著者

Shoma NISHIBORI Masashi SAKURAI Yumiko KAGAWA Kazuyuki UCHIDA Takayuki NAKAGAWA Masaya IGASE Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0003, (Released:2023-05-02)

被引用文献数

1

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Immunotherapy is a breakthrough in human cancer therapy and has become a major concern in veterinary oncology. However, in cats, many unclear points of the tumor microenvironment exist, including immune checkpoint molecules. A reason is that very few monoclonal antibodies have been proven to react with feline molecules. Therefore, this study investigated whether anti-human programmed cell death ligand 1 (PD-L1) monoclonal antibody, clone 28-8, which is currently commercially available, can also recognize feline PD-L1 by flow cytometry, immunoprecipitation, and immunohistochemical (IHC) staining. We confirmed that the antibody’s specificity by flow cytometry and immunoprecipitation using NIH3T3 cells transfected with feline PD-L1. Additionally, we revealed that PD-L1 was expressed on the surface of some feline cell lines by flow cytometry and clone 28-8 antibody unbound to the cells where feline PD-L1 was knocked out. Furthermore, IHC analysis revealed that PD-L1 was expressed in macrophages in the spleen and lymph nodes from healthy cats and mast cell tumor cells. Therefore, we indicated that the clone 28-8 antibody is a valuable tool in detecting feline PD-L1, and further analysis of tumor tissues is expected in the future.

著者

Toshitaka KANEI Munetaka IWATA Hiroaki KAMISHINA Takuya MIZUNO Sadatoshi MAEDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0468, (Released:2021-12-03)

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C-C chemokine receptor 7 (CCR7) contributes to cell homing to lymph nodes (LNs). Recent studies reported that CCR7 is also expressed in tumor cells, which correlates with LN metastasis in various cancers. However, the expression of CCR7 in tumor cells is unknown in dogs due to the lack of appropriate antibodies. In the present study, a fusion protein of C-C chemokine ligand 19 (CCL19) was employed as an alternative method to CCR7 antibodies. The fusion CCL19 protein specifically detected CCR7 expressed in canine lymphoma cell lines, which showed active chemotaxis to both canine and mouse ligands. The present study will help further research on the involvement of canine CCR7 in LN metastasis.

著者

Osamu SAKAI Shoji OGINO Toshihiro TSUKUI Masaya IGASE Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.83, no.10, pp.1495-1499, 2021 (Released:2021-10-02)

参考文献数

21

被引用文献数

2

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Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.

著者

Osamu SAKAI Shoji OGINO Toshihiro TSUKUI Masaya IGASE Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0326, (Released:2021-08-19)

被引用文献数

2

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Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.

著者

Masaya IGASE Yuki MORINAGA Masahiro KATO Toshihiro TSUKUI Yusuke SAKAI Masaru OKUDA Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.82, no.4, pp.483-487, 2020 (Released:2020-04-15)

参考文献数

13

被引用文献数

1

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DEP domain-containing 1B (DEPDC1B) is involved in the regulation of cell de-adhesion and actin cytoskeleton activity during the G2/M transition of the cell cycle, and its overexpression has been proven to be associated with cancer progression in several human cancers. Canine DEPDC1B was identified as a gene that was overexpressed in canine lymphoma tissues in our previous study. However, in dogs, the protein expression of DEPDC1B remains to be determined due to the lack of a specific monoclonal antibody. Here, we developed rat monoclonal antibodies against canine DEPDC1B and characterized their applicability for immunodetection assays. Our findings demonstrated that these antibodies are functional and can be important tools to investigate the precise role of DEPDC1B in canine tumors.

著者

Shunya TSUJI Ryotaro YABE Tatsuya USUI Takuya MIZUNO Takashi OHAMA Koichi SATO

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.15-0707, (Released:2016-05-05)

被引用文献数

8

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Lymphoma is one of the most common malignant tumors in canine. Protein phosphatase 2A (PP2A), a well-conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. Perphenazine (PPZ) is one of the phenothiazines and widely used as an antipsychotic drug. Recently, it is reported that PPZ directly binds with scaffolding subunit of PP2A complex and exerts anti-tumor effects on human T cell acute lymphoblastic leukemia. However, the effect of PPZ on canine lymphoma has not been studied. Here, we investigated the potential therapeutic role of PPZ and its molecular mechanism in canine T-cell lymphoma. In canine T-cell lymphoma cell lines, UL-1 and Ema, PPZ decreased cell survival in a dose-dependent manner. Increased caspase 3 activity and Annexin V positive cells suggested that PPZ induced apoptosis. PPZ dephosphorylated Akt, MEK1/2 and ERK1/2. Akt inhibitor, but not MEK1/2 inhibitor and ERK1/2 inhibitor, induced cell death, indicating the importance of Akt dephosphorylation for the anti-tumor effect of PPZ. Finally, we observed enhanced PP2A activity by PPZ treatment. The present results for the first time revealed that PPZ induced canine lymphoma cells apoptosis through Akt dephosphorylation via PP2A activation. Our study suggests the possible therapeutic application of phenothiazines for canine T-cell lymphoma.

著者

Masaya IGASE Kenji BABA Takako SHIMOKAWA-MIYAMA Shunsuke NOGUCHI Takuya MIZUNO Masaru OKUDA

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.15-0180, (Released:2015-06-11)

被引用文献数

5

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A 6-year-old spayed female Jack Russell Terrier presented with a 1-month history of lethargy, anorexia, vomiting, and weight loss. The dog was fed beef and chicken jerky treats daily in addition to a commercial diet. Laboratory tests revealed azotemia, hypokalemia, hyperchloremia, metabolic acidosis, and glucosuria with normoglycemia. Urine amino acid analysis showed significant amino acid loss into the urine. Thus, Fanconi syndrome was diagnosed, and based on the case history and extensive diagnostic testing, excessive consumption of jerky treats was strongly suspected as the cause. Glucosuria resolved 7 days after the withdrawal of jerky treats and fluid therapy. Aminoaciduria was substantially, but not completely, improved 3 months after diagnosis. Mild azotemia remained, suggesting chronic renal disease. To the best of our knowledge, this is the first reported case of Fanconi syndrome following the consumption of jerky treats in Japan.

著者

Chung Chew HWANG Masami MOCHIZUKI Ken MAEDA Masaru OKUDA Takuya MIZUNO

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.13-0472, (Released:2013-11-27)

被引用文献数

1 5

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Reovirus infection is common in mammals. However, seroepidemiological data of reovirus neutralizing antibodies are limited in dogs. In this study, sera of 65 healthy dogs from six prefectures across Japan were tested for neutralizing antibodies against reovirus serotype 1 strain Lang (T1L), serotype 2 strain Amy (T2A) and serotype 3 strain Dearing (T3D) using plaque reduction neutralization test (PRNT). Seropositivity against reovirus T1L, T2A and T3D was 53.85%, 33.85% and 46.15%, respectively. Distribution of reovirus seropositive samples displayed no distinguishable geographical pattern. However, reovirus seropositivity increases with age and in dogs housed outdoor. Co-infection of multiple reovirus serotypes in dogs is also possible. These data will provide valuable insights towards the usage of reovirus in oncolytic virotherapy in canine cancers.

著者

Saori UMEKI Yasuo EMA Ryoichi SUZUKI Masahito KUBO Toshiharu HAYASHI Yasuhiko OKAMURA Jumpei YAMAZAKI Hajime TSUJIMOTO Kenji TANI Hiroko HIRAOKA Masaru OKUDA Takuya MIZUNO

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.4, pp.467-474, 2013 (Released:2013-05-02)

参考文献数

11

被引用文献数

5 26

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Five novel, canine lymphoma cell lines (Ema, CLC, CLK, Nody-1 and UL-1) were established from dogs suffering from lymphoma and characterized in vitro and in vivo. All cell lines, except CLC, were characterized with T-cell phenotypes, by flow cytometric analysis and polymerase chain reaction for antigen receptor rearrangement. Cell proliferation rates and transcriptional levels of MYC, PTEN, KIT and FLT3 varied between each cell line. Intraperitoneal xenotransplantation of Ema, CLC, Nody-1 and UL-1 lymphoma cell lines into NOD/SCID mice induced ascites, intraperitoneal tumors and severe infiltration of lymphoma cells into the pancreas and mesentery. Establishment of novel canine lymphoma cell lines with different characteristics is critical for elucidating the pathophysiology of canine lymphoma and improving current therapies.

著者

Nobuyuki FUJIWARA Hideyoshi KAWASAKI Ryotaro YABE Dale J. CHRISTENSEN Michael P. VITEK Takuya MIZUNO Koichi SATO Takashi OHAMA

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.3, pp.349-354, 2013 (Released:2013-04-01)

参考文献数

31

被引用文献数

10 18

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Lymphoma is one of the most common malignant tumors in canine. Chemotherapy results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as a tumor suppressor and plays a critical role in mammalian cell transformation. Increased protein levels of SET, endogenous PP2A inhibitor, have been reported to correlate with poor prognosis in human leukemia. Here, we test the potential therapeutic role for a SET antagonist in canine lymphoma. We observed SET protein levels increased in multiple canine lymphoma cell lines compared with primary peripheral blood cells. A novel SET antagonist OP449 increased PP2A activity and effectively killed SET high-expressing canine lymphoma cells, but not SET low-expressing cells. Caspase-3 activation and enhanced Annexin V positive staining were observed after OP449 treatment, suggesting apoptotic cell death by OP449. Consistent with this, pan-caspase inhibitor Z-VAD-FMK blocked OP449 induced cell death. These data demonstrated the potential therapeutic application of SET antagonists for canine lymphoma.

著者

Yuka HARA Junko SUZUKI Keita NOGUCHI Yutaka TERADA Hiroshi SHIMODA Takuya MIZUNO Ken MAEDA

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.13-0003, (Released:2013-03-26)

被引用文献数

4 7

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Morbilliviruses use signaling lymphocyte activation molecule (SLAM) as a receptor for their entry to cells. In this study, a complete gene encoding SLAM of a domestic cat was identified. The identity of feline SLAM with canine one was 73%, and feline SLAM formed the same cluster with those of carnivores. Furthermore, feline cell expressing feline SLAM supported growth of canine distemper virus (CDV) as well as that expressing canine one. These results indicated that feline SLAM can function as a receptor for morbilliviruses, and our established feline cells that express feline SLAM might be useful for analysis of morbilliviruses originated from felids.

著者

Nobuyuki FUJIWARA Hideyoshi KAWASAKI Ryotaro YABE Dale J. CHRISTENSEN Michael P. VITEK Takuya MIZUNO Koichi SATO Takashi OHAMA

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.12-0366, (Released:2012-11-05)

被引用文献数

9 18

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Lymphoma is one of the most common malignant tumors in canine. Chemotherapy results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as a tumor suppressor and plays a critical role in mammalian cell transformation. Increased protein levels of SET, endogenous PP2A inhibitor, have been reported to correlate with poor prognosis in human leukemia. Here, we test the potential therapeutic role for a SET antagonist in canine lymphoma. We observed SET protein levels increased in multiple canine lymphoma cell lines compared with primary peripheral blood cells. A novel SET antagonist OP449 increased PP2A activity and effectively killed SET high-expressing canine lymphoma cells, but not SET low-expressing cells. Caspase-3 activation and enhanced Annexin V positive staining were observed after OP449 treatment, suggesting apoptotic cell death by OP449. Consistent with this, pan-caspase inhibitor Z-VAD-FMK blocked OP449 induced cell death. These data demonstrated the potential therapeutic application of SET antagonists for canine lymphoma.

著者

Takumi OKAWA Hiroko HIRAOKA Yuko WADA Kenji BABA Kazuhito ITAMOTO Takuya MIZUNO Masaru OKUDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.1112200735, (Released:2011-12-27)

被引用文献数

4 5

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The second malignancies are frequent complications in the human patient with chronic lymphocytic leukemia (CLL). However, the clinical details and outcome of this phenomenon were unclear in the canine counterparts. Here we report a dog with high-grade lymphoma concurrent with T-cell CLL. A 10-year-old male golden retriever presented with lymphadenopathies. The lymph nodes contained large-sized lymphocytes, raising suspicion of high-grade lymphoma. Meanwhile, small-lymphocytic lymphocytosis in the peripheral blood was consistent with CLL. Interestingly, molecular biological analyses revealed that CLL cells were T-cell type, whereas lymphoma cells were B-cell type. Chemotherapy using the L-VCA short protocol was effective for 155 days, but the dog died on day 194 after diagnosis, despite rescue therapies.