Tomoya Haraguchi
Yamaguchi University
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Featured researches published by Tomoya Haraguchi.
Melanoma Research | 2015
Shunsuke Noguchi; Takashi Mori; Takayuki Nakagawa; Kazuhito Itamoto; Tomoya Haraguchi; Takuya Mizuno
Melanoma is a poor-prognosis cancer in both humans and dogs. We have elucidated the antitumor mechanisms of antioncogenic microRNA (miR)-203 which is downregulated in human melanoma, as well as in canine melanoma. The aim of this study was to clarify the mechanism of this downregulation. We focused on epigenetic aberration of miR-203 transcription. Treatment with 5-aza-2′-deoxycitidine (5-aza) markedly upregulated the expression level of miR-203 in almost all of the cell lines tested. Furthermore, bisulfite sequencing or methylation-specific PCR showed DNA methylation of CpG islands upstream of the miR-203 coding region (MIR203) in both human and canine melanoma cells, as well as in canine clinical specimens, but not in human normal melanocytes. The results of a luciferase activity assay showed obvious suppression of the transcription of miR-203 by DNA methylation. The use of the luciferase activity assay for CREB1 and an inhibition assay of miR-203 function performed with an miR-203 inhibitor confirmed the contribution of miR-203 upregulation toward the negative regulation of the target gene of miR-203. These results indicate that canine melanoma might be a preclinical model of human melanoma for epigenetic studies. In addition, this study suggests that agents that can demethylate MIR203 could be a common promising therapeutic agent for the treatment of human and canine melanomas.
Journal of Veterinary Medical Science | 2015
Yasuhisa Oishi; Kenji Tani; Hiroshi Nakazawa; Kazuhito Itamoto; Tomoya Haraguchi; Yasuho Taura
Liver contrast X-ray computed tomography (CT) has been used for evaluation of hepatic vessels for liver transplantation, liver lobectomy, interventional radiology and diagnosis of hepatocellular carcinoma in humans. However, there remains scant available anatomical information on normal hepatic vessels in the veterinary field. In this study, visualization of hepatic vessels was evaluated in 32 normal beagle dogs by X-ray contrast CT using triple phase images. The following hepatic vessels were clearly visualized: arterial, portal and hepatic veins. With regards to the running patterns of the portal vein and hepatic vein, there were no significant differences between the dogs. However, the hepatic artery exhibited some differences in each dog. In particular, the hepatic artery of the quadrate lobe and the right lateral lobe had many running patterns. The results of the present study could be useful for veterinary diagnosis, surgery and interventional radiology.
Journal of Veterinary Medical Science | 2014
Yasutaka Oda; Kenji Tani; Yusuke Asari; Luiz Fernando Quintanilha; Tomoya Haraguchi; Yutaka Momota; Masaaki Katayama; Kazuhito Itamoto; Hiroshi Nakazawa; Yasuho Taura
ABSTRACT Regenerative therapy has begun to be clinically applied in humans and dogs to treat neurological disorders, such as spinal cord injury (SCI). Here, we show the therapeutic potential of transplantation of cultured canine bone marrow stromal cells (BMSCs) into mice with SCI. Canine BMSC transplantation therapy was performed, immediately after the spinal cord was injured. Canine BMSC therapy enhanced functional recovery of the hind limbs in mice with SCI. Nestin-positive cells were observed only in the lesion of mice with SCI that received BMSCs. These results suggest that canine BMSCs promote functional recovery in mice with SCI and that migration of nestin-positive cells may contribute to the efficacy of the BMSC treatment.
Veterinary and Comparative Oncology | 2018
Chung Chew Hwang; Masaya Igase; Masashi Sakurai; Tomoya Haraguchi; K. Tani; Kazuhito Itamoto; T. Shimokawa; Munekazu Nakaichi; Yuki Nemoto; Shunsuke Noguchi; Matt Coffey; Masaru Okuda; Takuya Mizuno
Oncolytic virotherapy is a novel treatment involving replication-competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 108 to 5.0 × 109 TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group- Common Terminology Criteria for Adverse Events (VCOG-CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti-reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post-treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well-tolerated and can be given safely to tumour-bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours.
World Journal of Stem Cells | 2017
Harumichi Itoh; Shimpei Nishikawa; Tomoya Haraguchi; Yu Arikawa; Shotaro Eto; Masato Hiyama; Toshie Iseri; Yoshiki Itoh; Munekazu Nakaichi; Yusuke Sakai; Kenji Tani; Yasuho Taura; Kazuhito Itamoto
AIM To identify and characterize functionally distinct subpopulation of adipose-derived stem cells (ADSCs). METHODS ADSCs cultured from mouse subcutaneous adipose tissue were sorted fluorescence-activated cell sorter based on aldehyde dehydrogenase (ALDH) activity, a widely used stem cell marker. Differentiation potentials were analyzed by utilizing immunocytofluorescece and its quantitative analysis. RESULTS Approximately 15% of bulk ADSCs showed high ALDH activity in flow cytometric analysis. Although significant difference was not seen in proliferation capacity, the adipogenic and osteogenic differentiation capacity was higher in ALDHHi subpopulations than in ALDHLo. Gene set enrichment analysis revealed that ribosome-related gene sets were enriched in the ALDHHi subpopulation. CONCLUSION High ALDH activity is a useful marker for identifying functionally different subpopulations in murine ADSCs. Additionally, we suggested the importance of ribosome for differentiation of ADSCs by gene set enrichment analysis.
Journal of Veterinary Medical Science | 2017
Tomoya Haraguchi; Shiho Kimura; Harumichi Itoh; Shimpei Nishikawa; Masato Hiyama; Kenji Tani; Toshie Iseri; Yoshiki Itoh; Munekazu Nakaichi; Yasuho Taura; Kazuhito Itamoto
This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery. CRP level was recorded at 12, 24 and 48 hr after surgery. The VAS and UMPS scores showed no significant intergroup differences. Compared to IG, LAG had significantly lower surgical time (45 ± 9.91 min vs 64 ± 5.30 min; P<0.05), incision length (46 ± 8.21 mm vs 129 ± 19.49 mm; P<0.05), CRP level (12 hr after surgery; 4.58 ± 1.58 mg/dl vs 12.4 ± 1.34 mg/dl; P<0.01), and COR level (1 hr after surgery; 10.79 ± 3.07 µg/dl vs 15.9 ± 3.77 µg/dl; P<0.05). IL-6 levels showed no significant intergroup differences at any time point. However, LAG resulted in lower IL-6 levels than did IG at all postoperative time points. Neither procedure resulted in significant surgical complications. LAG produced lower surgical stress than did IG, suggesting that LAG is a safe, minimally invasive, and highly useful technique for preventing canine gastric dilatation-volvulus. Nevertheless, since this study used experimental models, its usefulness should be evaluated in future cases.
Journal of Veterinary Medical Science | 2017
Harumichi Itoh; Shimpei Nishikawa; Tomoya Haraguchi; Yu Arikawa; Masato Hiyama; Shotaro Eto; Toshie Iseri; Yoshiki Itoh; Kenji Tani; Munekazu Nakaichi; Yasuho Taura; Kazuhito Itamoto
Adipose-derived stem cells (ADSCs) are abundant and readily obtained, and have been studied for their clinical applicability in regenerative medicine. Some surface antigens have been identified as markers of different ADSC subpopulations in mice and humans. However, it is unclear whether functionally distinct subpopulations exist in dogs. To address this issue, we evaluated aldehyde dehydrogenase (ALDH) activity—a widely used stem cell marker in mice and humans—by flow cytometry. Approximately 20% of bulk ADSCs showed high ALDH activity. Compared to cells with low activity (ALDHLo), the high-activity (ALDHHi) subpopulation exhibited a higher capacity for adipogenic and osteogenic differentiation. This is the first report of distinct ADSC subpopulations in dogs that differ in terms of adipogenic and osteogenic differentiation potential.
Journal of Veterinary Medical Science | 2014
Yasutaka Oda; Kenji Tani; Atsunobu Isozaki; Tomoya Haraguchi; Kazuhito Itamoto; Hiroshi Nakazawa; Yasuho Taura
ABSTRACT Bone marrow stromal cell (BMSC) transplantation has been reported as treatments that promote functional recovery after spinal cord injury (SCI) in humans and animals. Polyethylene glycol (PEG) has been also reported as treatments that promote functional recovery after spinal cord injury (SCI) in humans and animals. Therefore, administration of PEG combined with BMSC transplantation may improve outcomes compared with BMSC transplantation only in SCI model mice. SCI mice were divided into a control-group, BMSC-group, PEG-group and BMSC+PEG-group. BMSC transplantation and PEG administration were performed immediately after surgery. Compared to the control-group, PEG- and BMSC+PEG-groups showed significant locomotor functional recovery 4 weeks after therapy. We observed no significant differences among the groups. In the BMSC- and BMSC+PEG-groups, immunohistochemistry showed that many neuronal cells aggressively migrated toward the glial scar from the region rostral of the lesion site. In the control- and PEG-groups, the boundary of the injured regions was covered with astrocytes, and a few neuronal cells were migrated toward the glial scar. We conclude that combined BMSC transplantation with PEG treatment showed no synergistic effects on locomotor functional recovery or beneficial cellular events. Further studies may improve the effect of the treatment, including modification of the timing of BMSC transplantation.
Veterinary Surgery | 2017
Yasuhisa Oishi; Kenji Tani; Koushiro Ozono; Kazuhito Itamoto; Tomoya Haraguchi; Yasuho Taura
OBJECTIVE To determine the effects of selective transcatheter arterial embolization (TAE) in the normal canine liver. STUDY DESIGN Experimental study. ANIMALS Adult Beagle dogs (n = 5). METHODS Gelatin sponge particles (GSPs) were injected through a microcatheter for selective embolization of the left hepatic artery in normal dogs. Computed tomography (CT) and histology were performed during an 8-week observation period; biochemical analysis data were obtained during a 12-week observation period after TAE. RESULTS Embolization was successful in all dogs and did not induce any change in the clinical appearance of dogs. Postoperative CT was consistent with recanalization of the artery within 2 weeks of embolization in all dogs. Hepatic enzyme levels increased temporarily after embolization but gradually returned to normal ranges. Histological examinations did not differ between treated and untreated liver tissues. CONCLUSION TAE appears safe in normal dogs observed for 12 weeks. Arterial recanalization seems to occur within 2 weeks after injection of GSPs in the left hepatic artery. IMPACT/CLINICAL RELEVANCE Selective TAE of the hepatic artery was well tolerated in normal dogs. Selective TAE may be applicable to canine hepatocellular carcinoma.Objective To determine the effects of selective transcatheter arterial embolization (TAE) in the normal canine liver. Study design Experimental study. Animals Adult Beagle dogs (n = 5). Methods Gelatin sponge particles (GSPs) were injected through a microcatheter for selective embolization of the left hepatic artery in normal dogs. Computed tomography (CT) and histology were performed during an 8-week observation period; biochemical analysis data were obtained during a 12-week observation period after TAE. Results Embolization was successful in all dogs and did not induce any change in the clinical appearance of dogs. Postoperative CT was consistent with recanalization of the artery within 2 weeks of embolization in all dogs. Hepatic enzyme levels increased temporarily after embolization but gradually returned to normal ranges. Histological examinations did not differ between treated and untreated liver tissues. Conclusion TAE appears safe in normal dogs observed for 12 weeks. Arterial recanalization seems to occur within 2 weeks after injection of GSPs in the left hepatic artery. Impact/clinical relevance Selective TAE of the hepatic artery was well tolerated in normal dogs. Selective TAE may be applicable to canine hepatocellular carcinoma.
Open veterinary journal | 2017
Harumichi Itoh; Kazuhito Itamoto; Shotaro Eto; Tomoya Haraguchi; Shimpei Nishikawa; Kenji Tani; Yoshiki Itoh; Masato Hiyama; Toshie Iseri; Munekazu Nakaichi; Yasuho Taura
Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping. Magnetic resonance imaging showed compression of the spinal cord and indentation of caudal cerebellum. The diagnosis was Chiari-like malformation, atlantoaxial subluxation with ventral displacement of C2, atlanto-occipital overlapping, and syringomyelia. The dog underwent foramen magnum decompression, dorsal laminectomy of C1, and ventral fixation of the atlantoaxial joint. Soon after the operation, voluntary movements of the legs were recovered. Finally, the dog could stand and walk without assistance. The dog had complicated malformations at the craniocervical junction but foramen magnum decompression and dorsal laminectomy for Chiari-like malformation, and ventral fixation for atlantoaxial subluxation resulted in an excellent clinical outcome.