掲載種別：研究論文（学術雑誌）   共著区分：共著   国際・国内誌：国際誌  

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>常電圧放射線発生装置（オルソボルテージ）を用いて治療した口腔内悪性黒色腫の犬の17症例について回顧的研究を行った．治療プロトコルは1回8Gyを週1回，4週間とし総線量32Gyとした．肉眼病変に対する治療反応は73.3％で認められ，無進行期間及び生存期間中央値はそれぞれ126日，241日であった．ステージ別の生存期間はステージⅠが中央値に達せず，Ⅱが258日，Ⅲが80.5日，Ⅳが115日であり，診断時転移の有無（あり71日，なし303日），外科切除の有無（あり582日，なし164日），治療反応（CR 438日，それ以外154.5日）が有意に生存期間と関連していた．放射線障害はほぼ全例で認められたものの，多くは軽度であり，犬の口腔内悪性腫瘍に対する常電圧放射線治療は有用な治療オプションになりうると思われた．</p>

DOI： 10.12935/jvma.76.e55

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1111/ahe.12931

PubMed

掲載種別：研究論文（学術雑誌）  

<p>症例は8歳4カ月のバーニーズ・マウンテンドッグ，去勢雄であり，肺腫瘤の精査を目的に帯広畜産大学動物医療センターを紹介受診した．切除組織の病理学的検査にて肺原発の組織球性肉腫と診断し，第36病日よりロムスチンによる術後抗がん剤治療を行った．ロムスチン5回目投与時に右兼部に5cm大の皮下腫瘤を認め，細胞診にて組織球性肉腫の転移病変と診断した．ドキソルビシンを使用したが効果はみられず病変は11cm大まで増大した．第172病日よりリン酸トセラニブの投与を開始したところ転移病変は急速に退縮し1.5cm大まで縮小した．しかし第301病日に転移病変の再増大と胸水貯留を認め，ビンクリスチンを投与するも反応なく第318病日に斃死した．一時的ではあったものの，リン酸トセラニブの劇的な効果がみられた稀な症例と思われた．</p>

DOI： 10.12935/jvma.76.e202

掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

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

掲載種別：研究論文（学術雑誌）   国際・国内誌：国内誌  

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

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

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

共著区分：共著  

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

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

共著区分：共著  

共著区分：共著  

掲載種別：研究論文（学術雑誌）   国際・国内誌：国内誌  

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

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

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

掲載種別：研究論文（学術雑誌）   国際・国内誌：国内誌  

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