Language：Japanese   Publisher：Research in Veterinary Science  

Hepatocellular carcinoma (HCC) is the most common liver tumor in dogs. MicroRNA (miRNA) dysregulation and its clinical significance have been reported in dog and human cancers, including HCC. However, determining the whole miRNA transcriptomic profile is essential for diagnosis and therapeutics. Here, we determined the miRNA transcriptomic profile of canine HCC. First, miRNA expression from three control liver tissues and three canine HCC patients was analyzed via small RNA next-generation sequencing (NGS). After analyzing the sequencing reads, differential miRNA (DEmiRNA) expression was further confirmed in the clinical samples and three HCC cell lines via qRT-PCR. The functional pathways of the DEmiRNAs were analyzed from an experimentally validated human miRNA-target database. Our study revealed 20 upregulated and nine downregulated miRNAs. Among them, 10 miRNAs were further validated by qRT-PCR. qRT-PCR and NGS revealed similar miRNA expression patterns. Furthermore, we investigated the signaling pathways based on the KEGG pathway analysis and performed a functional analysis of the dysregulated miRNAs in canine HCC. The upregulated miRNAs mainly play a role in the p53 and cell cycle pathways and function in DNA damage repair and differentiation. In contrast, the downregulated miRNAs are involved in cancer and cell cycle pathways and mainly function in cell differentiation. Further, these miRNAs may be investigated in light of miRNA-based diagnosis and therapies.

DOI： 10.1016/j.rvsc.2025.105903

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PubMed

Language：Japanese   Publisher：Veterinary Sciences  

Lymphadenomegaly is well described in dogs with neoplastic diseases but can also reflect inflammation. However, its role in assessments of inflammation is little reported in the veterinary literature. Lymph nodes are most easily assessed superficially through palpation, but computed tomography (CT) enables the evaluation of deep lymph nodes. Accordingly, we investigated associations between the maximal lymph node diameter and plasma concentrations of C-reactive protein (CRP) and white blood cell (WBC) count, as inflammatory markers, targeting three deep lymph nodes (sternal, cranial mediastinal, and internal iliac). We evaluated data from small dogs with non-neoplastic diseases that underwent synchronous CT and blood biochemistry at our institution. We found that the sternal lymph node diameter was significantly greater in dogs with clinically elevated CRP than those with clinically unremarkable CRP (p = 0.04) and significantly correlated with CRP (r = 0.32; p < 0.01). We found no significant association with CRP for the cranial mediastinal or internal iliac lymph node. Thus, we consider CT-measured sternal lymphadenomegaly a clinically valuable finding for the comprehensive evaluation of systemic inflammation. We anticipate further research may highlight the utility of CT lymph node measurements for such evaluations.

DOI： 10.3390/vetsci12040356

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PubMed

Language：Japanese   Publisher：Veterinary and Animal Science  

In the veterinary field, the utility of disease-identification models that use comprehensive circulating microRNA (miRNA) profiles produced through measurements based on next-generation sequencing (NGS) remains unproven. To integrate NGS technology with automated machine learning (autoML) to create a comprehensive circulating miRNA profile and to assess the clinical utility of a disease-screening model derived from this profile. The study involved dogs diagnosed with or being treated for various diseases, including tumors, across multiple veterinary clinics (n = 254), and healthy dogs without apparent diseases (n = 91). miRNA was extracted from EDTA-treated plasma, and a comprehensive analysis was conducted of one million reads per sample using NGS. Then autoML technology was applied to develop a diagnostic model based on miRNA. Among these models, the one with the highest performance was chosen for evaluation. The diagnostic model, based on the comprehensive circulating miRNA profile developed in this study, achieved an AUC score of 0.89, with a sensitivity of 85 % and a specificity of 88 % for the disease samples. The miRNA-based diagnostic model demonstrated high sensitivity for disease groups and has the potential to be an effective screening test. This study indicates that a comprehensive miRNA profile in dog plasma could serve as a highly sensitive blood biomarker.

DOI： 10.1016/j.vas.2024.100414

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PubMed

Language：Japanese   Publisher：Genes  

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC.

DOI： 10.3390/genes15081024

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PubMed

Language：Japanese   Publisher：Veterinary Clinical Pathology  

A 6-year-old spayed female Scottish Fold cat presented with lethargy and anorexia. A complete blood cell count indicated severe anemia and mild thrombocytopenia. Examination of peripheral blood smears revealed marked changes in the erythroid lineage, including the presence of basophilic stippling and Howell-Jolly bodies as well as an increase in nucleated erythrocytes, polychromatophils, ovalocytes, and schistocytes. Additionally, some erythrocytes contained a ring or figure-eight shaped structure known as a Cabot ring, which were especially observed in polychromatophilic erythrocytes. Hemolytic diseases (Mycoplasma infection and IMHA) were diagnostically excluded, and the cat was treated through prednisolone administration, whole blood transfusion, and administration of vitamins (K2 and B12); however, the anemia progressively worsened. Cabot rings were observed until Day 22 and subsequently disappeared as the number of nucleated RBCs increased, and the erythrocyte lineage shifted to immature population. On Day 42, peripheral blood examination revealed further left shifting and appearance of many rubriblasts. The patient died at home on Day 43. Necropsy revealed neoplastic cells infiltrating the bone marrow and other organs, which were immunopositive to CD71 which is an erythroid lineage marker. In humans, Cabot rings have been observed in megaloblastic anemia, lead poisoning, myelodysplastic syndrome, and myelofibrosis; further, they are thought to be related to stressed bone marrow and dyserythropoiesis. This is the first case report of a cat with Cabot rings, which are suggestive of defects in erythroid lineage production.

DOI： 10.1111/vcp.13340

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PubMed

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Event date： 2023.9

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：鹿児島   Country：Japan  

Event date： 2023.9

Presentation type：Oral presentation (general)  

Event date： 2023.8

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2022

Venue：オンライン  

Event date： 2021.9

Presentation type：Oral presentation (general)  

Award type：Award from Japanese society, conference, symposium, etc. 

Audience： General

Type：Lecture