Resumo
This study aimed to evaluate the serum concentration of vitamin D (25-Hydroxyvitamin D) and acute phase proteins (APPs; alpha-1 acid glycoprotein, haptoglobin, transferrin, ceruloplasmin, albumin, IgA, IgG and alpha-1 - antitrypsin) as potential biomarkers for prognostic and therapy response in dogs with multicentric lymphoma submitted to the CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) chemotherapy protocol. Thirteen dogs with multicentric lymphoma classified as high grade by cytology were included in the treatment group (GL), while ten healthy dogs were included in the control group (GC). Serum was collected in the weeks T0, T5 and T10 of CHOP chemotherapy protocol, for the GL group, and in a single collection, for the GC group. All the collected samples were evaluated for the APPs and vitamin D concentrations through electrophoresis and chemiluminescence methods, respectively. Diagnostic and staging tests were performed for all the dogs in the GL group, and included cytopathology, histopathology and immunohistochemistry of the affected lymph node. Of these dogs, 9 achieved a complete response and 4 a partial response to the treatment. Data analysis was performed with the R software. The results demonstrated that serum concentrations of IgA, haptoglobin and α1-acid glycoprotein were significantly different between the groups and also between the different chemotherapy times analyzed (p<0.05), indicating that these proteins can be considered as sensitive biomarkers for lymphoma in dogs. Furthermore, the α1-acid glycoprotein showed prognostic value for the disease, with 63% specificity. However, vitamin D concentration was not correlated with prognosis of the dogs with lymphoma.
Objetivou-se caracterizar a concentração sérica da vitamina D e das PFAs (Proteínas de Fase Aguda) (alfa-1 glicoproteína ácida, haptoglobina, transferrina, ceruloplasmina, albumina, IgA, IgG e alfa-1 antitripsina) em cães com linfoma multicêntrico, submetidos ao tratamento quimioterápico com protocolo CHOP (Ciclofosfamida, Doxorrubicina, Vincristina e Prednisona), determinando o valor prognóstico desses marcadores para a doença. Foram avaliadas as concentrações séricas das PFAs, através do método da eletroforese e as concentrações da vitamina D, através da quimioluminescência em dois grupos experimentais, um grupo de 13 cães com linfoma multicêntrico classificados como alto grau pela citologia (GL) durante as semanas T0, T5 e T10 do tratamento com protocolo quimioterápico antineoplásico e em um grupo de 10 animais saudáveis para compor o grupo controle (GC), em coleta única. Para isso, foi realizado o diagnóstico, estadiamento e avaliação de resposta terapêutica dos 13 pacientes com linfoma multicêntrico através de técnicas de citopatologia, histopatologia, imuno-histoquímica do linfonodo periférico acometido. Foi observado que 9 pacientes tiveram resposta completa e 4 pacientes tiveram resposta parcial ao tratamento. Os dados foram analisados através do software R. Os resultados indicam que as diferenças entre as variáveis IgA, haptoglobina e α1-glicoproteína ácida foram significativas entre os grupos, e entre os diferentes momentos da quimioterapia (p< 0,05), indicando que podem ser marcadores sensíveis ao linfoma em cães. A α1-glicoproteína ácida apresentou valor prognóstico para o linfoma, com 63% de especificidade. Porém a vitamina D não apresentou valor prognóstico para o linfoma multicêntrico em cães.
Assuntos
Animais , Cães , Biomarcadores , Doenças do Cão , Linfoma/tratamento farmacológico , Linfoma/veterinária , Vitamina D/imunologia , Proteínas de Fase Aguda/imunologia , Reação de Fase Aguda/veterinária , CãesResumo
Background: Lymphomas are considered uncommon in goats, being the multicentric form with the highest number of cases for the species. Primary intranasal lymphomas are often diagnosed in dogs, cats, and humans. In the literature, there is only a description of a multicentric case involving the frontal sinuses and mucosa of the nasal cavity in a goat; therefore, it is important to describe unusual cases of this disease for the inclusion of new clinical and pathological characteristics in the ruminant clinic medicine. The objective of this work is to describe a case of T-cell lymphoma in the nasal cavity of a young goat. Case: The animal had dyspnea and respiratory noise for 15 days. Clinical examination showed nodulation in the right nasal cavity associated with serosanguinous secretion. Tracheostomy was performed; however, after 30 days the animal was euthanized. A sagittal plane of the head showed a pinkish-gray mass in the right and left nasal cavity, with a smooth, multilobulated surface, smooth adhering to the rostral portion of the dorsal concha and occluding the dorsal nasal meatus. Submandibular lymph nodes were slightly enlarged. Histopathological examination of the nasal cavity revealed a non-encapsulated, poorly delimited and ulcerated tumor composed of round cells arranged in a mantle supported by a discrete fibrovascular stroma extending the mucosa and lamina propria. Cells were round with sparse, eosinophilic and poorly delimited cytoplasm. Nuclei varied from round to elongated with condensed chromatin and evident nucleoli. Occasionally, aberrant nuclei, reniform shape and multinucleated cells were seen. Pleomorphism was moderate characterized by anisocytosis and anisocariosis. Typical and atypical mitosis were frequent (0-4 per field of highest magnification [400x]). Amidst the neoplasm, there were multifocal areas of necrosis and hemorrhage associated with a mild lymphocytic inflammatory infiltrate. Immunohistochemistry showed positive immunostaining for Vimentin antibodies and CD3, and negative for pan CK and CD20. Discussion: The lymphomas immunophenotyping is little used when it comes to farm animals, and there are few studies that use this technique for the definitive diagnosis of these neoplasms for small ruminants. The use of this technique must be considered in each case, in order to determine the pathogenesis, the accurate diagnosis and the origin of the neoplastic lymphocytes. In goats, T-cell lymphomas are the most diagnosed, although cases of multicentric B-cell lymphomas with ocular involvement have been diagnosed. In view of the clinical picture of the case described, infectious rhinitis already described in goats, such as aspergillosis and protothecosis, should be included as differential diagnoses. However, the anatomopathological findings facilitate the direction of the diagnosis, since infectious rhinitis presents as nodules / ulcerated masses or focal areas of necrosis associated with purulent secretion and in the histopathological examination it is possible to observe the intralesional etiological agents. In addition, the enzootic ethmoidal tumor must be included, as it has similar clinical signs and affects young animals, but they are adenomas/adenocarcinomas that affect the ethmoidal nasal shells induced by a retrovirus. Lymphomas in the caprine species are rare in the Northeastern semi-arid, but that in the present diagnostic routine occasionally occurs, being important the first description of its nasal shape for its inclusion in the differential diagnoses of diseases that present with clinical obstruction and dyspnea for the species.
Assuntos
Animais , Ruminantes , Imunofenotipagem/veterinária , Linfoma de Células T/veterinária , Cavidade Nasal , Neoplasias Hematológicas/veterinária , Dispneia/veterináriaResumo
Background: Peripheral neuropathies result in sensory, motor or autonomic dysfunctions due to impairment of peripheral spinal or cranial nerves. Neoplasms such as lymphoma are cited as one of the many aetiological causes and it mayaffect the nerve directly, by compression, or indirectly (paraneoplastic) by remote action of the neoplasm located in anextra-neural site. This study aimed to report two cases of cranial nerve neuropathy (trigeminal and facial) associated withcanine lymphoma, contributing to a better understanding of its paraneoplastic effects on the nervous system, as well asthe diagnosis and treatment of these conditions.Cases: Two cases of canine lymphoma associated with possible signs of paraneoplastic peripheral neuropathy were attendedat the Veterinary Hospital from the Universidade Federal de Minas Gerais (HV UFMG). Case 1. A spayed mixed breedbitch, with lethargy and unilateral exophthalmos. Brain computed tomography revealed a retrobulbar mass and cytology wasdiagnostic for extranodal lymphoma. Subsequent to computed tomography, the dog was presented with hypotrophy of thefacial musculature and difficulty in grasping food, consistent with trigeminal nerve palsy, which resolved after institutionof the 19-week chemotherapy protocol from the University of Wisconsin. Nevertheless, disease reccurred and a rescueprotocol was initiated. Case 2. A female Dalmatian, spayed, was diagnosed with multicentric lymphoma, after cytologyof the left mandibular lymph node. Chemotherapy was initiated with the same protocol of the previous case. However,the disease progressed and it was observed facial asymmetry with ptosis of the left eyelid, pina and lips, in addition todifficulty in grasping food, suggesting facial and trigeminal cranial nerve palsy. Clinical signs resolved after institutionof a rescue chemotherapy protocol. However, in both cases, disease progression and poor clinical condition resulted in...
Assuntos
Feminino , Animais , Cães , Doenças do Nervo Facial/veterinária , Doenças do Nervo Trigêmeo/veterinária , Linfoma/veterinária , Biópsia/veterinária , Tomografia/veterináriaResumo
Background: Peripheral neuropathies result in sensory, motor or autonomic dysfunctions due to impairment of peripheral spinal or cranial nerves. Neoplasms such as lymphoma are cited as one of the many aetiological causes and it mayaffect the nerve directly, by compression, or indirectly (paraneoplastic) by remote action of the neoplasm located in anextra-neural site. This study aimed to report two cases of cranial nerve neuropathy (trigeminal and facial) associated withcanine lymphoma, contributing to a better understanding of its paraneoplastic effects on the nervous system, as well asthe diagnosis and treatment of these conditions.Cases: Two cases of canine lymphoma associated with possible signs of paraneoplastic peripheral neuropathy were attendedat the Veterinary Hospital from the Universidade Federal de Minas Gerais (HV UFMG). Case 1. A spayed mixed breedbitch, with lethargy and unilateral exophthalmos. Brain computed tomography revealed a retrobulbar mass and cytology wasdiagnostic for extranodal lymphoma. Subsequent to computed tomography, the dog was presented with hypotrophy of thefacial musculature and difficulty in grasping food, consistent with trigeminal nerve palsy, which resolved after institutionof the 19-week chemotherapy protocol from the University of Wisconsin. Nevertheless, disease reccurred and a rescueprotocol was initiated. Case 2. A female Dalmatian, spayed, was diagnosed with multicentric lymphoma, after cytologyof the left mandibular lymph node. Chemotherapy was initiated with the same protocol of the previous case. However,the disease progressed and it was observed facial asymmetry with ptosis of the left eyelid, pina and lips, in addition todifficulty in grasping food, suggesting facial and trigeminal cranial nerve palsy. Clinical signs resolved after institutionof a rescue chemotherapy protocol. However, in both cases, disease progression and poor clinical condition resulted in...(AU)
Assuntos
Animais , Feminino , Cães , Linfoma/veterinária , Doenças do Nervo Trigêmeo/veterinária , Doenças do Nervo Facial/veterinária , Tomografia/veterinária , Biópsia/veterináriaResumo
O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias após ao início do tratamento com hidroxiureia.
The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient's anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.
Assuntos
Animais , Cães , Leucemia Mielogênica Crônica BCR-ABL Positiva/veterinária , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Cães/imunologia , Tratamento Farmacológico/veterinária , Hidroxiureia/uso terapêutico , Antineoplásicos/uso terapêutico , Sobrevida , Anemia/veterinária , Leucocitose/veterináriaResumo
Background: Multiple myelomas (MM) are malignant neoplasms originating in the bone marrow plasmacytes, and are characterized by the presence of persistent hyperglobulinemia. Although they are rarely found in domestic animals, the canine species is most affected. In felines, they represent less than 1% of hematopoietic neoplasms, and mainly occur in older animals aged 10-12 years. The aim of the present study was to report a case of multiple myeloma, with extramedullary plasmocytosis in a feline. Case: A 3-year-old feline, female, mixed breed, with a history of apathy, anorexia, halitosis, and vomiting was referred to the Laboratório Regional de Diagnóstico (LRD) at the Universidade Federal de Pelotas (UFPel). Oral examination revealed a cyanotic oral mucosa and ulcerative lesions on the gingiva. The necropsy showed generalized lymphadenomegaly, splenomegaly, and hemorrhagic diathesis. Organ fragments were collected and fixed in 10% buffered formalin. After 48 h, the samples were cleaved, embedded in paraffin, and stained using the routine hematoxylin and eosin technique. Selected sections were subjected to immunohistochemistry (IHC) using the streptavidin-biotin method. The CD79a, CD138, CD3, and MUM1 antibodies were used. Histopathological evaluation of the bone marrow revealed hypercellularity with predominant round pleomorphic cells (90%), which presented an eccentric basophilic nucleus and abundant eosinophilic cytoplasm. The same neoplastic cells infiltrated the gingival mucosa, lymph nodes, spleen, liver, kidneys, heart, lungs, and brain. The IHC showed positive immunostaining for MUM1 and CD138 antibodies. Discussion: The diagnosis of MM in the present study was based on histopathology and by IHC. According to the literature, the presence of neoplastic plasmocytes in the bone marrow (>20%)...
Assuntos
Feminino , Animais , Gatos , Medula Óssea/patologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/veterinária , Neoplasias Hematológicas/veterinária , Imuno-Histoquímica/veterinária , Neoplasias da Medula Espinal/veterináriaResumo
Background: Multiple myelomas (MM) are malignant neoplasms originating in the bone marrow plasmacytes, and are characterized by the presence of persistent hyperglobulinemia. Although they are rarely found in domestic animals, the canine species is most affected. In felines, they represent less than 1% of hematopoietic neoplasms, and mainly occur in older animals aged 10-12 years. The aim of the present study was to report a case of multiple myeloma, with extramedullary plasmocytosis in a feline. Case: A 3-year-old feline, female, mixed breed, with a history of apathy, anorexia, halitosis, and vomiting was referred to the Laboratório Regional de Diagnóstico (LRD) at the Universidade Federal de Pelotas (UFPel). Oral examination revealed a cyanotic oral mucosa and ulcerative lesions on the gingiva. The necropsy showed generalized lymphadenomegaly, splenomegaly, and hemorrhagic diathesis. Organ fragments were collected and fixed in 10% buffered formalin. After 48 h, the samples were cleaved, embedded in paraffin, and stained using the routine hematoxylin and eosin technique. Selected sections were subjected to immunohistochemistry (IHC) using the streptavidin-biotin method. The CD79a, CD138, CD3, and MUM1 antibodies were used. Histopathological evaluation of the bone marrow revealed hypercellularity with predominant round pleomorphic cells (90%), which presented an eccentric basophilic nucleus and abundant eosinophilic cytoplasm. The same neoplastic cells infiltrated the gingival mucosa, lymph nodes, spleen, liver, kidneys, heart, lungs, and brain. The IHC showed positive immunostaining for MUM1 and CD138 antibodies. Discussion: The diagnosis of MM in the present study was based on histopathology and by IHC. According to the literature, the presence of neoplastic plasmocytes in the bone marrow (>20%)...(AU)
Assuntos
Animais , Feminino , Gatos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/veterinária , Neoplasias Hematológicas/veterinária , Medula Óssea/patologia , Imuno-Histoquímica/veterinária , Neoplasias da Medula Espinal/veterináriaResumo
O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias(AU)
The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patients anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.(AU)
Assuntos
Animais , Cães , Cães/anormalidades , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/veterinária , Técnicas de Laboratório Clínico , Tratamento FarmacológicoResumo
O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias
The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patients anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.
Assuntos
Animais , Cães , Cães/anormalidades , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/veterinária , Tratamento Farmacológico , Técnicas de Laboratório ClínicoResumo
A via Janus Kinase (JAK) e do transdutor de sinal e ativador de transcrição (STAT) desempenham papéis importantes na patogênese de neoplasias hematopoiéticas. A ativação da via JAK2/STAT3 promove o crescimento e sobrevivência celular em uma variedade de linfomas humanos. Há uma necessidade de compreender a participação da via JAK2/STAT3 em linfomas caninos difusos de grandes células B e do potencial terapêutico dos inibidores de JAK no tratamento dessa doença. O objetivo do presente estudo foi avaliar a expressão de JAK2-STAT3 em linfomas difusos de grandes células B e o impacto do uso de inibidores de JAK2 como AZD1480 e CYT387 no crescimento in vitro dessa linhagem tumoral. Foi realizada técnica de imuno-histoquímica com os anticorpos anti-STAT3 e anti-STAT3 fosforilado (p-STAT3) em linfonodos acometidos por linfoma difuso de grandes células B e comparado à linfonodos normais e reativos. Para avaliação do efeito terapêutico dos inibidores de JAK2 (AZD1480 e CYT387) foi realizado ensaio de viabilidade celular pelo método de azul de tripan utilizando linhagens celulares de linfoma difuso de grandes células B (CLBL-1) e análise de apoptose por citometria de fluxo utilizando o sistema Annexin V. Houve aumento significativo na expressão de STAT3 e p-STAT3 em linfomas difusos de grandes células B em comparação com linfonodos normais. Ambos os fármacos inibiram o crescimento celular em proporções dependentes da dose administrada e houve um aumento significativo nas taxas de apoptose das células tratadas com inibidores de JAK-2 em comparação ao grupo controle tratado com DMSO. Este é o primeiro estudo a avaliar a via JAK2/STAT3 em linfomas difusos de grandes céluslas B canino e esses dados permitem compreender e explorar o potencial terapêutico dos inibidores de JAK permitindo estudos futuros da eficácia clínica desses fármacos na oncologia veterinária
The Janus Kinase (JAK) and signal transducer and activator of transcription (STAT) pathway play important roles in the pathogenesis of hematologic malignancies. Activated JAK2-STAT3 signaling pathway promotes the growth and survival of a variety of lymphomas in human. There is a great demand for understanding JAK-STAT pathway in canine diffuse large B cell lymphoma (DLBCLs) and evaluating the therapeutic potential of JAK inhibitors. Our study aims to evaluate the expression of JAK2-STAT3 pathway in canine DLBCLs and to assess the impact of AZD1480 and CYT387, two novel JAK inhibitors, on canine DLBCL cell growth. Immunohistochemistry was performed in canine DLBCLs, normal and reactive lymph nodes with primary antibodies against STAT3 and phosphorylated STAT3 (p-STAT3). To evaluate the therapeutic effect of novel JAK inhibitors, canine DLBCL cell line CLBL-1 was treated with either AZD1480 or CYT387 and trypan blue viability assay was performed post treatment. There was a significant increase in expression of STAT3 and pSTAT3 in canine DLBCLs compared with the normal lymph node. Both AZD1480 and CYT387 inhibited canine DLBCL cells in a dose dependent manner. This is the first study to evaluate the JAK2/STAT3 pathway in canine DLBCLs. The knowledge of JAK2-STAT3 activity in canine DLBCLs enables us to understand and explore the therapeutic potential of JAK inhibitors. The dose dependent cell growth inhibition by novel JAK inhibitors in this study will lead into the future studies of the underlying mechanism