
3.
Transfusion ; 54(3): 727-34, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23901836

RESUMO

BACKGROUND: It is well established that hematocrit (Hct) influences whole blood thromboelastography (TEG) tracings. Previous studies showed hypercoagulable TEG tracings in anemic patients despite clinical expectations that anemia often prolongs bleeding. TEG is a viscoelastic assessment of clot kinetics, and Hct is the main determinant of whole blood viscosity. TEG changes in anemia may be an in vitro artifact due to Hct effect on blood viscosity rather than true in vivo changes in hemostasis. The effect of changes in whole blood viscosity on TEG independent of Hct is not well understood. STUDY DESIGN AND METHODS: Twenty-one blood samples from seven dogs were manipulated to produce one of three Hct conditions (45, 20, and 10%). Each was tested in two situations: viscosity adjusted to normal by adding alginate (ALG) or dilution with equal volume of saline (SAL). Both samples were analyzed with TEG simultaneously. RESULTS: Twenty percent Hct plus ALG and 10% Hct plus ALG were significantly more viscous than their SAL counterparts (p=0.0156). Ten percent Hct plus SAL, 20% Hct plus SAL, and 45% Hct plus SAL all had different viscosities (p=0.006). Twenty percent Hct plus SAL and 10% Hct plus SAL had significantly shorter K and higher angle, MA, and G compared to their ALG counterparts as well as 45% Hct plus SAL (p<0.05). CONCLUSIONS: ALG samples with low Hct, normal viscosity showed hypocoagulable tracings, whereas SAL samples with low Hct, low viscosity showed hypercoagulable tracings. TEG variables are influenced by whole blood viscosity altered with ALG, independently of Hct.


Assuntos
Eritrócitos/metabolismo , Hematócrito/efeitos adversos , Tromboelastografia , Animais , Cães , Feminino , Masculino , Viscosidade
4.
Vet Parasitol Reg Stud Reports ; 51: 101026, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772642

RESUMO

Recent studies demonstrated that Greyhounds are commonly infected with Ancylostoma caninum and these infections have been shown to be resistant to anthelmintics. This study evaluated samples submitted to a commercial reference laboratory (IDEXX Laboratories) for canine fecal flotation zinc sulfate centrifugation and coproantigen immunoassay between January 1, 2019, and July 30, 2023 for evidence that Greyhounds were more often positive for Ancylostoma spp. (hookworms) compared to other breeds. The purpose of the study was to determine if Greyhounds were more likely to be hookworm-positive compared to other breeds, if Greyhounds on preventives with efficacy against hookworm infections are more likely to test positive than other breeds, if their infections take longer to resolve, to estimate how long this takes and to assess whether the proportion of hookworm positive tests for all breeds is increasing over time. Records of 25,440,055 fecal results were obtained representing 17,671,724 unique dogs. Of these, 49,795 (∼0.3%) were Greyhounds. The overall odds ratio (OR) of 15.3 (p < 0.001) suggests that Greyhounds are at significantly higher risk than other breeds for hookworm positive float findings, and the OR of 14.3 (p < 0.001) suggests significantly higher risk for hookworm antigen positive results. The median time to negative testing event from the Turnbull distribution estimate was in the interval of 1-2 days for other breeds and 71-72 days for Greyhounds. These results provide evidence that anthelmintic resistant A. caninum strains may be having population-level impacts on the frequency and duration of infections in Greyhounds. The findings have broader health implications beyond Greyhounds as MADR A. caninum strains could spread to other breeds and even pet owners.


Assuntos
Ancylostoma , Doenças do Cão , Fezes , Animais , Cães , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Fezes/parasitologia , Estudos Retrospectivos , Ancylostoma/isolamento & purificação , Infecções por Uncinaria/veterinária , Infecções por Uncinaria/parasitologia , Infecções por Uncinaria/diagnóstico , Imunoensaio/veterinária , Imunoensaio/métodos , Ancilostomíase/veterinária , Ancilostomíase/diagnóstico , Ancilostomíase/parasitologia , Antígenos de Helmintos/análise , Antígenos de Helmintos/imunologia , Feminino , Masculino
5.
Vet Surg ; 41(5): 594-603, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22712787

RESUMO

OBJECTIVE: To evaluate the effects of epsilon aminocaproic acid (EACA) on the prevalence of postoperative bleeding in retired racing Greyhounds (RRG), and to assess its effects on selected thrombelastography (TEG) and fibrinolysis variables. STUDY DESIGN: Double-blinded, prospective, randomized study. METHODS: 100 RRG had elective ovariohysterectomy or orchiectomy and were administered EACA or placebo for 3 days after surgery. TEG variables were analyzed preoperatively and 24, 48, and 72 hours after surgery. RESULTS: Thirty percent (15/50) of RRG in the placebo group had delayed postoperative bleeding starting 36-48 hours after surgery compared with 10% (5/50) in the EACA group (P = .012). On the TEG variables, the slopes for R and K time were significantly different between treatment groups (P <.05); the R and K time decreased over time in the EACA group after surgery whereas they increased in the placebo group. The angle, maximal amplitude (MA), and G slopes were also significantly different between treatment groups (P = .001, .001, and .006, respectively). The angle, MA, and G increased postoperatively over time in the EACA group and decreased in the placebo group. All these changes are supportive of hypercoagulability associated with EACA administration. CONCLUSION: Postoperative administration of EACA significantly decreased the prevalence of postoperative bleeding in RRG undergoing surgery by increasing the clot strength.


Assuntos
Ácido Aminocaproico/uso terapêutico , Doenças do Cão/prevenção & controle , Histerectomia/veterinária , Orquiectomia/veterinária , Ovariectomia/veterinária , Hemorragia Pós-Operatória/veterinária , Animais , Doenças do Cão/etiologia , Cães , Método Duplo-Cego , Feminino , Hemostáticos/uso terapêutico , Histerectomia/efeitos adversos , Masculino , Razão de Chances , Orquiectomia/efeitos adversos , Ovariectomia/efeitos adversos , Hemorragia Pós-Operatória/prevenção & controle , Fatores de Risco
6.
Acta Crystallogr D Biol Crystallogr ; 67(Pt 5): 395-402, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21543841

RESUMO

This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Šresolution. GrHb was found to crystallize with an α1ß1 dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.


Assuntos
Cães/metabolismo , Hemoglobina A/química , Hemoglobina A/metabolismo , Oxigênio/metabolismo , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Multimerização Proteica , Estrutura Quaternária de Proteína , Alinhamento de Sequência
7.
Top Companion Anim Med ; 45: 100558, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34246821

RESUMO

Greyhounds have developed numerous physiologic and hematologic adaptations specific to the breed. Adult Greyhounds have significantly higher serum creatinine (sCr) concentrations than non-Greyhound dogs; this is primarily attributed to their large muscle mass. Adult Greyhounds also have significantly higher symmetric dimethylarginine (SDMA) concentrations than non-Greyhound dogs. In this study we evaluated serum SDMA and sCr concentrations in 48 Greyhound pups from 11 litters, with no exposure to racing, in order to determine if the higher SDMA or sCr concentration in adults is a breed-related trait or is associated with extra-physiological causes (e.g., racing environment, drug administration, etc.). The distribution of SDMA concentration for all the pups (mean: 0.70 µmol/L; 95% CI: 0.70-0.74 µmol/L) was not statistically different from that found in a group of 183 adult Greyhounds; whereas, distribution of sCr concentration in the pups (mean: 76.9 µmol/L; 95% CI: 70.7-83.1 µmol/L) was significantly different than that observed in adult Greyhounds, suggesting that the 2 samples were drawn from different populations. This study provides evidence to support that the higher serum SDMA concentration in Greyhounds is a breed-related trait.


Assuntos
Registros , Animais , Arginina/análogos & derivados , Cães , Registros/veterinária
8.
Can Vet J ; 51(10): 1157-60, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21197211

RESUMO

A 2.5-year-old, female llama with weight loss and lethargy had a packed cell volume (PCV) of 45% which increased to 57% over 3 wk. Transrectal ultrasonography revealed a mass of mixed echogenicity involving the right ovary, which was removed. A histopathological diagnosis of granulosa theca cell tumor was made. This is the first report of its kind in a llama.


Assuntos
Camelídeos Americanos , Neoplasias Ovarianas/veterinária , Policitemia/veterinária , Animais , Feminino , Tumor de Células da Granulosa/diagnóstico , Tumor de Células da Granulosa/cirurgia , Tumor de Células da Granulosa/veterinária , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Policitemia/diagnóstico , Policitemia/cirurgia , Resultado do Tratamento
9.
Am J Vet Res ; 81(6): 499-505, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32436791

RESUMO

OBJECTIVE: To assess the effect of packed RBC (pRBC) transfusion on thromboelastographic (TEG) tracings in dogs with naturally occurring anemia. ANIMALS: 22 clinically anemic dogs that received a pRBC transfusion. PROCEDURES: For each dog, a blood sample was collected before and within 3 hours after completion of the pRBC transfusion for a CBC, nonactivated TEG analysis, and measurement of blood viscosity. Wilcoxon signed rank tests were used to compare CBC, viscosity, and TEG variables between pretransfusion and posttransfusion blood samples. Multivariable linear regression was used to assess the effects of pretransfusion-posttransfusion changes in Hct, WBC count, and platelet count on changes in TEG variables. RESULTS: Median posttransfusion Hct (21%; range, 13% to 34%) was significantly greater than the median pretransfusion Hct (12.5%; range, 7% to 29%). Packed RBC transfusion was associated with a median increase in Hct of 6.2% (range, 1.2% to 13%). Maximum amplitude significantly decreased from 74.9 to 73.8 mm and clot strength significantly decreased from 14,906 to 14,119 dynes/s after pRBC transfusion. Blood viscosity significantly increased, whereas platelet and WBC counts significantly decreased after transfusion. Multivariable linear regression revealed that pretransfusion-posttransfusion changes in Hct, WBC count, and platelet count were not associated with changes in TEG variables. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that pRBC transfusion had only small effects on the TEG tracings of hemodynamically stable dogs. Therefore, large changes in TEG tracings following pRBC transfusion are unlikely to be the result of the transfusion and should be investigated further.


Assuntos
Anemia/veterinária , Transfusão de Eritrócitos/veterinária , Animais , Transfusão de Sangue/veterinária , Doenças do Cão , Cães , Hematócrito/veterinária , Tromboelastografia/veterinária
10.
J Vet Intern Med ; 34(5): 1759-1767, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33463770

RESUMO

BACKGROUND: Aortic thrombosis (ATh) is an uncommon condition in dogs, with limited understanding of risks factors, outcomes, and treatments. OBJECTIVES/HYPOTHESIS: To describe potential risk factors, outcome, and treatments in dogs with ATh. ANIMALS: Client-owned dogs with a diagnosis of ATh based on ultrasonographic or gross necropsy examination. METHOD: Multicentric retrospective study from 2 academic institutions. RESULTS: One hundred dogs were identified. Anti-thrombin diagnosis, 35/100 dogs were nonambulatory. The dogs were classified as acute (n = 27), chronic (n = 72), or unknown (n = 1). Fifty-four dogs had at least one comorbidity thought to predispose to ATh, and 23 others had multiple comorbidities. The remaining 23 dogs with no obvious comorbidities were classified as cryptogenic. Concurrent illnesses potentially related to the development of ATh included protein-losing nephropathy (PLN) (n = 32), neoplasia (n = 22), exogenous corticosteroid administration (n = 16), endocrine disease (n = 13), and infection (n = 9). Dogs with PLN had lower antithrombin activity than those without PLN (64% and 82%, respectively) (P = .04). Sixty-five dogs were hospitalized with 41 subsequently discharged. Sixteen were treated as outpatient and 19 euthanized at admission. In-hospital treatments varied, but included thrombolytics (n = 12), alone or in combination with thrombectomy (n = 9). Fifty-seven dogs survived to discharge. Sixteen were alive at 180 days. Using regression analysis, ambulation status at the time of presentation was significantly correlated with survival-to-discharge (P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Dogs with ATh have a poor prognosis, with nonambulatory dogs at the time of presentation having worse outcome. Although the presence of comorbid conditions associated with hypercoagulability is common, an underlying cause for ATh was not always identified.


Assuntos
Doenças do Cão , Trombose , Animais , Testes de Coagulação Sanguínea/veterinária , Doenças do Cão/tratamento farmacológico , Cães , Proteinúria/veterinária , Estudos Retrospectivos , Trombose/veterinária
11.
J Am Anim Hosp Assoc ; 45(1): 14-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19122059

RESUMO

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.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Doenças do Cão/tratamento farmacológico , Lomustina/uso terapêutico , Sarcoma de Mastócitos/veterinária , Prednisona/uso terapêutico , Animais , Antineoplásicos Alquilantes/efeitos adversos , Doenças do Cão/cirurgia , Cães , Quimioterapia Combinada , Feminino , Falência Hepática/etiologia , Falência Hepática/veterinária , Lomustina/efeitos adversos , Masculino , Sarcoma de Mastócitos/tratamento farmacológico , Sarcoma de Mastócitos/cirurgia , Estudos Retrospectivos , Análise de Sobrevida
12.
Vet Clin Pathol ; 38(2): 219-23, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19470149

RESUMO

BACKGROUND: Retired racing Greyhounds are popular as pets. Greyhounds have several differences in physiological values compared with other breeds, including lower serum alpha- and beta-globulin concentrations. We hypothesized that lower acute phase protein (APP) concentrations could contribute to lower alpha- and beta-globulin concentrations in this breed. OBJECTIVES: The purpose of this study was to compare serum concentrations of several APPs in Greyhounds with those of other dog breeds. METHODS: We measured the serum concentrations of C-reactive protein (CRP), haptoglobin (Hp), acid-soluble glycoprotein (ASG), ceruloplasmin (CP), and serum amyloid A (SAA) in 15 clinically healthy retired racing Greyhounds and 11 age- and gender-matched healthy nonGreyhound controls using previously validated methods. Results were compared by Student's t-tests. RESULTS: The concentration of Hp by both colorimetric and immunoturbidimetric methods was significantly lower in Greyhounds than in nonGreyhound dogs (P=.0009 and .019, respectively). The concentration of ASG was also significantly (P=.007) lower in Greyhounds, but CRP and CP concentrations were not significantly different between groups. SAA concentration was below the detection limit of the method in all dogs. CONCLUSIONS: The low serum concentrations of Hp and ASG should be taken into consideration when interpreting APP results in Greyhounds. Because both Hp and some ASG migrate in the alpha-globulin fraction, these results may explain the low alpha-globulin concentrations in Greyhounds.


Assuntos
Proteínas de Fase Aguda/química , Cães/sangue , Animais , Feminino , Masculino
14.
J Am Vet Med Assoc ; 254(11): 1329-1334, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067178

RESUMO

CASE DESCRIPTION: A 36-kg (79-lb) castrated male Greyhound (dog 1) and a 25-kg (55 lb) spayed female Greyhound (dog 2) underwent general anesthesia for dental care with similar perianesthetic protocols on multiple occasions from 2013 to 2016. Both dogs had periodontal disease but were otherwise deemed healthy. Both dogs developed clinically relevant hyperkalemia, with signs including loss of P waves on ECG tracings, during multiple anesthetic events. CLINICAL FINDINGS: Dog 1 developed hyperkalemia during 2 of 2 anesthetic events, with ECG changes noted during the first event. Dog 2 developed hyperkalemia during 3 of 4 anesthetic events, with ECG changes identified during the second and third events. Serum potassium concentration for both dogs was within the reference range prior to and between anesthetic events. No underlying etiopathogenesis for hyperkalemia was identified for either dog. TREATMENT AND OUTCOME: In each hyperkalemic event, the clinician stopped the dental procedure and continued to provide supportive care and monitoring while the dog recovered from anesthesia. The ECG changes resolved, and serum potassium concentration returned to the reference range rapidly after inhalant anesthetic administration was discontinued. The dogs were discharged from the hospital without further complications. CLINICAL RELEVANCE: Hyperkalemia in anesthetized Greyhounds resulted in serious cardiac conduction abnormalities, which could be potentially fatal if not recognized and promptly treated. Further investigation into the etiopathogenesis, prevention and treatment strategies, and genetic or familial components of this condition is indicated.


Assuntos
Doenças do Cão/diagnóstico , Hiperpotassemia/veterinária , Anestesia Geral/veterinária , Animais , Cães , Feminino , Hiperpotassemia/diagnóstico , Masculino
15.
Am J Vet Res ; 69(4): 519-26, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18380584

RESUMO

OBJECTIVE: To evaluate the biological activity of dihydroartemisinin on canine osteosarcoma cell lines in vitro. SAMPLE POPULATION: 4 canine osteosarcoma cell lines. PROCEDURES: Cell viability assays were performed on canine osteosarcoma cell lines OSCA2, OSCA16, OSCA50, and D17 after 24, 48, and 72 hours of treatment with dihydroartemisinin at concentrations of 0.1 to 100 microM. Apoptosis was assessed by use of an ELISA for free nuclosomal DNA fragmentation and by western blot analysis for cleavage of caspase 3. Cell cycle analysis was performed by use of staining with propidium iodide and flow cytometry. Detection of reactive oxygen species (ROS) was conducted in the D17 cell line by use of 6-carboxy-2',7'-dihydrofluorescein diacetate and flow cytometry. RESULTS: The concentration of dihydroartemisinin required for 50% inhibition of cell viability (IC50) was achieved in all 4 canine osteosarcoma cell lines and ranged from 8.7 to 43.6 microM. Induction of apoptosis was evident as an increase in nucleosomal DNA fragmentation, cleavage of caspase 3, and an increase in the population in the sub G0/G1 phase of the cell cycle detected by flow cytometry. Exposure to dihydroartemisinin also resulted in a decrease in the G0/G1 population. Iron-dependent generation of ROS was detected in dihydroartemisinin-treated D17 cells; ROS generation increased in a dose-dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Incubation with dihydroartemisinin resulted in biological activity against canine osteosarcoma cell lines, which included induction of apoptosis and arrest of the cell cycle. Clinical trials of dihydroartemisinin in dogs with osteosarcoma should be conducted.


Assuntos
Antineoplásicos/farmacologia , Artemisininas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/veterinária , Doenças do Cão/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/veterinária , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting/veterinária , Neoplasias Ósseas/patologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA , Doenças do Cão/patologia , Cães , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo/veterinária , Concentração Inibidora 50 , Osteossarcoma/patologia , Espécies Reativas de Oxigênio/metabolismo
16.
Vet Clin Pathol ; 37(4): 397-402, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19055574

RESUMO

An 11-year-old female spayed domestic shorthair cat was referred to The Ohio State University Veterinary Teaching Hospital (OSU-VTH) for evaluation of a 6 x 4 x 3.5 cm mass in the left midcervical region causing increased respiratory sounds and lateral deviation of the trachea. A fine needle aspirate of the mass was obtained before referral and the cytology results were compatible with a reactive lymph node. Immunocytochemistry showed increased numbers of CD3+ T lymphocytes and small numbers of CD20+ and CD79a+ medium to large lymphocytes. Differential diagnoses from the referral pathologist were T-cell-rich B-cell lymphoma and feline Hodgkin's-like lymphoma. A subsequent fine needle aspirate performed at the OSU-VTH showed similar results. On flow cytometry the majority of cells were CD3+ T lymphocytes that were double positive for CD4 and CD8 (73%), compatible with either a double-positive (CD4+CD8+) T-cell lymphoma or lymphocytes from ectopic thymic tissue. The mass was surgically removed. Histopathology and immunohistochemistry of the mass revealed a predominant population of CD3+ small lymphocytes and small numbers of medium to large lymphocytes with moderate anisocytosis and anysokaryosis. A population of cytokeratin-positive epithelial cells surrounded small microcystic structures filled with eosinophilic material and structures interpreted as Hassall's corpuscles. These findings were consistent with thymic tissue and a diagnosis of ectopic thymoma was made. PCR results for lymphocyte antigen receptor rearrangement (PARR) were negative. The cat had no evidence of disease 16 months after removal of the mass. To our knowledge this is the first report of an ectopic cervical thymoma in a cat. The clinical and diagnostic features of this unusual case will be useful in helping veterinarians and pathologists obtain a presurgical diagnosis and establish a prognosis for similar lesions.


Assuntos
Doenças do Gato/diagnóstico , Timoma/veterinária , Animais , Doenças do Gato/patologia , Gatos , Coristoma/patologia , Feminino , Timoma/diagnóstico , Timoma/patologia , Timo/patologia
17.
J Zoo Wildl Med ; 39(3): 472-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18817015

RESUMO

A 15-year-old female ground cuscus (Phalanger gymnotis) was presented with an isolated ulcerated, nonhealing lesion on the lateral thorax. Histopathology and immunohistochemistry were diagnostic for cutaneous T-cell lymphoma with incomplete excision. Oral chemotherapy with CCNU (lomustine) resulted in clinical remission that lasted 255 days, with no appreciable toxicity. Tumor recurrence was treated with radiation therapy, which resulted in 120 additional days of clinical remission. Subsequently, the tumor developed at a distant site and the cuscus was humanely euthanized. A slight decrease in appetite early in disease progression was the only adverse effect noted throughout the treatment period. Oral, minimally invasive chemotherapy, and adjunct radiation therapy were viable treatment options for this ground cuscus and should be considered for treatment of neoplasia in other nontraditional species.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Lomustina/uso terapêutico , Linfoma Cutâneo de Células T/veterinária , Phalangeridae , Neoplasias Torácicas/veterinária , Animais , Terapia Combinada , Evolução Fatal , Feminino , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/radioterapia , Indução de Remissão/métodos , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/radioterapia
18.
Cancer Res ; 78(13): 3421-3431, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29724721

RESUMO

Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that osteosarcoma tumors show a high frequency of somatic copy-number alterations (SCNA), affecting key oncogenes and tumor-suppressor genes. The across-breed results are similar to what has been observed for human osteosarcoma, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported) and 11 significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human osteosarcoma. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in osteosarcoma. This study points to the likely importance of histone modifications in osteosarcoma and highlights the strong genetic similarities between human and dog osteosarcoma, suggesting that canine osteosarcoma may serve as an excellent model for developing treatment strategies in both species.Significance: Canine osteosarcoma genomics identify SETD2 as a possible oncogenic driver of osteosarcoma, and findings establish the canine model as a useful comparative model for the corresponding human disease. Cancer Res; 78(13); 3421-31. ©2018 AACR.


Assuntos
Doenças do Cão/genética , Histona-Lisina N-Metiltransferase/genética , Osteossarcoma/genética , Animais , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Modelos Animais de Doenças , Doenças do Cão/patologia , Cães , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Osteossarcoma/patologia , Proteína Supressora de Tumor p53/genética , Sequenciamento do Exoma
19.
J Vet Intern Med ; 21(6): 1243-50, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18196733

RESUMO

BACKGROUND: Adoption of retired racing Greyhounds has become increasingly popular during the past decade. To date, research has focused on the physiologic and clinicopathologic peculiarities of Greyhounds but there is little published information on disease prevalence in the breed. OBJECTIVE: The objective of this study is to determine the prevalence of disease in retired racing Greyhounds. ANIMALS: In this study, 747 Greyhounds were used. METHODS: A standardized survey method was used, and survey responses were collected by an Internet survey. Owners could answer a survey for every Greyhound that they had owned since January 1, 2005. RESULTS: Of the 692 eligible participants, 441 (63.7% response rate) completed surveys for 747 Greyhounds. The mortality rate for Greyhounds within the 2-year period was 15% (113 of 747 died). The most common cause of death reported was cancer (66 dogs, 58%), and the most common type of cancer listed as the cause of death was osteosarcoma (28 dogs, 25%). The most commonly reported groups of diseases or disorders were skeletal (232 dogs, 33%), skin (197 dogs, 28%), digestive (132 dogs, 18%), cancer (94 dogs, 13%), and endocrine (85 dogs, 11.9%). Forty-five percent of Greyhounds diagnosed with cancer and 6% of the overall population had osteosarcoma. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study can be used by veterinary researchers to continue to investigate the most common diseases in this population. As more retired racing Greyhounds enter the pet population, the results of this study will help educate veterinarians and owners about the most prevalent diseases in the breed.


Assuntos
Doenças do Cão/epidemiologia , Internet , Inquéritos e Questionários , Animais , Comportamento Animal , Cães , Prevalência , Estados Unidos/epidemiologia
20.
J Vet Intern Med ; 21(6): 1355-63, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18196747

RESUMO

BACKGROUND: Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses. HYPOTHESIS: The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma. ANIMALS: One hundred and one dogs with multicentric lymphoma. METHODS: Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost. RESULTS: There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively). CONCLUSION AND CLINICAL IMPORTANCE: Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Cães , Feminino , Linfoma/tratamento farmacológico , Masculino , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Vincristina/efeitos adversos , Vincristina/uso terapêutico
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