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1.
Vet Comp Oncol ; 22(1): 136-148, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38243867

RESUMO

Canine cutaneous mastocytosis (CM) is rare in contrast to canine mast cell tumours. In humans, CM commonly affects children and is usually indolent with possible spontaneous resolution. Systemic mastocytosis (SM) with bone marrow involvement typically affects adults, can have a poor outcome, and often includes skin lesions. 'Mastocytosis in the skin' (MIS) is the preferred term of skin lesions, if bone marrow evaluations are not available, which is often the cases in dogs. In human SM and CM, KIT mutations are often detected. The veterinary literature suggests clinical resemblances between human and canine MIS, but data is limited, and KIT mutations are rarely assessed. This retrospective study describes clinicopathological findings, treatment and outcome of 11 dogs with suspected MIS. Dogs with multiple mast cell tumours were excluded. Histopathology reports (n = 5) or slides (n = 6) were reviewed. KIT mutation analysis including exons 8, 9, 11, 14 and 17 were analysed in eight dogs. Median age at diagnosis was 4 years (range, 1-12). Typical clinical signs included multifocal to generalised nodules and papules. Histologically, skin lesions were characterised by dermal infiltration of well-differentiated mast cells. KIT mutations were detected in 3/8 dogs (exon 9: n = 2; exon 11: n = 1). One dog had mastocytaemia suggesting possible SM. Glucocorticoids were mostly successful with lesion improvement in all treated dogs (n = 8). This cohort highlights resemblances between human and canine MIS. Further studies are required to confirm these findings and establish diagnostic criteria for CM and MIS associated with SM in dogs.


Assuntos
Doenças do Cão , Mastocitose Cutânea , Mastocitose Sistêmica , Mastocitose , Cães , Humanos , Animais , Estudos Retrospectivos , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Mastocitose/diagnóstico , Mastocitose/veterinária , Mastocitose/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/veterinária , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/veterinária , Mastocitose Cutânea/genética , Proteínas Proto-Oncogênicas c-kit/genética
2.
J Vet Diagn Invest ; 34(2): 288-291, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35075959

RESUMO

A male Malayan tiger cub developed well-circumscribed, erythematous, alopecic lesions on the face, torso, and paws when 1-wk-old. Biopsies of a torso lesion and a right front paw lesion at 1-mo-old confirmed cutaneous mast cell tumors (MCTs). MCTs on the paws grew into pendulous masses up to 6.5 cm in diameter by 3-mo-old, but those on the face and torso regressed. Fine-needle aspiration of the spleen at 3-mo-old revealed marked mast cell infiltration. The spleen and the right paw cutaneous MCT were removed; the paw MCT recurred within 7 d. A 12-bp tandem duplication, suggesting a somatic mutation, was identified in exon 8 of c-KIT in DNA extracted from the cutaneous MCT on the right paw and from one over the torso, but not from the spleen. Remaining MCTs on the paws regressed slowly following splenectomy and had completely regressed by 1-y-old. At 7-y-old, there was no recurrence of any mast cell disease. Mast cell disease in this tiger cub is similar to a report in a domestic kitten and to pediatric mastocytosis in humans, which commonly begins in infancy, improves by adolescence, and is associated with somatic c-kit mutations. To our knowledge, mastocytosis has not been reported previously in a juvenile exotic felid.


Assuntos
Doenças do Gato , Mastocitose , Tigres , Animais , Gatos , Feminino , Masculino , Mastocitose/genética , Mastocitose/patologia , Mastocitose/veterinária , Proteínas Proto-Oncogênicas c-kit/genética , Baço/patologia
3.
Aust Vet J ; 98(3): 96-99, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31919836

RESUMO

BACKGROUND: To the authors' knowledge, this is the first report of mast cell neoplasia in a koala (Phascolarctos cinereus). CASE REPORT: An adult female koala was presented for rapidly deteriorating health and death of a pouch young. Significant weight loss was apparent despite supplemental feeding; the abdomen was distended; and the koala was weak and mentally depressed. Haematology revealed a significant mastocytosis with a concurrent population of atypical mononuclear cells. The koala was euthanised and tissues were collected for histology. Bone marrow, lymph node, lung, stomach and spleen exhibited significant infiltration by mast cells. Atypical round cells consistent with those identified in the peripheral blood were also identified in the marrow. A diagnosis of systemic mastocytosis and probable mast cell leukaemia was made. Immunocytochemical and immunohistochemical staining was not able to further characterise the atypical cell population, and the mast cells exhibited only weak staining with CD117. CONCLUSION: The histological diagnosis, in this case, was systemic mastocytosis and myeloproliferative disease of uncertain origin. There was a dominant population of mast cells in the peripheral blood and marrow, and a population of circulating atypical mononuclear cells, appearing similar to mast cell leukaemia-acute myeloid leukaemia in humans.


Assuntos
Leucemia de Mastócitos/veterinária , Mastocitose Sistêmica/veterinária , Mastocitose/veterinária , Phascolarctidae , Adulto , Animais , Feminino , Humanos , Mastócitos
4.
Vet Comp Oncol ; 18(3): 409-415, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31930651

RESUMO

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow-up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.


Assuntos
Quimioterapia Adjuvante/veterinária , Doenças do Cão/tratamento farmacológico , Mastocitose/veterinária , Neoplasias Cutâneas/veterinária , Animais , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Feminino , Itália , Metástase Linfática , Masculino , Mastocitose/tratamento farmacológico , Mastocitose/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/veterinária , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Sobrevida
5.
Vet Comp Oncol ; 18(3): 389-401, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31863546

RESUMO

Conflicting evidence exists regarding the importance of routine abdominal ultrasound (US) with hepatic and splenic fine needle aspiration (FNA) cytology during staging of canine mast cell tumours (MCT). The objective of this study was to correlate ultrasonographic and cytologic findings in dogs with strictly defined high-risk MCTs and to determine the influence on outcome. Our hypothesis was that US poorly predicts visceral metastasis in high-risk MCTs and that early metastasis is associated with improved outcome when compared to overt metastasis. US of liver and spleen correlated to cytologic results, categorized as no metastasis, early metastasis or overt metastasis. Of 82 dogs prospectively enrolled, 18% had early visceral metastasis and 7% had overt metastasis on cytology; 67% with visceral metastasis had regional LN metastasis. US was a poor predictor of metastasis with sensitivity, specificity, positive predictive value and negative predictive value for the spleen of 67%, 68%, 21% and 94%, respectively and for the liver of 29%, 93%, 56% and 82%, respectively. Median time to progression (TTP) for dogs with no metastasis, early metastasis and overt metastasis was not reached, 305 and 69 days, respectively (P < .001). Median survival time (MST) for the 3 groups were not reached, 322 and 81 days, respectively (P < .001). High Patnaik or Kiupel grade, early metastasis, overt metastasis and adequate local control were significantly associated with outcome. Early visceral metastasis was associated with poorer outcome compared to dogs without metastasis, however, a subset of dogs experienced long-term control.


Assuntos
Doenças do Cão/diagnóstico por imagem , Neoplasias Hepáticas/veterinária , Mastocitose/veterinária , Neoplasias/veterinária , Neoplasias Esplênicas/veterinária , Ultrassonografia/veterinária , Animais , Cães , Feminino , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Mastocitose/diagnóstico por imagem , Mastocitose/patologia , Metástase Neoplásica/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Prognóstico , Sensibilidade e Especificidade , Neoplasias Esplênicas/diagnóstico por imagem , Neoplasias Esplênicas/secundário , Ultrassonografia/métodos
6.
Rev. bras. ciênc. vet ; 26(3): 64-68, jul./set. 2019. ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-1491641

RESUMO

Uma égua puro sangue árabe, com 3 anos de idade, pertencente ao rebanho experimental da FMVZ-USP apresentou lesões tumorais cutâneas nos membros pélvicos direito e esquerdo com aproximadamente um ano de evolução. Notou-se nova formação cutânea com crescimento rápido na região do pescoço, e desde então, as lesões dos membros ganharam características inflamatórias. Foi realizada punção aspirativa da lesão do pescoço para análise citológica, em que se identificou infiltrado eosinofílico. Optou-se pelo início de tratamento conservativo com três infiltrações intralesionais consecutivas com corticoesteroide. A partir da falta de sucesso das infiltrações foram realizadas as excisões cirúrgicas totais dos nódulos do pescoço, membro pélvico direito e esquerdo. Todos os materiais obtidos dos procedimentos cirúrgicos foram enviados para avaliação histopatológica e imuno-histoquímica, nas quais se confirmou o diagnóstico de mastocitoma cutâneo. O animal recebeu alta após a cicatrização das feridas cirúrgicas e remissão dos sinais, e não demonstrou recidivas ou outras complicações advindas das lesões tumorais. Algumas neoplasias cutâneas são bem descritas e de comum ocorrência na espécie equina, como o sarcoide, melanoma, papiloma e tumor de células escamosas. Já o mastocitoma cutâneo consiste em neoplasia cutânea rara nessa espécie. Segundo a literatura, não parece existir uma predileção racial para o aparecimento deste tumor, entretanto, alguns autores citam o acometimento maior nos animais Puro Sangue Árabe. Para o estabelecimento do diagnóstico definitivo é importante a associação dos exames físico, histopatológico e imuno-histoquímico e, apesar desta neoplasia ser de raro aparecimento nos equinos, deve ser sempre considerada como diagnóstico diferencial.


A 3 year-old mare, Arab, that belongs to the experimental herd of FMVZ-USP presented cutaneous tumor lesions on right and left posterior limb with approximately one year of evolution. A new formation with rapid growth was observed on the neck region, and since then, the limbs lesion gained inflammatory characteristics. Aspirative punction was performed on the neck formation in order to submit the sample to cytological analyses, in which eosinophilic infiltrate was identified. At this point, a conservative approach was chosen with three consecutive corticoid infiltrations. With lack of success of infiltrative therapy, neck, right and left posterior limbs lesions were surgically removed. The materials obtained from surgical procedures were sent to histophatological and immunohistrochemical evaluation that confirmed cutaneous mastocytoma diagnosis. The mare was discharged after all surgical wound were healed and after full remission of clinical signs, and did not show relapses or any other complication from tumor lesions. Some cutaneous tumors are well described and commonly occur in horses, such as sarcoids, melanoma, papilloma and squamous cell carcinoma. Cutaneous mastocytoma is considered a rare cutaneous tumor in this species. According to literature, equine mastocytoma do not have breed predilection, however, some authors mention a greater involvement in Purebreed Arabian horses. In order to establish a definitive diagnosis, it is important to associate physical exams to histophatological an immunohistochemical evaluation and, even though rare in horses, this neoplasm must be considered as a differential diagnosis.


Assuntos
Feminino , Animais , Cavalos , Mastocitoma Cutâneo/patologia , Mastocitoma Cutâneo/veterinária , Mastocitose/veterinária , Imuno-Histoquímica/veterinária , Neoplasias Cutâneas/veterinária
8.
J Vet Intern Med ; 32(6): 2061-2068, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30353992

RESUMO

BACKGROUND: No biomarkers for the early detection of gastrointestinal (GI) toxicosis secondary to antineoplastic treatment are recognized in veterinary medicine. Toceranib causes GI toxicosis in dogs. HYPOTHESIS/OBJECTIVE: To assess if changes in plasma cytokeratin 18 (CK18) concentration, measured in dogs being treated with toceranib phosphate, can predict the onset of GI toxicosis. We hypothesize that an increase in CK18 concentrations will be detected before the development of GI toxicosis in dogs treated with toceranib phosphate. ANIMALS: Twenty healthy client-owned dogs and 25 client-owned dogs with surgically excised mast cell tumor (MCT). METHODS: Prospective cohort study. Dogs were treated with toceranib (2.75 mg/kg PO q48h). Plasma was collected weekly for 4 weeks. Plasma CK18 concentration was measured on days 0, 7, 14, 21, and 28. vascular endothelial growth factor was measured on days 0 and 28. RESULTS: Mean plasma CK18 concentration on day 0 in dogs with MCT was not significantly different than healthy controls (313.5 ± 592.8 pg/mL, 119.7 ± 76.9 pg/mL, mean ± SD P = 0.27). Mean plasma CK18 concentration decreased by 98.69 pg/mL from day 0 to day 28 (P < 0.001). Plasma CK18 concentration was not a significant predictor of the development of signs of GI toxicosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma CK18 concentration was not a clinically useful biomarker for the early detection of GI toxicosis secondary to toceranib administration in dogs with MCTs.


Assuntos
Antineoplásicos/efeitos adversos , Doenças do Cão/induzido quimicamente , Gastroenteropatias/veterinária , Indóis/efeitos adversos , Queratina-18/sangue , Pirróis/efeitos adversos , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Doenças do Cão/sangue , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Gastroenteropatias/sangue , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , Masculino , Mastocitose/tratamento farmacológico , Mastocitose/veterinária , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular/sangue
9.
J Comp Pathol ; 163: 6-9, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30213375

RESUMO

Stem cell factor (SCF) is a ligand of the molecule Kit, which is expressed in mast cells and is important for mast cell proliferation, migration and survival. Mast cell tumours (MCTs) are associated with mutations of c-kit, a proto-oncogene encoding the Kit protein. In this study, we examined SCF expression in 23 samples of feline MCTs. SCF expression was detected in 10 cutaneous MCTs and a case of splenic mastocytosis. In the cutaneous MCTs, SCF-positive tumour cells were located at the margins. Kit was expressed in eight of the 10 cutaneous cases of SCF-expressing MCTs. In these cases, Kit-positive cells were located near to SCF-positive cells, and SCF/Kit double-positive tumour cells were found. Ki67-positive tumour cells were not found near to SCF-positive cells. These results suggest that SCF autocrine/paracrine mechanisms are involved in the expansion of cutaneous MCTs, but not in tumour proliferation.


Assuntos
Doenças do Gato/metabolismo , Mastocitoma Cutâneo/veterinária , Mastocitose/veterinária , Neoplasias Cutâneas/veterinária , Fator de Células-Tronco/metabolismo , Animais , Doenças do Gato/patologia , Gatos , Proliferação de Células , Feminino , Masculino , Mastocitoma Cutâneo/metabolismo , Mastocitoma Cutâneo/patologia , Mastocitose/metabolismo , Mastocitose/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
10.
Vet Comp Oncol ; 16(4): 511-517, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29961972

RESUMO

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May-Grünwald-Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS-stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high-grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging.


Assuntos
Corantes/uso terapêutico , Doenças do Cão/diagnóstico , Amarelo de Eosina-(YS)/uso terapêutico , Mastocitose/veterinária , Azul de Metileno/uso terapêutico , Animais , Biópsia por Agulha Fina/veterinária , Doenças do Cão/patologia , Cães , Mastócitos/patologia , Mastocitose/diagnóstico , Mastocitose/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/patologia , Mastocitose Cutânea/veterinária , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/patologia , Mastocitose Sistêmica/veterinária , Prognóstico , Estudos Prospectivos
11.
Vet Comp Oncol ; 16(3): 392-398, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29498186

RESUMO

The objective of this prospective study was to evaluate agreement and reliability of calliper-based measurements of locally invasive subcutaneous malignant tumours in dogs. Four raters measured the longest diameter of 12 subcutaneous tumours (7 soft tissue sarcomas and 5 mast cell tumours) from 11 client-owned dogs during 3 randomized, blinded measurement trials, both pre- and post-sedation. Inter- and intra-rater reliability was evaluated using intra-class correlation coefficient (ICC) and agreement was evaluated using Bland-Altman plots. Inter- and intra-rater reliability was good (ICC range of 0.8694-0.89520) and excellent (ICC range of 0.9720-0.9966), respectively. For agreement calculations, an a priori clinically relevant limit of agreement of 10 mm was set. Inter- and intra-rater agreement was unacceptable with inter-rater limits of agreement ranging from 15.9 to 55.6 mm and intra-rater limit of agreement ranging from 11.9 to 28.1 mm. Review of the measurement trial photographs revealed that calliper orientation changes were frequent, occurring in 9/12 (75%) and 8/12 (67%) pre- and post-sedation cases. No significant correlation was found between inter-rater measurement standard deviations and calliper orientation changes or dog body condition score. These findings suggest veterinarians may have poor agreement in determining the gross edge of tumours, which is expected to introduce bias and inconsistency in tumour staging, assessing response to therapy, and surgical margin planning. Due to the potential consequences for veterinary cancer patients, future studies are needed to validate the present findings.


Assuntos
Doenças do Cão/patologia , Margens de Excisão , Mastocitose/veterinária , Neoplasias de Tecidos Moles/veterinária , Tela Subcutânea/patologia , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/cirurgia , Cães , Feminino , Masculino , Mastocitose/diagnóstico , Mastocitose/patologia , Mastocitose/cirurgia , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Tela Subcutânea/cirurgia
12.
Vet Radiol Ultrasound ; 59(4): 461-468, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29570234

RESUMO

The goal of this prospective pilot study was to use naturally occurring canine mast cell tumors of various grades and stages as a model for attempting to determine how glucose uptake and markers of biologic behavior are correlated. It was hypothesized that enhanced glucose uptake, as measured by 2-[fluorine-18]fluoro-d-glucose-positron emission tomography/computed tomography (F18 FDG PET-CT), would correlate with histologic grade. Dogs were recruited for this study from a population referred for treatment of cytologically or histologically confirmed mast cell tumors. Patients were staged utilizing standard of care methods (abdominal ultrasound and three view thoracic radiographs), followed by a whole body F18 FDG PET-CT. Results of the F18 FDG PET-CT were analyzed for possible metastasis and standard uptake value maximum (SUVmax ) of identified lesions. Incisional or excisional biopsies of the accessible mast cell tumors were obtained and histology performed. Results were then analyzed to look for a possible correlation between the grade of mast cell tumors and SUVmax . A total of nine animals were included in the sample. Findings indicated that there was a correlation between grade of mast cell tumors and SUVmax as determined by F18 FDG PET-CT (p-value = 0.073, significance ≤ 0.1). Based on the limited power of this study, it is felt that further research to examine the relationship between glucose utilization and biologic aggressiveness in canine mast cell tumors is warranted. This study was unable to show that F18 FDG PET-CT was a better staging tool than standard of care methods.


Assuntos
Doenças do Cão/diagnóstico por imagem , Fluordesoxiglucose F18/química , Mastocitose/veterinária , Gradação de Tumores/veterinária , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/veterinária , Radiografia Torácica/veterinária , Ultrassonografia/veterinária , Animais , Cães , Glucose/metabolismo , Mastocitose/diagnóstico por imagem , Gradação de Tumores/métodos , Palpação/métodos , Palpação/veterinária , Paracentese/métodos , Paracentese/veterinária , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radiografia Torácica/métodos , Compostos Radiofarmacêuticos/química , Ultrassonografia/métodos
13.
Vet Comp Oncol ; 16(3): 330-336, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29322606

RESUMO

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour-infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)-positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3-positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3-positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.


Assuntos
Doenças do Cão/imunologia , Linfócitos do Interstício Tumoral/fisiologia , Neoplasias/veterinária , Linfócitos T Reguladores/patologia , Adenocarcinoma/imunologia , Adenocarcinoma/veterinária , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/veterinária , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/veterinária , Estudos de Casos e Controles , Doenças do Cão/diagnóstico , Cães , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/veterinária , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/veterinária , Mastocitose/imunologia , Mastocitose/veterinária , Neoplasias Bucais/imunologia , Neoplasias Bucais/veterinária , Neoplasias/diagnóstico , Neoplasias/imunologia , Prognóstico , Resultado do Tratamento
14.
J Vet Sci ; 19(2): 162-171, 2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-28927253

RESUMO

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.


Assuntos
Doenças do Cão/metabolismo , MicroRNAs/metabolismo , Neoplasias/metabolismo , Animais , Neoplasias da Mama/metabolismo , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma/metabolismo , Linfoma/veterinária , Neoplasias Mamárias Animais/metabolismo , Mastocitose/metabolismo , Mastocitose/veterinária , Neoplasias/veterinária
15.
Vet Comp Oncol ; 16(1): 20-27, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28168776

RESUMO

BACKGROUND: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited information on treatment outcomes of cats with this disease. MATERIALS AND METHODS: This retrospective study evaluated treatment outcomes in 64 cats with splenic MCT. Cats were categorized into the following treatment groups: splenectomy (A, n = 20); splenectomy with chemotherapy (B, n = 20); chemotherapy alone (C, n = 15); or supportive care (D, n = 9). RESULTS: Median tumor specific survival (MTSS) was: 856, 853, 244, 365 days for groups A, B, C, and D, respectively. The MTSS was not significantly different between the 4 groups. However, comparing cats that had splenectomy (A and B) versus those that did not (C and D), the MTSS was 856 and 342 days, respectively (p=0.008). None of the prognostic factors analyzed significantly influenced survival. CONCLUSION: Splenectomy (+/- chemotherapy) significantly prolongs survival in cats with mast cell tumors. The role of chemotherapy remains unknown.


Assuntos
Doenças do Gato/diagnóstico , Mastocitose/veterinária , Neoplasias Esplênicas/veterinária , Animais , Antineoplásicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Doenças do Gato/cirurgia , Doenças do Gato/terapia , Gatos , Terapia Combinada/veterinária , Feminino , Masculino , Mastocitose/diagnóstico , Mastocitose/tratamento farmacológico , Mastocitose/terapia , Prognóstico , Estudos Retrospectivos , Esplenectomia/veterinária , Neoplasias Esplênicas/diagnóstico , Resultado do Tratamento
16.
Vet Pathol ; 55(1): 182-186, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29050542

RESUMO

In 5 Japanese Black steers (2-2.4 years old) that originated from 5 different feedlots, the livers were found at slaughter to have multiple nodular or cordlike lesions (5 steers) and an extensive fibrotic area (1 steer). Microscopic changes included extensive fibroplasia in the portal tracts and chronic proliferative endophlebitis-like lesions confined to the portal vein branches. Fibroplasia was much more prominent in the macroscopic fibrotic lesion of 1 steer. Portal vein branches presented irregular variciform dilation of the vascular lumen and fibroplastic changes in the subendothelial areas that showed occasional hemorrhage and were simultaneously infiltrated with large numbers of mast cells and moderate to large numbers of eosinophils. Within these subendothelial regions, not only did mast cells exhibit cytologically atypical features, but they also formed multifocal nodules. The venous lesions may represent a variant of mastocytosis with specific involvement of the hepatic portal vein branches in cattle.


Assuntos
Doenças dos Bovinos/patologia , Hepatopatias/veterinária , Mastocitose/veterinária , Animais , Bovinos , Japão , Fígado/patologia , Hepatopatias/patologia , Masculino , Mastocitose/patologia , Veia Porta/patologia
17.
Vet Immunol Immunopathol ; 188: 84-88, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28615132

RESUMO

Imatinib-resistance is a major therapeutic problem in human chronic myeloid leukemia, human gastrointestinal stromal tumors, and canine mast cell tumors. In the present study, we identified the secondary mutation c.2006C>T in c-KIT exon 14 in a mast cell tumor obtained from a dog carrying c.1663-1671del in exon 11 and showing resistance to imatinib. The mutation in exon 14 resulted in substitution of threonine with isoleucine at position 669, which was located at the center of the ATP binding site as a gatekeeper and played an important role in binding to imatinib. Transfectants were constructed to survey the functions of these mutations in exons 11 and 14. The transfectant with mutant KIT encoded by c-KIT carrying c.1663-1671del showed constitutive ligand-independent phosphorylation that was suppressed by imatinib, indicating a gain-of-function mutation. Furthermore, the transfectant with mutant KIT encoded by c-KIT carrying both c.1663-1671del and c.2006C>T caused ligand-independent phosphorylation, which was not suppressed by imatinib. From these results, we concluded that the mutation c.2006C>T in c-KIT exon 14 was an imatinib-resistance mutation in a canine mast cell tumor. These findings revealed, for the first time, a mechanism of imatinib resistance in a clinical case of canine mast cell tumor.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Mastocitose/veterinária , Proteínas Proto-Oncogênicas c-kit/genética , Animais , Cães , Resistencia a Medicamentos Antineoplásicos/genética , Mastocitose/tratamento farmacológico , Mastocitose/genética , Deleção de Sequência/genética
19.
Vet Comp Oncol ; 15(4): 1382-1392, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28467670

RESUMO

COX-2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours (MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX-2, CD31, Ki-67, MAC-387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival (OS) was analysed. COX-2 intensity (P = 0.016), but not COX-2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik (P = 0.002) and Kiupel (P < 0.001) grading systems. Cox-2 intensity was also associated with higher Ki-67 scores (P = 0.009), higher mitotic index (P = 0.022) and higher microvascularization density (P = 0.045). No association was observed for COX-2 intensity and CD3-T lymphocyte (P = 0.377) and macrophage infiltration (P = 0.261) by MAC-387 immunollabelling, suggesting an active role of COX-2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Doenças do Cão/metabolismo , Mastocitose/veterinária , Neovascularização Patológica/veterinária , Animais , Proliferação de Células , Doenças do Cão/mortalidade , Doenças do Cão/patologia , Cães , Feminino , Masculino , Mastocitose/metabolismo , Mastocitose/mortalidade , Mastocitose/patologia , Mastocitose Cutânea/metabolismo , Mastocitose Cutânea/mortalidade , Mastocitose Cutânea/patologia , Mastocitose Cutânea/veterinária , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Estudos Retrospectivos
20.
Schweiz Arch Tierheilkd ; 159(3): 171-177, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28248186

RESUMO

INTRODUCTION: In this study we compared the outcomes of dogs with incompletely-excised grade-2 mast cell tumors (incompletely- excised grade-2 MCTs) either adjuvantly treated or not. Dogs with a grade-2 mast cell tumour (MCT) excised either incompletely or with narrow (<5mm) margins, without local recurrence or metastasis at the time of presentation and with a minimum follow-up of 10 months were included in the study. Dogs were separated in 2 groups: treatment (surgery, radiation therapy, chemotherapy or combination of those) and no-treatment. The original excision was incomplete in 90 dogs and narrow in 25 dogs. Ninety-two cases (80%) were treated and 23 (20%) were not treated, but only monitored. Pathology after revision excision found no signs of residual disease in 47/56 cases (84%). Local recurrence was confirmed in 7 dogs, suspected but not confirmed in 2 dogs. Metastatic disease was confirmed in 13 dogs and suspected but not confirmed in 11 dogs. Forty-six dogs died and 69 were still alive at the time of data collection. The 1-yr and 2-yr survival rates were 92% and 82%, respectively. No statistical differences were found regarding disease-free intervals, survival times, recurrence rates, metastatic rates, 1-year and 2-year survival rates between groups, or depending on treatment modality within the treatment group. Based on the finding that the outcome of incompletely-excised grade-2 MCTs was unaffected by adjuvant treatments, this study suggests that immediate systematic adjuvant treatment of incompletely-excised grade-2 MCTs may not be recommended over attentive monitoring and action upon uncommon recurrence.


Dans la présente étude, on compare le devenir de chiens présentant des mastocytomes de grade 2 incomplètement excisés, selon qu'ils ont reçu un traitement adjuvant ou qu'ils aient simplement été sous surveillance. On a pris en compte des chiens chez lesquels des mastocytes de grade 2 ont été incomplètement excisés ou l'ont été avec une marge étroite (<5mm) et qui ne présentaient pas de signe de récidive locale ou de métastases au moment de l'examen avec un suivi de minimum 10 mois. Les chiens ont été classés en deux groupes, l'un avec des traitements (chimiothérapie, radiothérapie, chirurgie ou combinaison de ces traitements) et l'autre sans autre traitement. L'excision originelle était incomplète chez 90 chiens et présentait des marges étroites chez 25 chiens. 92 cas (80%) ont reçu un traitement et 23 (20%) ont été surveillés sans traitement. Les résultats de l'histologie après une excision de révision n'ont pas fait état de signes d'une affection tumorale restante dans 47/56 cas (84%). Une récidive locale a été confirmée chez 7 chiens et supposée mais pas confirmée chez 2 chiens. Des métastases ont été confirmées chez 13 chiens, supposées mais non confirmées chez 11. Au moment du relevé des données, 46 chiens étaient décédés et 69 encore en vie. Le taux de survie à 1 respectivement à 2 ans était de 92% respectivement 82%. Il n'y avait pas de différence statistiquement significative entre les deux groupes en ce qui concerne les intervalles entre les affections, la durée de la survie, le taux de récidive, le taux de métastases, le taux de survie à 1 et à 2 ans ou entre les divers traitements dans le groupe des animaux traités. Les résultats de cette étude montrent que des traitements adjuvants n'influencent pas le résultat en présence de mastocytes de degré 2 incomplètement excisés. Un traitement adjuvant systématique lors de mastocytes de degré 2 incomplètement excisés ne peut donc pas être recommandé par rapport à une surveillance attentive et un traitement lors de récidive diagnostiquée.


Assuntos
Doenças do Cão/terapia , Mastocitose/veterinária , Animais , Antineoplásicos/uso terapêutico , Terapia Combinada , Cães , Seguimentos , Lomustina/uso terapêutico , Mastocitose/mortalidade , Mastocitose/terapia , Reoperação , Resultado do Tratamento
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