Prospective pilot study utilizing changes in quantitative values obtained on serial fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in dogs with appendicular osteosarcoma before and after stereotactic body radiation therapy (SBRT) and carboplatin chemotherapy to assess for prediction of survival and therapeutic effectiveness.

Serial fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography-CT (PET/CT) is commonly used in human oncology to prognosticate and evaluate for therapeutic effectiveness. In this pilot study, dogs with naturally occurring appendicular osteosarcoma were evaluated with serial 18F-FDG PET/CT in an attempt to assess for response to therapy, prognostic factors, and appropriateness of imaging intervals. Fourteen dogs were enrolled in the trial. All dogs had the initial 18F-FDG PET/CT (PET1), with nine dogs having their end-of-therapy 18F-FDG PET/CT (EoT PET) 3 months after stereotactic body radiation therapy (SBRT) to the primary tumor. The median percent change from the PET1 to the EoT PET for the standard uptake value maximum (SUVmax%) was -58% (range: -17 to -88%), metabolic tumor volume (MTV%) was -99.8% (range: -65 to -100%), and total lesion glycolysis (TLG%) was -99.8% (range: -75 to -100%), all of which were significant (P < .05, <.05, and <.05, respectively). On evaluation, it was found that volumes of GTV and CTV were significant for survival (P < .05 and <.05), MTV1, TLG1, and SUVmax on the EoT PET (SUVmaxEoT) were predictive of metastasis (P < .05), and the SUVmax% was significantly correlated to the time to first event (P < .05). Based on this data, serial 18F-FDG PET/CT performed 3 months after SBRT can show a significant reduction in avidity, and the quantitative data collected may help predict metastatic disease in canine appendicular osteosarcoma.

Successful surgical resection of a multilobular osteochondrosarcoma arising from the costal cartilage in a cat.

A 10-year-old neutered male cross-bred cat was referred to our clinic for a solid mass tightly fixed to the right side of the thoracic wall from the 2nd to 4th ribs. Computed tomography revealed the mass had remarkable calcifications and arose from the 3rd costal cartilage. After removal, it was diagnosed histopathologically as a multilobular osteochondrosarcoma (MLO). For tumor resection, extremely wide surgical margins included 6 costal cartilages and 3 sternal segments were required; however, the tumor was successfully resected, followed by reconstruction of the thoracic wall using artificial materials. The cat recovered uneventfully and was good in health for ~4 y. This is apparently the first report of surgical resection of MLO from the costal cartilage of a cat. Key clinical message: To our knowledge, this is the first report of MLO from the costal cartilage in a cat, demonstrating aggressive surgical resection despite extremely wide surgical margins.

Résection chirurgicale réussie d'un ostéochondrosarcome multilobulaire provenant du cartilage costal chez un chatUn chat croisé mâle castré de 10 ans a été référé à notre clinique pour une masse solide bien fixée sur le côté droit de la paroi thoracique de la 2e à la 4e côte. La tomodensitométrie a révélé que la masse présentait des calcifications remarquables et provenait du 3e cartilage costal. Après retrait, il a été diagnostiqué histopathologiquement comme un ostéochondrosarcome multilobulaire (MLO). Pour la résection tumorale, des marges chirurgicales extrêmement larges comprenaient 6 cartilages costaux et 3 segments sternaux; cependant, la tumeur a été réséquée avec succès, suivie d'une reconstruction de la paroi thoracique à l'aide de matériaux artificiels. Le chat s'est rétabli sans incident et était en bonne santé pendant environ 4 ans. Il s'agit apparemment du premier rapport de résection chirurgicale de MLO du cartilage costal d'un chat.Message clinique clé:À notre connaissance, il s'agit du premier rapport de MLO du cartilage costal chez un chat, démontrant une résection chirurgicale agressive malgré des marges chirurgicales extrêmement larges.(Traduit par Dr Serge Messier).

Use of a haired angularis oris axial pattern flap in a dog to correct a large oronasal fistula secondary to resection of a hard palate multilobular osteochondrosarcoma.

A 6-year-old neutered male mixed-breed dog underwent curative-intent surgical resection of a hard palatal multilobular osteochondrosarcoma and closure of the defect using bilateral buccal mucosal flaps. However, failure of the flaps resulted in a massive hard palatal defect that was subsequently repaired using a haired skin angularis oris axial pattern flap. This report describes the clinical outcome using this surgical approach and novel complications encountered. Key clinical message: The haired skin angularis oris axial pattern flap appears to be a suitable and robust option for reconstruction of large palatal defects.

Utilisation d'un lambeau cutanée poilus avec rotation axiale au niveau de l'artère angularis oris chez un chien pour corriger une fistule oronasale volumineuse secondaire à la résection d'un ostéochondrosarcome multilobulaire du palais dur. Un chien croisé mâle castré de 6 ans a subi une résection chirurgicale à visée curative d'un ostéochondrosarcome multilobulaire du palais dur et une fermeture de l'anomalie par des lambeaux de la muqueuse buccale. Cependant, la défaillance des lambeaux a entraîné un défaut important du palais dur qui a ensuite été réparé à l'aide d'un lambeau de peau avec poils avec rotation axiale au niveau de l'artère angularis oris. Ce rapport décrit les résultats cliniques de cette approche chirurgicale et les nouvelles complications rencontrées.Message clinique clé :L'utilisation d'un lambeau de peau avec poils avec rotation axiale au niveau de l'artère angularis oris semble être une option appropriée et robuste pour la reconstruction des défauts importants du palais.(Traduit par Dr Serge Messier).

Osteosarcoma of the wing in a sulfur-crested cockatoo.

A 26-year-old female sulfur-crested cockatoo (Cacatua galerita) was evaluated for vocalizing through the night and extending her right wing. Physical examination revealed a large, firm mass extending from the humerus to the distal aspect of the elbow. Computed tomography confirmed a large aggressive mass of the right distal humerus with a large soft tissue component, severe osteolysis, and adjacent periosteal proliferation. Fine-needle aspirates of the mass were most compatible with sarcoma, and osteosarcoma was prioritized. An unstained slide was treated with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase (NBT/BCIP) substrate for ALP detection and was strongly positive, confirming a diagnosis of osteosarcoma. A month later, the patient underwent wing amputation and arrested during recovery from anesthesia. Post-mortem examination and histopathology were consistent with osteosarcoma. This case report highlights a rare occurrence of osteosarcoma in a cockatoo as well as its cytologic and histologic features. Additionally, this report provides support for NBT/BCIP application in ALP-expressing tumors, a cytochemical stain that has been minimally investigated in avian species.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product. METHODS: Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach. RESULTS: Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment. CONCLUSIONS: Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

A retrospective Italian Society of Veterinary Oncology (SIONCOV) study of 56 cats with appendicular osteosarcoma.

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.

Metastatic Osteosarcoma of the Distal Femur in a Korean Water Deer (Hydropotes inermis argyropus).

A free-living female Korean water deer (Hydropotes inermis argyropus) was found with swelling in the left femur. Radiographic and histopathologic examination confirmed distal femoral osteosarcoma with metastases to the inguinal lymph node and the lungs; there are no previous reports of osteosarcoma in water deer.

Outcomes of 35 dogs with craniomaxillofacial osteosarcoma treated with stereotactic body radiation therapy.

Canine craniomaxillofacial osteosarcoma (OSA) is most commonly treated surgically; however, in cases where surgery is not feasible or non-invasive treatment is desired, stereotactic body radiation therapy (SBRT) may be elected for local tumour control. In this study, we evaluated 35 dogs treated with SBRT. Nine dogs (26%) had calvarial, seven (20%) had mandibular and 19 (54%) had maxillary OSA. Median time to first event (TFE) was 171 days, and overall median survival time (MST) was 232 days. Site-specific MSTs were 144 days for mandible, 236 days for calvarium and 232 days for maxilla (p = .49). Pulmonary metastatic disease was observed in 12/35 (34%) patients and was detected pre-SBRT in six dogs (17%) and post-SBRT in the remaining six dogs (17%). Eighteen adverse events post-SBRT were documented. Per veterinary radiation therapy oncology group criteria, five were acute (14%) and three were late (9%) grade 3 events. Neurological signs in two dogs were suspected to be early-delayed effects. Cause of death was local progression for 22/35 (63%) patients, metastasis for 9/35 (26%) patients and unknown for four. On univariate analysis, administration of chemotherapy was associated with a longer TFE (p = .0163), whereas volume of gross tumour volume was associated with a shorter TFE (p = .023). Administration of chemotherapy and five fractions versus single fraction of SBRT was associated with increased survival time (p = .0021 and .049). Based on these findings, a treatment protocol incorporating chemotherapy and five fractions of SBRT could be considered for dogs with craniomaxillofacial OSA electing SBRT with careful consideration of normal tissues in the field.

Updates in Osteosarcoma.

Clinical care of osteosarcoma (OSA) in dogs has seen little change during the past 2 decades, relying on amputation and platinum-based chemotherapy for pain control and survival. Recent advancements offer hope for improved outcomes. Genomic research reveals shared genetic abnormalities between canine and human OSA. Multidimensional imaging provides valuable staging and prognostic information. Limb-sparing approaches including stereotactic body radiation therapy are routine. Ablative therapies such as microwave ablation and histotripsy show promise. Immunotherapy including cell therapy and immune checkpoint inhibition are available. Radiopharmaceuticals are tuned to target OSA cells directly. These innovations may enhance treatment and prognosis for dogs with OSA.

Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs.

Osteosarcoma (OS) is a heterogeneous, aggressive malignancy of the bone that disproportionally affects children and adolescents. Therapeutic interventions for OS are limited, which is in part due to the complex tumor microenvironment (TME). As such, we used single-cell RNA sequencing (scRNA-seq) to describe the cellular and molecular composition of the TME in 6 treatment-naïve dogs with spontaneously occurring primary OS. Through analysis of 35,310 cells, we identified 41 transcriptomically distinct cell types including the characterization of follicular helper T cells, mature regulatory dendritic cells (mregDCs), and 8 tumor-associated macrophage (TAM) populations. Cell-cell interaction analysis predicted that mregDCs and TAMs play key roles in modulating T cell mediated immunity. Furthermore, we completed cross-species cell type gene signature homology analysis and found a high degree of similarity between human and canine OS. The data presented here act as a roadmap of canine OS which can be applied to advance translational immuno-oncology research.

Reconstruction surgery using polypropylene mesh after extensive resection of a costal osteosarcoma in a dog.

Osteosarcoma is the most common tumour that develops in the chest wall of dogs; an extensive excision is the treatment of choice. Various methods have been reported for reconstruction of chest wall defects following extensive excision. The objective of this report was to describe the complete resection of an extensive costal osteosarcoma with an extended resection of the ribs and part of the diaphragm in a dog. An 11-year-old neutered, male, miniature pinscher was presented with dyspnoea: An extensive mass was observed, stretching from the right chest wall to the abdominal wall. On computed tomography, the mass originated from the right 9th rib and exceeded the 6th rib on the cranial side and the 13th rib on the caudal side; it was compressing the lungs, diaphragm, liver, stomach and duodenum. When the patient's condition was medically stabilized, the tumour was removed from the right 9th rib. In consideration of the surgical margin, the 5th-13th ribs were excised, and the tumour was resected with the thoracoabdominal wall and part of the diaphragm. The missing thoracoabdominal wall and section of the diaphragm were reconstructed using two sheets of a polypropylene mesh. Postoperatively, flail chest was observed, although dyspnoea was not observed in the patient. Histopathological examination confirmed the diagnosis of osteosarcoma with a clean margin. Although 60.6 months have passed post-surgery, no metastasis has reoccurred. In this case, complete resection and reconstruction of the chest wall and diaphragm were achieved using a polypropylene mesh without fatal postoperative complications, despite extensive osteosarcoma resection.

Three cases of dogs with osteosarcoma of the forelimb treated with liquid nitrogen for limb-sparing surgery using autologous bone.

Osteosarcoma treatment with limb-sparing surgery using liquid nitrogen can be applied to canine patients experiencing diminished quality of life after leg amputation. In particular, forelimb amputation may affect gait more than hindlimb amputation. In this study, limb-sparing surgery using liquid nitrogen was applied to primary osteosarcomas arising in the proximal scapula of a Welsh Corgi, the proximal humerus of a Golden Retriever, and the distal radius of a Great Pyrenees, according to the protocol of Tsuchiya et al. In all cases, postoperative radiographic examination revealed bone union between the treated and matrix bones. All patients recovered their gait postoperatively. These results suggest that limb-sparing surgery using liquid nitrogen-treated autologous bone is an effective option for patients with osteosarcoma.

Osteosarcoma of the hard palate in a dog - case report / [Osteossarcoma em palato duro de cão - relato de caso]

The osteosarcoma (OSA) is the most diagnosed primary bone cancer in canine patients. This work reports a case of a canine, six years old, mongrel, female, intact, with an OSA in the hard palate. Physical examination detected a firm mass in the palate. Thoracic radiographs, hematological and biochemical exams, histopathological exams and computed tomography were requested. A chondroblastic OSA was diagnosed and the tumor was characterized by immunohistochemistry. There was never evidence of metastasis in this case. The treatment consisted of the combination of conventional chemotherapy, metronomic chemotherapy, and palliative care, aiming at greater survival and well-being of the patient since surgical excision was not possible due to the location and extension of the tumor. Osteogenic sarcomas of the hard palate are rarely seen and described in the literature. In this article we present a characterization of the osteosarcoma with uncommon localization in the hard palate.(AU)

O osteossarcoma (OSA) é a neoplasia óssea primária mais diagnosticada em pacientes caninos. Este trabalho relata o caso de um canino, com seis anos de idade, sem raça definida, fêmea, não castrado, apresentando OSA em região de palato duro. Ao exame clínico, constatou-se uma massa de consistência firme em região palatina. Além do exame clínico, foram solicitadas radiografias torácicas, exames hematológicos e bioquímicos, exames histopatológicos e tomografia computadorizada. Fora então dado o diagnóstico de OSA condroblástico, e o tumor foi caracterizado pela imuno-histoquímica. Não foram observadas evidências de metástases nesse caso. O tratamento instituído consistiu na combinação de quimioterapia convencional, quimioterapia metronômica e cuidados paliativos, almejando maior sobrevida e bem-estar do paciente, uma vez que a excisão cirúrgica não foi possível devido à localização e à extensão do tumor. Neste artigo, apresentou-se uma caracterização do osteossarcoma com localização incomum no palato duro.(AU)

Fibroblastic osteosarcoma in a white-eared opossum (Didelphis albiventris) / Osteossarcoma fibroblástico em gambá-de-orelha-branca (Didelphis albiventris)

Osteosarcoma is characterized by the production of osteoid or woven bone, using neoplastic osteoblasts. It is the most common primary bone neoplasm in canines and humans. This neoplasm was previously reported in all vertebrate classes, including a wide variety of mammals. However, there is no case report describing this neoplasm in Didelphis albiventris. Therefore, the objective of this manuscript is to describe the clinical-pathological aspects of fibroblastic osteosarcoma in D. albiventris. A wild adult male white-eared opossum (D. albiventris) arrived at the zoological park of the "Universidade de Caxias do Sul" with a swollen left thoracic limb. After a general clinical examination, the animal was transferred to the Veterinary Clinic of "Universidade de Caxias do Sul" for radiographic examination of the left thoracic limb and thorax. Additionally, some material was collected through fine needle aspiration (FNA) for cytologic evaluation. The radiographic findings and cytologic evaluation indicated osteosarcoma. The animal was euthanized due to severe clinical conditions and guarded prognosis. During necropsy, macroscopic analysis of the viscera was performed, fragments of various organs were collected and fixed in 10% neutral buffered formalin. All fragments were processed following routine histological techniques. The histopathological evaluation confirmed osteosarcoma, which was classified as a fibroblastic subtype. Case reports are crucial for the knowledge of incidence, prevalence, and behavior of the current mentioned disease, as well as other diseases, in species with such limited information. In order to obtain a decisive diagnosis, a few different examination methods were associated. Although the observations presented are based on a single case, this neoplasm had a similar clinical presentation to that described in other species.(AU)

O osteossarcoma é caracterizado pela produção de osteoide ou osso imaturo, por osteoblastos neoplásicos. É a neoplasia óssea primária mais comum em caninos e humanos. Essa neoplasia já foi relatada em todas as classes de vertebrados, incluindo uma grande variedade de mamíferos. Não havendo descrição dessa neoplasia até o momento em Didelphis albiventris. O objetivo deste trabalho é descrever aspectos clínico-patológicos de um caso de osteossarcoma fibroblástico em D. albiventris. Chegou para atendimento no Zoológico da Universidade de Caxias do Sul um gambá-de-orelha-branca (D. albiventris), macho, adulto, de vida livre com aumento de volume no membro torácico esquerdo. Após avaliação clínica geral, o animal foi encaminhado para a Clínica Veterinária da Universidade de Caxias do Sul para realização de radiografia do membro torácico esquerdo e de tórax, sendo também realizada coleta de material por punção aspirativa por agulha fina (PAAF) para avaliação citológica. Os achados radiográficos e da avaliação citológica foram sugestivos de osteossarcoma. Devido ao estado clínico grave e prognóstico reservado optou-se pela eutanásia. Durante a necropsia realizou-se a análise macroscópica das vísceras, foram coletados fragmentos de diversos órgãos, fixados em formalina 10%, processados pelas técnicas histológicas de rotina. Na avaliação histopatológica confirmou-se a suspeita de osteossarcoma sendo classificado no subtipo fibroblástico. A descrição de relatos é fundamental para conhecimento da incidência, prevalência e comportamento desta e de outras doenças em espécies que as informações são limitadas. A associação de diferentes métodos de exames foram necessários para a obtenção de um diagnóstico definitivo. Embora as observações apresentadas se baseiem em um caso único, esta neoplasia possuiu apresentação clínica semelhante a descrita em outras espécies.(AU)

Beta Lapachone blocks the cell cycle and induces apoptosis in canine osteosarcoma cells / Beta Lapachona bloqueia o ciclo celular e induz apoptose em células de osteossarcoma canino

Osteosarcoma is a malignant tumor of primitive bone cells with a high incidence in dogs and humans. The need for more effective drugs with less adverse consequences has pushed the development of chemotherapeutic agents from plants and other natural sources. The aim of this study was to verify the cytotoxic effects of beta-lapachone, a compound present in the sawdust of Tabebuia sp. (popularly known as ipê) wood, on canine osteosarcoma cells subcultured and treated in different concentrations (0.1µm, 0.3µm e 1.0µm) and exposure times (24h, 48h e 72h). Results were obtained through Trypan blue dye exclusion, tetrazolium reducing method, cell survival assay, Annexin V-FITC and Propidium Iodine labeling, JC-1 dye labeling and cell cycle kinetics e analysis. The group treated with 0.3µm beta-lapachone presented higher decrease in cell viability (80.27%, 24h, 47.41%, 48h and 35.19%, 72h) and greater progression of cytotoxicity (19.73%, 24h, 52.59%, 48h and 64.81%, 72h). The lower IC50 (0.180µm) was verified in the group treated for 72 hours. Cell growth after treatment decreased as concentration and time of exposure increased, with 0.50% survival fraction at the concentration of 1.0µm. Initial apoptosis was the most frequent type of cell death in all groups, reaching bottom in the 24-hour group treated with 0.1µm (4.26%) and peaking in the 72-hour group treated with 1.0µm (85.89%). Mitochondrial depolarization demonstrated a dose-dependent phenomenon, indicating the intrinsic apoptosis. Cell growth inhibition by blocking cell cycle in the G0/G1 phase related to the exposure the time. β-lapachone is cytotoxic for canine osteosarcoma cells, induces apoptosis and promotes cell cycle arrest in G0/G1 phase.(AU)

O osteossarcoma é o tumor maligno das células ósseas primitivas, com alta incidência em cães e humanos. A necessidade de medicamentos mais efetivos, com menor consequência adversa, tem gerado esforços para o desenvolvimento de agentes quimioterápicos compostos por plantas e outras fontes naturais. O objetivo deste estudo foi verificar os efeitos citotóxicos da beta lapachona, um composto presente na serragem da madeira do ipê, sobre células de osteossarcoma canino subcultivadas e submetidas ao tratamento, de acordo com as diferentes concentrações (0.1µm, 0.3µm e 1.0µm) e tempo de exposição (24h, 48h e 72h). Os resultados foram obtidos por meio dos métodos de exclusão do corante azul de Tripan e de redução do tetrazólio, além dos ensaios de sobrevivência celular, de dupla marcação com Anexina V-FITC e Iodeto de Propídio, de marcação com o corante JC-1 e pela análise da cinética do ciclo celular. O grupo tratado com 0.3µm de beta lapachona apresentou melhor regressão da viabilidade celular (80,27%, 24h; 47,41%, 48h e 35,19%, 72h) e maior progressão da citotoxicidade (19,73%, 24h; 52,59%, 48h e 64,81%, 72h). O menor IC50 (0.180µm) ocorreu no grupo tratado por 72 horas. O crescimento celular após o tratamento foi menor, de acordo com o aumento da concentração e tempo de exposição, apresentando 0,50% de fração de sobrevivência na concentração de 1.0µm. A apoptose inicial foi o tipo de morte celular mais frequente em todos os grupos, menor no grupo de 24 horas tratado com 0.1µm (4,26%) e maior no grupo de 72 horas tratado com 1.0µm (85,89%). A despolarização mitocondrial ocorreu de maneira dose dependente, indicando a ocorrência de apoptose intrínseca. A β lapachona possui efeitos citotóxicos em células de osteossarcoma canino, induz apoptose e promove o bloqueio do ciclo celular na fase G0/G1.(AU)

The importance of clinical, histopathological and immunohistochemical marking for differential diagnosis of non-hematopoietic gastrointestinal mesenchymal neoplasms in dogs: literature review / Importância da avaliação clínica, anatomopatológica e imuno-histoquímica para o diagnóstico diferencial das neoplasias mesenquimais gastrointestinais não hematopoiéticas em cães: revisão de literatura

Gastrointestinal neoplasms in dogs represent a challenge for the veterinary clinician and surgeon as they are mostly malignant and when the owner notices the primary clinical changes the disease may already be in an advanced stage. Due to the high clinical and histopathological similarity between mesenchymal gastrointestinal neoplasms, it is often impossible to establish the definitive morphological diagnosis using light microscopy alone. In addition, there are only a few articles describing the anatomopathological and immunohistochemical characteristics, which make its complete characterization urgent and relevant in our context in order to assist the veterinary clinician, surgeon, and pathologist in establishing a precise diagnosis of these tumors.(AU)

As neoplasias gastrointestinais em cães representam casos desafiantes ao clínico e cirurgião, pois são em sua maioria malignas e, quando as primeiras alterações clínicas são notadas pelo proprietário do animal, a doença pode estar em estágio de desenvolvimento muito avançado. Devido à elevada similaridade clínica e histopatológica entre as neoplasias gastrointestinais mesenquimais, muitas vezes não é possível estabelecer o diagnóstico morfológico definitivo apenas com a microscopia de luz. Acrescenta-se que são poucos os artigos que descrevem as características anatomopatológicas e imuno-histoquímicas das neoplasias mesenquimais gastrointestinais que acometem os cães, o que torna premente a caracterização destas em nosso contexto, com o intuito de auxiliar clínico, cirurgião e patologista veterinário a estabelecer o diagnóstico destes tumores.(AU)

Estudo biomecânico comparativo da resistência de segmentos ósseos de rádios de cães autoclavados ou desvitalizados em nitrogênio líquido / Biomechanical comparative study of the strength of bone segments from the radius of dogs autoclaved and devitalized in liquid nitrogen

O presente estudo comparou, por meio do ensaio de flexão em quatro pontos, a resistência de segmentos de rádios de cães autoclavados e desvitalizados em nitrogênio líquido. Avaliaram-se 40 rádios, que foram divididos em quatro grupos: grupo autoclave (GA), grupo controle autoclave (GCA), grupo nitrogênio (GN) e grupo controle nitrogênio (GCN). Os corpos de prova dos grupos GCA e GCN pertenciam ao lado contralateral dos grupos GA e GN, respectivamente. Os ossos foram autoclavados a 121°C, por 20min a 2atm. A desvitalização em nitrogênio foi realizada por meio da imersão em nitrogênio líquido, por 20min, seguida de descongelamento à temperatura ambiente, sendo finalizada por imersão em solução de NaCL a 0,9%, por mais 15min. Após os testes biomecânicos, foram comparadas as variáveis força máxima, rigidez, altura máxima à secção transversa do corpo de prova, deslocamento do baricentro em relação ao eixo x, flecha, tensão-tração, tensão-compressão e tensão máxima. Não foram encontradas diferenças estatisticamente significantes entre os grupos GN e GCN. Foram encontradas diferenças estatisticamente significantes entre os grupos GA e GCA somente na comparação da variável força máxima. A análise das variáveis tensão-tração, tensão-compressão e tensão máxima evidenciou diferenças estatisticamente significantes entre os grupos GA e GN, sendo os valores maiores para o grupo GA. Também foi realizada comparação entre os deltas (GN menos GCN e GA menos GCA), em que não foram observadas diferenças estatísticas.(AU)

The study compared through the four points bending test, the strength of bone segments autoclaved and devitalized in liquid nitrogen radius segments. 40 radius were used, collected and divided into 4 groups, as follows: Autoclave Group (GA), Control Autoclave Group (GCA), Nitrogen Group (NG) and Control Nitrogen Group (GCN). Bone segments from groups GCA and GCN were contralateral to GA and NG. The segments were autoclaved at 121ºC and 2 atm for 20 minutes. Nitrogen devitalization of the bone segments was obtained by 20 minutes immersion, followed by thawing at room temperature and 15 minutes immersion in 0.9% NaCL solution. After biomechanical tests the variables compared were maximum strength, stiffness, maximum hight trough the transverse section of the bone segment, centers of mass dislocation in relation to x axe, arrow, stress-tension, stress-compression and maximum stress. No statistically significant differences between the GN and GCN groups were found. Statistically significant differences were found between GA and GCA groups only in the comparison of the maximum force variable. The analysis of variable stress-tension, stress-compression and maximum stress showed statistically significant differences between the GA and GN groups, with higher values for the GA group. Comparison of the deltas (GN least GCN and GA least GCA) where no statistical differences were observed was also performed.(AU)