著者

Masaki MICHISHITA Namika SAITO Satoshi NOZAWA Rina FURUMOTO Takayuki NAKAGAWA Touko SATO Kazuhiko OCHIAI Daigo AZAKAMI Kinya KATAYAMA Rei NAKAHIRA Hiroyuki TAZAKI Yukino MACHIDA Toshiyuki ISHIWATA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0194, (Released:2019-07-15)

被引用文献数

8

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Cancer consists of heterogeneous cells that contain a small population of cells that possess stem cell properties; these cells, referred to as cancer stem cells (CSCs) or tumor-initiating cells, are involved in tumor progression and metastasis. Using a sphere-forming assay, canine mammary CSCs were found to be similar to human breast CSCs. Metabolic reprogramming has been recognized as a hallmark of various cancers. However, the significance of cellular metabolism in CSCs remains unclear. The aim of this study was to define the metabolic characteristics of CSCs derived from canine mammary tumors and gain an understanding of the maintenance of stemness. We identified metabolite profiles of canine mammary adenocarcinoma cell lines using gas chromatography-mass spectrometry. Metabolites were extracted from both adherent and sphere-forming cells derived from three cell lines. Sphere-forming cells were separated from adherent cells using an orthogonal, partial least squares discriminant analysis. Sphere-forming cells were found to contain high levels of the amino acids alanine, glycine and proline compared with adherent cells. They also had high levels of palmitoleate, palmitate and dihomo-gamma-linolenic acid compared with adherent cells. In a sphere-forming assay, palmitate increased the number of spheres for all cell lines. These results indicate that the sphere-forming cells derived from canine mammary adenocarcinoma cell lines have specific metabolic profiles that may be useful for the development of CSC-specific therapies targeting metabolic pathways and potential stemness biomarkers; these results also clarify the maintenance of stemness in canine mammary CSCs.

著者

Risako KAWATA Tatsuhito II Tatsuya HORI Yukino MACHIDA Kazuhiko OCHIAI Daigo AZAKAMI Toshiyuki ISHIWATA Masaki MICHISHITA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.81, no.2, pp.186-189, 2019 (Released:2019-02-09)

参考文献数

17

被引用文献数

1

---

A 14-year and 8-month-old intact male Amur tiger presented with an enlarged left testis, measuring 5.7 × 5.5 × 4.5 cm. The cut surface was mottled dark red to reddish brown in color. Microscopically, the enlarged left testis comprised round or polygonal neoplastic cells arranged in a diffuse sheet pattern. These neoplastic cells had a hyperchromatic nucleus and an abundant eosinophilic cytoplasm. Immunohistochemically, these neoplastic cells were positive for vimentin, chromogranin A, synaptophysin, melan-A, inhibin-α, and S100 and negative for desmin and WT-1. Based on these morphological and immunohistochemical findings, the tumor was diagnosed as a Leydig cell tumor.

著者

Shota KAWAKAMI Kazuhiko OCHIAI Yuiko KATO Masaki MICHISHITA Hinako HIRAMA Ryo OBARA Daigo AZAKAMI Masami WATANABE Toshinori OMI

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0362, (Released:2017-11-21)

---

Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional, or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K). The cIDH2 WT and R174K proteins were overexpressed in HeLa cells, and their presence was confirmed using an anti-human IDH2-WT mAb (clone: KrMab-3) and an anti-IDH2-R172K mAb (clone: KMab-1). The IDH2 activity between cIDH2 WT and cIDH2 R174K transfectants was compared by measuring the production of NADH and NADPH. NADPH production was lower for cIDH2 R174K than that for cIDH2 WT transfectants. Finally, we detected increased expression of hypoxia inducible factor-1 alpha (HIF-1α) in cIDH2 R174K transfectants. This indicates that mutations at R174 can potentially induce carcinogenesis in canine somatic cells.

著者

Takuya Evan KISHIMOTO Shoko YASHIMA Rei NAKAHIRA Eri ONOZAWA Daigo AZAKAMI Makoto UJIKE Kazuhiko OCHIAI Toshiyuki ISHIWATA Kimimasa TAKAHASHI Masaki MICHISHITA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.16-0412, (Released:2017-05-21)

被引用文献数

7

---

Cancer stem cells or tumor-initiating cells (TICs) are a small subpopulation of cells that have the capacity to self-renew, differentiate and initiate tumors. These cells may function in tumor initiation, aggression and recurrence. Whether spheres derived from canine rhabdomyosarcoma cells have stem cell-like properties is unclear. We induced sphere formation in the canine rhabdomyosarcoma cell lines, CMS-C and CMS-J, and characterized the spheres in vitro and in vivo. Sphere-forming cells were more resistant to vincristine, mitoxantrone and doxorubicin than adherent cells. Xenograft transplantation demonstrated that 1 × 103 sphere-forming cells derived from CMS-C were sufficient for tumor formation. The sphere assay showed that the sphere-forming cells were present in these tumors. These results suggest that the spheres derived from canine rhabdomyosarcoma cells may possess characteristics of TICs. This study provides the foundation for elucidating the contribution of TICs to rhabdomyosarcoma tumorigenesis.

著者

Daigo AZAKAMI Eri ONOZAWA Masahiro MIYABE Kazuhiko OCHIAI Masaki MICHISHITA Taichi HIRANO Yutaka MOMOTA Katsumi ISHIOKA Toshinori SAKO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0575, (Released:2016-02-09)

被引用文献数

2

---

A 12-year-old female American shorthair cat presented with a one-month history of hematuria and general lethargy. Abdominal ultrasonography revealed complete thickening of the left uterine wall. At a diagnostic laparotomy, a large mass arising from the left uterine horn was discovered, and ovariohysterectomy was performed. Histological diagnosis revealed a T-cell high-grade lymphoma of the uterus. After the ovariohysterectomy, the patient achieved complete remission and maintained by combination chemotherapy from 14 days after surgery. However, relapse occurred in the urinary bladder wall on day 287, and the patient died of postrenal acute renal failure on day 310. This is the first report of a feline case of primary uterine lymphoma that was treated with ovariohysterectomy followed by systemic chemotherapy.

著者

Satoshi NOZAWA Tomoko KIMURA Miyuki KURISHIMA Kana MIMURA Kaori SAEKI Yohei MIKI Hitomi ODA Akihiro MORI Yutaka MOMOTA Daigo AZAKAMI Katsumi ISHIOKA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0255, (Released:2015-11-22)

被引用文献数

1 7

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Nesfatin-1 is an anorexic peptide derived from a precursor, nucleobindin-2 (NUCB2), which is distributed in various organs, coexists with ghrelin in the gastric X/A-like cells and closely relates to an appetite control in rodents and humans. Nesfatin-1 may be a significant factor addressing the satiety also in veterinary medicine, however, there are few reports about nesfatin-1 in dogs. In the present study, we detected canine NUCB2/nesfatin-1 mRNA in various tissues, especially abundant in pancreas, gastrointestinal tracts, testis and cerebellum. We examined circulating nesfatin-1 concentrations and NUCB2/nesfatin-1 mRNA expressions in upper gastrointestinal tracts (gastric corpus, pyloric antrum and duodenum) in dogs fed on different types of diets. Plasma nesfatin-1 concentrations in the dogs were approximately 4 ng/ml and they did not change after feeding through the study, however, NUCB2/nesfatin-1 mRNA expressions in pyloric antrum were 1.84-fold higher in the dogs fed on a High fiber/High protein diet (P<0.001), 1.48-fold higher in the dogs fed on a High fat/Low protein diet (P<0.05) and 1.02-fold higher in the dogs fed on a Low fat/High carbohydrate diet (not significant) comparing to those on a control diet. It was concluded that High fiber/High protein and High fat/Low protein diets increased NUCB2/nesfatin-1 production in canine gastrointestinal tracts. These results may set the stage for further investigations of canine NUCB2/nesfatin-1, which may relate to satiety effects in dogs.

著者

Satoshi NOZAWA Hitomi ODA Ran AKIYAMA Kaori UEDA Kaori SAEKI Saori SHONO Natsuki MARUYAMA Atsuki MURATA Hiroyuki TAZAKI Akihiro MORI Yutaka MOMOTA Daigo AZAKAMI Toshinori SAKO Katsumi ISHIOKA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.14-0033, (Released:2014-05-15)

被引用文献数

2 5

---

Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, in which excess glucocorticoid causes insulin resistance. Disturbance of insulin action may be caused by multiple factors, including transcriptional modulation of insulin signal molecules which lie downstream of insulin binding to insulin receptors. In this study, gene expressions of insulin signal molecules were examined using neutrophils of the HAC dogs (the untreated dogs and the dogs which had been treated with trilostane). Insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B/Akt kinase (Akt)-2 and protein kinase C (PKC)-lambda were analyzed in the HAC dogs and compared with those from normal dogs. The IRS-1 gene expressions decreased by 37% and 35% of the control dogs in the untreated and treated groups, respectively. The IRS-2 gene expressions decreased by 61% and 72%, the PI3-K gene expressions decreased by 47% and 55% and the Akt-2 gene expressions decreased by 45% and 56% of the control dogs, similarly. Collectively, gene expressions of insulin signal molecules are suppressed in the HAC dogs, which may partially contribute to the induction of insulin resistance.

著者

Masaki Michishita Tatsuya Uto Ryota Nakazawa Hisashi Yoshimura Kikumi Ogihara Yuko Naya Tsuyoshi Tajima Daigo Azakami Seigo Kishikawa Toshiro Arai Kimimasa Takahashi

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.121, no.4, pp.339-342, 2013-04-20 (Released:2013-04-19)

参考文献数

15

被引用文献数

8 15

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Canine hemangiopericytoma (CHP) is characterized by frequent local recurrence and increased invasiveness. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis in tumors. The aim of the present study was to investigate the effect of a single dose of bevacizumab on a xenograft model of CHP. VEGF protein was secreted from cultured CHP cells and interacted with bevacizumab. Bevacizumab treatment suppressed tumor growth by inhibiting tumor angiogenesis, whereas no significant differences were observed in the proliferation index and apoptosis rates of treated and untreated mice. Thus, bevacizumab had antitumor effects in a xenograft model of CHP.

著者

Aritada YOSHIMURA Daigo AZAKAMI Miori KISHIMOTO Takahiro OHMORI Daiki HIRAO Shohei MORITA Shinogu HASEGAWA Tatsushi MORITA Ryuji FUKUSHIMA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.85, no.5, pp.541-545, 2023 (Released:2023-05-03)

参考文献数

25

---

A 6-year-old castrated male Cavalier King Charles Spaniel was referred to the Animal Medical Center, Tokyo University of Agriculture and Technology, for examination and treatment of recurrent pneumothorax. Chest radiography and computed tomography showed multiple cavitary lesions in the caudal right posterior lobe. These lesions were surgically excised via thoracotomy. Subsequent histopathological examination revealed paragonimiasis. In the postoperative review, we found that the owner had fed raw deer meat to the dog four months earlier. Deer meat has attracted attention as a source of Paragonimus in humans. To our knowledge, this is the first report of Paragonimus infection in a dog due to deer meat consumption.

著者

Shota KAWAKAMI Kazuhiko OCHIAI Yuiko KATO Masaki MICHISHITA Hinako HIRAMA Ryo OBARA Daigo AZAKAMI Masami WATANABE Toshinori OMI

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.80, no.1, pp.85-91, 2018 (Released:2018-01-27)

参考文献数

23

---

Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K). The cIDH2 WT and R174K proteins were overexpressed in HeLa cells, and their presence was confirmed using an anti-human IDH2-WT mAb (clone: KrMab-3) and an anti-IDH2-R172K mAb (clone: KMab-1). The IDH2 activity between cIDH2 WT and cIDH2 R174K transfectants was compared by measuring the production of NADH and NADPH. NADPH production was lower for cIDH2 R174K than that for cIDH2 WT transfectants. Finally, we detected increased expression of hypoxia inducible factor-1 alpha (HIF-1α) in cIDH2 R174K transfectants. This indicates that mutations at R174 can potentially induce carcinogenesis in canine somatic cells.

著者

Mio ISHIMORI Masaki MICHISHITA Hisashi YOSHIMURA Daigo AZAKAMI Kazuhiko OCHIAI Toshiyuki ISHIWATA Kimimasa TAKAHASHI

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0297, (Released:2017-07-21)

被引用文献数

11

---

A 7-year-old female domestic rabbit suffered from labored respiration, poor appetite, mild anemia and thrombocytopenia. Radioscopic examination revealed masses in multiple locations including the intrapleural cavity and spleen. Forty-three days after the first visit to a private veterinary clinic, the rabbit died of severe respiratory distress. Microscopically, all of the masses were composed of round to polygonal neoplastic cells with distinct cell borders that were arranged in a sheet pattern. Multinucleated giant neoplastic cells were often observed. Some neoplastic cells had phagocytozed one or more erythrocytes. Immunohistochemical staining revealed that the neoplastic cells expressed vimentin, CD204, Iba-1 and lysozyme, but not CD163. Based on the morphological and immunohistochemical findings, this case was diagnosed as disseminated histiocytic sarcoma with hemophagocytosis.

著者

Takuya Evan KISHIMOTO Shoko YASHIMA Rei NAKAHIRA Eri ONOZAWA Daigo AZAKAMI Makoto UJIKE Kazuhiko OCHIAI Toshiyuki ISHIWATA Kimimasa TAKAHASHI Masaki MICHISHITA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.79, no.7, pp.1155-1162, 2017 (Released:2017-07-07)

参考文献数

29

被引用文献数

7

---

Cancer stem cells or tumor-initiating cells (TICs) are a small subpopulation of cells that have the capacity to self-renew, differentiate and initiate tumors. These cells may function in tumor initiation, aggression and recurrence. Whether spheres derived from canine rhabdomyosarcoma cells have stem cell-like properties is unclear. We induced sphere formation in the canine rhabdomyosarcoma cell lines, CMS-C and CMS-J, and characterized the spheres in vitro and in vivo. Sphere-forming cells were more resistant to vincristine, mitoxantrone and doxorubicin than adherent cells. Xenograft transplantation demonstrated that 1 × 103 sphere-forming cells derived from CMS-C were sufficient for tumor formation. The sphere assay showed that the sphere-forming cells were present in these tumors. These results suggest that the spheres derived from canine rhabdomyosarcoma cells may possess characteristics of TICs. This study provides the foundation for elucidating the contribution of TICs to rhabdomyosarcoma tumorigenesis.

著者

Yutaka MOMOTA Junya YASUDA Mitsutaka IKEZAWA Jun SASAKI Masaaki KATAYAMA Kenji TANI Masahiro MIYABE Eri ONOZAWA Daigo AZAKAMI Katsumi ISHIOKA Toshinori SAKO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0652, (Released:2016-08-28)

被引用文献数

3

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Proliferative and necrotising otitis externa (PNOE) is a very rare disease affecting the ear canals and concave pinnae of kittens. This report describes a 5-month-old cat with PNOE. Histopathological examination confirmed the diagnosis. Treatment was initiated with local injection of methylprednisolone acetate into the lesions. The cat was subsequently treated with clobetasol propionate cream, a potent topical glucocorticoid ointment. The cat showed marked improvement. While topical treatment with tacrolimus, an immunosuppressive agent, is reported to be an effective therapy, to the best of our knowledge, this is the first report to treat PNOE with local corticosteroid therapy.

著者

Masahiro MIYABE Azusa GIN Eri ONOZAWA Mana DAIMON Hana YAMADA Hitomi ODA Akihiro MORI Yutaka MOMOTA Daigo AZAKAMI Ichiro YAMAMOTO Mariko MOCHIZUKI Toshinori SAKO Katsutoshi TAMURA Katsumi ISHIOKA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0031, (Released:2015-05-10)

被引用文献数

2 11

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G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4-5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs.

著者

Katsumi ISHIOKA Yumi SUZUKI Kana TAJIMA Sumire OHTAKI Masahiro MIYABE Mariko TAKASAKI Akihiro MORI Yutaka MOMOTA Daigo AZAKAMI Toshinori SAKO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.75, no.2, pp.173-177, 2013 (Released:2013-03-01)

参考文献数

15

被引用文献数

1 10

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Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C family chemokines, which mobilizes monocytes from bone marrow to the site of inflammation. To evaluate the clinical utility of canine MCP-1 as a blood test item, we measured serum MCP-1 concentrations in normal and ill dogs. Reference interval of canine MCP-1 was established as 115.6–176.9 pg/ml. Serum MCP-1 concentrations increased in the dogs affected with neoplastic (518.0 ± 84.8 pg/ml), inflammatory (257.0 ± 42.5 pg/ml) or other diseases (360.3 ± 45.2 pg/ml). The results showed high sensitivity of MCP-1 to detect neoplasia and inflammation. Moreover, MCP-1 increased in some cases in which C-reactive protein didn’t increase. MCP-1 might be helpful as a screening blood test marker for detection of neoplasia and inflammation in dogs.

著者

Katsumi ISHIOKA Yumi SUZUKI Kana TAJIMA Sumire OHTAKI Masahiro MIYABE Mariko TAKASAKI Akihiro MORI Yutaka MOMOTA Daigo AZAKAMI Toshinori SAKO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.12-0169, (Released:2012-09-14)

被引用文献数

1 10

---

Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C family chemokines, which mobilizes monocytes from bone marrow to the site of inflammation. To evaluate the clinical utility of canine MCP-1 as a blood test item, we measured serum MCP-1 concentrations in normal and ill dogs. Reference interval of canine MCP-1 was established as 115.6–176.9 pg/ml. Serum MCP-1 concentrations increased in the dogs affected with neoplastic (518.0 ± 84.8 pg/ml), inflammatory (257.0 ± 42.5 pg/ml) or other diseases (360.3 ± 45.2 pg/ml). The results showed high sensitivity of MCP-1 to detect neoplasia and inflammation. Moreover, MCP-1 increased in some cases in which C-reactive protein didn’t increase. MCP-1 might be helpful as a screening blood test marker for detection of neoplasia and inflammation in dogs.