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This file contains the legends for the 7 supplementary figures

This file contains supplementary figures showing prostate tumor kinetics (Fig S1) and histology (Fig S2) for the two mouse models, the validation of regimens (Fig S3 and S4), the effects of diets (Fig S5) and aging (Fig S6) on cancer hallmarks, and the results of cell studies complementary to main Figures 3 and 4.

Ehlers-Danlos syndrome (EDS) is a group of heterogeneous, rare diseases affecting the connective tissues. The main clinical signs of EDS are skin hyperextensibility, joint hypermobility, and skin fragility. Currently, the classification of EDS in humans distinguishes 13 clinical subtypes associated with variants in 20 different genes, reflecting the heterogeneity of this set of diseases. At present, variants in three of these genes have also been identified in dogs affected by EDS. The purpose of this study was to characterize the clinical and histopathological phenotype of an EDS-affected Chihuahua and to identify the causative genetic variant for the disease. The clinical examination suggested a diagnosis of classical EDS. Skin histopathology revealed an abnormally thin dermis, which is compatible with classical EDS. Whole-genome sequencing identified a heterozygous de novo 27 bp deletion in the COL5A2 gene, COL5A2:c.3388_3414del. The in-frame deletion is predicted to remove 9 amino acids in the triple-helical region of COL5A2. The molecular analysis and identification of a likely pathogenic variant in COL5A2 confirmed the subtype as a form of classical EDS. This is the first report of a COL5A2-related EDS in a dog.

Ehlers-Danlos syndrome (EDS) is a group of heterogeneous, rare diseases affecting the connective tissues. The main clinical signs of EDS are skin hyperextensibility, joint hypermobility, and skin fragility. Currently, the classification of EDS in humans distinguishes 13 clinical subtypes associated with variants in 20 different genes, reflecting the heterogeneity of this set of diseases. At present, variants in three of these genes have also been identified in dogs affected by EDS. The purpose of this study was to characterize the clinical and histopathological phenotype of an EDS-affected Chihuahua and to identify the causative genetic variant for the disease. The clinical examination suggested a diagnosis of classical EDS. Skin histopathology revealed an abnormally thin dermis, which is compatible with classical EDS. Whole-genome sequencing identified a heterozygous de novo 27 bp deletion in the

Retroperitoneal paragangliomas are rare tumors of the neuroendocrine system. Only a few canine case reports are available with rare descriptions of their imaging features. The objectives of this multi-center, retrospective case series study were to describe the diagnostic imaging features of confirmed retroperitoneal paragangliomas and specify their location. Medical records and imaging studies of 10 affected dogs with cytological or histopathologic results concordant with retroperitoneal paragangliomas were evaluated. Dogs had a median age of 9 years. Four of them had clinical signs and laboratory reports compatible with excessive production of catecholamines. Six ultrasound, four CT, four radiographic, and one MRI studies were included. The paragangliomas did not have a specific location along the aorta. They were of various sizes (median 33mm, range: 9–85mm of length). Masses had heterogeneous parenchyma in six of 10 dogs, regardless of the imaging modality. Strong contrast enhancement was found in all CT studies. Encircling of at least one vessel was detected in six of 10 masses, clear invasion of a vessel was identified in one of 10 masses. In five of 10 cases, the masses were initially misconstrued as lymph nodes by the on-site radiologist. Retroperitoneal paragangliomas appear along the abdominal aorta, often presenting heterogeneous parenchyma, possibly affecting the local vasculature, and displaying strong contrast enhancement on CT. Clinical signs can be secondary to mass effects or excessive catecholamine production. Underdiagnosis and misdiagnosis of this tumor are suspected as they can be silent, of small size, or confused with other structures.

OBJECTIVETo report clinical, surgical, and pathological findings in client-owned rabbits with histologically confirmed appendicitis.ANIMALS19 rabbits.PROCEDURESMedical records for client-owned rabbits that had a histologic diagnosis of appendicitis were reviewed.RESULTSMedian age of the rabbits at presentation was 24.0 months (range, 4 to 84 months). Seventeen cases occurred during the summer and fall seasons. Decreased appetite (17/19 rabbits), abnormal rectal temperature (hyperthermia, 9/16 rabbits; hypothermia, 4/16 rabbits), hypocalcemia (8/11 rabbits), and hypoglycemia (7/15 rabbits) were common signs. Abdominal ultrasonography and CT findings were suggestive of appendicitis in 6 of 8 rabbits and in 1 of 2 rabbits, respectively. Of the 6 rabbits that received medical treatment, 3 died at 48 hours, 1 died at 24 hours after hospitalization, and 1 died at 10 days after presentation; 1 rabbit was alive at 1,030 days after presentation. Of the 8 rabbits that underwent appendectomy, 3 died before discharge from the hospital and 1 died 113 days after surgery; 4 rabbits were alive at 315, 334, 1,433, and 1,473 days after presentation. The remaining 5 rabbits either died or were euthanized before treatment could be instituted. In each of the 19 rabbits, the appendix had evidence of severe inflammation with mucosal ulceration, heterophilic inflammation, and necrotic debris.CLINICAL RELEVANCEFor rabbits with decreased appetite and an apparently painful abdomen, hyperthermia, hypocalcemia, or hypoglycemia, appendicitis should be considered as a differential diagnosis. Further comparisons of medical and surgical treatments are required to establish treatment recommendations for rabbits with appendicitis.

Highlights • Immunodeficient mice are susceptible to spontaneous tumors which are rarely reported in patient-derived tumor xenografts (PDX) studies. • Quality control of PDX identity is required at each step on the preclinical assays to avoid erroneous conclusions. • Description of the approaches used for this PDX check should be clearly detailed in material and methods section., Patient-derived tumor xenograft (PDX) is now largely recognized as a key preclinical model for cancer research, mimicking patient tumor phenotype and genotype. Immunodeficient mice, well-known to develop spontaneous lymphoma, are required for PDX growth. As for all animal models used for further clinical translation, a robust experimental design is strongly required to lead to conclusive results. Here we briefly report unintentional co-engraftment of mouse lymphoma during expansion of well-established PDXs to illustrate the importance of systematic check of the PDX identity to avoid misinterpretation. Besides, this quality control based on complementary approaches deserves a more detailed description in materials and methods section to ensure experimental validity and reproducibility., Graphical Abstract Image, graphical abstract

International audience; A 6-y-old neutered male ferret (Mustela putorius furo) was presented because of a 1-mo history of progressive weight loss, chronic cough, and hair loss. On clinical examination, the animal was coughing, slightly depressed, moderately hypothermic, and had bilateral epiphora. Thoracic radiography was suggestive of severe multinodular interstitial pneumonia. Abdominal ultrasound examination revealed hepatosplenomegaly and mesenteric and pancreaticoduodenal lymphadenopathy. Fine-needle aspiration of the pancreaticoduodenal lymph node, followed by routine Romanowsky and Ziehl-Neelsen stains, revealed numerous macrophages containing myriad acid-fast bacilli, leading to identification of mycobacteriosis. Autopsy and histologic examination confirmed the presence of disseminated, poorly defined, acid-fast, bacilli-rich granulomas in the pancreaticoduodenal and mesenteric lymph nodes, intestines, and lungs. Destaining of May-Grunwald/Giemsa-stained slides with alcohol, and then restaining with Ziehl-Neelsen, revealed acid-fast rods and avoided repeat tissue sampling without affecting the Ziehl-Neelsen stain quality and cytologic features. Tissue samples were submitted for a PCR assay targeting the heat shock protein gene (hsp65) and revealed 100% homology with Mycobacterium genavense. We emphasize the use of special stains and PCR for identification of this potential zoonotic agent.

A 7-year-old, 34-kg, neutered male Labrador retriever was presented with a 1-year history of intermittent sneezing with occasional left-sided epistaxis. CT revealed a mass in the left nasal cavity. Histopathological analysis of rhinoscopy-guided tissue biopsies was consistent with chronic necrotic and ulcerative rhinitis. Surgical debridement by ventral rhinotomy was subsequently performed and histopathological diagnosis was leiomyoma. Complete resolution of the nasal discharge and reduced sneezing frequency were observed after surgery. Fourteen months postoperatively, CT detected no regrowth of the mass.

International audience; Genetically engineered mouse models offer essential opportunities to investigate the mechanisms of initiation and progression in melanoma. Here, we report a new simplified histopathology classification of mouse melanocytic lesions in Tyr::NRASQ61K derived models, using an interactive decision tree that produces homogeneous categories. Reproducibility for this classification system was evaluated on a panel of representative cases of murine melanocytic lesions by pathologists and basic scientists. Reproducibility, measured as inter-rater agreement between evaluators using a modified Fleiss' kappa statistic, revealed a very good agreement between observers. Should this new simplified classification be adopted, it would create a robust system of communication between researchers in the field of mouse melanoma models.

Melanoma is the deadliest skin cancer. RACK1 (Receptor for activated protein kinase C) protein was proposed as a biological marker of melanoma in human and domestic animal species harboring spontaneous melanomas. As a scaffold protein, RACK1 is able to coordinate the interaction of key signaling molecules implicated in both physiological cellular functions and tumorigenesis. A role for RACK1 in rewiring ERK and JNK signaling pathways in melanoma cell lines had been proposed. Here, we used a genetic approach to test this hypothesis in vivo in the mouse. We show that Rack1 knock-down in the mouse melanoma cell line B16 reduces invasiveness and induces cell differentiation. We have developed the first mouse model for RACK1 gain of function, Tyr::Rack1-HA transgenic mice, targeting RACK1 to melanocytes in vivo. RACK1 overexpression was not sufficient to initiate melanomas despite activated ERK and AKT. However, in a context of melanoma predisposition, RACK1 overexpression reduced latency and increased incidence and metastatic rate. In primary melanoma cells from Tyr::Rack1-HA, Tyr::NRasQ61K mice, activated JNK (c-Jun N-terminal kinase) and activated STAT3 (signal transducer and activator of transcription 3) acted as RACK1 oncogenic partners in tumoral progression. A sequential and coordinated activation of ERK, JNK and STAT3 with RACK1 is shown to accelerate aggressive melanoma development in vivo.

Objectives Radioiodine (131I) dose determination using radiotracer kinetic studies or scoring systems, and fixed relatively high 131I dose (ie, 4 or 5 mCi) administration, are effective and associated with prolonged survival times for hyperthyroid cats. The latter method is less complicated but could expose patients and veterinary personnel to unnecessary levels of radiation. The aim of this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131I dose for the treatment of 96 hyperthyroid cats with no length estimation for any palpated goitre ⩾20 mm, assess outcome and identify factors associated with survival. Methods Serum total thyroxine concentrations at diagnosis and at follow-up times, survival times and cause of death were recorded. Multivariable Cox regression analysis was used to identify factors associated with time to any cause of death from 131I therapy initiation. Results Administration of a median (interquartile range) dose of 3.35 mCi (3.27–3.44 mCi) radioiodine was an effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death related to hyperthyroidism was recorded. Median survival time was 3.0 years; the 1 and 2 year survival rates after 131I therapy were 90% and 78%, respectively. Low body weight (⩽3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence interval [CI] 2.22–16.67; P Conclusions and relevance This study suggests that a fixed 3.35 mCi 131I dose treatment is effective for hyperthyroid cats with goitre(s) with a maximal length estimation

Most pet rats have chronic respiratory disease, and end-stage complications are frequently fatal. Drug aerosol delivery in the form of nebulization of antibiotics, expectorants, and bronchodilators is often used as part of their treatment. As rats are obligate nasal breathers, aerosol delivery must be achieved by nasal inhalation, which has the anatomical limitation of a narrower airway lumen. In humans, aerosol delivery of many respiratory drugs is achieved by oral inhalation as it allows administration of very small particles with a concentration loss of only 20% in comparison with 85% by the nasal route. The aim of this pilot study was to determine whether a nebulized fluorescein solution would reach the lungs of rats as no data exists. Ten healthy 13-week-old female Sprague-Dawley rats were nebulized continuously for 15 minutes. The rats were euthanized, and a full postmortem examination was performed. The respiratory tract was sampled, fast-frozen in liquid nitrogen and preserved at −20 °C. Slides were examined with a fluorescence microscope to determine the distribution of fluorescein in the respiratory tract. Fluorescence was observed in the entire respiratory tract of all the nebulized rats, showing that nebulization is an efficient way to deliver medication directly into the alveoli.

Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355–65. ©2016 AACR.

Background Limited evidence exists in the literature regarding whether a specific mount is preferable to use for processing endoscopically obtained gastrointestinal biopsy specimens. Hypothesis/Objectives To compare 3 methods of handling endoscopically obtained gastrointestinal biopsy specimens from collection to laboratory processing and to determine if any technique produced superior results. Animals Twenty-three dogs and cats presented for gastrointestinal signs. Methods Prospective study of dogs and cats presented with gastrointestinal signs to a veterinary teaching referral hospital which underwent upper gastrointestinal endoscopy. Biopsy specimens were taken from the stomach and duodenum and submitted to the laboratory using 3 techniques: mounted on a cucumber slice, mounted on a moisturized synthetic foam sponge, and floating free in formalin. The techniques were compared with regard to the specimens' width, orientation, presence of artifacts, and pathologist's confidence in diagnosis. Results Twenty-three patients were included, with a total of 528 biopsies collected. Specimens on cucumber slice and on sponge were significantly wider (P < .001 and P = .001, respectively) compared to those floating free in formalin (mean width of 3.81 versus 3.31 and 2.52 mm, respectively). However, specimens on synthetic sponge had significantly fewer artifacts compared to those on cucumber slice (P = .05) and those floating free in formalin (P = .02). Confidence in the diagnosis also was superior with the sponge technique over floating free specimens (P = .002). Conclusions and Clinical Importance The use of mounted gastrointestinal biopsy specimens was superior over the use of specimens floating free in formalin. This technique improved the quality of the specimens and the pathologist's confidence in their histopathologic interpretation.

International audience; Ichthyoses represent a heterogeneous group of hereditary cornification disorders characterized by generalized scaling of the skin. An autosomal recessive congenital ichthyosis (ARCI) has been described in American Bulldogs and is caused by a variant in the NIPAL4 gene encoding for the ICHTHYIN protein. So far, this variant has not been described in other breeds. A 1.5-year-old female pedigreed American Bully was referred for generalized scaling and bad coat quality since adoption at 8 weeks of age. Clinical examination, cytological and histopathological examination, and DNA testing were performed. Clinical examination revealed a generalized scaling; cytological evaluation using impression with acetate tapes showed a secondary Malassezia dermatitis. Histopathological examination revealed a moderate to marked, diffuse, compact orthokeratotic hyperkeratosis with the formation of large scales. Few Malassezia were observed in the stratum corneum associated with minimal mixed perivascular inflammation and moderate epidermal hyperplasia. DNA testing of the dog revealed that he carries two defective alleles of the NIPAL4 gene previously described in the American Bulldog. We performed a commercially available breed detection test which, although not specifically testing for "American Bully" signatures, revealed a high probability of American Bulldog DNA signature within the past three generations. Topical treatment using a combination of keratolytic and keratomodulator shampoo, emollient and moisturizers spray and antimicrobial wipes achieved a marked clinical improvement after only 1 month. Continuous topical treatment was necessary to maintain clinical improvement. To the authors' knowledge, this is the first description of the deleterious NIPAL4 variant in an American Bully as well as the first description of clinical management and follow-up of ARCI in this breed.

WS® 1541 is a phytopharmaceutical drug combination containing a lipophilic extract from fruits of Sabal serrulata (WS® 1473) and an aqueous ethanolic extract from roots of Urtica dioica (WS® 1031). It is approved in several countries worldwide for the treatment of lower urinary tract syndrome (LUTS) linked to benign prostate hyperplasia (BPH). Clinical studies have demonstrated the efficacy of this unique combination in the treatment of BPH-related LUTS. However, its mechanisms of action in vivo remain partly uncharacterized. The aim of this study was to take advantage of a validated mouse model of BPH to better characterize its growth-inhibitory and anti-inflammatory properties. We used the probasin–prolactin (Pb-PRL) transgenic mouse model in which prostate-specific overexpression of PRL results in several features of the human disease including tissue hypertrophy, epithelial hyperplasia, increased stromal cellularity, inflammation, and LUTS. Six-month-old heterozygous Pb-PRL male mice were randomly distributed to five groups (11–12 animals/group) orally treated for 28 consecutive days with WS® 1541 (300, 600, or 900 mg/kg/day), the 5α-reductase inhibitor finasteride used as reference (5 mg/kg/day) or vehicle (olive oil 5 ml/kg/day). Administration of WS® 1541 was well tolerated and caused a dose-dependent reduction of prostate weight (vs. vehicle) that was statistically significant at the two highest doses. This effect was accompanied by a reduction in prostate cell proliferation as assessed by lower Ki-67 expression (qPCR and immunohistochemistry). In contrast, finasteride had no or only a mild effect on these parameters. The growth-inhibitory activity of WS® 1541 was accompanied by a strong anti-inflammatory effect as evidenced by the reduced infiltration of cells expressing the leukocyte common antigen CD45. In sharp contrast, finasteride significantly increased the prostate inflammatory status according to this readout. Molecular profiling (qPCR) of 23 selected pro-inflammatory genes confirmed the strong anti-inflammatory potency of WS® 1541 compared to finasteride. Since treatment of WS® 1541 did not interfere with transgene expression and activity in the prostate of Pb-PRL mice, the effects observed in this study are entirely attributable to the intrinsic pharmacological action of the drug combination.

Genetically engineered mouse models offer essential opportunities to investigate the mechanisms of initiation and progression in melanoma. Here, we report a new simplified histopathology classification of mouse melanocytic lesions in Tyr::NRAS

A 10-month-old male Campbell's Russian hamster ( Phodopus campbelli ) presented with a mass on the left forelimb. The mass was surgically excised, and the results of histopathology yielded a diagnosis of cutaneous botryomycosis, with corresponding clusters of large colonies of Gram-positive cocci. The results of the bacteriologic examination revealed Staphylococcus epidermidis . There was no evidence of patient immunosuppression based on diagnostic test results (e.g., hematology, plasma biochemistry panel, and serum electrophoresis). The mass recurred 5 months after resection. Surgical treatment was declined by the owner and an attempt to treat with antimicrobial medication was met with limited success. The animal was euthanized 7 months following the initial presentation. On histopathologic examination, a recurrent cutaneous botryomycosis was identified, associated with hepatic and splenic extramedullary granulopoiesis and hepatic pyogranulomas without granules and identifiable bacteria.

Summary The paired box gene 3 (Pax3) is expressed during pigment cell development. We tested whether the targeted allele Pax3GFP can be used as a reporter gene for pigment cells in the mouse. We found that enhanced green fluorescent protein (GFP) can be seen readily in every melanoblast and melanocyte in the epidermis and hair follicles of Pax3GFP/+ heterozygotes. The GFP was detected at all differentiation stages, including melanocyte stem cells. In the dermis, Schwann cells and nestin-positive cells of the piloneural collars resembling the nestin-positive hair follicle multipotent stem cells exhibited a weaker GFP signal. Pigment cells could be purified by fluorescent activated cell sorting and grown in vitro without feeder cells, giving pure cultures of melanocytes. The Schwann cells and nestin-positive cells of the piloneural collars were FACS-isolated based on their weak expression of GFP. Thus Pax3GFP can discriminate distinct populations of cells in the skin.

A stud dog was presented for acquired infertility. Haematospermia and teratozoospermia were found on two ejaculates 2 weeks apart. A presumptive diagnosis of prostatitis was made follo-wing ultrasound examination. An ultrasound-guided needle core biopsy was performed under general anaesthesia, revealing a mild chronic macrophagic and plasma cell prostatitis with intracytoplasmic amastigotes consistent with Leishmania spp. infection. Presence of Leishmania infantum, Leishmania donovani or Leishmania chagasi was confirmed by polymerase chain reaction in seminal plasma. Serology and serum protein electrophoresis confirmed the diagnosis of a subclinical active systemic leishmaniasis. A meglumine antimoniate and allopurinol treatment was given which clearly improved within 3 months both general condition and the quality of sperm. To the authors' knowledge, this is the first reported case of a prostatitis secondary to a Leishmania spp. infection. Subclinical systemic leishmaniasis should be considered in the differential diagnosis of infertility in dogs suffering from semen alterations.

International audience; Chronic traumatic brain injury is rare in man and has not been previously documented in dogs. This report describes a 2-year-old female American Staffordshire bull terrier that was referred with forelimb and hindlimb ataxia, decreased vigilance and disorientation following repeated aggression and physical abuse by its owner. A diffuse cortical lesion was suspected. Cerebrospinal fluid analysis revealed neutrophilic pleocytosis and computed tomography showed marked widening of the cerebral sulci with mild bilateral ventriculomegaly. The dog was humanely destroyed in view of the poor prognosis. Necropsy examination revealed narrowing of the cerebral cortical gyri and consequent widening of the sulci without distortion or displacement of the neural parenchyma. These features were consistent with bilateral diffuse cortical atrophy. Microscopically, there were chronic subarachnoid haemorrhages and the cortical subpial layer displayed spongiosis, capillary hyperplasia, astrocytosis, microgliosis and frequent neuronal necrosis occurring in a characteristic laminar pattern. This histopathological pattern of damage was significantly different from that previously described in people suffering from repeated traumatic brain injuries over a long period of time.

International audience; The role of the Pax3 gene in embryonic development of pigment cells is well characterized. By contrast, the function of Pax3 in melanoma development is controversial. Indeed, data obtained from cultured cells suggest that PAX3 may contribute to melanomagenesis. PAX3 is found to be overexpressed in melanomas and also in nevi compared with normal skin samples. Pax3 homozygous loss of function is embryonic lethal. To assess the role of Pax3 in melanoma development in vivo, we analyzed Pax3 haploinsufficiency in a mouse model of melanoma predisposition. The Pax3(GFP/+) knock-in reporter system was combined with the Tyr::NRAS(Q61K); Cdkn2a(-/-) mouse melanoma model. Melanoma development was followed over 18 months. Histopathological, immunohistochemical, and molecular analyses of lesions at different stages of melanoma progression were carried out. Fluorescence-activated cell sorting on GFP of cells from primary or metastatic melanoma was followed by ex-vivo transformation tests and in-vivo passaging. We report here that Tyr::NRAS(Q61K); Cdkn2a(-/-); Pax3(GFP/+) mice developed metastasizing melanoma as their Tyr::NRAS(Q61K); Cdkn2a(-/-); littermates. Histopathology showed no differences between the two genotypes, although Pax3 mRNA and PAX3 protein levels in Pax3(GFP/+) lesions were reduced by half. The Pax3(GFP) allele proved to be a convenient marker to identify and directly sort heterogeneous populations of melanoma cells within the tumor bulk at each stage of melanoma progression. This new mouse model represents an accurate and reproducible means for identifying melanoma cells in vivo to study the mechanisms of melanoma development.

A 10-year-old Jack Russell Terrier presented with a six-month history of chronic vomiting. Initial bloodwork and ultrasound demonstrated mild and non-specific changes. Vomiting dramatically improved upon feeding a home-made elimination diet, and clinical signs reappeared following a provocation trial. However, 12 weeks after the first visit, the dog became inappetent and lost weight despite this food change. A gastroscopy was performed, and histological examination of gastric mucosal samples revealed high-grade B-cell lymphoma, which was confirmed on immunohistochemistry. Systemic chemotherapy was initiated, and the dog survived 30 months on treatment. This is an exceptional long-term survival time of a dog presenting a gastric lymphoma and concurrent dietary intolerance.

A three-year-old male neutered domestic shorthair cat was presented for loss of vision associated with hyperthermia, lethargy and anorexia. Ophthalmic examination revealed a bilateral panuveitis. Cytological examination of aqueous and vitreous humours was performed and revealed a suppurative inflammation associated with numerous cocci. Enterococcus faecalis was identified by bacterial culture from aqueous and vitreous humour. No primary infection site was identified. Active uveitis resolved after systemic antibiotic therapy, but the vision loss was permanent. To the authors' knowledge, this is the first reported case of endogenous bacterial endophthalmitis secondary to E. faecalis infection in a cat.

Chantier qualité GA; International audience; The galectin-4 protein is mostly expressed in the digestive tract and is associated with lipid raft stabilization, protein apical trafficking, wound healing, and inflammation. While most mammalian species, including humans, have a single Lgals4 gene, some mice have two paralogues: Lgals4 and Lgals6. So far, their significant similarities have hindered the analysis of their respective expression and function. We took advantage of two antibodies that discriminate between the galectin-4 and galectin-6 proteins to document their patterns of expression in the normal and the dextran sodium sulfate (DSS)-damaged digestive tract in the mouse. In the normal digestive tract, their pattern of expression from tongue to colon is quite similar, which suggests functional redundancy. However, the presence of galectin-4, but not galectin-6, in the lamina propria of the DSS-damaged colon, its association with luminal colonic bacteria, and differences in subcellular localization of these proteins suggest that they also have distinct roles in the normal and the damaged mouse digestive tract. Our results provide a rare example of ancestral and derived functions evolving after tandem gene duplication.

An adult female African collared dove (Streptopelia roseogrisea) was presented for examination of a mass on the medial surface of the left wing. The mass had been present for 2 months but had grown rapidly over the previous 2 weeks. One week after presentation, the mass was surgically excised and the involved alular bone was removed. Results of histologic examination of the mass were consistent with an aneurysmal bone cyst. No underlying factor could be found in this case. The wound healing was uneventful, and no mass recurrence was observed during the following year. To our knowledge, this is the first report of an aneurysmal bone cyst in a columbiform bird.

The cases of 7 adult dogs with generalized seizures managed by surgical excision and radiation therapy for frontal lobe meningiomas were reviewed. The neurological examination was unremarkable in 6 of the 7 dogs. Five dogs were operated on using a bilateral transfrontal sinus approach and 2 using a unilateral sinotemporal approach to the frontal lobe. One dog was euthanized 14 d after surgery; radiation therapy was initiated 3 wk after surgery in the remaining 6 dogs. Long-term follow-up consisted of neurological examination and magnetic resonance imaging (MRI) and/or computed tomography (CT) scan after radiation therapy. The mean survival time for dogs that had surgery and radiation therapy was 18 mo after surgery. Frontal lobe meningiomas have been associated with poor prognosis. However, the surgical approaches used in these cases, combined with radiation therapy, allow a survival rate for frontal lobe meningiomas similar to that for meningiomas located over the cerebral convexities.

National audience

National audience

National audience

Chantier qualité GA; Gastro-intestinal Stromal Tumors (GIST) are digestive mesenchymal tumors. These rare tumors in Humans remain seldom diagnosed in veterinary medicine. Traditionally regarded as deriving from smooth muscle cells or Schwann cells, GIST are now recognized as a specific tumoral entity. They derive from interstitial cells of Cajal, pacemakers of the digestive tract. Their diagnosis is based on histological and immunohistochemical characteristics. They are immunohistochemically KIT-positive (a transmembrane tyrosine kinase receptor) and are often associated with mutations of the Kit gene. KIT is responsible for the development of new therapeutic molecules: tyrosine kinase inhibitors. In humans, these molecules have revolutionized the treatment of GIST, particularly resistant to radiotherapy and chemotherapy. In animals, tyrosine kinase inhibitors represent an important breakthrough that will allow interesting new therapeutic treatments.; Les gastro-intestinal stromal tumors (GIST) sont des tumeurs mésenchymateuses digestives. Ces tumeurs rares en pathologie humaine restent peu diagnostiquées en médecine vétérinaire. Longtemps considérées comme des tumeurs dérivées des fibres musculaires lisses ou des cellules de Schwann, les GIST sont aujourd’hui reconnues comme une entité tumorale à part entière. Elles dériveraient des cellules interstitielles de Cajal, pacemakers du tube digestif. Leur diagnostic repose sur des critères histologiques et immunohistochimiques. Elles sont caractérisées par un immunomarquage positif pour la protéine KIT (récepteur à activité tyrosine kinase) et souvent associées à des mutations du gène Kit. L’implication de KIT a contribué au développement d’approches thérapeutiques basées sur l’utilisation d’inhibiteurs de tyrosine kinase. Chez l’Homme, ils ont révolutionné le traitement des GIST, connues pour être résistantes à la radiothérapie et la chimiothérapie. Leurs propriétés ouvrent de nouvelles perspectives thérapeutiques chez l’animal.

The objective of this study was to develop a standard operating procedure for the analysis of skin wound healing using histomorphometrical measurements and mathematical data analyses. The mathematical model is derived from observations of normal cutaneous healing in the rabbit. It is designed to allow a simple scoring of the major steps of healing and remodelling. Full-thickness punch biopsies were performed on the skin of the back of New Zealand-white rabbits and healing was analyzed by histopathological examination after 2, 5, 9 and 14 days, using different staining techniques. Histomorphological measurements were also made. The thickness of the epidermis and neo-epidermis were compared. Several indices relative to wound severity and contraction were computed in an attempt to defi ne a global healing index. A remodelling index was calculated based on a colorimetric analysis with Mallory Trichrome staining and hair migration. The changes in indeks values seemed to correlate with the histopathological analysis. No material flaws appeared when this model was applied to the natural healing process. This model was developed for scoring and accurate comparative evaluation of the effects of various treatments, biomaterials or pharmacological preparations on soft tissue healing and remodelling in rabbits. Although the healing of cutaneous wounds in rabbits differs from that in humans, this model may still be relevant for screening new wound healing preparations., Cilj ovog istraživanja je razvijanje osnovne metode za analizu zaraštavanja kože služeći se histomorfometrijskim mjerenjima i matematičkom analizom podataka. Matematički je model nastao promatranjem fi ziološkoga zarastanja kože u kunića. Model je razvijen za jednostavno mjerenje osnovnih faza zarastanja i remodeliranja rane. Potpuna biopsija kože provedena je na leđnoj koži novozelandskih bijelih kunića te je analiza zarastanja promatrana histopatološki nakon drugoga, petoga, devetoga i četrnaestoga dana rabeći različite metode bojenja. Također su izvršena histomorfološka mjerenja. Uspoređene su vrijednosti debljine fi ziološkoga i novonastaloga epidermisa. Nekoliko indeksa povezanih sa zarastanjem i kontrakcijom kože pribrajani su s pokušajem utvrđivanja potpunoga indeksa zaraštavanja. Kolometrijska analiza s Mallory trichrome bojenjem korištena je za izračun remodelirajućega indeksa i promatranja migracije dlačnoga folikula. Promjene u vrijednosti indeksa mogu se povezati s histopatološkom analizom. Prirodni proces zarastanja promatran je bez utjecaja čimbenika koji mogu doprinijeti ishodu samoga zarastanja. Taj je model razvijen kako bi se moglo promatrati i uspoređivati različita liječenja, biomaterijali i farmakološki pripravci za zarastanje i remodeliranje mekoga tkiva u kunića. Unatoč razlici u zarastanju kože kunića i čovjeka, ovaj model može biti koristan za promatranje novih pripravaka za zaraštavanje rana.

This case describes a subcutaneous soft tissue tumour in a German Shepherd dog. Histologically, the lesion was characterized by proliferating ovoid cells, loosely arranged in a collagenous to myxoid stroma, and by numerous pseudoglandular structures lined by neoplastic cells. Immunohistochemically, neoplastic cells were labelled with vimentin, glial fibrillary acidic protein and S100 antibodies, but not with cytokeratin, desmin and smooth muscle actin antibodies. Ultrastructurally, neoplastic cells were characterized by numerous mitochondria surrounded by endoplasmic reticulum and contained few secondary lysosomes. This tumour was diagnosed as a subcutaneous peripheral nerve sheath tumour (PNST) with pseudoglandular architecture. This case illustrates the morphological diversity of PNST and provides new insight into the differential diagnosis of cutaneous tumours of similar morphology in the dog.

In the gastrointestinal tract, interstitial cells of Cajal (ICCs) generate a pacemaker activity. They produce electric slow waves that trigger and coordinate gut smooth muscle contractions. Interstitial cells of Cajal's slender shape is revealed by KIT immunostaining. Based on several features, including KIT expression and KIT dependence, ICC-like cells were identified in nongastrointestinal tissues. Here, we investigated in the mouse whether uterine contractions depend on ICC-like cells' activity. By labeling KIT-expressing cells, we found putative ICC-like cells in the uterus, observed as KIT-positive interstitial, long spindle-shaped cells with fine branched cytoplasm processes, distributed in muscular layers and in subepithelial connective tissue. We then checked the potential KIT dependence of ex vivo contractile activity of the uterus by combining genetic and pharmacological approaches, using the Kit W-v hypomorphic mutation, and imatinib as a KIT noncompetitive inhibitor. We found a significant reduction in frequency of longitudinal uterine contractions in Kit W-v/Kit W-v compared with Kit+/+ mice, whereas amplitude was unaffected. There was no difference in frequency or amplitude of circular uterine contractions between Kit W-v/Kit W-v and Kit+/+ mice. Ex vivo treatment of Kit+/+ uterine horns with imatinib resulted in a dose-dependent reduction of the frequency and amplitude of longitudinal myometrial contractions. Amplitude and frequency of circular contractions were unaffected in presence of imatinib. These concurrent results suggest that longitudinal contractions of the uterus depend on a KIT signaling pathway of ICC-like cells. The existence of ICC-like cells in the myometrium may enhance our understanding of uterine spontaneous contractile activity and suggest new approaches for treatment of uterine contractility disorders.

A CASE OF SCROTAL LEIOMYOSARCOMA IN A DOG E. Laloy, S. Chateau-Joubert, M. El Mrini, F. Rakotovao, M. Carlus, E. Reyes-Gomez, V. Delfosse and N. Cordonnier National Veterinary School of Alfort, France Introduction: Scrotal smooth muscle tumours are uncommon in man. They arise from the tunica dartos of the scrotum. They have not been reported in animals. Materials and Methods: A 6-year-old male shar pei dog presented with a single 1-cm diameter mass arising from the left scrotum. Surgical excision was performed and the nodule was fixed in 10% neutral buffered formalin, processed routinely and embedded in paraffin wax. Sections were stained with haematoxylin and eosin. Several sections were subjected to immunohistochemistry. Results: The neoplasm was well circumscribed, but unencapsulated. It showed multifocal contiguity with the dartos smooth muscle bundles. It comprised of short interlacing bundles of plump spindle cells within minimal collagenous stroma. The neoplastic cells had abundant eosinophilic cytoplasm and oval to elongated nuclei. Moderate anisokaryosis and anisocytosis were seen. There were seven mitotic figures per 10 high-power fields ( 40). Small focal areas of necrosis were present. The neoplastic cells were positive for vimentin and smooth muscle actin, while they were negative for melan A, glial fibrillary acidic protein (GFAP) and S100. A few cells were positive for desmin. Conclusions: The histological and immunohistochemical findings were most consistent with a scrotal leiomyosarcoma. This is the first report of scrotal leiomyosarcoma in a dog. MESOTELIOMA OF THE TUNICA VAGINALIS OF THE TESTIS IN THE DOG: AN UNCOMMON NEOPLASM WITH MALIGNANT BEHAVIOUR G.A. Ram irez*, A. Su arez-Bonnet y, A. Espinosa-de-los-Monteros y, J. Altimira* and M. Vilafranca* *HISTOVET Laboratory and yLas Palmas de Gran Canaria University, Spain Introduction: Mesotheliomas of the tunica vaginalis testis are extremely rare. The aim of this work is to describe the clinical, histological and immunohistochemical features as well as the clinical outcome of this neoplasm in the dog. Materials and Methods: Our records were reviewed for dogs with a diagnosis of testicular mesothelioma made between 1995 and 2011. Clinical histories and follow-up information were obtained from referring clinicians. Diagnoses were confirmed by re-review of paraffin wax-embedded specimens. Immunohistochemistry was also performed with a panel of antibodies including cytokeratins, vimentin and CEA. Results: Cases were presented as swelling of the scrotum. Ultrasonography revealed heterogeneous and irregular masses with a mixed echogenicity; anechoic effusion surrounding the affected testicles (hydrocele) was also common. Gross examination often revealed firm, polypoid or papillary, yellow to white masses with a solid cut surface. The tunica vaginalis was thickened, studded with nodules of varying size, and diffusely calcified in one case. Invasion of the spermatic cord was common. Microscopically, the tumours had epithelial features with papillary, tubulopapillary or solid patterns and consistently expressed cytokeratins and vimentin. Post-operative recovery was always uneventful, but worsening of general health was reported in a period of!7 months. Necropsy examination, when performed, confirmed abdominal metastatic disease. Conclusions: Mesothelioma of the tunica vaginalis testis in the dog is a rare malignant neoplasm with an aggressive behaviour and poor outcome.

Reference EPFL-ARTICLE-188431doi:10.1111/pcmr.12115View record in Web of Science Record created on 2013-09-09, modified on 2017-05-12