博士, 北海道大学獣医学研究院, Jun. 2021

日本小動物外科専門医, Jun. 2023

アジア獣医外科学会専門医, Apr. 2025

Life Science, Veterinary medical science

Bachelor's degree program, School of Veterinary Medicine

Doctoral (PhD) degree program, Graduate School of Veterinary Medicine

Clinical efficacy of anti-programmed death ligand 1 antibody HFC-L1/c4G12 in dogs with malignant tumors: an exploratory study.
Satoshi Takagi; Michihito Tagawa; Naoya Maekawa; Satoru Konnai; Yumiko Kagawa; Kenji Hosoya; Akinori Yamauchi; Ayano Kudo; Shintaro Kamo; Sangho Kim; Ryohei Kinoshita; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Hayato Nakamura; Yukinari Kato; Shigeki Kanazawa; Tomoyuki Abe; Takuya Furuta; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
The Journal of veterinary medical science, 87, 12, 1419, 1425, 01 Dec. 2025, [Domestic magazines]
English, Scientific journal, Cancer in dogs remains a major challenge in modern veterinary medicine. Immunotherapy using immune checkpoint inhibitors (ICIs) is available for various human tumor types, and recent veterinary clinical studies have shown that ICIs are a promising approach for treating canine cancers. A canine chimeric anti-PD-L1 antibody, c4G12 (HFC-L1), has been investigated for canine cancer immunotherapy; however, its clinical benefits have not been well characterized in tumors other than pulmonary metastatic (stage IV) oral malignant melanoma (OMM). To explore the efficacy and safety of HFC-L1, we conducted a clinical study in dogs with stage I-III OMM or other tumor types (n=12). HFC-L1 treatment at a dose of 5 mg/kg every 2 weeks was well tolerated, and no grade 3 or higher treatment-related adverse events were reported. Among the dogs eligible for response evaluation (n=10), a partial response was observed in one dog with squamous cell carcinoma, resulting in an objective response rate of 10%. In addition, in a dog with ceruminous cell carcinoma, clinical evidence of a tumor response was observed in metastatic lung lesions. Together, these results suggest that the HFC-L1 therapy is applicable for the treatment of various tumor types, although its clinical benefits should be further evaluated in clinical studies involving a larger number of dogs with each tumor type.

Successful surgical removal of a retroperitoneal paraganglioma in the celiac artery trifurcation in a dog.
Kyosuke Takeuchi; Kenji Hosoya; Ryo Owaki; Ryohei Kinoshita; Sangho Kim; Masahiro Okumura
BMC veterinary research, 21, 1, 651, 651, 07 Nov. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: Paraganglioma (PGL) is a general term for tumors that originate in the paraganglia in dogs, most commonly reported in the carotid and aortic bodies. Reports on surgical treatment are rare because these tumors develop near large blood vessels, and their prognosis remains unclear. In dogs, the indications for and safety of surgical procedures involving the celiac artery (CA) root and the dissection of its major branches have not been established. To the best of our knowledge, this is the first reported case of CA root involvement in canine PGL. CASE PRESENTATION: Surgery was performed on day 84 to remove a PGL tumor. The mass was firmly attached to the left lobe of the pancreas, portal vein, CA, and cranial mesenteric artery (CMA). Therefore, a combined resection was performed, including the spleen, left lobe of the pancreas, and left hepatic lymph nodes. Among the main branches of the CA, the splenic and left gastric arteries could not be separated and were transected. Consequently, the stomach wall became ischemic, and reduced pulsation of the left gastric and omental arteries was observed. To maintain blood supply, the common hepatic artery was preserved. After normalization of the stomach wall color, the CMA was separated from the mass, and the tumor was removed. Pathological examination confirmed that the mass was a PGL, with no metastasis to the hepatic lymph nodes. A computed tomography scan on day 265 revealed that blood flow in the common hepatic artery, portal vein, and left gastric region was well maintained. As of day 279, there was no evidence of metastasis or recurrence, and the patient remained in good condition. CONCLUSIONS: In this case, the main branches of the CA, except for the common hepatic artery, were transected to remove the mass; however, the patient was discharged without serious complications. This is attributable to recovery of blood flow from collateral routes. Considering this blood flow recovery and that intraoperative gastric ischemia was temporary, complete ligation of the CA root may be acceptable in some cases. Additionally, the prognosis for PGL was favorable when complete resection was achieved.

Exploratory, Randomized, Dose-Response Study of the Anti-PD-L1 Antibody HFC-L1/c4G12 in Dogs with Pulmonary Metastatic Oral Malignant Melanoma.
Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Naoya Maekawa; Satoru Konnai; Satoshi Takagi; Michihito Tagawa; Yumiko Kagawa; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Hayato Nakamura; Akinori Yamauchi; Ayano Kudo; Shintaro Kamo; Yukinari Kato; Shigeki Kanazawa; Tomoyuki Abe; Takuya Furuta; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
Veterinary sciences, 12, 9, 02 Sep. 2025, [International Magazine]
English, Scientific journal, Oral malignant melanoma (OMM) is a highly aggressive malignancy in dogs. The development of effective systemic therapies is urgently required to improve the treatment of canine OMM. Immunotherapy using immune checkpoint inhibitors (ICIs) has been investigated in canines following their dramatic success in human cancer treatment; however, there is still a need for extensive veterinary clinical studies to clarify and optimize their clinical benefits. Among the ICIs under development for canine cancer immunotherapy, c4G12 (HFC-L1), a canine chimeric anti-PD-L1 antibody, has shown promising efficacy in dogs with pulmonary metastatic OMM in previous clinical studies. However, the optimal dose of HFC-L1/c4G12 has not yet been determined. To explore the dose-response relationship of HFC-L1, a multicenter, randomized clinical study was conducted using three different doses (2, 5, or 10 mg/kg via intravenous infusion every 2 weeks) to treat dogs with pulmonary metastatic OMM (n = 8-9 per group). The safety profiles were similar among the dose groups, and numerically longer median overall survival was achieved in the higher dose groups (5 and 10 mg/kg) than in the 2 mg/kg group. Although the study was exploratory in nature with a small sample size, 5-10 mg/kg should be considered the preferred dose in future clinical studies using HFC-L1.

Outcomes and Prognostic Factors in Dogs With Presumed Intracranial Gliomas Treated With Definitive-Intent Intensity Modulated Radiation Therapy: 55 Cases (2014-2023).
Yohichi Fukuyama; Kenji Hosoya; Sangho Kim; Koangyong Sung; Tatsuya Deguchi; Genya Shimbo; Kazuyoshi Sasaoka; Ryouhei Kinoshita; Mitsuyoshi Takiguchi
Veterinary and comparative oncology, 25 Aug. 2025, [International Magazine]
English, Scientific journal, Radiation therapy (RT) is the treatment of choice for canine intracranial gliomas. Recently, modern advanced radiation techniques, including intensity modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), have become widely available in veterinary medicine. However, the glioma-specific therapeutic outcomes of patients treated with modern RT remain unclear. This study aimed to describe survival outcomes and tumour response and to identify whether any treatment, clinical, and imaging factors were predictive of prognosis in dogs with intracranial gliomas treated with definitive-intent IMRT alone. Medical records of dogs with presumed intracranial gliomas that underwent definitive-intent IMRT were retrospectively reviewed. Fifty-five dogs were included. Amongst them, 29 and 26 underwent fractionated RT (FRT) and stereotactic RT (SRT), respectively. In the 44 dogs that underwent follow-up magnetic resonance imaging (MRI), the overall measurable response rate was 77.3%. Clinical improvement was observed in 92% of the dogs. Local tumour regrowth and drop metastases were observed in 17 (30.9%) and 10 dogs (18.2%), respectively. The median overall survival, disease-specific survival, and progression-free survival were 432, 670, and 441 days, respectively. Seven dogs (12.7%) died during RT or within 6 weeks. There was no statistically significant difference in the survival times between FRT and SRT. In the multivariate analysis, poor performance status, tumour location in the diencephalon, and fluid-attenuated inversion recovery heterogeneity were significantly associated with shorter survival times. These findings suggest that definitive-intent RT results in tumour shrinkage and prolonged survival (432 days) with minimal radiation toxicity regardless of the RT protocol used. Performance status and MRI findings can be useful for predicting prognosis.

Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma
Tamami Suzuki; Kazuki Heishima; Jumpei Yamazaki; Masaya Yamazaki; Ryohei Kinoshita; Sangho Kim; Kenji Hosoya; Yuko Okamatsu-Ogura; Michihito Sasaki; Peng Xu; Takashi Kimura; Qin Yan; Keisuke Aoshima
Cold Spring Harbor Laboratory, 13 Aug. 2025
Hemangiosarcoma (HSA) is a malignant endothelial tumor that occurs frequently in dogs but is rare in other species including humans. Due to its aggressive behavior and limited therapeutic options, patient prognosis is generally poor. Tumor cells produce excess lactate via anerobic glycolysis, and it regulate gene expressions through histone lactylation in response to cellular metabolic conditions. However, how histone lactylation affects biological behavior under glucose-limited conditions in HSA remains unknown. Here, we established canine HSA cell lines and patient-derived xenograft models and investigated the role of histone lactylation during glucose deprivation. HSA cells exhibited higher global histone lactylation levels than normal endothelial cells. Although glucose restriction reduced global histone lactylation levels, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis revealed enrichment of lactylation peaks at transcription‑start sites (TSSs) of ATF4‑regulated stress‑response, asparagine biosynthesis and immune‑related genes. TSSs of stress-response genes were co-occupied with RNA polymerase II phosphorylated at serine 5 and showed increased gene expressions, suggesting that lactylation at TSSs activated transcription under glucose-deprived conditions. [U-13C]glutamine tracing indicated that HSA cells synthesized asparagine from glutamine when glucose was scarce. Asparagine supplementation modestly activated cell proliferation. In HSA patient tissues, H3K18la levels were heterogeneous, and M2-like macrophages preferentially infiltrated tumor regions showing low histone lactylation levels. Consistently, glucose‑starved HSA cells attracted macrophages and induced M2‑like polarization in vitro. These findings demonstrate that lysine lactylation, possibly histone lactylation, persists even under glucose-deprived conditions and regulate transcription that supports tumor cell survival and fosters a pro-tumor microenvironment.

Progressive myelomalacia with spinal cord disorders along with severe intradural hemorrhage in a cat.
Takafumi Sunaga; Shingo Miki; Fuka Takahashi; Keisuke Aoshima; Sangho Kim; Masahiro Okumura
The Journal of veterinary medical science, 87, 8, 954, 959, 01 Aug. 2025, [Domestic magazines]
English, Scientific journal, Progressive myelomalacia (PMM) is a severe neurological disorder. Although several case reports have been published, PMM is uncommon in cats. A 9-year-old neutered male domestic short-haired cat presented with hindlimb paraplegia. Based on the neurological examination, severe abnormalities in the L4-S3 segment were suspected. Based on magnetic resonance imaging findings, intervertebral disk herniation (IVDH) was suspected at the L5-L6 intervertebral disk. A hemilaminectomy and durotomy were performed. Four days after surgery, PMM was suspected, and the cat was euthanized. An autopsy was performed, and a histopathological examination confirmed PMM secondary to severe spinal disorders.

Calcinosis circumscripta of the extremities and the tongue with multifocal arterial calcification secondary to chronic kidney disease in a cat.
Ai Koshikawa; Shingo Miki; Sangho Kim; Takashi Kimura; Keisuke Aoshima
The Journal of veterinary medical science, 18 Jul. 2025, [Domestic magazines]
English, Scientific journal, A 3-year-old neutered male mixed-breed cat was presented with right urinary tract obstruction caused by a urolith and severe atrophy of the left kidney. In the next year and a half, chronic kidney disease (CKD) progressed, and several masses were identified in the extremities, along with an ulcer on the tongue. Histologically, the extremity masses consisted of calcium deposits separated by fibrovascular septa, and the tongue ulcer showed severe neutrophilic infiltration with pervasive calcium deposition. These lesions were diagnosed as calcinosis circumscripta (CCs). Concurrently, multifocal mineralization of the aorta and of small- to medium-sized arteries in several organs indicated widespread vascular calcification. Both extremity and vascular lesions were likely secondary to the excessive calcium-phosphate product caused by CKD. Although CCs in either the extremities or tongue has been reported in cats, this case is notable for the presence of CCs in both extremities and tongue with systemic vascular calcification.

Tensioning diaphragmoplasty for treating bilateral phrenic nerve paralysis in a dog.
S Matsumoto; K Hosoya; S Kim; M Okumura
The Journal of small animal practice, 66, 6, 425, 431, Jun. 2025, [International Magazine]
English, Scientific journal, A spayed female Miniature dachshund presented with a large mediastinal mass. During thymectomy, the left phrenic nerve, which was encircled by the neoplastic tissue, was resected en bloc with the tumour and the right phrenic nerve was damaged by thermal coagulation from electrosurgery. Postoperatively, the dog exhibited significant respiratory distress and paradoxical respiratory movement. Bilateral diaphragmatic paralysis was confirmed on inspiratory radiographs, and lack of structural abnormalities on thoracic computed tomography was noted. The dog collapsed 5 days postoperatively from respiratory fatigue. Thus, salvage surgery and tensioning diaphragmoplasty were performed. Briefly, The diaphragm was partially resected, primarily closed and reinforced with a polypropylene mesh sutured on the abdominal surface. Thereafter, the dog's condition improved significantly. The dog did not present with respiratory issues until she died of urothelial carcinoma on day 375. In conclusion, this surgical technique can be considered to re-establish the function of the diaphragm.

Glutathione-associated redox regulation alleviates radio-resistance of canine cancer stem-like cells with low proteasome activity.
Koangyong Sung; Kenji Hosoya; Tatsuya Deguchi; Koya Yamashita; Sangho Kim; Takafumi Sunaga; Hironobu Yasui; Osamu Inanami; Masahiro Okumura
Scientific reports, 15, 1, 18017, 18017, 23 May 2025, [International Magazine]
English, Scientific journal, Radio-resistance of cancer stem-like cells (CSCs) is associated with the failure of radiation therapy. ZsGreen1-positive (ZsG⁺) cells, which exhibit low proteasome activity, have been used to enable the detection and isolation of CSCs. However, the mechanisms of radio-resistance in canine tumor cells with low proteasome activity remain unclear. This study aimed to elucidate the radio-resistance mechanisms of ZsG+ cells by identifying a potential target of canine CSCs. ZsG+ cells, isolated using flow cytometric cell sorting, were compared with ZsG- cells. Sulfasalazine was used to suppress glutathione (GSH) synthesis by inhibiting xCT. In vitro experiments demonstrated a significantly higher radio-resistance in ZsG+ cells than in ZsG- cells. After X-irradiation, ZsG+ cells had fewer p53‑binding protein 1 (53BP1) foci, low reactive oxygen species (ROS) accumulation, and high GSH content. Sulfasalazine caused radiosensitization of ZsG+ cells with an increased number of 53BP1 foci by decreasing GSH contents and increasing ROS accumulation. The low proteasome activity played a role in xCT upregulation. In conclusion, canine tumor cells with low proteasome activity are radio-resistant due to high GSH content and low ROS accumulation. Sulfasalazine causes radiosensitization of the tumor cells by altering redox balance by inhibiting GSH synthesis for effective targeting of canine CSCs.

Development of caninized anti-CTLA-4 antibody as salvage combination therapy for anti-PD-L1 refractory tumors in dogs
Naoya Maekawa; Satoru Konnai; Kei Watari; Hiroto Takeuchi; Takeshi Nakanishi; Taro Tachibana; Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Ryo Owaki; Madoka Yokokawa; Yumiko Kagawa; Satoshi Takagi; Tatsuya Deguchi; Hiroshi Ohta; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
Frontiers in Immunology, 16, Frontiers Media SA, 20 May 2025
Scientific journal, Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy; however, the clinical efficacy of anti-PD-1/PD-L1 monotherapy is generally limited, highlighting the need to develop combination therapies. Dogs develop spontaneous tumors in immunocompetent settings, and anti-PD-1/PD-L1 antibodies exert similar clinical benefits. However, no clinically relevant anti-CTLA-4 antibody has been reported, limiting the value of canine tumors as comparative models for human ICI research. Here, canine CTLA-4 was molecularly characterized, and a caninized anti-CTLA-4 antibody (ca1C5) that blocks CTLA-4/ligand binding was developed. Treatment with ca1C5 increased cytokine production in canine immune cell cultures, and the immunostimulatory effect was enhanced when used in combination with the anti-PD-L1 antibody c4G12. As a proof-of-concept, a veterinary clinical study was conducted to demonstrate the safety and clinical efficacy of anti-CTLA-4 antibody as salvage combination therapy in dogs with advanced tumors refractory to prior c4G12 monotherapy. The combination treatment (c4G12 plus ca1C5) was well-tolerated, and evidence of antitumor activity was observed in one dog with oral malignant melanoma. Further studies are warranted to advance veterinary care for dogs and to better characterize canine ICI models for human onco-immunology research.

Evaluation of the course of improvement with molnupiravir treatment for feline infectious peritonitis.
Shino Yoshida; Mei Sugawara-Suda; Kazuyoshi Sasaoka; Noboru Sasaki; Nozomu Yokoyama; Kensuke Nakamura; Keitaro Morishita; Sangho Kim; Takafumi Sunaga; Mitsuyoshi Takiguchi
The Canadian veterinary journal = La revue veterinaire canadienne, 66, 5, 546, 554, May 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: To clarify the clinical course during molnupiravir treatment for feline infectious peritonitis (FIP). ANIMALS AND PROCEDURE: Cats diagnosed with FIP and treated with molnupiravir at Hokkaido University Veterinary Teaching Hospital (Sapporo, Hokkaido, Japan) were retrospectively reviewed. RESULTS: Eleven cats were eligible for inclusion. Six cats had effusive FIP and 5 had non-effusive FIP. In noneffusive cases, 2 cats had neurological abnormalities at diagnosis, whereas 1 additional cat developed neurological signs during treatment. The median initial dosage of molnupiravir was 13.0 mg/kg (range: 10.0 to 15.0 mg/kg), PO, q12h. One cat died after 11 d and the remaining 10 cats completed an 84-day course of treatment. All neurological cases were given dosage increases, extended treatment duration, or both. The median final dosage of molnupiravir in non-neuro-FIP cases was 13.1 mg/kg (range: 10.0 to 15.0 mg/kg), PO, q12h, whereas dosages in neuro-FIP cases were 15.0, 15.2, and 17.2 mg/kg, PO, q12h in the 3 affected cats, respectively. In non-neurological cases, dysrexia, lethargy, and high serum amyloid A were resolved within 15 d. Total follow-up duration ranged from 175 to 362 d. No relapses were observed. CONCLUSION AND CLINICAL RELEVANCE: Monitoring responses to molnupiravir treatment requires observing clinical signs and conducting clinicopathological evaluations, including acute-phase protein evaluation.

Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines.
Ryo Owaki; Kenji Hosoya; Tatsuya Deguchi; Satoru Konnai; Naoya Maekawa; Tomohiro Okagawa; Hironobu Yasui; Sangho Kim; Takafumi Sunaga; Masahiro Okumura
Molecular therapy. Oncology, 33, 1, 200946, 200946, 20 Mar. 2025, [International Magazine]
English, Scientific journal, A combination of irradiation and oclacitinib, a Janus kinase (JAK) inhibitor used in dogs, could lead to synergistic anticancer effects in canine tumors. However, the anti-tumor effects of oclacitinib remain unclear. This study investigated the radio-sensitizing effect of oclacitinib in canine tumors and determined its underlying mechanisms using osteosarcoma (HMPOS), malignant melanoma (CMeC), and thyroid adenocarcinoma (CTAC) cell lines. A clonogenic assay and a tumor growth assessment in a xenograft mouse model (BALB/cAJcl-nu/nu) were performed to evaluate the radio-sensitizing effects of oclacitinib. Oclacitinib enhanced the radio-sensitivity of tumor cells both in vitro and in vivo. The signal transducer and activator of transcription (STAT)3 expression was activated and suppressed by oclacitinib in X-irradiation-exposed cells. Oclacitinib enhanced radiation-induced apoptosis only in HMPOS cells by inhibiting anti-apoptotic genes. In addition, oclacitinib inhibited the transcription of cell-cycle-regulating genes and arrested cell cycle progression from the G1 phase to subsequent phases. In conclusion, oclacitinib enhanced radio-sensitivity both in vitro and in vivo by triggering apoptosis and impeding cell cycle progression via STAT3 inhibition in canine tumor cell lines. This study suggested the clinical therapeutic potential of oclacitinib and radiation therapy in enhancing treatment efficacy and outcomes in canine tumors.

Xenotransfusion of Canine Packed Red Blood Cells to a Cat for Emergency Treatment of Acute Hemorrhage after Thymectomy
Sou MATSUMOTO; Kenji HOSOYA; Kazuki KOJIMA; Kyousuke TAKEUCHI; Ryouhei KINOSHITA; Sangho KIM; Masahiro OKUMURA
Japanese Journal of Veterinary Anesthesia & Surgery, 56, 2, 44, 50, Japanese Society of Veterinary Anesthesia and Surgery, 2025
Scientific journal

Diverse genome-wide DNA methylation alterations in canine hepatocellular tumours.
Yu Asari; Jumpei Yamazaki; Oo Thandar; Tamami Suzuki; Keisuke Aoshima; Kyosuke Takeuchi; Ryohei Kinoshita; Sangho Kim; Kenji Hosoya; Teita Ishizaki; Yumiko Kagawa; Jaroslav Jelinek; Shoko Yokoyama; Noboru Sasaki; Hiroshi Ohta; Kensuke Nakamura; Mitsuyoshi Takiguchi
Veterinary medicine and science, 22 Jul. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Canine hepatocellular tumours (HCTs) are common primary liver tumours. However, the exact mechanisms of tumourigenesis remain unclear. Although some genetic mutations have been reported, DNA methylation alterations in canine HCT have not been well studied. OBJECTIVES: In this study, we aimed to analyse the DNA methylation status of canine HCT. METHODS: Tissues from 33 hepatocellular carcinomas, 3 hepatocellular adenomas, 1 nodular hyperplasia, 21 non-tumour livers from the patients and normal livers from 5 healthy dogs were used. We analysed the DNA methylation levels of 72,367 cytosine-guanine dinucleotides (CpG sites) in all 63 samples. RESULTS AND CONCLUSIONS: Although a large fraction of CpG sites that were highly methylated in the normal liver became hypomethylated in tumours from most patients, we also found some patients with less remarkable change or no change in DNA methylation. Hierarchical clustering analysis revealed that 32 of 37 tumour samples differed from normal livers, although the remaining 5 tumour livers fell into the same cluster as normal livers. In addition, the number of hypermethylated genes in tumour livers varied among tumour cases, suggesting various DNA methylation patterns in different tumour groups. However, patient and clinical parameters, such as age, were not associated with DNA methylation status. In conclusion, we found that HCTs undergo aberrant and diverse patterns of genome-wide DNA methylation compared with normal liver tissue, suggesting a complex epigenetic mechanism in canine HCT.

Enhanced Systemic Antitumour Immunity by Hypofractionated Radiotherapy and Anti-PD-L1 Therapy in Dogs with Pulmonary Metastatic Oral Malignant Melanoma.
Tatsuya Deguchi; Naoya Maekawa; Satoru Konnai; Ryo Owaki; Kenji Hosoya; Keitaro Morishita; Motoji Nakamura; Tomohiro Okagawa; Hiroto Takeuchi; Sangho Kim; Ryohei Kinoshita; Yurika Tachibana; Madoka Yokokawa; Satoshi Takagi; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
Cancers, 15, 11, 01 Jun. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Although immune checkpoint inhibitors (ICIs), such as the anti-programmed death-ligand 1 (PD-L1) antibody, have been developed for the treatment of canine malignant melanoma, desirable clinical efficacies have not been achieved. Recent studies in humans have suggested that radiation therapy (RT) combined with ICIs induces robust systemic antitumour immunity in patients with cancer. This study retrospectively examined the therapeutic efficacy of combination therapy (hypofractionated RT and anti-PD-L1 antibody [c4G12]) in dogs with pulmonary metastatic oral malignant melanoma. The intrathoracic clinical benefit rate (CBR)/median overall survival (OS) in the no RT (n = 20, free from the effect of RT), previous RT (n = 9, received RT ≤8 weeks prior to the first c4G12 dose), and concurrent RT (n = 10, c4G12 therapy within ±1 week of the first RT fraction) groups were 10%/185 days, 55.6%/283.5 days (p < 0.05 vs. no RT group), and 20%/129 days (p > 0.05 vs. no RT group), respectively. The adverse events were considered to be tolerable in the combination therapy. Thus, hypofractionated RT before the initiation of c4G12 therapy can be an effective approach for enhancing the therapeutic efficacy of immunotherapy, with acceptable safety profiles. Further prospective clinical studies are required to confirm the findings of this study.

Retrospective study of feline tracheal mass lesions.
Hideyuki Kanemoto; Aki Fujiwara-Igarashi; Tetsuya Kobayashi; Kei Harada; Masanao Ichimata; Sangho Kim; Kenji Hosoya; Hirotaka Tomiyasu; Aki Ohmi; Hajime Tsujimoto
Journal of feline medicine and surgery, 25, 5, 1098612X231164611, May 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVES: This multicentre, retrospective observational study aimed to describe the clinical presentation, diagnostic methods, treatment and outcomes of cats with tracheal masses. METHODS: Eighteen cats from five academic or secondary/tertiary animal hospitals were included. RESULTS: The median age at diagnosis was 10.7 years (mean 9.5; range 1-17). There were nine castrated males, seven spayed females, one intact male and one intact female. Fourteen (78%) were domestic shorthairs, one (6%) was an Abyssinian, one (6%) was an American Shorthair, one (6%) was a Bengal and one (6%) was a Scottish Fold. The most common presenting complaints included chronic respiratory distress or dyspnoea (n = 14), followed by wheezing/gagging (n = 12), coughing (n = 5) and voice changes (n = 5). There was cervical tracheal involvement in 16/18, and two showed involvement of the intrathoracic trachea. The following methods were used for diagnosis: ultrasound-guided fine-needle biopsy (UG-FNB) and cytology (n = 8), bronchoscopic forceps biopsy and histopathology (n = 5), surgical resection and histopathology (n = 3), forceps biopsy via an endotracheal tube (n = 1) and histology of tissue sputtered from a cough (n = 1). Lymphoma was most often diagnosed (n = 15), followed by adenocarcinoma (n = 2) and squamous cell carcinoma (n = 1). Most lymphoma cases received chemotherapy with or without radiation according to various protocols, and partial (n = 5) or complete responses (n = 8) were noted. Kaplan-Meier survival data for cats with lymphoma revealed a median survival time of 214 days (95% confidence interval >149 days), which was significantly longer than that of other types of tumours (21 days). CONCLUSIONS AND RELEVANCE: Lymphoma was the most prevalent diagnosis, and showed a good response to chemotherapy with or without radiation therapy. Various diagnostic procedures were performed, and UG-FNB and cytology are good diagnostic procedures for cervical tracheal lesions. Owing to the variety of treatment protocols at different centres, it was impossible to compare outcomes.

In vitro chondrotoxicity of bupivacaine, levobupivacaine and ropivacaine and their effects on caspase activity in cultured canine articular chondrocytes.
Carol Mwale; Takafumi Sunaga; Yanlin Wang; Eugene C Bwalya; H M Suranji Wijekoon; Sangho Kim; Masahiro Okumura
The Journal of veterinary medical science, 09 Mar. 2023, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Bupivacaine, levobupivacaine and ropivacaine are potent, long acting, amide-type local anesthetics that have several clinical applications including intra-articular administration. The objectives of this study were to evaluate their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic or intrinsic pathways of apoptosis in canine articular chondrocytes. Chondrocytes in monolayer culture were treated with culture medium as the control, or with 0.062% (0.62 mg/mL) bupivacaine, 0.062% levobupivacaine, and 0.062% ropivacaine for 24 hr. Cell viability was evaluated using the live/dead, 3-(4,5-dimehylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), and Cell Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The MTT and CCK-8 assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local anesthetics decreased chondrocyte viability after 24 hr (P˂0.001). Apoptosis was induced through both the extrinsic and intrinsic pathways. Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P˂0.001). Levobupivacaine increased caspase-3 (P=0.03) while ropivacaine did not significantly upregulate activity for all three caspases. Caspase inhibition did not suppress bupivacaine chondrotoxicity whereas inhibition of caspase-8 and caspase-9 decreased ropivacaine chondrotoxicity and mildly attenuated levobupivacaine chondrotoxicity. In summary, the level of chondrotoxicity, the type of caspase activated, the level of caspase activation, and the response to caspase inhibitors was dependent on the type of local anesthetic. Therefore, ropivacaine may be a safer choice for intra-articular administration compared to levobupivacaine and bupivacaine.

In vitro chondrotoxicity of bupivacaine at low concentrations in cultured canine articular chondrocytes
Carol Mwale; Takafumi Sunaga; Yanlin Wang; Eugene C. Bwalya; H. M; Suranji Wijekoon; Sangho Kim; Masahiro Okumura
Japanese Journal of Veterinary Research, 71, 1, 1, 11, Mar. 2023, [Peer-reviewed]
English, Scientific journal

Regulation of programmed death ligand 1 expression by interferon-γ and tumour necrosis factor-α in canine tumour cell lines.
Ryo Owaki; Tatsuya Deguchi; Satoru Konnai; Naoya Maekawa; Tomohiro Okagawa; Kenji Hosoya; Sangho Kim; Takafumi Sunaga; Masahiro Okumura
Veterinary and comparative oncology, 21 Feb. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Expression of programmed death ligand 1 (PD-L1) on tumor cells provides an immune evasion mechanism by inducing suppression of cytotoxic T cells. Various regulatory mechanisms of PD-L1 expression have been described in human tumours, however, little is known in canine tumours. To investigate whether inflammatory signaling is involved in PD-L1 regulation in canine tumours, the effects of interferon (IFN)-γ and tumour necrosis factor (TNF)-α treatment were examined in canine malignant melanoma cell lines (CMeC and LMeC) and an osteosarcoma cell line (HMPOS). The protein level of PD-L1 expression was upregulated by IFN-γ and TNF-α stimulation. Upon IFN-γ stimulation, all cell lines showed an increase in expression of PD-L1, signal transducer and activator of transcription (STAT)1, STAT3 and genes regulated by STAT activation. Upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib. Contrastingly, upon TNF-α stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF-κB) gene RELA and genes regulated by NF-κB activation, whereas expression of PD-L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF-κB inhibitor, BAY 11-7082. The expression level of cell surface PD-L1 induced by IFN-γ and TNF-α treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-γ and TNF-α stimulation is regulated via the JAK-STAT and NF-κB signaling pathways, respectively. These results provide insights into the role of inflammatory signaling in PD-L1 regulation in canine tumours. This article is protected by copyright. All rights reserved.

Safety and clinical efficacy of an anti-PD-L1 antibody (c4G12) in dogs with advanced malignant tumours.
Naoya Maekawa; Satoru Konnai; Kenji Hosoya; Sangho Kim; Ryohei Kinoshita; Tatsuya Deguchi; Ryo Owaki; Yurika Tachibana; Madoka Yokokawa; Hiroto Takeuchi; Yumiko Kagawa; Satoshi Takagi; Hiroshi Ohta; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Yasuhiko Suzuki; Tomohiro Okagawa; Shiro Murata; Kazuhiko Ohashi
PloS one, 18, 10, e0291727, 2023, [International Magazine]
English, Scientific journal, Immune checkpoint inhibitors (ICIs) have been developed for canine tumour treatment, and pilot clinical studies have demonstrated their antitumour efficacy in dogs with oral malignant melanoma (OMM). Although ICIs have been approved for various human malignancies, their clinical benefits in other tumour types remain to be elucidated in dogs. Here, we conducted a clinical study of c4G12, a canine chimeric anti-PD-L1 antibody, to assess its safety and efficacy in dogs with various advanced malignant tumours (n = 12) at the Veterinary Teaching Hospital of Hokkaido University from 2018 to 2023. Dogs with digit or foot pad malignant melanoma (n = 4), osteosarcoma (n = 2), hemangiosarcoma (n = 1), transitional cell carcinoma (n = 1), nasal adenocarcinoma (n = 1), B-cell lymphoma (n = 1), or undifferentiated sarcoma (n = 2) were treated with 2 or 5 mg/kg c4G12 every 2 weeks. Treatment-related adverse events of any grade were observed in eight dogs (66.7%), including elevated aspartate aminotransferase (grade 3) in one dog (8.3%) and thrombocytopenia (grade 4) in another dog (8.3%). Among dogs with target disease at baseline (n = 8), as defined by the response evaluation criteria for solid tumours in dogs (cRECIST), one dog with nasal adenocarcinoma and another with osteosarcoma experienced a partial response (PR), with an objective response rate of 25.0% (2 PR out of 8 dogs; 95% confidence interval: 3.2-65.1%). These results suggest that c4G12 is safe and tolerable and shows antitumor effects in dogs with malignant tumours other than OMM. Further clinical studies are warranted to identify the tumour types that are most likely to benefit from c4G12 treatment.

Pentosan polysulfate sodium promotes redifferentiation to the original phenotype in micromass-cultured canine articular chondrocytes and exerts molecular weight-dependent effects
Yanlin WANG; Takafumi SUNAGA; Carol MWALE; Ekkapol AKARAPHUTIPORN; Sangho KIM; Masahiro OKUMURA
Journal of Veterinary Medical Science, Japanese Society of Veterinary Science, 2023, [Peer-reviewed]
Scientific journal

Transcriptome and proteome analysis of dogs with precursor targeted immune-mediated anemia treated with splenectomy.
Mei Sugawara-Suda; Keitaro Morishita; Osamu Ichii; Takashi Namba; Keisuke Aoshima; Yumiko Kagawa; Sangho Kim; Kenji Hosoya; Nozomu Yokoyama; Noboru Sasaki; Kensuke Nakamura; Jumpei Yamazaki; Mitsuyoshi Takiguchi
PloS one, 18, 5, e0285415, 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Precursor-targeted immune-mediated anemia (PIMA) in dogs is characterized by persistent non-regenerative anemia and ineffective erythropoiesis, and it is suspected to be an immune-mediated disease. Most affected dogs respond to immunosuppressive therapies; however, some are resistant. In this study, we carried out splenectomy as an alternative therapy for refractory PIMA in dogs, and analyzed gene expression levels in the spleen of dogs with or without PIMA and in serum before and after splenectomy. A total of 1,385 genes were found to express differentially in the spleens from dogs with PIMA compared with healthy dogs by transcriptome analysis, of which 707 genes were up-regulated, including S100A12, S100A8, and S100A9 that are linked directly to the innate immune system and have been characterized as endogenous damage-associated molecular patterns. Furthermore, immunohistochemistry confirmed that S100A8/A9 protein expression levels were significantly higher in dogs with PIMA compared with those in healthy dogs. A total of 22 proteins were found to express differentially between the serum samples collected before and after splenectomy by proteome analysis, of which 12 proteins were up-regulated in the samples before. The lectin pathway of complement activation was identified by pathway analysis in pre-splenectomy samples. We speculated that S100A8/9 expression may be increased in the spleen of dogs with PIMA, resulting in activation of the lectin pathway before splenectomy. These findings further our understanding of the pathology and mechanisms of splenectomy for PIMA.

Canine mast cell tumors: When to worry about aggressive behavior pre-surgically.
Sangho Kim; Arata Matsuyama
The Canadian veterinary journal = La revue veterinaire canadienne, 63, 12, 1261, 1263, Dec. 2022, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy.
Naoya Maekawa; Satoru Konnai; Yumie Asano; Yamato Sajiki; Tatsuya Deguchi; Tomohiro Okagawa; Kei Watari; Hiroto Takeuchi; Satoshi Takagi; Kenji Hosoya; Sangho Kim; Hiroshi Ohta; Yukinari Kato; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
Scientific reports, 12, 1, 9265, 9265, 03 Jun. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE2), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE2, interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE2, MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE2 confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE2 suppressed IL-2 and interferon (IFN)-γ production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE2 biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE2 may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy.

Antitumor activity of the dual PI3K/mTOR inhibitor gedatolisib and the involvement of ABCB1 in gedatolisib resistance in canine tumor cells.
Yusuke Murase; Kenji Hosoya; Takachika Sato; Sangho Kim; Masahiro Okumura
Oncology reports, 47, 4, Apr. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The phosphatidylinositol 3‑kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway is a therapeutic target for various types of human tumors, and dual PI3K/mTOR inhibitors demonstrate antitumor activities in both preclinical and clinical studies. However, resistance mechanisms limit their abilities. As the molecular mechanisms involved in the cellular resistance are not clear in any canine tumors, an understanding of resistance mechanisms would support the potential use of dual PI3K/mTOR inhibitors in canine tumors. The antitumor activity of gedatolisib on cell viability, protein phosphorylation, and cell cycle distribution was assessed using 12 canine tumor cell lines from 6 types of tumors. In addition, the molecular determinants involved in the cellular sensitivity to gedatolisib were explored by investigating the involvement of serum‑and‑glucocorticoid‑induced kinase 1 (SGK1), PIK3CA, and ATP‑binding cassette, subfamily B, member 1 (ABCB1). The results demonstrated that gedatolisib decreased cell viability in all cell lines, with IC50 values <1 µM in 10 of the 12 lines. Gedatolisib inhibited Akt and mTOR complex 1 substrate phosphorylation and induced G0/G1 cell cycle arrest. However, certain cell lines with higher IC50 values were more resistant to these effects. These cell lines exhibited higher ABCB1 activity and the ABCB1 inhibitor cyclosporin A enhanced the decrease of cell viability caused by gedatolisib. SGK1 overexpression did not confer resistance to gedatolisib. The mutations of E545K and H1047R in PIK3CA were not observed. The present results indicated that gedatolisib decreased cell viability in canine tumor cell lines and ABCB1 played an important role in gedatolisib resistance, supporting the potential use of gedatolisib for canine tumors.

Direct renal pelvicocystostomy using tube cystoplasty in a cat with ureteral obstruction.
K Hoshi; K Hosoya; S Takagi; S Kim; M Okumura
The Journal of small animal practice, 23 Jan. 2022, [Peer-reviewed], [International Magazine]
English, We describe a surgical technique to re-establish urine flow in a 3-year-old Scottish Fold cat. A ureteral stent and subcutaneous urinary bypass failed after their placement due to rapid mineralisation of the lumen. Direct pelvicocystostomy anastomosis using a modified tube cystoplasty technique was performed. A wide rectangular apex-based full-thickness flap was created from the ventral aspect of the urinary bladder, which was sutured longitudinally to form a large-diameter tube. The resulting tube-shaped portion of the bladder was then directly anastomosed to the renal pelvis. No major postoperative complications were observed and no further recurrence of obstruction of the upper urinary tract was noted during follow-up. The cat died at home 481 days postoperatively from an undetermined cause. A pelvicocystostomy technique can be considered as an alternative salvage surgical technique for obstructive ureteral disease in cats.

Pentosan polysulfate regulates hepcidin expression in native Mongolian horses
Suranji WIJEKOON; Mijiddorj TSOGBADRAKH; Takafumi SUNAGA; Yanlin WANG; Carol MWALE; Sangho KIM; Damdinsuren ALIMAA; Masahiro OKUMURA
Journal of Veterinary Medical Science, 84, 10, 1437, 1441, Japanese Society of Veterinary Science, 2022, [Peer-reviewed]
Scientific journal

Pentosan polysulfate regulates hepcidin 1-facilitated formation and function of osteoclast derived from canine bone marrow.
Suranji Wijekoon; Takafumi Sunaga; Yanlin Wang; Carol Mwale; Sangho Kim; Masahiro Okumura
PloS one, 17, 3, e0265596, 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis by inhibiting osteoblast function and promoting osteoclastogenesis. Pentosan polysulfate (PPS) is a heparin analogue and promising novel therapeutic for osteoarthritis (OA). This study was undertaken to determine whether PPS inhibits hepcidin-facilitated osteoclast (OC) differentiation and iron overload. Canine (n = 3) bone marrow mononuclear cells were differentiated to OC by macrophage colony-stimulating factor and receptor-activator of nuclear factor kappaB ligand with the treatment of hepcidin1 (200, 400, 800, 1200 nmol/L) and PPS (1, 5, 10, 20, 40 μg/mL). Differentiation and function of OC were accessed using tartrate-resistant acid phosphate staining and bone resorption assay while monitoring ferroportin1 (FPN1) and iron concentration by immunocytochemistry. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9, nuclear factor of activated-T-cells cytoplasmic 1 and FPN1 was examined. Hepcidin1 showed significant enhancement of OC number at 800 nmol/L (p<0.01). PPS impeded hepcidin-facilitated OC at 1, 5 and 10 μg/mL and reduction of resorption pits at 5 and 10 μg/mL (p< 0.01). All OC specific genes were downregulated with PPS, specifically in significant manner with CTK at higher concentrations. However, heparin induced FPN1 internalization and degradation was inhibited at higher concentrations of PPS while restoring iron-releasing capability of OC. We demonstrate for the first time that PPS is a novel-inhibitor of hepcidin-facilitated OC formation/function which might be beneficial for treatment of OA and osteoporosis.

The expression of histone lysine demethylase 2B in canine hemangiosarcoma is associated with disease progression
Kevin Christian M. Gulay; Keisuke Aoshima*; Sangho Kim; Ryusei Kitaguchi; Atsushi Kobayashi; Takashi Kimura; *Corresponding author
Veterinary and Comparative Oncology, Wiley, 20 Dec. 2021, [Peer-reviewed]
Scientific journal

Visualizing the cancer stem-like properties of canine tumour cells with low proteasome activity.
Koangyong Sung; Kenji Hosoya; Yusuke Murase; Tatsuya Deguchi; Sangho Kim; Takafumi Sunaga; Masahiro Okumura
Veterinary and comparative oncology, 20, 1, 324, 335, 31 Oct. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cancer stem-like cells (CSCs) cause treatment failure in various tumours; however, establishing CSC-targeted therapies has been hampered by difficulties in the identification and isolation of this small sub-population of cells. Recent studies have revealed that tumour cells with low proteasome activity display a CSC phenotype that can be utilized to image CSCs in canines. This study visualizes and reveals the CSC-like properties of tumour cells with low proteasome activity in HMPOS (osteosarcoma) and MegTCC (transitional cell carcinoma), which are canine cell lines. The parent cells were genetically engineered to express ZsGreen1, a fluorescent protein connected to the carboxyl-terminal degron of canine ornithine decarboxylase that accumulates with low proteasome activity (ZsG+ cells). ZsG+ cells were imaged and the mode of action of this system was confirmed using a proteasome inhibitor (MG-132), which increased the ZsGreen1 fluorescence intensity. The CSC-like properties of ZsG+ cells were evaluated on the basis of cell divisions, cell cycle, the expression of CSC markers and tumourigenicity. ZsG+ cells underwent asymmetric divisions and had a low percentage of G0/G1 phase cells; moreover, ZsG+ cells expressed CSC markers such as CD133 and showed a large tumourigenic capability. In histopathological analysis, ZsG+ cells were widely distributed in the tumour samples derived from ZsG+ cells and in the proliferative regions of the tumours. The results of this study indicate that visualized canine tumour cells with low proteasome activity have a CSC-like phenotype and that this visualization system can be utilized to identify and isolate canine CSCs.

Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS.
Tatsuya Deguchi; Kenji Hosoya; Shango Kim; Yusuke Murase; Kumiko Yamamoto; Tomoki Bo; Hironobu Yasui; Osamu Inanami; Mahiro Okumura
Molecular therapy oncolytics, 22, 143, 151, 24 Sep. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Metformin has many anti-cancer effects, alone or in combination with radiation. However, the mechanism underlying its radio-sensitized effect is still unclear, especially for cancer stem-like cells (CSCs). Here, the radio-sensitized effect of metformin was investigated, and its mechanism was revealed in CSCs derived from canine osteosarcoma cell line (HMPOS), a canine osteosarcoma cell line. Spheroid cells (SCs) were used as CSCs-rich cells derived from sphere formation, and SCs were compared with normal adherent culture cells (ACs). The radio-sensitizing effect of metformin using clonogenic assay and tumor growth in mice xenograft model were evaluated, and the mechanism of its radio-sensitization focusing on mitochondrial function was revealed. Metformin significantly enhanced radio-sensitivity of SCs through its inhibition of the mitochondrial function, as shown by decreased oxygen consumption, decreased mitochondrial membrane potential, and decreased ATP production. Additionally, SCs had a higher ability of mitochondrial respiration than ACs, which may have caused difference of their sensitivity of metformin and irradiation. In conclusion, mitochondrial function might play an important role in the sensitivity of metformin and irradiation, and drugs that target mitochondrial respiration, such as metformin, are promising radio-sensitizers to target CSCs.

Safety and efficacy of a nonmyeloablative pretransplant conditioning regimen using total lymphoid irradiation with volumetric modulated arc therapy in healthy dogs: A pilot study.
Sangho Kim; Kenji Hosoya; Natsuki Fukayama; Tatsuya Deguchi; Masahiro Okumura
Veterinary medicine and science, 7, 4, 1120, 1130, 13 Mar. 2021, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Allogeneic hematopoietic cell transplantation (HCT) has been an effective treatment for human patients with haematological malignancies (Baron & Storb, 2006; Bair et al., 2020; Copelan et al., 2019). However, the optimal pretransplant conditioning treatment is unclear in canine allogeneic HCT. This pilot study aimed to evaluate the safety and efficacy of total lymphoid irradiation (TLI) with volumetric modulated arc therapy (VMAT) for a nonmyeloablative HCT conditioning. Six healthy dogs were treated with 8 or 12 Gy TLI using VMAT. Haematological and physical changes were recorded over 8 weeks. To assess the effect of peripheral lymphocyte condition, lymphocyte subset and proliferative ability were examined. At the end of the experiment, necropsy was performed. All dogs showed mild-to-moderate neutropenia and thrombocytopenia, and these haematological changes resolved spontaneously. One dog treated with 8 Gy TLI developed transient cutaneous infection. No major complication was seen in the other seven dogs. Myelocytes and erythroblast cytopenia of bone marrow were detected in two dogs treated with 12 Gy TLI. This study is the first report of TLI using VMAT in dogs, and results suggest that this regimen is a feasible nonmyeloablative treatment.

PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma.
Naoya Maekawa; Satoru Konnai; Maki Nishimura; Yumiko Kagawa; Satoshi Takagi; Kenji Hosoya; Hiroshi Ohta; Sangho Kim; Tomohiro Okagawa; Yusuke Izumi; Tatsuya Deguchi; Yukinari Kato; Satoshi Yamamoto; Keiichi Yamamoto; Mikihiro Toda; Chie Nakajima; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
NPJ precision oncology, 5, 1, 10, 10, 12 Feb. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.

Canine Transforming Growth Factor-β Receptor 2-Ig: A Potential Candidate Biologic for Melanoma Treatment That Reverses Transforming Growth Factor-β1 Immunosuppression.
Hiroto Takeuchi; Satoru Konnai; Naoya Maekawa; Satoshi Takagi; Hiroshi Ohta; Noboru Sasaki; Sangho Kim; Tomohiro Okagawa; Yasuhiko Suzuki; Shiro Murata; Kazuhiko Ohashi
Frontiers in veterinary science, 8, 656715, 656715, 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cancer cells can evade host immune systems via multiple mechanisms. Transforming growth factor beta 1 (TGF-β1) is an immunosuppressive cytokine that induces regulatory T cell (Tregs) differentiation and is involved in immune evasion mechanisms in cancer. The inhibition of the TGF-β1 signaling pathway can suppress cancer progression and metastasis through the modulation of anticancer immune responses. However, to best of our knowledge, no implementation of treatments targeting TGF-β1 has been reported in dog cancers. This study aimed to examine whether TGF-β1 is upregulated in canine cancers. We measured TGF-β1 concentrations in culture supernatants of canine melanoma cell lines and in serum samples from dogs with oral malignant melanoma. TGF-β1 production was observed in several cell lines, and serum TGF-β1 levels were elevated in dogs with oral malignant melanoma. Interestingly, the addition of recombinant TGF-β1 to canine peripheral blood mononuclear cell cultures decreased Th1 cytokine production and increased differentiation of CD4+CD25+Foxp3+ lymphocytes, suggesting that TGF-β1 is immunosuppressive in canine immune systems. We developed a decoy receptor for TGF-β, namely TGF-βRII-Ig, by identifying an open reading frame of the canine TGFBR2 gene. TGF-βRII-Ig was prepared as a recombinant fusion protein of the extracellular region of canine TGF-βRII and the Fc region of canine IgG-B. As expected, TGF-βRII-Ig bound to TGF-β1. In the presence of TGF-β1, the treatment with TGF-βRII-Ig increased Th1 cytokine production and decreased the differentiation of CD4+CD25+Foxp3+ lymphocytes. Our results suggest that TGF-βRII-Ig competitively inhibits the immunosuppressive effects of TGF-β1 and thereby activates immune responses. This study demonstrated the potential of TGF-βRII-Ig as a novel biologic for canine melanoma.

Effects of pentosan polysulfate on cell proliferation, cell cycle progression and cyclin-dependent kinases expression in canine articular chondrocytes.
Ekkapol Akaraphutiporn; Eugene C Bwalya; Sangho Kim; Takafumi Sunaga; Ryosuke Echigo; Masahiro Okumura
The Journal of veterinary medical science, 82, 8, 1209, 1218, 28 Aug. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Pentosan polysulfate (PPS) is a semi-synthetic sulfated polysaccharide compound which has been shown the benefits on therapeutic treatment for osteoarthritis (OA) and has been proposed as a disease modifying osteoarthritis drugs (DMOADs). This study investigated the effects of PPS on cell proliferation, particularly in cell cycle modulation and phenotype promotion of canine articular chondrocytes (AC). Canine AC were treated with PPS (0-80 µg/ml) for 24, 48 and 72 hr. The effect of PPS on cell viability, cell proliferation and cell cycle distribution were analyzed by MTT assay, DNA quantification and flow cytometry. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) and glycosaminoglycan (GAG) quantification. PPS significantly reduced AC proliferation through cell cycle modulation particularly by maintaining a significantly higher proportion of chondrocytes in the G1 phase and a significantly lower proportion in the S phase of the cell cycle in a concentration- and time-dependent manner. While the proportion of chondrocytes in G1 phase corresponded with the significant downregulation of cyclin-dependent kinase (CDK) 1 and 4. Furthermore, the study confirms that PPS promotes a chondrogenic phenotype of AC through significant upregulation of collagen type II (Col2A1) mRNA and GAG synthesis. The effect of PPS on the inhibition of chondrocyte proliferation while promoting a chondrocyte phenotype could be beneficial in the early stages of OA treatment, which transient increase in proliferative activity of chondrocytes with subsequent phenotypic shift and less productive in an essential component of extracellular matrix (ECM) is observed.

耳下腺を温存し口腔アプローチで唾石による導管開口部の閉塞を治療した犬の1例
高木 哲; 竹内 恭介; 細谷 謙次; 星野 有希; 金 尚昊; 伊丹 貴晴; 山根 由久; 華園 究
日本獣医師会雑誌, 73, 7, 379, 382, (公社)日本獣医師会, Jul. 2020, [Peer-reviewed]
Japanese

Outcomes following balloon dilation for management of urethral obstruction secondary to urothelial carcinoma in dogs: 12 cases (2010-2015).
Kim S; Hosoya K; Takagi S; Okumura M
Journal of the American Veterinary Medical Association, 255, 3, 330, 335, Aug. 2019, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, OBJECTIVE: To describe outcomes for dogs that underwent balloon dilation for palliative treatment of urethral obstruction caused by urothelial carcinoma. ANIMALS: 12 client-owned dogs. PROCEDURES: Medical records were searched to identify dogs with urothelial (bladder, urethra, or prostate) carcinoma that underwent balloon dilation for treatment of urethral obstruction between April 2010 and December 2015. Information regarding history, signalment, clinical signs, diagnostic imaging findings, balloon dilation technique, clinical outcomes, complications, and additional treatments was obtained by review of medical records. RESULTS: Improvement in clinical signs of urethral obstruction was observed after the initial dilation procedure for 9 of 12 dogs. Urethral obstruction was known to recur in 5 dogs 48 to 296 days after the initial procedure. Three of these dogs underwent a second dilation procedure, with clinical improvement in all 3 dogs for 41 to 70 days. One of 2 dogs that had a third procedure after the second reobstruction had clinical improvement in urinary tract signs until subsequent death from metastatic disease 22 days later. Complications included hematuria, urinary incontinence, and dysuria; these resolved within a few days after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Urethral balloon dilation was a minimally invasive procedure that provided relief of urethral obstruction from urothelial carcinoma in most dogs of the study population. Prospective studies are needed to identify optimal techniques for balloon dilation in dogs with neoplastic urethral obstructions and to identify patients that are likely to benefit most from the treatment.

Analysis of radiosensitivity of cancer stem-like cells derived from canine cancer cell lines.
Deguchi T; Hosoya K; Murase Y; Koangyong S; Kim S; Okumura M
Veterinary and comparative oncology, 17, 2, 119, 129, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cancer stem-like cells (CSCs) are self-renewing cells comprising a small subpopulation in tumours, and generate differentiated progeny through asymmetric division. It has been shown that CSCs are resistant to ionizing radiation, and this feature could be one of the mechanisms of tumour recurrence after radiation therapy. Much attention has been focused on to target CSCs; however, difficult of isolating CSCs and lack of knowledge on their radiosensitivity have limited this kind of research in veterinary medicine. In the present study, sphere-forming cells (SC), cultured using sphere formation method, were isolated from four type of canine tumour cell lines and evaluated if they have CSCs-like properties by expression of CSCs markers (real-time polymerase chain reaction) and capacity of tumorigenesis (xenograft transplantation in nude mice), and were assessed radiosensitivity (clonogenic survival assay) and DNA repair kinetics (immunofluorescence staining for p53-binding protein 1) after X-ray irradiation in comparison with the corresponding normal adherent culture cells (AC). All SCs were isolated using sphere formation and showed high gene expression of CD133 and tumorigenic ability as compared with AC. All SCs were significantly resistant against X-ray irradiation as compared with AC. In addition, the amount of DNA double-strand breaks after X-ray irradiation were significantly lower in SC compared with the corresponding AC. These results indicate that SC isolated through sphere formation possess CSCs-like characteristics and CSCs are important factor that affect radiosensitivity in canine tumours. In addition, radioresistance of CSCs may depend on reaction of DNA double-strand break after X-ray exposure.

Anti-arthritic effect of pentosan polysulfate in rats with collagen-induced arthritis.
Suranji Wijekoon HM; Kim S; Bwalya EC; Fang J; Aoshima K; Hosoya K; Okumura M
Research in veterinary science, 122, 179, 185, Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Pentosan polysulfate (PPS) is currently under investigation as a potential disease-modifying antiarthritic agent. In the present study the effects of PPS on arthritic profiles based on clinical score, ankle size, histological changes, and activity of inflammatory mediators using collagen-induced arthritic rat are reported. Model of arthritis was developed in Sprague Dawley rats by intradermal injection of bovine type II collagen emulsified with incomplete Freund's adjuvant. The rats were randomly divided into four groups: normal control, arthritic control, arthritic rats treated with PPS (at dose level 20 μg/g) and arthritic rats treated with meloxicam (2 μg/g). The treatment was continued daily until the day 30. Arthritic biomarkers (cartilage oligomeric matrix protein and tartrate-resistant acid phosphatase 5b) in synovial fluid, expression of inflammatory mediators (interleukin-1β, and tumor necrosis factor-α) and osteoclast marker genes (cathepsin K, tartrate-resistant acid phosphatase) in synovial membrane were measured. Daily administration of PPS to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery based on clinical score and histopathological evidence. Intriguingly, identical downregulation pattern of arthritis profiles, biological markers as well as relative mRNA levels of osteoclast markers and cytokines were monitored in arthritic rats treated with PPS. In conclusion, PPS exerted protective effects against collagen-induced arthritis in rats. The results suggest that PPS acts as an anti-inflammatory and anti-arthritic agent in decreasing the arthritic effects in collagen-induced arthritic rats.

Mandibular vascular hamartoma in a cat.
Takagi S; Kagawa Y; Hanazono K; Murakami S; Deguchi T; Izumi Y; Hosoya K; Kim S; Okumura M
The Journal of veterinary medical science, 80, 9, 1456, 1458, Sep. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 10-year-old cat presented for evaluation with a 1-month history of salivation and oral bleeding. A right mandibular mass was palpated and computed tomography examination revealed entire bone proliferation. Mandibular bone biopsy was performed, and histopathological diagnosis was vascular hamartoma. The cat suddenly died on day 140.

Independent chondrogenic potential of canine bone marrow-derived mesenchymal stem cells in monolayer expansion cultures decreases in a passage-dependent pattern.
Bwalya EC; Wijekoon HS; Fang J; Kim S; Hosoya K; Okumura M
The Journal of veterinary medical science, 80, 11, 1681, 1687, Sep. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Although chondroinductive growth factors are considered necessary for chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSC), independent and spontaneous chondrogenesis has been previously demonstrated in adult horses, bovine calves and adult human BMSC. Surprisingly, adult canine BMSC under similar culture conditions previously failed to demonstrate chondrogenesis. The present study evaluated independent chondrogenic potential of BMSC sourced from three young dogs in the absence of known chondroinductive factors. BMSC were culture expanded in 10% DMEM up to third passage (P3). At each passage, the phenotype of BMSC was evaluated by RT-PCR gel electrophoresis and qPCR. BMSC exhibited a chondrogenic phenotype in the absence of dexamethasone and TGF-β1 as verified by the expression of Sox-9, type II collagen and aggrecan. Sox-9 was significantly downregulated (P<0.05) from P1-P3 compared to P0 while type II and X collagen, and aggrecan were significantly downregulated at P3 compared to P0. There was a significant (P<0.01) negative correlation between passaging and Sox-9, type II collagen and aggrecan gene expression. These results indicate that independent chondrogenic potential and phenotype retention of BMSC decreases in a passage-dependent pattern. Therefore, caution should be exercised for future experiments evaluating the chondrogenic potential of BMSC after extensive expansion cultures in 10% DMEM.

Comparison of three mobilization protocols for peripheral blood stem cell apheresis with Spectra Optia continuous mononuclear cell protocol in healthy dogs.
Kim S; Hosoya K; Kobayashi A; Okumura M
Veterinary and comparative oncology, 17, 1, 61, 68, Sep. 2018, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Peripheral blood stem cell (PBSC) transplantation following consolidation therapy is a feasible treatment option for canine haematological malignancies. In veterinary medicine, haematopoietic stem cells are generally mobilized into peripheral circulation using a granulocyte colony-stimulating factor (G-CSF). This pilot study aimed to evaluate the haematopoietic stem cell mobilization effect of three different regimens for PBSC apheresis with Spectra Optia continuous mononuclear cell (CMNC) protocol in healthy dogs. Stem cell mobilization was performed using high-dose plerixafor (CXCR-4 inhibitor) alone, a G-CSF alone, or a combination of the low-dose plerixafor and G-CSF. Three dogs were assigned to each mobilization protocol. Regardless of the mobilization protocol, the total blood volume processed was uniformly set as 270 mL/kg and many PBSCs, defined as CD34+/CD45dim cells, within the apheresis product were compared. Changes in complete blood count, PBSC counts, and blood chemistry analysis were monitored before, during, and after apheresis. All dogs tolerated the apheresis procedure using the Spectra Optia system with minimal adverse effects. The mean PBSC counts of the apheresis products for plerixafor, G-CSF, and the combination groups were 1.3 ± 0.24, 4.2 ± 0.47, and 6.4 ± 0.9 × 106 cells/kg, respectively. The apheresis procedure using Spectra Optia CMNC protocol in dogs is safe and feasible. Furthermore, PBSC mobilization with a combination of G-CSF and plerixafor appeared more effective than either compound alone in mobilizing PBSC to the peripheral blood in dogs.

Inhibitory effects of sodium pentosan polysulfate on formation and function of osteoclasts derived from canine bone marrow
H.M.Suranji Wijekoon; Eugene C. Bwalya; Jing Fang; Sangho Kim; Kenji Hosoya; Masahiro Okumura
BMC Veterinary Research, 14, 1, 152, BioMed Central Ltd., 02 May 2018, [Peer-reviewed]
English, Scientific journal

Pentosan Polysulfate Sodium Restores the Phenotype of Dedifferentiated Monolayer Canine Articular Chondrocytes Cultured in Alginate Beads
Eugene Bwalya; Sangho Kim; Jing Fang; HM Suranji Wijekoon; Kenji Hosoya; Masahiro Okumura
Journal of Tissue Science & Engineering, 09, 01, OMICS Publishing Group, 2018, [Peer-reviewed]
Scientific journal

Differentiation potential of synoviocytes derived from joints with cranial cruciate ligament rupture and medial patella luxation in dogs
H. M. Suranji Wijekoon; Kazuhide Toyota; Sangho Kim; Jing Fang; Eugene C. Bwalya; Kenji Hosoya; Masahiro Okumura
RESEARCH IN VETERINARY SCIENCE, 114, 370, 377, Oct. 2017, [Peer-reviewed]
English, Scientific journal

Effects of pentosan polysulfate and polysulfated glycosaminoglycan on chondrogenesis of canine bone marrow-derived mesenchymal stem cells in alginate and micromass culture
Eugene C. Bwalya; Sangho Kim; Jing Fang; H. M. Suranji Wijekoon; Kenji Hosoya; Masahiro Okumura
JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 7, 1182, 1190, Jul. 2017, [Peer-reviewed]
English, Scientific journal

Pentosan polysulfate inhibits IL-1 beta-induced iNOS, c-Jun and HIF-1 alpha upregulation in canine articular chondrocytes
Eugene C. Bwalya; Sangho Kim; Jing Fang; H. M. Suranji Wijekoon; Kenji Hosoya; Masahiro Okumura
PLOS ONE, 12, 5, e0177144, May 2017, [Peer-reviewed]
English, Scientific journal

Chronological differential effects of proinflammatory cytokines on rankl-induced osteoclast differentiation of canine bone marrow-derived macrophages
Suranji Wijekoon; Eugene C. Bwalya; Jing Fang; Sangho Kim; Kenji Hosoya; Masahiro Okumura
Journal of Veterinary Medical Science, 79, 12, 2030, 2035, Japanese Society of Veterinary Science, 2017, [Peer-reviewed]
English

Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog
Sangho Kim; Kenji Hosoya; Satoshi Takagi; Masahiro Okumura
JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION, 51, 6, 407, 412, Nov. 2015, [Peer-reviewed], [Lead author]
English, Scientific journal

Compensatory cellular reactions to nonsteroidal anti-inflammatory drugs on osteogenic differentiation in canine bone marrow-derived mesenchymal stem cells.
Oh N; Kim S; Hosoya K; Okumura M
The Journal of veterinary medical science, 76, 5, 629, 636, May 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

胸腔鏡下結紮術を適用した先天性体肺動脈瘻の犬の1例
細谷謙次; 細谷謙次; 丸子冬聖; 大山紀彦; 大脇稜; 川元誠; 木之下怜平; 金尚昊; 金尚昊; 奥村正裕, 日本獣医麻酔外科学会学術集会抄録集(CD-ROM), 110th, 2025

患者腫瘍組織移植モデル(PDX)を用いた犬の前立腺癌・移行上皮癌に対するダブラフェニブの有効性の評価
大橋咲子; 木之下怜平; 木之下怜平; 青島圭佑; 山尾結衣; 山崎淳平; 金尚昊; 細谷謙次; 山崎淳平; 金尚昊; 細谷謙次; 滝口満喜, 日本獣医学会学術集会講演要旨集, 167th, 2024

ポリ硫酸ペントサンのPI3K/Akt経路を介したイヌ関節軟骨細胞における細胞増殖の抑止および分化度の調節に対する効果
王 延りん; Carol Mwale; 金 尚昊; 須永 隆文; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 165回, [HS3P, 02], Sep. 2022
(公社)日本獣医学会, Japanese

胸管の単離遮断により治療した特発性乳び胸の犬の2例
細谷謙次; 細谷謙次; 大脇稜; 竹内恭介; 木之下怜平; 金尚昊; 奥村正裕, 日本獣医麻酔外科学会学術集会抄録集(Web), 103rd, 2022

回盲部切除を実施した犬および猫14例の長期的合併症に関する回顧的研究
大脇稜; 細谷謙次; 細谷謙次; 竹内恭介; 木之下怜平; 金尚昊; 奥村正裕, 日本獣医麻酔外科学会学術集会抄録集(Web), 105th, 2022

門脈静脈連結部での選択的結紮に術中超音波ガイドが有用であった右肝区域肝内門脈体循環短絡症の犬の1例
松本創; 細谷謙次; 細谷謙次; 大脇稜; 大山紀彦; 竹内恭介; 木之下怜平; 金尚昊; 滝口満喜; 奥村正裕, 日本獣医麻酔外科学会学術集会抄録集(Web), 105th, 2022

イヌの肝細胞腫瘍におけるDNAメチル化の網羅的解析
淺利 友; 山崎 淳平; Oo Thander; 細谷 謙次; 金 尚昊; 木之下 怜平; 竹内 恭介; 賀川 由美子; 佐々木 東; 中村 健介; 滝口 満喜, 日本獣医学会学術集会講演要旨集, 164回, [HSO, 30], Sep. 2021
(公社)日本獣医学会, Japanese

犬軟骨細胞における一酸化窒素産生とアポトーシスに対するペントサン多硫酸ナトリウムの抑制 分子量依存作用(Inhibition of Pentosan Polysulfate Sodium on nitric oxide production and apoptosis in Canine Chondrocytes: a molecular weight dependent effect)
Wang Yanlin; Carol Mwale; Ekkapol Akaraphutiporn; 金 尚昊; 須永 隆文; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 164回, [HSO, 42], Sep. 2021
(公社)日本獣医学会, English

ブピバカインの軟骨毒性に対するペントサン多硫酸(PPS)の作用(Effects of Pentosan polysulfate(PPS) on bupivacaine chondrotoxicity)
Carol Mwale; Wang Yanlin; Ekkapol Akaraphutiporn; Eugene Bwalya; Suranji Wijekoon; 金 尚昊; 須永 隆文; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 164回, [HSO, 45], Sep. 2021
(公社)日本獣医学会, English

非再生性免疫介在性貧血の犬における脾臓摘出術前後の血清中蛋白の網羅的解析
菅原 芽伊; 山崎 淳平; 森下 啓太郎; 金 尚昊; 細谷 謙次; 佐々木 東; 中村 健介; 滝口 満喜, 日本獣医学会学術集会講演要旨集, 164回, [HSO, 60], Sep. 2021
(公社)日本獣医学会, Japanese

膀胱鏡ガイド下ホルミウム YAGレーザー焼灼により治療した異所性尿管の犬の1例
松本 創; 細谷 謙次; 木之下 怜平; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 65, 8, 261, 261, Aug. 2021
(公社)北海道獣医師会, Japanese

重度肝線維化を伴う好酸球性肉芽腫を認めた好酸球増多症候群の若齢小型犬の1例
篠原 正義; 田村 昌大; 金 尚昊; 賀川 由美子; 滝口 満喜, 北海道獣医師会雑誌, 65, 8, 262, 262, Aug. 2021
(公社)北海道獣医師会, Japanese

三次元CADモデルが内視鏡外科の手術支援に有用であったの犬の2例
細谷 謙次; 大脇 稜; 松本 創; 木之下 怜平; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 65, 8, 267, 267, Aug. 2021
(公社)北海道獣医師会, Japanese

胸腔内異所性肝組織からの出血を認めた犬の1例
金尚昊; 大脇稜; 賀川由美子; 細谷謙次; 奥村正裕, 日本獣医麻酔外科学会学術集会抄録集(Web), 102nd, 2021

犬の口腔内悪性黒色腫に対する抗Programmed death-Ligand 1抗体療法と放射線治療におけるアブスコパル効果の誘導解析
大脇稜; 出口辰弥; 細谷謙次; 今内覚; 前川直也; 立花由莉加; 中村基司; 金尚昊; 須永隆文; 奥村正裕, 北海道獣医師会雑誌, 65, 8, 2021

犬の強度変調回転放射線治療における10 MV Flattening Filter Freeビームの有用性の検討
西澤一希; 出口辰弥; 細谷謙次; 細谷謙次; 森下啓太郎; 森下啓太郎; 金尚昊; 木之下怜平; 竹内恭介; 奥村正裕, 北海道獣医師会雑誌, 65, 8, 2021

プロテアソーム活性を用いて可視化したイヌ腫細胞株由来Cancer stem-like cellsの解析
Sung Koangyong; 細谷 謙次; 村瀬 優介; 出口 辰弥; 金 尚昊; 須永 隆文; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 163回, 289, 289, Oct. 2020
(公社)日本獣医学会, Japanese

耳下腺を温存し口腔アプローチで唾石による導管開口部の閉塞を治療した犬の1例
高木 哲; 竹内 恭介; 細谷 謙次; 星野 有希; 金 尚昊; 伊丹 貴晴; 山根 由久; 華園 究, 日本獣医師会雑誌, 73, 7, 379, 382, Jul. 2020
(公社)日本獣医師会, Japanese

両側横隔神経麻痺による呼吸不全に対し、横隔膜縫縮術/メッシュ縫着術を実施した犬の1例
松本 創; 細谷 謙次; 桜井 雄平; 金 尚昊; 石塚 友人; 寺澤 元子; 奥村 正裕, 日本獣医師会雑誌, 73, 4, 203, 204, Apr. 2020
(公社)日本獣医師会, Japanese

犬のがん幹細胞を標的とした放射線治療に向けた基礎研究
出口 辰弥; 細谷 謙次; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 63, 9, 405, 410, Sep. 2019
(公社)北海道獣医師会, Japanese

イヌ移行上皮癌細胞株におけるABCB1を介したPI3K/mTOR二重阻害剤獲得耐性機構(ABCB1-mediated acquired resistance to a dual PI3K/mTOR inhibitor in a canine transitional cell carcinoma cell line)
村瀬 優介; 細谷 謙次; 出口 辰弥; 金 尚昊; 奥村 正裕, 日本癌学会総会記事, 78回, P, 3142, Sep. 2019
(一社)日本癌学会, English

Tetra-EDTAを用いてSUBの閉塞解除を試みた猫の1例
竹内 恭介; 金 尚昊; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 63, 8, 350, 350, Aug. 2019
(公社)北海道獣医師会, Japanese

犬の先天性肝外門脈体循環シャントの術後合併症率と危険因子に関する回顧的研究
鈴木 理紗; 細谷 謙次; 金 尚昊; 森下 啓太郎; 大田 寛; 滝口 満喜; 奥村 正裕, 北海道獣医師会雑誌, 63, 8, 349, 349, Aug. 2019
(公社)北海道獣医師会, Japanese

犬の副腎摘出術における術前/周術期内分泌学的管理が総周術期死亡率に与える影響に関する回顧的検討
細谷 謙次; 高木 哲; 金 尚昊; 星 清貴; 竹内 恭介; 松本 創; 石塚 友人; 賀川 由美子; 奥村 正裕, 日本獣医麻酔外科学雑誌, 50, Suppl.1, 309, 309, Jun. 2019
(一社)日本獣医麻酔外科学会, Japanese

右心房内三尖弁レベルに達する腫瘍栓を形成した左副腎褐色細胞腫の犬の一例
細谷 謙次; 竹内 恭介; 松本 創; 佐藤 敬近; 石塚 友人; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 50, Suppl.1, 310, 310, Jun. 2019
(一社)日本獣医麻酔外科学会, Japanese

犬の肥大性幽門胃疾患に対する幽門部分切除を併用したY-U幽門形成術
竹内 恭介; 細谷 謙次; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 50, Suppl.1, 342, 342, Jun. 2019
(一社)日本獣医麻酔外科学会, Japanese

犬の肥大性幽門胃疾患に対する幽門部分切除を併用したY-U幽門形成術
竹内恭介; 細谷謙次; 金尚昊; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 1, 2019

右心房内三尖弁レベルに達する腫瘍栓を形成した左副腎褐色細胞腫の犬の一例
細谷謙次; 竹内恭介; 松本創; 佐藤敬近; 石塚友人; 金尚昊; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 1, 2019

犬の副腎摘出術における術前/周術期内分泌学的管理が総周術期死亡率に与える影響に関する回顧的検討
細谷謙次; 高木哲; 金尚昊; 星清貴; 竹内恭介; 松本創; 石塚友人; 賀川由美子; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 1, 2019

右心房内三尖弁レベルに達する腫瘍栓を形成した左副腎褐色細胞腫の犬の一例
細谷謙次; 竹内恭介; 松本創; 佐藤敬近; 石塚友人; 金尚昊; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 2, 2019

犬の副腎摘出術における術前/周術期内分泌学的管理が総周術期死亡率に与える影響に関する回顧的検討
細谷謙次; 高木哲; 金尚昊; 星清貴; 竹内恭介; 松本創; 石塚友人; 賀川由美子; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 2, 2019

唾液腺造影CTおよび術中唾液腺染色が手術支援に有用であった犬の2例
竹内恭介; 細谷謙次; 新坊弦也; 金尚昊; 木之下怜平; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 2, 2019

下垂体性副腎皮質機能亢進症に対して定位放射線治療を実施した犬の3例
今井健友; 出口辰弥; 細谷謙次; 細谷謙次; 森下啓太郎; 森下啓太郎; 金尚昊; 佐々木東; 大菅辰幸; 奥村正裕, 北海道獣医師会雑誌, 63, 8, 2019

定位手術的照射法により患肢を温存した脛骨軟骨肉腫の犬の1例
松本創; 細谷謙次; 出口辰也; 弘川治喜; 木之下怜平; 金尚昊; 奥村正裕, 日本獣医麻酔外科学雑誌(Web), 50, Supplement 2, 2019

イヌ骨肉腫細胞株由来Cancer stem-like cellsのミトコンドリアの放射線反応性の解析
出口辰弥; 細谷謙次; 金尚昊; 山本久美子; 房知輝; 安井博宣; 稲波修; 奥村正裕, 日本酸化ストレス学会学術集会プログラム・抄録集, 72nd, 2019

診断にCT検査が有用であった結腸捻転の犬の2例
竹内恭介; 金尚昊; 大田寛; 華園究; 新坊弦也; 石塚友人; 細谷謙次; 奥村正裕, 北海道獣医師会雑誌, 62, 8, 343, 343, 24 Aug. 2018
(公社)北海道獣医師会, Japanese

術前からダイナミックな血圧変動を呈した褐色細胞腫を良好に麻酔管理した犬の1例
小島 一輝; 石塚 友人; 金 尚昊; 竹内 恭介; 細谷 謙次; 滝口 満喜; 奥村 正裕, 北海道獣医師会雑誌, 62, 8, 336, 336, Aug. 2018
(公社)北海道獣医師会, Japanese

洞不全症候群を併発する犬の麻酔管理におけるイソプレナリンの使用経験
佐藤 敬近; 石塚 友人; 小島 一輝; 大菅 辰幸; 金 尚昊; 上條 弘美; 奥村 正裕, 北海道獣医師会雑誌, 62, 8, 336, 336, Aug. 2018
(公社)北海道獣医師会, Japanese

下顎骨骨折に対してロッキングプレートによる整復を実施した犬の5例
上條 太貴; 越後 良介; 金 尚昊; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 62, 8, 346, 346, Aug. 2018
(公社)北海道獣医師会, Japanese

肘関節内側コンパートメント症候群に対して尺骨外反骨切り術を実施した犬の1例
榎土 慶; 金 尚昊; 小川 純也; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 62, 8, 346, 346, Aug. 2018
(公社)北海道獣医師会, Japanese

術後48時間で再拡張性肺水腫の発生が疑われた慢性横隔膜ヘルニアの猫の一例
竹内 恭介; 高木 哲; 細谷 謙次; 金 尚昊; 石塚 友人; 奥村 正裕, 日本獣医麻酔外科学雑誌, 49, Suppl.1, 326, 326, Jun. 2018
(一社)日本獣医麻酔外科学会, Japanese

変性性腰仙椎狭窄症に対する術後の短期的な治療反応に関連する因子の検討
竹内恭介; 越後良介; 木原秀哉; 華園究; 金尚昊; 伊丹貴晴; 石塚友人; 奥村正裕, 日本獣医麻酔外科学雑誌, 48, Supplement 2, 215, 215, 20 Nov. 2017
(一社)日本獣医麻酔外科学会, Japanese

SUBの早期閉塞に対して膀胱フラップによる膀胱-腎盂尿管移行部吻合術を実施した尿管結石の猫の1例
星 清貴; 細谷 謙次; 金 尚昊; 高木 哲; 奥村 正裕, 日本獣医麻酔外科学雑誌, 48, Suppl.2, 223, 223, Nov. 2017
(一社)日本獣医麻酔外科学会, Japanese

犬の心基底部腫瘍に対する放射線治療における過喚起誘発性無呼吸と強度変調回転照射法を用いた呼吸性移動対策
加藤大; 出口辰弥; 細谷謙次; 金尚昊; 石塚友人; 華園究; 高木哲; 星野有希; 奥村正裕, 北海道獣医師会雑誌, 61, 8, 336, 336, 10 Aug. 2017
(公社)北海道獣医師会, Japanese

犬腫瘍症例におけるリン酸トセラニブ投与の血管造影CTを用いた短期的評価
高木哲; 華園究; 細谷謙次; 石塚友人; 和泉雄介; 星野有希; 金尚昊; 奥村正裕, 北海道獣医師会雑誌, 61, 8, 334, 334, 10 Aug. 2017
(公社)北海道獣医師会, Japanese

下顎に発生した血管過誤腫の猫の1例
村上祥子; 高木哲; 賀川由美子; 石塚友人; 華園究; 金尚昊; 星野有希; 細谷謙次; 奥村正裕, 北海道獣医師会雑誌, 61, 8, 344, 344, 10 Aug. 2017
(公社)北海道獣医師会, Japanese

犬の変性性腰仙椎狭窄症に対するX線とMRIを用いた画像解析に関する検討
木原秀哉; 越後良介; 華園究; 金尚昊; 細谷謙次; 奥村正裕, 北海道獣医師会雑誌, 61, 8, 338, 338, 10 Aug. 2017
(公社)北海道獣医師会, Japanese

耳下腺導管の開口部切開・拡張により治癒した唾石症の犬の1例
竹内恭介; 高木哲; 細谷謙次; 星野有希; 金尚昊; 華園究; 伊丹貴晴; 石塚友人; 奥村正裕, 北海道獣医師会雑誌, 61, 8, 344, 344, 10 Aug. 2017
(公社)北海道獣医師会, Japanese

頸部椎間板ヘルニアに起因する呼吸障害を人工呼吸で管理したミニチュアダックスフンドの2例
小島 一輝; 石塚 友人; 高木 哲; 越後 良介; 武内 亮; 村上 祥子; 金 尚昊; 星野 有希; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 61, 8, 337, 337, Aug. 2017
(公社)北海道獣医師会, Japanese

犬の腫瘍におけるPI3K/mTOR二重阻害剤を用いたテーラーメイド治療のための効果予測因子の探索
村瀬 優介; 細谷 謙次; 佐藤 敬近; 金 尚昊; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 160回, 457, 457, Aug. 2017
(公社)日本獣医学会, Japanese

イヌの腫瘍細胞株由来Cancer stem-like cellsの放射線反応性の解析
出口 辰弥; 細谷 謙次; 村瀬 優介; 金 尚昊; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 160回, 460, 460, Aug. 2017
(公社)日本獣医学会, Japanese

コラーゲン誘発性関節炎(CIA)ラットにおけるポリ硫酸ペントサン(PPS)の抗関節炎作用(Anti-arthritis effect of Pentosan Polysulfate(PPS) in rats with collagen-induced arthritis(CIA))
Wijekoon Suranji; Bwalya Eugene C; 青島 圭佑; Fang Jing; 金 尚昊; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 160回, 468, 468, Aug. 2017
(公社)日本獣医学会, English

ポリ硫酸ペントサン(PPS)は犬関節軟骨細胞におけるIL-1β誘導性iNOS、c-JUNおよびHIF-1αの上方制御を抑制する(Pentosan polysulfate(PPS) inhibits IL-1β induced iNOS, c-Jun and HIF-1α upregulation in canine articular chondrocytes)
Bwalya Eugene C; Wijekoon Suranji; 金 尚昊; Fang Jing; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 160回, 469, 469, Aug. 2017
(公社)日本獣医学会, English

長期管理中にSUBが閉塞した猫の1例
星 清貴; 高木 哲; 金 尚昊; 星野 有希; 細谷 謙次; 奥村 正裕, 日本獣医麻酔外科学雑誌, 48, Suppl.1, 367, 367, Jun. 2017
(一社)日本獣医麻酔外科学会, Japanese

犬腫瘍症例におけるリン酸トセラニブ関連有害事象の発生頻度に関する回顧的研究
細谷謙次; 高木哲; 星野有希; 金尚昊; 出口辰弥; 奥村正裕, 日本臨床獣医学フォーラム年次大会プロシーディング, 19th, Vol.1, 2017

環椎・軸椎不安定症の犬におけるCTおよびMRI所見の回顧的検討
華園究; 大田寛; 越後良介; 細谷謙次; KIM Sangho; 伊丹貴晴; 石塚友人; 奥村正裕, 動物臨床医学会年次大会プロシーディング, 37th, 2, 293‐294, 294, 18 Nov. 2016
動物臨床医学会, Japanese

真菌性椎間板脊椎炎の犬の一例
金 尚昊; 細谷 謙次; 村上 祥子; 奥村 正裕, 日本獣医麻酔外科学雑誌, 47, Suppl.2, 193, 193, Nov. 2016
(一社)日本獣医麻酔外科学会, Japanese

腫瘍随伴低血糖を呈した胃消化管間質腫瘍の犬の1例
星野 有希; 渡辺 清正; 石塚 友人; 高木 哲; 細谷 謙次; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 47, Suppl.2, 213, 213, Nov. 2016
(一社)日本獣医麻酔外科学会, Japanese

頭蓋内腫瘤性病変の犬64例における放射線治療成績と予後因子の解析
細谷謙次; 金尚昊; 出口辰弥; 星清貴; 武内亮; 坂本英一; 華園究; 石塚友人; 柄本浩一; 星野有希; 高木哲; 奥村正裕, 北海道獣医師会雑誌, 60, 8, 414, 414, 10 Aug. 2016
(公社)北海道獣医師会, Japanese

リン酸トセラニブ投与を実施した再発性鼻腔腫瘍の犬14症例の回顧的研究
出口 辰弥; 細谷 謙次; 金 尚昊; 高木 哲; 星野 有希; 奥村 正裕, 北海道獣医師会雑誌, 60, 8, 409, 409, Aug. 2016
(公社)北海道獣医師会, Japanese

スコティッシュフォールドの骨軟骨形成不全症に対して低線量放射線療法を実施した1症例
星 清貴; 細谷 謙次; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, 北海道獣医師会雑誌, 60, 8, 415, 415, Aug. 2016
(公社)北海道獣医師会, Japanese

重度の尿管拡張・狭窄に対して側側吻合により尿路変更した猫の1症例
武内 亮; 高木 哲; 星 清貴; 細谷 謙次; 星野 有希; 金 尚昊; 伊丹 貴晴; 石塚 友人; 奥村 正裕, 北海道獣医師会雑誌, 60, 8, 421, 421, Aug. 2016
(公社)北海道獣医師会, Japanese

猫の全身麻酔導入時の安全な気管挿管のためのロクロニウム併用
佐藤 敬近; 石塚 友人; 金 尚昊; 星野 有希; 細谷 謙次; 高木 哲; 奥村 正裕, 北海道獣医師会雑誌, 60, 8, 423, 423, Aug. 2016
(公社)北海道獣医師会, Japanese

ペントサン多硫酸ナトリウムはアルギン酸ビーズ培養中の内包化単層関節軟骨細胞の再分化を促進する(Pentosan polysulfate Sodium promotes redifferentiaton of monolayer articular chondrocytes encapsulated in alginate beads culture)
Bwalya Eugene C; 金 尚昊; Fang Jing; Wijekoon Suranji; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 159回, 452, 452, Aug. 2016
(公社)日本獣医学会, English

犬における膝蓋骨脱臼または前十字靱帯断裂を有する膝関節由来の滑膜細胞の鑑別能(Differentiation potential of synoviocytes derived from joints with concurrent patella luxation or cranial cruciate ligament rupture in dogs)
Wijekoon Suranji; 豊田 一秀; 金 尚昊; Fang Jing; Bwalya Eugene C; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 159回, 453, 453, Aug. 2016
(公社)日本獣医学会, English

体重10kg前後の犬における末梢血造血幹細胞採取の条件検討
小林 鮎実; 金 尚昊; 細谷 謙次; 加藤 大; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 159回, 453, 453, Aug. 2016
(公社)日本獣医学会, Japanese

アルファキサロンとプロポフォール麻酔導入が犬の循環動態に及ぼす影響の比較
伊丹貴晴; 細谷謙次; 高木哲; 金尚昊; 出口辰弥; 華園究; 奥村正裕, 日本獣医麻酔外科学雑誌, 47, Supplement 1, 279, 279, 05 Jun. 2016
(一社)日本獣医麻酔外科学会, Japanese

フレンチブルドッグにおける全耳道切除後の合併症について
星野 有希; 高木 哲; 細谷 謙次; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 47, Suppl.1, 342, 342, Jun. 2016
(一社)日本獣医麻酔外科学会, Japanese

十二指腸浸潤を伴うガストリノーマに対して、十二指腸-膵臓分節切除を実施した犬の1例
星 清貴; 細谷 謙次; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, 日本獣医麻酔外科学雑誌, 47, Suppl.1, 343, 343, Jun. 2016
(一社)日本獣医麻酔外科学会, Japanese

再発性悪性末梢神経腫瘍に対して放射線治療を実施した犬の5例
出口 辰弥; 細谷 謙次; 高木 哲; 越後 良介; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 46, Suppl.2, 221, 221, Dec. 2015
(一社)日本獣医麻酔外科学会, Japanese

猫の尿管結石・閉塞23例における内科療法の反応と外科手術法の検討
星 清貴; 高木 哲; 細谷 謙次; 星野 有希; 中村 健介; 森下 啓太郎; 金 尚昊; 奥村 正裕, 日本獣医麻酔外科学雑誌, 46, Suppl.2, 227, 227, Dec. 2015
(一社)日本獣医麻酔外科学会, Japanese

肝臓未分化肉腫に併発した肝嚢胞によりBudd-Chiari様症候群を呈した犬の一例
下出 亜里咲; 高木 哲; 伊丹 貴晴; 金 尚昊; 星野 有希; 細谷 謙次; 奥村 正裕, 日本獣医麻酔外科学雑誌, 46, Suppl.2, 235, 235, Dec. 2015
(一社)日本獣医麻酔外科学会, Japanese

ソマトトロピン産生性下垂体腫瘍によりインスリン抵抗性を呈した糖尿病の猫の1例
和泉雄介; 細谷謙次; 早川小百合; 森下啓太郎; 華園究; 星野有希; 高木哲; 金尚昊; 奥村正裕, 北海道獣医師会雑誌, 59, 8, 394, 394, 10 Aug. 2015
(公社)北海道獣医師会, Japanese

脊髄への播種が疑われた神経膠腫の犬の2例
星 清貴; 細谷 謙次; 武内 亮; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, 北海道獣医師会雑誌, 59, 8, 386, 386, Aug. 2015
(公社)北海道獣医師会, Japanese

異所性副腎皮質腺癌により多飲多尿を認めた犬の1例
出口 辰弥; 細谷 謙次; 松本 隆; 賀川 由美子; 高木 哲; 星野 有希; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 59, 8, 395, 395, Aug. 2015
(公社)北海道獣医師会, Japanese

遠位橈尺骨骨折に対してテーラーメイドプレートを用いて整復を行った犬1症例
豊田 一秀; 金 尚昊; 細谷 謙次; 安田 準; 首藤 文栄; 奥村 正裕, 北海道獣医師会雑誌, 59, 8, 400, 400, Aug. 2015
(公社)北海道獣医師会, Japanese

内視鏡併用下にて尿管側より腎結石摘出術を行った犬の1例
下出 亜里咲; 高木 哲; 金 尚昊; 星野 有希; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 59, 8, 401, 401, Aug. 2015
(公社)北海道獣医師会, Japanese

Hydropulsion法により気道閉塞解除を実施した犬の1例
坂本 英一; 細谷 謙次; 高木 哲; 星野 有希; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 59, 8, 403, 403, Aug. 2015
(公社)北海道獣医師会, Japanese

症例から学ぶシリーズ 猫の下顎扁平上皮癌において下顎4分の3切除を行った7例
岩木 芳美; 細谷 謙次; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, Joncol: Japanese Journal of Veterinary Clinical Oncology, 11, 2, 81, 84, Jul. 2015
(株)ファームプレス, Japanese

再発性多小葉性骨軟骨肉腫に対して定位放射線治療を行った犬の一例
金 尚昊; 細谷 謙次; 奥村 正裕, 日本獣医麻酔外科学雑誌, 46, Suppl.1, 255, 255, Jun. 2015
(一社)日本獣医麻酔外科学会, Japanese

多分割照射法による根治的放射線治療に関する有効性と有害事象発生率の回顧的調査
武内 亮; 細谷 謙次; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, 日本獣医師会雑誌, 68, 5, 325, 326, May 2015
(公社)日本獣医師会, Japanese

腱鞘の悪性巨細胞腫の猫の1例
和泉 雄介; 細谷 謙次; 賀川 由美子; 高木 哲; 星野 有希; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 360, 360, Aug. 2014
(公社)北海道獣医師会, Japanese

多中心型リンパ腫の犬26例における高用量サイクロフォスファミドを用いた地固め療法の検討
金 尚昊; 細谷 謙次; 出口 辰弥; 高木 哲; 星野 有希; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 361, 361, Aug. 2014
(公社)北海道獣医師会, Japanese

小型犬におけるドキソルビシンの最大耐容量に関する検討
金 尚昊; 細谷 謙次; 高木 哲; 星野 有希; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 362, 362, Aug. 2014
(公社)北海道獣医師会, Japanese

犬における全腹部照射(Whole Abdominal Irradiation:WAI)プロトコールの検討
出口 辰弥; 細谷 謙次; 高木 哲; 星野 有希; 中村 健介; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 362, 362, Aug. 2014
(公社)北海道獣医師会, Japanese

猫の下顎扁平上皮癌において下顎4分の3切除を行った6症例
岩木 芳美; 細谷 謙次; 高木 哲; 星野 有希; 金 尚昊; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 373, 373, Aug. 2014
(公社)北海道獣医師会, Japanese

4歳齢の毛球の食道内塞栓により発見された右大動脈弓遺残の猫の1例
村上 翔輝; 高木 哲; 中村 健介; 岩木 芳美; 金 尚昊; 星野 有希; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 373, 373, Aug. 2014
(公社)北海道獣医師会, Japanese

副腎摘出術を実施した犬19例の手術成績に関する回顧的検討
星 清貴; 高木 哲; 細谷 謙次; 金 尚昊; 星野 有希; 奥村 正裕, 北海道獣医師会雑誌, 58, 8, 379, 379, Aug. 2014
(公社)北海道獣医師会, Japanese

実験的軟骨欠損における犬の関節軟骨下骨病変の特徴
金 尚昊; 小谷 章朗; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 157回, 495, 495, Aug. 2014
(公社)日本獣医学会, Japanese

頸部腫瘍に対して緩和的放射線治療を実施した犬の4例
金 尚昊; 細谷 謙次; 橋場 香野; 高木 哲; 星野 有希; 奥村 正裕, 北海道獣医師会雑誌, 57, 8, 394, 394, Aug. 2013
(公社)北海道獣医師会, Japanese

浸潤性脂肪腫に対して外科的処置を行った犬の3例
金 尚昊; 細谷 謙次; 高木 哲; 星野 有希; 奥村 正裕, 獣医麻酔外科学雑誌, 44, Suppl.1, 209, 209, Jun. 2013
(一社)日本獣医麻酔外科学会, Japanese

尿道ステント設置後早期に再閉塞を生じた前立腺癌の犬の1例
細谷 謙次; 金 尚昊; 星野 有希; 高木 哲; 奥村 正裕, 獣医麻酔外科学雑誌, 44, Suppl.1, 272, 272, Jun. 2013
(一社)日本獣医麻酔外科学会, Japanese

炎症刺激による培養馬軟骨細胞の形質転換の特徴に関する研究
金 尚昊; 海道 磨里; 細谷 謙次; 星野 有希; 高木 哲; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 155回, 186, 186, Mar. 2013
(公社)日本獣医学会, Japanese

非ステロイド性抗炎症薬に対する犬骨髄由来間葉系幹細胞の骨分化維持能
呉 南佶; 金 尚昊; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 155回, 262, 262, Mar. 2013
(公社)日本獣医学会, Japanese

犬膀胱移行上皮癌におけるがん遺伝子DEKの治療標的としての有用性の検討
岩野 公美; 山崎 裕毅; 呉 南佶; 足立 真美; 金 尚昊; 星野 有希; 高木 哲; 細谷 謙治; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 155回, 262, 262, Mar. 2013
(公社)日本獣医学会, Japanese

経皮的尿管ステント設置術を実施した犬の5症例
金 尚昊; 細谷 謙次; 睦良田 尚充; 星野 有希; 高木 哲; 奥村 正裕, 動物臨床医学会年次大会プロシーディング, 33回, 2, 15, 16, Nov. 2012
動物臨床医学会, Japanese

腫瘍性疾患により前肢跛行を呈した犬の回顧的研究
金 尚昊; 星野 有希; 細谷 謙次; 高木 哲; 奥村 正裕, 北海道獣医師会雑誌, 56, 8, 405, 405, Aug. 2012
(公社)北海道獣医師会, Japanese

犬の骨髄由来間葉系幹細胞の骨分化における非ステロイド性抗炎症薬の影響
呉 南佶; 山崎 裕毅; 金 尚昊; 細谷 謙次; 高木 哲; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 154回, 319, 319, Aug. 2012
(公社)日本獣医学会, Japanese

培養馬腱細胞における分化マーカーおよび細胞代謝関連因子の解析
野村 基惟; 金 尚昊; 細谷 謙次; 高木 哲; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 153回, 193, 193, Mar. 2012
(公社)日本獣医学会, Japanese

馬の腱および軟骨の細胞外基質代謝関連分子に関する基礎的研究
金 尚昊; 高木 哲; 細谷 謙次; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 151回, 186, 186, Mar. 2011
(公社)日本獣医学会, Japanese

尿道腫瘍による排尿障害に対し尿路拡張用バルーンカテーテルを用いた犬の3例
山崎裕毅; 高木哲; 金尚昊; 小儀直子; 細谷謙次; 奥村正裕, 日本獣医師会獣医学術学会年次大会講演要旨集, 2010, 2011

MRSA感染による橈尺骨癒合不全の犬の一症例 感染部切除と抗菌剤含有ゼラチン製剤による治療経験
青木 由徳; 小儀 直子; 金 尚昊; 高木 哲; 細谷 謙次; 奥村 正裕, 獣医麻酔外科学雑誌, 41, Suppl.2, 192, 192, Dec. 2010
(一社)日本獣医麻酔外科学会, Japanese

犬脾臓線維組織球結節の肝転移症例の1治療例
細谷 謙次; 石崎 恵子; 山崎 裕毅; 金 尚昊; 大田 寛; 森 伸介; 高木 哲; 奥村 正裕, 北海道獣医師会雑誌, 54, 8, 451, 451, Aug. 2010
(公社)北海道獣医師会, Japanese

尿路拡張用バルーンカテーテルを用いて治療した尿道腫瘍の犬の1例
金 尚昊; 高木 哲; 小儀 直子; 細谷 謙次; 奥村 正裕, 北海道獣医師会雑誌, 54, 8, 453, 453, Aug. 2010
(公社)北海道獣医師会, Japanese

培養馬滑膜および軟骨細胞における多硫酸化グリコサミノグリカンの抗炎症効果発現機序
住江 康晴; 須永 隆文; 光田 健太; 金 尚昊; 細谷 謙次; 高木 哲; 奥村 正裕, 日本獣医学会学術集会講演要旨集, 149回, 286, 286, Mar. 2010
(公社)日本獣医学会, Japanese

温血種馬における球節滑膜パッド内の骨軟骨片離断
金尚昊; 高木哲; 奥村正裕, 北海道獣医師会雑誌, 53, 5, 2009

X線読影メソッド : 多角的にみる犬と猫の疾患
藤原, 亜紀; 一戸, 登夢; 鈴木, 亮平; 華園, 究; 五十嵐, 寛高; 塗木, 貴臣; 金, 尚昊; 小島, 龍成; 神野, 信夫; 島田, 昌和; 鈴木, 周二; 濱本, 裕仁; 堀, あい; 大石, 実樹; 宮, 直人; 鴫原, 果映; 中澤, 優太; 堀, 達也; 村井, 義也; 小林, 正典; 徳田, 智
Eduward press, Nov. 2022, 9784866711843, 775p, Japanese

【猫の口腔内扁平上皮癌】放射線療法
金 尚昊
Joncol: Japanese Journal of Veterinary Clinical Oncology 17(2) 29-33, Jul. 2021

【胆嚢関連疾患 総まとめ】疾患 肝外胆管閉塞
金 尚昊
CLINIC NOTE 17(6) 38-43, Jun. 2021

【肝臓腫瘍の外科】術前検査
金 尚昊
SURGEON 25(3) 6-8, May 2021

【肝臓腫瘍の外科】肝葉切除術 アプローチ法
金 尚昊
SURGEON 25(3) 34-39, May 2021

【肝臓腫瘍の外科】肝葉切除術 左肝区域の切除術
金 尚昊
SURGEON 25(3) 51-56, May 2021

【気管と肺の腫瘍】内科療法と放射線療法
金 尚昊
Joncol: Japanese Journal of Veterinary Clinical Oncology 17(1) 21-23, Jan. 2021

X線読影メソッド(第25回) 骨疾患 転移性骨腫瘍
金 尚昊
CLINIC NOTE 16(9) 67-77, Sep. 2020

X線読影メソッド(第25回) 骨疾患 成長板早期閉鎖
金 尚昊
CLINIC NOTE 16(9) 78-85, Sep. 2020

【肥満細胞腫2020 犬と猫の肥満細胞腫、面白いところを集めました!】犬の肥満細胞腫 リンパ節の取り扱い 治療編
Veterinary Oncology 7(3) 16-34, Jul. 2020

【悪性黒色腫-理解を深め、明日の診療への自信を磨く!】北海道大学における口腔内悪性黒色腫の外科手術+放射線治療
金 尚昊
Veterinary Oncology 6(4) 74-78, Oct. 2019

X線読影メソッド第10回 整形外科疾患各論 骨原発性腫瘍
金 尚昊
CLINIC NOTE 15(6) 49-61, Jun. 2019

X線読影メソッド第10回 整形外科疾患各論 骨折
金 尚昊
CLINIC NOTE 15(6) 62-71, Jun. 2019

X線読影メソッド(第8回) 整形外科疾患 馬尾症候群・変性性腰仙椎狭窄症
金 尚昊
CLINIC NOTE 15(4) 74-79, Apr. 2019

【緩和ケアと終末期医療 死にゆく動物に寄り添うために】泌尿器腫瘍
金 尚昊
Veterinary Oncology 6(2) 40-45, Apr. 2019

【猫の疾患 総まとめ(後編)】猫のリンパ腫
金 尚昊
CLINIC NOTE 15(3) 18-34, Mar. 2019

【猫の疾患 総まとめ(中編)】猫の乳腺腫瘍
金 尚昊
CLINIC NOTE 15(2) 6-17, Feb. 2019

【Oncologic Emergency 腫瘍症例における急変、緊急対応を徹底マスターする!】気胸
金 尚昊
Veterinary Oncology 6(1) 30-36, Jan. 2019

【Oncologic Emergency 腫瘍症例における急変、緊急対応を徹底マスターする!】胸水・血胸
金 尚昊
Veterinary Oncology 6(1) 38-44, Jan. 2019

症例から学ぶCPC 膀胱および尿道の腫瘍 移行上皮癌
金 尚昊
Joncol: Japanese Journal of Veterinary Clinical Oncology 15(1) 64-79, Jan. 2019

犬の組織球性腫瘍疾患
金 尚昊
Joncol: Japanese Journal of Veterinary Clinical Oncology 13(1) 93-98, Jan. 2017

猫の口腔内扁平上皮癌：放射線療法
金 尚昊
第23回 日本獣医がん学会, Invited oral presentation
26 Jan. 2021 - 16 Feb. 2021, [Invited]

気管と肺の腫瘍：化学療法および放射線療法
金 尚昊
第22回 日本獣医がん学会, Invited oral presentation
23 Aug. 2020, [Invited]

はじめての副腎摘出術
金 尚昊
2019年度 獣医麻酔外科学会北海道地区講習会, Public discourse
16 Sep. 2019, [Invited]

動物軟部外科・腫瘍内科セミナー
金 尚昊
北海道小動物獣医師会道南セミナー, Public discourse
28 Jul. 2019, [Invited]

症例から学ぶCPC：膀胱腫瘍の診断と治療
金 尚昊
第19回 日本獣医がん学会, Nominated symposium
08 Jul. 2018

脛骨粗面前方転位術（TTA）の理論と実際
金 尚昊
2017年度 獣医麻酔外科学会北海道地区講習会, Public discourse
25 Nov. 2017, [Invited]

犬組織球性疾患の診断と治療
金 尚昊
第15回 日本獣医がん学会, Invited oral presentation
26 Jun. 2016, [Invited]

伴侶動物獣医療実習, 2024年, 学士課程, 獣医学部

最新獣医外科学特論, 2024年, 博士後期課程, 獣医学院

伴侶動物夜間・救急獣医療実習, 2024年, 学士課程, 獣医学部

臨床疾病学特論, 2024年, 博士後期課程, 獣医学院

プレクリニカル実習, 2024年, 学士課程, 獣医学部

総合専門臨床特論, 2024年, 博士後期課程, 獣医学院

伴侶動物獣医療実習Ⅰ, 2024年, 学士課程, 獣医学部

軟部組織外科学, 2024年, 学士課程, 獣医学部

伴侶動物獣医療実習Ⅱ, 2024年, 学士課程, 獣医学部

アドバンスト演習, 2024年, 学士課程, 獣医学部

夜間・救急獣医療実習Ⅰ, 2024年, 学士課程, 獣医学部

アドバンスト演習, 2024年, 学士課程, 獣医学部

総合獣医療実習, 2024年, 学士課程, 獣医学部

アドバンスト演習, 2024年, 学士課程, 獣医学部

獣医コミュニケーション演習, 2024年, 学士課程, 獣医学部

伴侶動物獣医療実習Ⅰ, 2024年, 学士課程, 獣医学部

伴侶動物獣医療実習Ⅱ, 2024年, 学士課程, 獣医学部

夜間・救急獣医療実習Ⅰ, 2024年, 学士課程, 獣医学部

総合獣医療実習, 2024年, 学士課程, 獣医学部

プレクリニカル実習, 2024年, 学士課程, 獣医学部

臨床腫瘍学, 2024年, 学士課程, 獣医学部