著者

Sho YOSHIMOTO Daiki KATO Satoshi KAMOTO Kie YAMAMOTO Masaya TSUBOI Masahiro SHINADA Namiko IKEDA Yuiko TANAKA Ryohei YOSHITAKE Shotaro ETO Kohei SAEKI James CHAMBERS Yuko HASHIMOTO Kazuyuki UCHIDA Ryohei NISHIMURA Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.20-0026, (Released:2020-04-03)

被引用文献数

6

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Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various human cancers. HER2-targeted therapies showed clinical responses in humans with HER2-positive tumors. The incidence of canine primary lung cancer (cPLC) is increasing, but there are no effective systemic therapies for dogs with late-stage cPLC. HER2-targeted therapy could be an option for cPLC, but HER2 expression in cPLC remains unknown. We evaluated HER2 expression in cPLC. Immunohistochemical analysis revealed that 3 samples (19%) scored 3+; 8 (50%), 2+; 5 (31%); and 1+ and 0 (0%), 0. Of the cPLC tissues, 69% were HER2 positive (scored ≥2+). These data would lead to further evaluation of the role of HER2 in cPLC as a mechanism of malignancy and therapeutic target.

著者

Siew Mei ONG Kohei SAEKI Mun Keong KOK Takayuki NAKAGAWA Ryohei NISHIMURA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0029, (Released:2019-07-15)

被引用文献数

2

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Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo. In cell culture, YM155 enhanced the cytotoxic effect of etoposide against canine OSA cell lines; however, the molecular mechanism behind this effect was heterogeneous, as only one cell line had an elevated apoptotic level. In addition, this effect was not associated with survivin suppression in two of the cell lines. These results suggest that the molecular target of YM155 is not restricted to survivin alone. When tested on a murine xenograft model, the average tumor volume of the combination treatment group (YM155, 5 mg/kg, intraperitoneally, 5 consecutive days/week; and etoposide, 20 mg/kg, intraperitoneally, every 5 days) was 66% smaller than the control group, although this difference was not statistically significant (P=0.17). Further studies to improve the treatment protocol are necessary to confirm the findings of this study.

著者

Sho YOSHIMOTO Daiki KATO Satoshi KAMOTO Kie YAMAMOTO Masaya TSUBOI Masahiro SHINADA Namiko IKEDA Yuiko TANAKA Ryohei YOSHITAKE Shotaro ETO Kohei SAEKI James Kenn CHAMBERS Ryohei KINOSHITA Kazuyuki UCHIDA Ryohei NISHIMURA Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0019, (Released:2019-05-29)

被引用文献数

12

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Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0–3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.

著者

Kota YOSHIDA Saori YOSHIDA Nan CHOISUNIRACHON Tomochika SAITO Kaori MATSUMOTO Kohei SAEKI Manabu MOCHIZUKI Ryohei NISHIMURA Nobuo SASAKI Takayuki NAKAGAWA

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.14-0104, (Released:2014-06-16)

被引用文献数

3 14

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It is known that epithelial mesenchymal transition (EMT) contributes to the acquisition of malignant property in human cancers. However, the role of EMT in canine tumors remains to be elucidated. To evaluate the correlation between expression levels of protein markers involved in EMT and clinicopathological characteristics in canine mammary gland tumors, immunohistochemistry using antibodies against ZO-1, E-cadherin, vimentin, N-cadherin and fibronectin was performed on 119 clinical tissue samples. Consequently, loss of ZO-1 and E-cadherin, and gain of vimentin and N-cadherin were more frequently observed in malignant tumors than in benign tumors. However, there was no correlation among expression of these molecules. Univariate and multivariate analysis identified that loss of E-cadherin independently had a low one-year survival rate (adjusted odds ratio: 2.3, P=0.02). These results suggested that EMT might relate to acquisition of malignancy, and additionally, E-cadherin was strongly correlated with malignant behavior in canine mammary gland tumors.

著者

Mona UCHIDA Kohei SAEKI Shingo MAEDA Satoshi TAMAHARA Tomohiro YONEZAWA Naoaki MATSUKI

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.16-0120, (Released:2016-05-30)

被引用文献数

5

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Apoptosis inhibitor of macrophage (AIM) is initially reported to protect macrophages from apoptosis. In this study, we determined the effect of AIM on the macrophage-derived tumor, histiocytic sarcoma cell lines (HS) of dogs. Five HS and five other tumor cell lines were used. When recombinant canine AIM was applied to non-serum culture media, cell numbers of all the HS and two of other tumor cell lines decreased dose-dependently. The DNA fragmentation, TUNEL staining and flow cytometry tests revealed that AIM induced both of apoptosis and cell cycle arrest in the HS. Although AIM is known as an apoptosis inhibitor, these results suggest that a high dose of AIM could have an opposite function in HS and some tumor cell lines.

著者

Nguyen V. SON James K. CHAMBERS Takanori SHIGA Takuya E. KISHIMOTO Shotaro KIKUHARA Kohei SAEKI Reina FUJIWARA Masaya TSUBOI Ryohei NISHIMURA Kazuyuki UCHIDA Hiroyuki NAKAYAMA

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.7, pp.1125-1128, 2018 (Released:2018-07-12)

参考文献数

19

被引用文献数

8

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A 12-year-old intact male Welsh Corgi was presented with enlargement of the right scrotum. Both testicles were surgically removed and histopathologically examined. On gross examination, white nodules were found in the epididymis and ductus deferens. Histopathologically, the nodules developed continuously from the tunica vaginalis testis of the right scrotum and consisted of spindle-shaped neoplastic cells that invaded the surrounding tissue. Immunohistochemically, the neoplastic cells were diffusely positive for vimentin, cytokeratin and Wilms tumor-1 (WT-1). Based on these findings, the tumor was diagnosed as sarcomatoid mesothelioma. The dog presented with respiratory distress 122 days after surgery and clinical examination found multiple metastatic lesions in the lung, abdominal lymph nodes and peritoneum. The dog died 144 days after surgery due to disease progression.

著者

Satoko SUGIMOTO Shingo MAEDA Masaya TSUBOI Kohei SAEKI James K. CHAMBERS Tomohiro YONEZAWA Kenjiro FUKUSHIMA Reina FUJIWARA Kazuyuki UCHIDA Hajime TSUJIMOTO Naoaki MATSUKI Koichi OHNO

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.6, pp.874-877, 2018 (Released:2018-06-06)

参考文献数

18

被引用文献数

2

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A 6-year 5-month-old spayed female Scottish Fold cat presented with a one-month history of gait abnormalities, increased salivation, and decreased activity. A blood test showed hyperammonemia and increased serum bile acids. Imaging tests revealed multiple shunt vessels indicating acquired portosystemic shunt. Histopathologic analysis of liver biopsy showed features consistent with liver hypoperfusion, such as a barely recognizable portal vein, increased numbers of small arterioles, and diffuse vacuolar degeneration of hepatocytes. These findings supported the diagnosis of primary hypoplasia of the portal vein/microvascular dysplasia, (PHPV/MVD). To our knowledge, this is the first case of feline PHPV/MVD that developed multiple acquired portosystemic shunts and presented with hepatic encephalopathy.

著者

Nguyen V. SON James K. CHAMBERS Takanori SHIGA Takuya E. KISHIMOTO Shotaro KIKUHARA Kohei SAEKI Reina FUJIWARA Masaya TSUBOI Ryohei NISHIMURA Kazuyuki UCHIDA Hiroyuki NAKAYAMA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.18-0186, (Released:2018-05-23)

被引用文献数

8

---

A 12-year-old intact male Welsh Corgi was presented with enlargement of the right scrotum. Both testicles were surgically removed and histopathologically examined. On gross examination, white nodules were found in the epididymis and ductus deferens. Histopathologically, the nodules developed continuously from the tunica vaginalis testis of the right scrotum and consisted of spindle-shaped neoplastic cells that invaded the surrounding tissue. Immunohistochemically, the neoplastic cells were diffusely positive for vimentin, cytokeratin and Wilms tumor-1 (WT-1). Based on these findings, the tumor was diagnosed as sarcomatoid mesothelioma. The dog presented with respiratory distress 122 days after surgery and clinical examination found multiple metastatic lesions in the lung, abdominal lymph nodes and peritoneum. The dog died 144 days after surgery due to disease progression.

著者

Satoko SUGIMOTO Shingo MAEDA Masaya TSUBOI Kohei SAEKI James K. CHAMBERS Tomohiro YONEZAWA Kenjiro FUKUSHIMA Reina FUJIWARA Kazuyuki UCHIDA Hajime TSUJIMOTO Naoaki MATSUKI Koichi OHNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0648, (Released:2018-04-09)

被引用文献数

2

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A 6-year 5-month-old spayed female Scottish Fold cat presented with a one-month history of gait abnormalities, increased salivation, and decreased activity. A blood test showed hyperammonemia and increased serum bile acids. Imaging tests revealed multiple shunt vessels indicating acquired portosystemic shunt. Histopathologic analysis of liver biopsy showed features consistent with liver hypoperfusion, such as a barely recognizable portal vein, increased numbers of small arterioles, and diffuse vacuolar degeneration of hepatocytes. These findings supported the diagnosis of primary hypoplasia of the portal vein/microvascular dysplasia, (PHPV/MVD). To our knowledge, this is the first case of feline PHPV/MVD that developed multiple acquired portosystemic shunts and presented with hepatic encephalopathy.

著者

Kohei SAEKI Yoshifumi ENDO Kazuyuki UCHIDA Ryohei NISHIMURA Nobuo SASAKI Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.74, no.2, pp.227-230, 2012 (Released:2012-03-02)

参考文献数

34

被引用文献数

8 13

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The numbers of tumor infiltrating T lymphocytes, B lymphocytes and antigen presenting cells were evaluated in an immunohistochemical manner in 140 canine spontaneous mammary gland tumor (MGT) tissues. As a result, we found a statistically significant increase in the number of intratumoral T lymphocytes (23.2 ± 23.8) in the malignant MGT group (n=51) compared with the benign MGT group (14.0 ± 16.0, n=89; P<0.05). Moreover, the high T lymphocyte infiltration in the malignant group correlated with poor prognosis in multivariate analysis (P<0.05). This study indicated the relationship between increased infiltrating T lymphocytes and canine MGT malignancy.