Characterization of IGF2R Molecular Expression in Canine Osteosarcoma as Part of a Novel Comparative Oncology Approach.

Progress in prognostic factors, treatments, and outcome for both canine and human osteosarcoma (OS) has been minimal over the last three decades. Surface overexpression of the cation independent mannose-6-phosphate/insulin-like growth factor receptor type 2 (IGF2R) has been proven to occur in human OS cells. Subsequently, radioimmunotherapy (RIT) targeting IGF2R has demonstrated promising preliminary results. The main aims of this study were to investigate the expression of IGF2R in spontaneously occurring canine OS cells using immunohistochemistry (IHC) on archived biopsy samples and to assess its prognostic significance. Thirty-four dogs were included in the study. All cases showed that 80-100% of OS cells stained positive for IGF2R. IGF2R overexpression alone was not shown to have prognostic significance using both visual and quantitative methods of IHC staining intensity. This study has established for the first time the consistent expression of IGF2R in spontaneously occurring canine OS. This comparative oncology approach will allow further investigation into RIT as a novel treatment modality; first in canines and then in humans with OS. In addition, further studies should be performed to assess the true prognostic significance of IGF2R overexpression.

Comparison of Fine Arts- and Pathology-Based Observational Skills Training for Veterinary Students Learning Cytology.

Keen observational skills are essential for veterinarians; however, the development of these skills is not usually an explicit part of the veterinary curriculum. Fine arts-based (FAB) observation training has been shown to improve medical students' observational skills and might also improve veterinary students' observational skills. We compared FAB and pathology-based (PB) observation training in a veterinary cytology course. Students initially wrote a pre-test in which they described two cytology images and one art image, followed by participation in either FAB or PB observation training. Both groups completed a similar post-test immediately after training and a delayed post-test 4 weeks later following instruction in cytology. Differences between groups were noted only in the immediate post-test cytology descriptions. The PB group used significantly more specific vocabulary terms and significantly more accurate observations than the FAB group, suggesting an immediate benefit to the discipline-specific information gained in the PB observation training. In the delayed post-test, results for both groups were similar. The FAB group significantly increased their use of specific vocabulary terms and maintained but did not increase accurate observations following cytology instruction, while accurate observations decreased significantly for the PB group. The FAB group might have been able to generalize their observation skills to the discipline of cytology and to better retain these skills. Neither type of training resulted in both achievement and maintenance of the highest recorded scores for accurate observations. Both FAB and PB training led to improved observational skills, and explicit observation training may be useful for veterinary students.

Tolerance of Ambiguity in Veterinary Students at the Beginning and End of a Second-year Clinical Pathology Course.

Tolerance of ambiguity (TOA) is essential for veterinarians because ambiguity and uncertainty are unavoidable aspects of veterinary practice. However, TOA has been little investigated in veterinarians or veterinary students. In this article, the 27-item Tolerance of Ambiguity of Veterinary Students (TAVS) scale, including eight additional clinical pathology-specific items, is used to evaluate TOA in veterinary students at the beginning and end of a clinical pathology course. Clinical pathology is often one of the first subjects in which students encounter ambiguity because real-life cases are used in teaching. The hypotheses are that TOA will increase across the course and that TOA will correlate with the final grade in the course. Analysis of the TAVS scale revealed very good inter-item reliability (α = 0.80) and a positive correlation between the original TAVS items and the new clinical pathology items (ρ = 0.63). Students demonstrated a significant increase in TOA across the course for TAVS items and a similar trend for clinical pathology items. Four items related to affinity for complexity and novice view showed significant increases in TOA. Two items related to discomfort from uncertainty showed significant decreases. There was no correlation between TOA and final grade in the course. Students rated their personal frustration with ambiguity in the course as low and did not think ambiguity in cases was problematic for teaching. The results suggest that the increased TOA at the end of the course might relate to students being taught-and learning how to cope with-ambiguity through the real-life cases used for teaching.

Using Fine Arts-Based Training to Develop Observational Skills in Veterinary Students Learning Cytology: A Pilot Study.

Arts-based training has been shown to improve medical students' observational skills. Veterinarians also need keen observational skills. Student veterinarians are expected to develop their observational skills; however, this training is usually not an explicit part of the veterinary curriculum. The impact of arts-based observation training has not been investigated in veterinary students learning cytology. In this pilot study, we compared student descriptions of art and cytology images before and immediately after receiving arts-based observation training. After 10 hours of cytology instruction, we again tested students' observational skills and asked for feedback via a survey. Pre-tests and post-tests were scored following a rubric based on expert descriptions of the images. Scores for art image descriptions were higher for both the immediate and delayed post-tests compared to the pre-test (p < .05). Scores for cytology image descriptions were higher for the immediate post-test than the pre-test, but this difference was not significant. Despite 10 hours of cytology instruction between post-tests, scores for cytology image descriptions were lower for the delayed post-test than the immediate post-test, but again, this difference was not significant. Student feedback on the arts-based observation training was positive. Overall, our results suggest that arts-based training may improve student observational skills, although context could be important, as the improvement in description was only significant for art images. Further investigation with a larger cohort of students and a control group that does not receive arts-based training would be valuable.

Equine small intestinal angiomatosis.

Multiple red, raised nodules multifocally distributed along the serosal surface of the normal and the nonviable jejunum were identified in a 24-year-old neutered male horse undergoing surgery for removal of the strangulating lipoma around the jejunum. Histologically, these nodules consisted of many significantly and variably dilated, blood-filled vascular channels lined by a single layer of flattened, well-differentiated endothelial cells with occasional thrombi within a mildly thickened fibrous stroma. A diagnosis of intestinal angiomatosis was proposed. To the best of the authors' knowledge, this is the second report of small intestinal angiomatosis in a horse.

Angiomatose du petit intestin équin. De multiples nodules rouges surélevés distribués de manière multifocale le long de la surface séreuse du jéjunum viable et non-viable furent identifiés chez un cheval mâle castré âgé de 24 ans soumis à une chirurgie pour le retrait d'un lipome étranglant autour du jéjunum. Histologiquement, ces nodules consistaient en de nombreux canaux vasculaires remplis de sang dilatés de manière significative et variable, et tapissés par une couche unique de cellules endothéliales aplaties et bien différenciées avec à l'occasion des thrombi à l'intérieur d'un stroma fibreux légèrement épaissi. Un diagnostic d'angiomatose intestinale fut proposé. Au meilleur de la connaissance des auteurs, ceci constitue le deuxième rapport d'angiomatose du petit intestin chez un cheval.(Traduit par Dr Serge Messier).

Extraskeletal osteosarcoma associated with a benign hair follicle tumor in a dog.

A rare presentation of an extraskeletal osteosarcoma, suspected to have evolved from chronic inflammation associated with a benign hair follicle tumor in a dog is described. The patient was treated with surgical excision, carboplatin, and toceranib. The patient had an extended disease-free interval and a survival time of 45.4 months.

Ostéosarcome extra-squelettique associé avec une tumeur bénigne d'un follicule pileux chez un chien. On décrit la rare présentation d'un ostéosarcome extra-squelettique, suspecté d'avoir évolué à partir d'une inflammation chronique associée à une tumeur bénigne d'un follicule pileux chez un chien. Le patient fut traité avec excision chirurgicale, carboplatine et toceranib. Le patient eut un intervalle prolongé exempt de maladie et un temps de survie de 45,4 mois.(Traduit par Dr Serge Messier).

Peritoneal fluid immunocytochemistry used for the diagnosis of a possible case of equine gastrointestinal B-cell lymphoma.

After physical examination, ultrasonographic evaluation of thorax and abdomen, and peritoneal fluid analysis, gastrointestinal neoplasia with suspected diffuse peritoneal metastasis was diagnosed in a 17-year-old Arabian gelding. The owner elected euthanasia and declined postmortem examination. Immunocytochemistry analysis of the peritoneal fluid resulted in a diagnosis of B-cell lymphoma.

Immunocytochimie du liquide péritonéal utilisée pour le diagnostic d'un cas possible de lymphome gastro-intestinal à cellules B. Après un examen physique, une évaluation échographique du thorax et de l'abdomen et une analyse du liquide péritonéal, une néoplasie gastro-intestinale avec métastase péritonéale diffuse suspectée a été diagnostiquée chez un hongre arabe âgé de 17 ans. Le propriétaire a choisi l'euthanasie et a refusé l'examen postmortem. L'analyse par immunohistochimie du liquide péritonéal a donné lieu à un diagnostic de lymphome à cellules B.(Traduit par Isabelle Vallières).

Hemorrhagic cystitis in a dog receiving carboplatin.

An 8 yr old castrated male Labrador retriever mixed-breed dog with osteosarcoma (OSA) of the left proximal humerus receiving carboplatin presented 10 days after the third chemotherapy treatment with hematuria, stranguria, and pollakiuria. A presumptive diagnosis of hemorrhagic cystitis was made based on clinical signs, urinalysis, and cytologic analysis of a traumatic catheterization sample. Carboplatin was removed from the chemotherapy treatment plan and was substituted with doxorubicin. The dog was treated with meloxicam for pain, and the cystitis signs subsided over a period of 4 wk. Carboplatin is commonly used as adjuvant chemotherapy for dogs with OSA following amputation and is not known to cause hematuria in dogs, although there are reports of this occurring in humans. To the authors' knowledge, there are no reports in the veterinary literature of this toxicity.

Intraocular sarcoma associated with a rupture lens in a rabbit (Oryctolagus cuniculus).

This case report describes the clinical manifestations and ocular pathology of an intraocular sarcoma in a spayed female 7-year-old rabbit that developed clinical signs consistent with phacoclastic uveitis at 6 months of age, which was left untreated for most of the next 6 years. Ophthalmologic examination confirmed pupillary occlusion, aqueous flare, fibrin, and lens debris within the anterior chamber of the right eye. The right eye was blind and phthisical. The tentative clinical diagnosis was chronic phacoclastic uveitis, and a routine transconjunctival enucleation of the right eye was completed. The globe was formalin-fixed and submitted for histologic examination. Light microscopic examination revealed a ruptured cataractous lens, uveitis, retinal detachment, and an intraocular sarcoma centered around the lens. Immunohistochemical (IHC) staining was positive for smooth muscle actin and vimentin and negative for Desmin and cytokeratin intermediate filaments.

Single high-dose radiation therapy and liquid fiducial markers can be used in dogs with incompletely resected soft tissue sarcomas.

OBJECTIVE: To evaluate the outcome and effects of single high-dose radiation therapy with the aid of liquid fiducial markers in dogs following resection of soft tissue sarcomas (STSs). ANIMALS: 36 client-owned dogs. METHODS: Dogs with a histologic diagnosis of a grade II or III STS that underwent liquid fiducial guided single fraction, 20-Gy stereotactic radiation therapy following surgical excision of an STS between May 2017 and March 2019 were prospectively enrolled in this study. Data collected from the medical records included patient signalment, tumor-related information, treatment details, and outcome. Kaplan-Meier survival analysis was performed for overall survival time (OST) and disease-free interval (DFI). The median OST and DFI were not reached, so restricted mean OST and DFI were also calculated. RESULTS: 36 dogs were included in the study. All dogs underwent radiation therapy a mean of 36.1 days (range, 20 to 59 days) after surgery. Acute and delayed radiation toxicity effects occurred in 80.5% and 36.1% of dogs, respectively, all of which affected the skin. Tumor recurrence was noted in 24.3% of dogs with a median time to recurrence of 272 days (range, 14 to 843 days). The restricted mean OST was 1,556 days (range, 1,383 to 1,728 days) and restricted mean DFI was 1,330 days (range, 1,101 to 1,559 days). CLINICAL RELEVANCE: The results of this study showed that administering a single 20-Gy fraction of radiation in combination with a liquid fiducial marker to treat marginally or incompletely resected STS in the absence of gross disease resulted in similar OST and DFI compared to other previously reported radiation protocols.

Image-Based Dosimetry in Dogs and Cross-Reactivity with Human Tissues of IGF2R-Targeting Human Antibody.

BACKGROUND: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. Here, we examine the dosimetry in beagle dogs and cross-reactivity with human tissues of a novel human antibody, IF3, that targets the insulin growth factor receptor type 2 (IGF2R), which is overexpressed on OS cells, making it a candidate for radioimmunotherapy of OS. METHODS: [89Zr]Zr-DFO-IF3 was injected into three healthy beagle dogs. PET/CT was conducted at 4, 24, 48, and 72 h. RAPID analysis was used to determine the dosimetry of [177Lu]Lu-CHXA"-IF3 for a clinical trial in companion dogs with OS. IF3 antibody was biotinylated, and a multitude of human tissues were assessed with immunohistochemistry. RESULTS: PET/CT revealed that only the liver, bone marrow, and adrenal glands had high uptake. Clearance was initially through renal and hepatobiliary excretion in the first 72 h followed by primarily physical decay. RAPID analysis showed bone marrow to be the dose-limiting organ with a therapeutic range for 177Lu calculated to be 0.487-0.583 GBq. Immunohistochemistry demonstrated the absence of IGF2R expression on the surface of healthy human cells, thus suggesting that radioimmunotherapy with [177Lu]Lu-CHXA"-IF3 will be well tolerated. CONCLUSIONS: Image-based dosimetry has defined a safe therapeutic range for canine clinical trials, while immunohistochemistry has suggested that the antibody will not cross-react with healthy human tissues.

Identification of potential plasma protein biomarkers for feline pancreatic carcinoma by liquid chromatography tandem mass spectrometry.

In both humans and cats, pancreatic carcinoma is an aggressive cancer with a grave prognosis. Proteomics techniques have successfully identified several blood-based biomarkers of human pancreatic neoplasia. Thus, this study aims to investigate whether similar biomarkers can be identified in the plasma of cats with FePAC by using liquid chromatography tandem mass spectrometry (LC-MS/MS). To facilitate evaluation of the low abundance plasma proteome, a human-based immunodepletion device (MARS-2) was first validated for use with feline plasma. Marked reduction and/or complete removal of albumin and immunoglobulins was confirmed by analysis of electrophoretograms and mass spectral data. Subsequently, plasma collected from 9 cats with pancreatic carcinoma (FePAC), 10 cats with symptomatic pancreatitis, and 10 healthy control cats was immunodepleted and subjected to LC-MS/MS. Thirty-seven plasma proteins were found to be differentially expressed (p < .05 in one-way ANOVA, FC >2 in fold change analysis). Among these proteins, ETS variant transcription factor 4 (p < .05) was overexpressed, while gelsolin (p < .01), tryptophan 2,3-dioxygenase (p < .05), serpin family F member 1 (p < .01), apolipoprotein A-IV (p < .01) and phosphatidylinositol-glycan-specific phospholipase D (p < .05) were down-regulated in cats with FePAC. Further studies on these potential biomarkers are needed to investigate their diagnostic value.

Novel Human Antibodies to Insulin Growth Factor 2 Receptor (IGF2R) for Radioimmunoimaging and Therapy of Canine and Human Osteosarcoma.

Etiological and genetic drivers of osteosarcoma (OS) are not well studied and vary from one tumor to another; making it challenging to pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all of standard and patient-derived OS cell lines, making it an ideal therapeutic target for development of antibody-based drugs. Monoclonal antibodies, targeting IGF2R, can be conjugated with alpha- or beta-emitter radionuclides to deliver cytocidal doses of radiation to target IGF2R expression in OS. This approach known as radioimmunotherapy (RIT) can therefore be developed as a novel treatment for OS. In addition, OS is one of the common cancers in companion dogs and very closely resembles human OS in clinical presentation and molecular aberrations. In this study, we have developed human antibodies that cross-react with similar affinities to IGF2R proteins of human, canine and murine origin. We used naïve and synthetic antibody Fab-format phage display libraries to develop antibodies to a conserved region on IGF2R. The generated antibodies were radiolabeled and characterized in vitro and in vivo using human and canine OS patient-derived tumors in SCID mouse models. We demonstrate specific binding to IGF2R and tumor uptake in these models, as well as binding to tumor tissue of canine OS patients, making these antibodies suitable for further development of RIT for OS.

Assessment of neutrophil function in canine cancer patients undergoing chemotherapy and correlation with neutrophil numbers.

Decreased neutrophil function following administration of chemotherapy has been reported in dogs with lymphoma. The first objective of our study was to determine if neutrophil oxidative burst and phagocytic activity are affected by chemotherapy 7 to 10 days following initiation of treatment in dogs with lymphoma and non-lymphoma malignancies. The second objective was to determine if there is a correlation between neutrophil numbers and neutrophil function before or after initiation of chemotherapy. Flow cytometric assessment of neutrophil oxidative burst and phagocytosis following stimulation with Escherichia coli was performed in 9 dogs diagnosed with lymphoma and 17 non-lymphoma tumor-bearing dogs pre- and post-chemotherapy, as well as 14 tumor-free control dogs. Spearman rank correlation was performed to determine if blood neutrophil numbers and neutrophil function were significantly correlated. Lymphoma patients showed significantly reduced percentage neutrophil oxidative burst post-chemotherapy compared to healthy controls as well as compared to pre-chemotherapy values (P = 0.0022 and P = 0.0020, respectively). Lymphoma patients also exhibited significantly reduced neutrophil phagocytosis activity post-chemotherapy compared to controls and pre-chemotherapy values (P = 0.0016 and P = 0.014, respectively). Dogs with non-lymphoma malignancies also showed a significant decrease in both percentage oxidative burst and phagocytosis post-chemotherapy compared to pre-chemotherapy values (P = 0.00040 and P = 0.029, respectively). Neutrophil numbers and function were not significantly correlated. The results of the study suggest that chemotherapeutic treatment decreases neutrophil oxidative burst and phagocytic activity 7 to 10 days post-treatment in dogs with various malignancies. Furthermore, neutrophil numbers cannot be used to predict neutrophil function.

Une diminution de la fonction des neutrophiles après l'administration d'une chimiothérapie a été rapportée chez des chiens atteints de lymphome. Le premier objectif de notre étude était de déterminer si la stimulation oxydative des neutrophiles et l'activité phagocytaire sont affectées par la chimiothérapie 7 à 10 jours après le début du traitement chez les chiens atteints de lymphomes et de tumeurs malignes non lymphomateuses. Le deuxième objectif était de déterminer s'il existe une corrélation entre les nombres de neutrophiles et la fonction des neutrophiles avant ou après le début de la chimiothérapie. L'évaluation par cytométrie en flux de la stimulation oxydative des neutrophiles et de la phagocytose après stimulation par Escherichia coli a été réalisée chez neuf chiens diagnostiqués avec un lymphome et 17 chiens avec des tumeurs non lymphomateuses avant et après la chimiothérapie, ainsi que 14 chiens témoins sans tumeur. Une corrélation des rangs de Spearman a été effectuée pour déterminer si les nombres de neutrophiles sanguins et la fonction des neutrophiles étaient significativement corrélés. Les patients atteints de lymphome ont montré un pourcentage significativement réduit de stimulation oxydative des neutrophiles après la chimiothérapie par rapport aux témoins sains ainsi que par rapport aux valeurs pré-chimiothérapie (P = 0,0022 et P = 0,0020, respectivement). Les patients atteints de lymphome ont également présenté une activité de phagocytose par les neutrophiles significativement réduite après la chimiothérapie par rapport aux témoins et aux valeurs pré-chimiothérapie (P = 0,0016 et P = 0,014, respectivement). Les chiens atteints de tumeurs malignes non lymphomateuses ont également montré une diminution significative du pourcentage de stimulation oxydative et de la phagocytose post-chimiothérapie par rapport aux valeurs pré-chimiothérapie (P = 0,00040 et P = 0,029, respectivement). Les nombres et la fonction des neutrophiles n'étaient pas significativement corrélés. Les résultats de l'étude suggèrent que le traitement chimiothérapeutique diminue la poussée oxydative des neutrophiles et l'activité phagocytaire 7 à 10 jours après le traitement chez les chiens atteints de diverses tumeurs malignes. De plus, les nombres de neutrophiles ne peuvent pas être utilisés pour prédire la fonction des neutrophiles.(Traduit par Docteur Serge Messier).

Radioimmunotherapy Targeting IGF2R on Canine-Patient-Derived Osteosarcoma Tumors in Mice and Radiation Dosimetry in Canine and Pediatric Models.

BACKGROUND: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently created a novel human antibody, IF3 to IGF2R, which binds to this receptor on both human and canine OS tumors. Here, we evaluated the efficacy and safety of radioimmunotherapy with 177Lu-labeled IF3 of mice bearing canine-patient-derived tumors and performed canine and human dosimetry calculations. METHODS: Biodistribution and microSPECT/CT imaging with 111In-IF3 was performed in mice bearing canine OS Gracie tumors, and canine and human dosimetry calculations were performed based on these results. RIT of Gracie-tumor-bearing mice was completed with 177Lu-IF3. RESULTS: Biodistribution and imaging showed a high uptake of 111In-IF3 in the tumor and spleen. Dosimetry identified the tumor, spleen and pancreas as the organs with the highest uptake. RIT was very effective in abrogating tumor growth in mice with some spleen-associated toxicity. CONCLUSIONS: These results demonstrate that RIT with 177Lu-IF3 targeting IGF2R on experimental canine OS tumors effectively decreases tumor growth. However, because of the limitations of murine models, careful evaluation of the possible toxicity of this treatment should be performed via nuclear imaging and image-based dosimetry in healthy dogs before clinical trials in companion dogs with OS can be attempted.

Use of serum amyloid A in serum and synovial fluid to detect eradication of infection in experimental septic arthritis in horses.

While serum amyloid A (SAA) has been investigated as a potential marker for septic arthritis in horses, no study has reported on whether SAA can be used to detect eradication of joint infection. Therefore, the objective of this study was to investigate whether the eradication of joint infection in experimentally induced septic arthritis in horses can be detected using serum and synovial fluid SAA. A total of 17 horses were randomly assigned to 3 groups. A middle carpal joint of each horse was injected with saline (control group, n = 3), lipopolysaccharide (LPS) (nonseptic synovitis group, n = 6), or Escherichia coli (septic arthritis group, n = 8) on day 0. Starting on day 1, horses underwent treatment for septic arthritis. Sequential samples of serum and synovial fluid were collected, and quantification of SAA was carried out. Concentrations of serum and synovial fluid SAA were compared among groups and time points. A concurrent study was conducted and determined that infection was eradicated on day 4 in this experimental model of septic arthritis. Concentrations of serum and synovial fluid SAA rapidly increased after inoculation of E. coli and were highest on day 3 and day 4, respectively. Thereafter, both serum and synovial fluid SAA decreased with eradication of joint infection, although they remained significantly increased from baseline until day 9 and day 10, respectively. Serum and synovial fluid SAA did not increase in the control or nonseptic synovitis group. These findings suggest that serial measurements rather than a single measurement of SAA are required to determine eradication of infection from septic arthritis in horses.

Bien que l'amyloïde sérique (SAA) fut étudiée comme marqueur potentiel pour l'arthrite septique chez les chevaux, aucune étude n'a rapporté si SAA peut être utilisée pour détecter l'élimination d'une infection articulaire. Ainsi, l'objectif de la présente étude était d'examiner si l'élimination d'une infection articulaire lors d'arthrite septique induite expérimentalement chez les chevaux peut être détectée en utilisant la SAA du sérum et du liquide synovial. Un total de 17 chevaux fut réparti de manière aléatoire en trois groupes. Une articulation carpienne médiale de chaque cheval fut injectée avec de la saline (groupe témoin, n = 3), du lipopolysaccharide (LPS) (groupe synovite non-septique, n = 6) ou Escherichia coli (groupe arthrite septique, n = 8) au jour 0. En débutant au jour 1, les chevaux furent soumis à un traitement pour arthrite septique. Des échantillons séquentiels de sérum et de liquide synovial furent prélevés et la quantification de SAA effectuée. Les concentrations de SAA dans le sérum et le liquide synovial furent comparées parmi les groupes et à différents temps. Une étude concomitante était menée et a déterminé que l'infection était éliminée au jour 4 dans ce modèle expérimental d'arthrite septique. Les concentrations de SAA dans le sérum et le liquide synovial ont rapidement augmenté après l'inoculation d'E. coli et étaient maximales au jour 3 et au jour 4, respectivement. Par la suite, les concentrations de SAA du sérum et du liquide synovial ont diminué avec l'élimination de l'infection articulaire, bien qu'elles soient demeurées augmentées significativement par rapport au seuil de base jusqu'au jour 9 et jour 10, respectivement. Les concentrations de SAA du sérum et du liquide synovial n'ont pas augmenté dans les groupes témoin et synovite non-septique. Ces résultats suggèrent que des mesures en série plutôt qu'une mesure unique de SAA sont requises pour déterminer l'élimination de l'infection lors d'arthrite septique chez les chevaux.(Traduit par Docteur Serge Messier).

Granulocytic anaplasmosis in three dogs from Saskatoon, Saskatchewan.

Three dogs from Saskatoon, Saskatchewan were diagnosed with acute granulocytic anaplasmosis. Fever, lethargy, inappetence, vomiting, diarrhea, and lameness were reported. Lymphopenia, thrombocytopenia, and splenomegaly were identified in all dogs. Inclusions were identified within the cytoplasm of blood neutrophils, and infection with Anaplasma phagocytophilum was confirmed by polymerase chain reaction.

Use of standard diagnostic techniques to determine eradication of infection in experimental equine septic arthritis.

Septic arthritis is an important disease in horses, necessitating aggressive and prolonged therapy. In order to guide therapy, reliable methods of detecting the eradication of infection are needed. Therefore, the objective of this study was to investigate detection of eradication of infection in an experimental model of equine septic arthritis using standard diagnostic techniques. For this purpose, 17 adult horses were assigned to 3 experimental groups. The middle carpal joint of each horse was injected with Escherichia coli (Septic group, n = 8), lipopolysaccharide (LPS) (LPS group, n = 6), or sterile saline (Control group, n = 3) at day 0. Contralateral joints were not injected. Standard therapy was applied to all joints except non-injected joints in the Control group at day 1. Sequential samples of synovial fluid (SF) were collected for bacterial culture using 3 culture media [Columbia blood agar (CBA), brain heart infusion broth (BHI), and Signal blood culture medium] and for cytological evaluation [percentage neutrophils (PN), total nucleated cell count (TNCC), and total protein (TP)]. Escherichia coli-specific polymerase chain reaction (PCR) was carried out to detect E. coli DNA in synovial fluid. Culture and PCR were positive for E. coli in all joints injected with E. coli at day 1 and 1 joint was positive on BHI at day 4. Based on the results of bacterial culture, PCR, and TNCC, the elimination of infection in our experimental model occurred by day 4 post-infection in 6 out of 7 cases. Total protein (TP) and PN remained elevated at clinical threshold used for diagnosis of septic arthritis until day 14. In our experimental model of E. coli-induced arthritis, we conclude that TP and PN may not be good indicators for detecting the eradication of bacterial infection caused by E. coli from infected and subsequently treated joints.

L'arthrite septique est une pathologie importante chez les chevaux, nécessitant une thérapie agressive et prolongée. Afin de guider la thérapie, des méthodes fiables pour détecter l'éradication de l'infection sont requises. Ainsi, l'objectif de la présente étude était d'examiner la détection de l'éradication de l'infection dans un modèle expérimental d'arthrite septique équine en utilisant des techniques diagnostiques standards. À cet effet, 17 chevaux adultes ont été assignés à trois groupes expérimentaux. L'articulation carpienne moyenne de chaque cheval a été injectée avec Escherichia coli (groupe septique, n = 8), du lipopolysaccharide (LPS) (groupe LPS, n = 6), ou de la saline stérile (groupe témoin, n = 3) au jour 0. Les articulations contra-latérales n'ont pas été injectées. Au jour 1, une thérapie standard fut appliquée à toutes les articulations sauf les articulations non-injectées dans le groupe témoin. De manière séquentielle des échantillons de liquide synovial (LS) furent prélevés pour culture bactérienne en utilisant trois milieux de culture [gélose au sang Columbia (CBA), bouillon coeur-cerveau (BHI), et hémoculture Signal] et pour évaluation cytologique [pourcentage de neutrophiles (PN), dénombrement total de cellules nucléées (DTCN), et la quantité de protéines totales (PT)]. Une réaction d'amplification en chaîne par la polymérase (ACP) spécifique à E. coli a été réalisée afin de détecter l'ADN d'E. coli dans le LS. La culture et l'ACP étaient positives pour E. coli dans toutes les articulations injectées avec E. coli au jour 1 et une articulation était positive avec le BHI au jour 4. Sur la base des résultats des cultures bactériennes, de l'ACP, et du DTCN, l'élimination de l'infection dans notre modèle expérimental est survenue au jour 4 post-infection dans 6 des 7 cas. Les valeurs de PT et de PN sont demeurées élevées au seuil clinique utilisé pour diagnostiquer une arthrite septique jusqu'au jour 14. Dans notre modèle expérimental d'arthrite induite par E. coli, nous concluons que les valeurs de PT et de PN ne seraient pas de bons indicateurs pour détecter l'éradication de l'infection bactérienne causée par E. coli dans des articulations infectées et subséquemment traitées.(Traduit par Docteur Serge Messier).

Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors.

Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commercial OS tumors in mice with radiolabeled antibody to IGF2R and to investigate IGF2R expression on canine OS tumors. IGF2R expression on human commercial lines 143B and SaOS2 and PDX lines OS-17, OS-33 and OS-31 was evaluated by FACS. The biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb was performed in 143B and OS-17 tumor-bearing SCID mice and followed by radioimmunotherapy (RIT) with 177Lutetium-2G11 and safety evaluation. IGF2R expression in randomly selected canine OS tumors was measured by immunohistochemistry. All OS cell lines expressed IGF2R. Biodistribution and microSPECT/CT revealed selective uptake of 2G11 mAb in 143B and OS-17 xenografts. RIT significantly slowed down the growth of OS-17 and 143B tumors without local and systemic toxicity. Canine OS tumors expressed IGF2R. This study demonstrates the feasibility of targeting IGF2R on OS in PDX and spontaneous canine tumors and sets the stage for further development of RIT of OS using comparative oncology.

A dog with osteosarcoma which metastasized to the eye months before metastasis to other organs.

A 9-year-old male Shih Tzu with osteosarcoma had a forelimb amputation and underwent chemotherapy. During chemotherapy, the right eye was enucleated due to refractory glaucoma, and was diagnosed as anterior uveal malignant melanoma. The dog lived for 4 months after the enucleation without treatment. After the dog died, the mass in the eye was re-evaluated immunohistochemically, and it was diagnosed as metastasis of appendicular osteosarcoma. Metastasis of appendicular osteosarcoma to the anterior chamber is quite rare, and the clinical course which showed clinically detectable metastases to the eye before systemic multi-organ metastases was quite unique.