RESUMO
BACKGROUND: The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up-regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK-STAT signaling pathway in DLBCL of dogs. HYPOTHESIS: STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen-activated protein kinase ERK1/2 in DLBCL of dogs. ANIMALS: Forty-three client-owned dogs diagnosed with DLBCL by histopathology METHODS: Retrospective analysis of DLBCL in dogs, including patient characteristics and treatment, immunohistochemistry, and protein expressions by Western blot. RESULTS: A higher percentage of STAT3 and p-STAT3 immunolabelled cells were observed in DLBCL of dogs when compared to normal canine lymph nodes. In STAT3 immunolabelled cells, STAT3 has higher nuclear expression in lymphoma samples than in normal or reactive lymph nodes. In addition to up-regulated STAT3 expression and activation, mitogen-activated kinase ERK1/2 activation is up-regulated in DLBCL of dogs. CONCLUSION AND CLINICAL IMPORTANCE: Compared with the normal canine lymph node, DLBCL of dogs has up-regulated STAT3 pathway. Our results support future investigation of JAK inhibitors in the treatment of DLBCL in dogs.
Assuntos
Doenças do Cão/patologia , Janus Quinases/biossíntese , Linfoma Difuso de Grandes Células B/veterinária , Fator de Transcrição STAT3/biossíntese , Animais , Doenças do Cão/metabolismo , Cães , Feminino , Imuno-Histoquímica , Linfonodos/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Estudos Retrospectivos , Transdução de Sinais , Regulação para CimaRESUMO
We interrogated the neurokinin-1 receptor (NK-1R)/substance P (SP) pathway in canine melanoma tumour tissues and cell lines. NK-1R messenger RNA (mRNA) and protein expression were observed in the majority of tumour tissues. Immunohistochemical assessment of archived tissue sections revealed NK-1R immunoreactivity in 11 of 15 tumours, which may have diagnostic, prognostic and therapeutic utility. However, we were unable to identify a preclinical in vitro cell line or in vivo xenograft model that recapitulates NK-1R mRNA and protein expression documented in primary tumours. While maropitant inhibited proliferation and enhanced apoptosis in cell lines, in the absence of documented NK-1R expression, this may represent off-target effects. Furthermore, maropitant failed to suppress tumour growth in a canine mouse xenograft model derived from a cell line expressing mRNA but not protein. While NK-1R represents a novel target, in the absence of preclinical models, in-species clinical trials will be necessary to investigate the therapeutic potential for antagonists such as maropitant.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma/veterinária , Quinuclidinas/farmacologia , Receptores da Neurocinina-1/metabolismo , Animais , Linhagem Celular Tumoral , Doenças do Cão , Cães , Camundongos , Camundongos Nus , Neoplasias Experimentais/metabolismo , Antagonistas dos Receptores de Neurocinina-1/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Neurocinina-1/genéticaRESUMO
A 4-year-old spayed female Golden Retriever was presented for evaluation of a rostral maxillary gingival mass. An en bloc resection was performed after histologic diagnosis of ameloblastic fibroma from an incisional biopsy specimen. Histologically, the tumor was composed of (1) poorly differentiated vimentin-positive mesenchymal cells that surrounded islands and (2) thin anastomosing trabeculae of odontogenic epithelium that variably coexpressed pancytokeratin and vimentin. To the authors' knowledge, this is the first report of ameloblastic fibroma in a dog. The clinical, radiographic, and histologic findings in this case are compared to those in other domestic animals and humans.
Assuntos
Doenças do Cão/patologia , Neoplasias Maxilares/veterinária , Odontoma/veterinária , Animais , Doenças do Cão/cirurgia , Cães , Feminino , Imuno-Histoquímica/veterinária , Neoplasias Maxilares/patologia , Odontoma/patologiaRESUMO
This article describes 11 cases of neuronal embryonal neoplasia in captive adult teleost fish. Neoplasms were located within 1 or both eyes of 8 fish and the skin of 3 other fish. Ocular neoplasms most often presented as unilateral or bilateral exophthalmia. Seven ocular and 1 cutaneous mass were composed of small triangular (carrot-shaped) neoplastic cells with Flexner-Wintersteiner-type rosette formation. Mass location and histologic and ultrastructural features were suggestive of retinoblastomas. One ocular mass was composed of ribbons and rosettes of neoplastic cells with multiple areas of neuronal differentiation and was diagnosed as a teratoid medulloepithelioma. A cutaneous mass from an electric eel (Electrophorus electricus) consisted of rosettes and streams of elongate neoplastic cells. The epidermal electroreceptor (ampullary) organ was considered as an origin. Although distant metastases were not observed, neoplasms were generally locally aggressive with postexcision recurrence. There was occasional spread to or de novo occurrence within the contralateral eye.