Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

Oral squamous cell carcinoma is a highly invasive malignant neoplasm in cats. Recently, tumor stroma, known as tumor microenvironments, have been considered to play an essential role in tumor progression. However, their role in feline squamous cell carcinoma remains unclear. This study aimed to reveal the cancer microenvironment of feline oral squamous cell carcinoma and evaluate the pathological mechanisms of progression. We used 16 samples from 17 cats with oral squamous cell carcinoma which were examined using light microscopy, immunohistochemistry, and in situ hybridization. Feline oral squamous cell carcinomas had two types of stroma namely, fibrotic and myxoid stromal reaction patterns, which were easily distinguished using hematoxylin–eosin staining. The myxoid stroma was rich in hyaluronic acid, which may have been produced by neoplastic cells. Furthermore, the presence of myxoid stroma was correlated with histological parameters, including the appearance of cancer- associated fibroblasts and tumor budding. Periostin protein expression was also frequently observed in the stroma of feline oral squamous cell carcinoma and was significantly more common in the myxoid stromal reaction pattern group than in the fibrotic group. Positive signals for periostin mRNA were detected in stromal cancer- associated fibroblasts. This study indicates that the interaction between neoplastic cells and stromal reaction pattern components, such as hyaluronic acid and periostin, may be involved in tumor malignancy. Therefore, we propose that focus be placed not only on the tumor tissue but also on the characterization of the stroma for diagnosing feline oral squamous cell carcinoma.

<p>A retrospective study was conducted on 17 dogs with oral malignant melanoma treated with orthovoltage radiation therapy. The radiation therapy protocol was 8 Gy once a week for 4 weeks with a total dose of 32 Gy. Overall response rate to macroscopic lesions was 73.3%. The median progression free interval and median survival time for all dogs were 126 and 241 days, respectively. The median survival times for dogs with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were not reached, 258, 80.5, 115 days, respectively. Significant associations with survival time were found for presence of metastatic disease at the time of diagnosis (presence, 71 days vs. absence, 303 days), administration of surgical therapy (performed, 582 days vs. not performed, 164 days), therapeutic response (CR, 438 days vs. PR, SD, PD, 154.5 days). The side effects of the radiation therapy were observed in almost all cases, but most were mild. This study pointed out that our orthovoltage radiation therapy was an effective approach for canine oral malignant melanoma.</p>

DOI： 10.12935/jvma.76.e55

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Clinical signs of extrahepatic portosystemic shunts (EHPSS) depend on the amount of blood shunted. In this study, dogs with EHPSS without noticeable clinical signs including 34 left gastro-phrenic, 3 left gastro-azygos and 2 left spleno-gonadal shunts were evaluated. In dogs with EHPSS without noticeable clinical signs, the median maximum diameter of the shunt vessel was significantly smaller compared to PV (p < 0.005). Whenever the diameter of the EHPSS is small in relation to the diameter of the PV, it seems likely that no obvious clinical signs of EHPSS are observed by the owners.

DOI： 10.1111/ahe.12931

PubMed

Publishing type：Research paper (scientific journal)  

<p>An 8-year-4-month-old male Bernese Mountain dog was referred to the Obihiro University of Agriculture and Veterinary Medicine because of a pulmonary mass. The dog was diagnosed with pulmonary histiocytic sarcoma, and a lung lobectomy was performed. The pulmonary mass was confirmed to be histiocytic sarcoma by histopathological examination. We discovered a subcutaneous mass 5 cm in diameter on the right side of the hind flank on the fifth administration of lomustine (on day 119). It was diagnosed as metastatic lesion of histiocytic sarcoma by cytological examination. Therefore, we started administering doxorubicin instead of lomustine, but no effect was observed, and the metastatic lesion increased to a diameter of 11 cm. Then, we started treatment with toceranib phosphate on day 172. The metastatic lesions rapidly regressed. However, on day 301, the re-enlargement of the metastatic lesion in the hind flank and pleural effusion were observed. The patient was treated with vincristine, but died on day 318 without any response. The present case appears to be a rare case in which toceranib phosphate had a dramatic effect on canine histiocytic sarcoma.</p>

DOI： 10.12935/jvma.76.e202

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Swimmer puppy syndrome is a disease found in neonatal puppies mainly characterized by the inability to stand, but its direct cause is unknown. Since swimmer puppies were observed infrequently but continuously among the Labrador retriever colony at the Hokkaido Guide Dogs for the Blind Association in Japan, based on their birth record and pedigree, factors related to the onset of swimmer puppy syndrome in Labrador retrievers were examined. RESULTS: The total number of offspring over seven years was 436, of which 16 were swimmer puppies. Most of the affected puppies except one recovered steadily. As for the swimmer puppies, the litter size was significantly lower, and the body weights on the 10th and 28th day after delivery were significantly higher than the non-symptomatic puppies. These results suggested that the onset may be related to weight gain in the neonatal stages due to a small litter size. According to the genetic analysis, 26 ancestors common to the affected individuals were confirmed, but the causative individual could not be identified with the inbreeding coefficient. The heritability of the swimmer-puppy onset trait was 0.80, and the heritability for the the 10th-day body-weight trait was equally high at 0.78, both of which strongly suggest genetic involvement. CONCLUSIONS: In this study, the onset of swimmer puppy syndrome in the Labrador retrievers was associated with litter size and early weight gain, and result of study suggests that genetic influence might be involved.

DOI： 10.1186/s12917-022-03226-3

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

To develop a novel tear substitute (TS) containing sodium hyaluronate (SH) and dodecahydrosqualene (DHS, squalane), we improved the prescription of a previously developed TS containing saline, 0.5% SH and 1% castor oil (CO), which had corneal protective effects against 60-min desiccation in a porcine dry eye model and viscosity of 106.8 mPa·S. Fresh porcine eyes were treated with a TS containing saline, 0.1%, 0.25%, 0.3% or 0.5% SH, and 1% CO or 1%, 2.5% or 5% DHS, and TS-treated eyes were desiccated for up to 180 min. The corneal damage was evaluated by the staining score of methylene blue (MB), absorbance of MB extracted from the cornea, the staining density of lissamine green (LG) and histopathology. The viscosities of the examined TS were also measured. A saline/0.5% SH/1% DHS solution had corneal protective effects for 90 min under desiccation and a viscosity of 110.0 mPa·s. A TS with saline, 0.1%, 0.25% or 0.3% SH and 1% or 2.5% DHS did not have better protective effects than a saline/0.5% SH/1% DHS solution, although a saline/0.3% SH/5% DHS solution exhibited greater corneal protection against 180-min desiccation on MB and LG staining and histopathological examination, and its viscosity was 34.5 mPa·s, which was similar to the 29.5 mPa·s of 0.3% SH. The saline/0.3% SH/5% DHS solution is available as a novel 3-hr long-lasting TS containing mucinomimetic and liquid oil components to treat and relieve dry eye symptoms in animals and humans.

DOI： 10.1292/jvms.21-0496

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVE:  The aim of this study was to evaluate the effect of stem positioning on the biomechanical performance of a novel, collared, short-stem total hip implant under compression and torsion ex vivo. STUDY DESIGN:  Six canine cadaveric femurs were implanted with a collared short-stem femoral implant. Canal flare index (CFI), stem angle, absolute and relative cut heights and relative size were measured radiographically and used as independent variables. Biomechanical performance of the construct was evaluated using physiologic loading (loading) and supraphysiologic loading (failure) protocols. RESULTS:  During loading protocols, compressive stiffness was influenced by absolute cut height (p = 0.018). During failure protocols, peak torque was influenced by CFI (p = 0.004) and craniocaudal relative size (p = 0.005). Peak load and torsional stiffness were not impacted by any of the radiographic variables (p > 0.05). Three of six femurs developed longitudinal fractures originating at the medial calcar at the time of failure. CONCLUSION:  The biomechanical performance of the collared short-stem implant was positively impacted by preserving more of the femoral neck, having a higher CFI and using a smaller implant size relative to the femoral neck isthmus.

DOI： 10.1055/s-0041-1735290

PubMed

Kind of work：Joint Work  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Due to drug resistance, commonly used anti-Babesia drugs have limited efficacy against babesiosis and inflict severe side effects. Tafenoquine (TAF) was approved by the U.S. Food and Drug Administration in 2018 for the radical cure of Plasmodium vivax infection and for malaria prophylaxis. Here, we evaluated the efficacy of TAF for the treatment of Babesia infection and elucidated the suspected mechanisms of TAF activity against Babesia parasites. Parasitemia and survival rates of Babesia rodhaini-infected BALB/c and SCID mice were used to explore the role of the immune response in Babesia infection after TAF treatment. Parasitemia, survival rates, body weight, vital signs, complete blood count, and blood biochemistry of B. gibsoni-infected splenectomized dogs were determined to evaluate the anti-Babesia activity and side effects of TAF. Then, to understand the mechanism of TAF activity, hydrogen peroxide was used as an oxidizer for short-term B. rodhaini incubation in vitro, and the expression levels of antioxidant enzymes were confirmed using B. microti-infected mice by reverse transcription-quantitative PCR (qRT-PCR). Acute B. rodhaini and B. gibsoni infections were rapidly eliminated with TAF administration. Repeated administration of TAF or a combination therapy with other antibabesial agents is still needed to avoid a potentially fatal recurrence for immunocompromised hosts. Caution about hyperkalemia should be taken during TAF treatment for Babesia infection. TAF possesses a babesicidal effect that may be related to drug-induced oxidative stress. Considering the lower frequency of glucose-6-phosphate dehydrogenase deficiency in animals compared to that in humans, TAF use on Babesia-infected farm animals and pets is eagerly anticipated.

DOI： 10.1128/AAC.00204-21

PubMed

Kind of work：Joint Work  

Kind of work：Joint Work  

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

A 1-year-old male mixed breed dog presented for the evaluation of progressive hindlimb paresis. Neurological examination indicated a spinal cord lesion between the 3rd thoracic and 3rd lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intramedullary spinal cord lesion located at the level of the 1st and 2nd lumbar vertebrae. Following cytoreductive surgery of the mass, palliative radiation therapy was administered. A diagnosis of nephroblastoma was made based on histological examination. After radiation therapy, the disappearance of the spinal lesion was confirmed by MRI. The dog was improved from gait abnormality and alive at 16 months postoperatively, with slight signs of neurological dysfunction.

DOI： 10.1292/jvms.20-0068

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Circulating tumor DNA (ctDNA), which carries tumor-specific mutations, is an emerging candidate biomarker for malignancies and for monitoring disease status in various human tumors. Recently, BRAF V595E mutation has been reported in 80% of dogs with urothelial carcinoma. This study investigates the BRAF V595E allele concentration in circulating cell-free DNA (cfDNA) and assesses the clinical significance of BRAF-mutated ctDNA levels in canines with urothelial carcinoma. A total of 15 dogs with urothelial carcinoma were included. cfDNA concentration was measured using a real-time polymerase chain reaction (PCR) of the LINE-1 gene. To measure the concentration of the mutated BRAF gene in cfDNA, allele-specific real-time PCR with a locked nucleic acid probe was performed. BRAF mutations were detected in 11 (73%) of the 15 tested tumor samples. BRAF-mutated ctDNA concentrations were significantly higher in dogs with the BRAF mutation (14.05 ± 13.51 ng/ml) than in wild-type dogs (0.21 ± 0.41 ng/ml) (p = 0.031). The amount of BRAF-mutated ctDNA in plasma increased with disease progression and responded to treatment. Our results show that BRAF-mutated ctDNA can be detected using allele-specific real-time PCR in plasma samples of canines with urothelial carcinoma with the BRAF V595E mutation. This ctDNA analysis may be a potentially useful tool for monitoring the progression of urothelial carcinoma and its response to treatment.

DOI： 10.1371/journal.pone.0232365

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

This study proposed a novel radiographic positioning in order to image the cranioventral lung region using a portable X-ray unit and digital radiography system. In the novel position, calves were restrained in a chute and a unilateral forelimb was pulled cranially with the contralateral forelimb tied to the chute; the forelimbs were then spread cranio-caudally as in a scissor position (Three-legged view: TL view). In a preliminary study, we applied the TL view for imaging of 14 clinically healthy calves. In a clinical study, accuracy in detecting cranioventral lung lesions was compared between the standard standing view and the TL view for 19 calves, which were culled from herd; the results of postmortem examination were used as gold standard. Seven evaluators independently interpreted the images. The median (range) number of trials and the time for obtaining optimal position were 2 (1-7) and 263 sec (105-488), respectively in 14 healthy calves. Calves thicker than approximately 40 cm were not considered candidates for TL view in this setting because of difficulty in restraint and the low output of the portable X-ray unit. The TL view improved the detection of consolidation in the cranioventral lung region, compared with the standard view. The TL view was considered an optional view when the cranioventral lung region was an area of interest, because this view was relatively easy to perform and required a small number of personnel, even for large calves.

DOI： 10.1292/jvms.18-0333

PubMed