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145 results on '"Nishimura, Maki"'

4. PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma

Author

Maekawa, Naoya, Konnai, Satoru, Nishimura, Maki, Kagawa, Yumiko, Takagi, Satoshi, Hosoya, Kenji, Ohta, Hiroshi, Kim, Sangho, Okagawa, Tomohiro, Izumi, Yusuke, Deguchi, Tatsuya, Kato, Yukinari, Yamamoto, Satoshi, Yamamoto, Keiichi, Toda, Mikihiro, Nakajima, Chie, Suzuki, Yasuhiko, Murata, Shiro, and Ohashi, Kazuhiko

Published
2021
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7. Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

Author

1000070829035, Maekawa, Naoya, 1000040396304, Konnai, Satoru, Asano, Yumie, Otsuka, Takumi, Aoki, Eri, Takeuchi, Hiroto, Kato, Yukinari, Kaneko, Mika K., Yamada, Shinji, Kagawa, Yumiko, Nishimura, Maki, Takagi, Satoshi, Deguchi, Tatsuya, Ohta, Hiroshi, Nakagawa, Takayuki, 1000090206540, Suzuki, Yasuhiko, 1000080829036, Okagawa, Tomohiro, 1000010579163, Murata, Shiro, 1000090250498, Ohashi, Kazuhiko, 1000070829035, Maekawa, Naoya, 1000040396304, Konnai, Satoru, Asano, Yumie, Otsuka, Takumi, Aoki, Eri, Takeuchi, Hiroto, Kato, Yukinari, Kaneko, Mika K., Yamada, Shinji, Kagawa, Yumiko, Nishimura, Maki, Takagi, Satoshi, Deguchi, Tatsuya, Ohta, Hiroshi, Nakagawa, Takayuki, 1000090206540, Suzuki, Yasuhiko, 1000080829036, Okagawa, Tomohiro, 1000010579163, Murata, Shiro, 1000090250498, and Ohashi, Kazuhiko

Abstract

Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-gamma stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.

Published
2023

8. PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma

Author

Maekawa, Naoya, Konnai, Satoru, Nishimura, Maki, Kagawa, Yumiko, Takagi, Satoshi, Hosoya, Kenji, Ohta, Hiroshi, Kim, Sangho, Okagawa, Tomohiro, Izumi, Yusuke, Deguchi, Tatsuya, Kato, Yukinari, Yamamoto, Satoshi, Yamamoto, Keiichi, Toda, Mikihiro, Nakajima, Chie, Suzuki, Yasuhiko, Murata, Shiro, Ohashi, Kazuhiko, Maekawa, Naoya, Konnai, Satoru, Nishimura, Maki, Kagawa, Yumiko, Takagi, Satoshi, Hosoya, Kenji, Ohta, Hiroshi, Kim, Sangho, Okagawa, Tomohiro, Izumi, Yusuke, Deguchi, Tatsuya, Kato, Yukinari, Yamamoto, Satoshi, Yamamoto, Keiichi, Toda, Mikihiro, Nakajima, Chie, Suzuki, Yasuhiko, Murata, Shiro, and Ohashi, Kazuhiko

Abstract

type:Article, 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.

Published
2023

9. Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

Author

Maekawa, Naoya, Konnai, Satoru, Asano, Yumie, Otsuka, Takumi, Aoki, Eri, Takeuchi, Hiroto, Kato, Yukinari, Kaneko, Mika K., Yamada, Shinji, Kagawa, Yumiko, Nishimura, Maki, Takagi, Satoshi, Deguchi, Tatsuya, Ohta, Hiroshi, Nakagawa, Takayuki, Suzuki, Yasuhiko, Okagawa, Tomohiro, Murata, Shiro, Ohashi, Kazuhiko, Maekawa, Naoya, Konnai, Satoru, Asano, Yumie, Otsuka, Takumi, Aoki, Eri, Takeuchi, Hiroto, Kato, Yukinari, Kaneko, Mika K., Yamada, Shinji, Kagawa, Yumiko, Nishimura, Maki, Takagi, Satoshi, Deguchi, Tatsuya, Ohta, Hiroshi, Nakagawa, Takayuki, Suzuki, Yasuhiko, Okagawa, Tomohiro, Murata, Shiro, and Ohashi, Kazuhiko

Abstract

Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-gamma stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.

Published
2023

10. Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

Author

Maekawa, Naoya, primary, Konnai, Satoru, additional, Asano, Yumie, additional, Otsuka, Takumi, additional, Aoki, Eri, additional, Takeuchi, Hiroto, additional, Kato, Yukinari, additional, Kaneko, Mika K., additional, Yamada, Shinji, additional, Kagawa, Yumiko, additional, Nishimura, Maki, additional, Takagi, Satoshi, additional, Deguchi, Tatsuya, additional, Ohta, Hiroshi, additional, Nakagawa, Takayuki, additional, Suzuki, Yasuhiko, additional, Okagawa, Tomohiro, additional, Murata, Shiro, additional, and Ohashi, Kazuhiko, additional

Published
2023
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23. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice

Author

Terkawi, Mohamad Alaa, Nishimura, Maki, and Furuoka, Hidefumi

Subjects
Phagocytes, phagocytosis, Plasmodium yoelii, macrophages
Abstract

application/pdf, In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality.

Published
2016

29. Ultrasound Imaging of Mammary Glands in Dairy Heifers at Different Stages of Growth

Author

Nishimura, Maki, Yoshida, Tetsuya, El-Khodery, Sabry, Miyoshi, Masafumi, Furuoka, Hidefumi, Yasuda, Jun, and Miyahara, Kazuro

Subjects
mammary gland, animal structures, ultrasound, animal diseases, dairy heifer
Abstract

application/pdf, To obtain B-mode ultrasound images of mammary glands in dairy heifers at different stages of growth, 25 clinically normal Holstein heifers were used. The heifers were divided into 5 groups (n=5/group) by stage of their growth: 2-month-old (group 1), 5-month-old (group 2), postpuberty (group 3), mid (group 4), and late (group 5) pregnancy. Furthermore, the sections of mammary glands were observed grossly at postmortem examination in one heifer in each group. Ultrasound images varied with the development of mammary glands. In group 1, the mammary glands had distinctive ultrasonographic findings: an oval to fusiform homogeneous hypoechoic structure. In all groups except group 1, mammary tissue consists of two major areas: a homogeneous, medium echogenic area and a poorly-defined, heterogeneous, hypoechoic area mostly in the superficial part. The superficial hypoechoic area spread more extensively and more irregularly with the development of mammary glands. Most pregnant heifers had irregular and extremely hypoechoic or anechoic areas like lactiferous sinus in the glands. The gross findings of mammary glands suggested that the hypoechoic areas of various shapes represented the lactiferous sinus and ducts. Thus, these results indicate that B-mode ultrasound imaging can visualize the internal structures of udders and could be a useful tool for evaluation of mammary glands in heifers.

Published
2011

33. First Case of Echinococcus multilocularis Infection in a Zoo-Housed Flying Squirrel (Pteromys volans orii)

Author

Oikawa, Eri, Shimura, Ryoji, Nishimura, Maki, and Furuoka, Hidefumi

Subjects
flying squirrel, Hokkaido, animal diseases, parasitic diseases, fungi, Echinococcus multilocularis, new host record, pathology
Abstract

application/pdf, A 33 month-old male flying squirrel kept in a zoo developed progressive dyspnea and died. Macroscopically, the liver and lung were enlarged with numerous nodular vesicles. Histologically, these organs were replaced by numerous collapsed vesicles demarcated by fibrous tissues. The cysts lined by a cellular, germinal layer contained numerous brood capsules with abundant production of well-developed protoscolices. Protoscolices were about 80–100 μm in diameter, and had hooks being visible as refractive structures. This zoo locates in the east of Hokkaido where is an endemic area of Echinococcus multilocularis infection. From epidemiology and pathological findings, this animal was diagnosed as E.multilocularis infection. This report describes the pathology of the first case of E. multilocularis infection in a flying squirrel.

Published
2013

40. Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microti Infection in Mice

Author

Terkawi, Mohamad Alaa, primary, Cao, Shinuo, additional, Herbas, Maria S., additional, Nishimura, Maki, additional, Li, Yan, additional, Moumouni, Paul Franck Adjou, additional, Pyarokhil, Asadullah Hamid, additional, Kondoh, Daisuke, additional, Kitamura, Nobuo, additional, Nishikawa, Yoshifumi, additional, Kato, Kentaro, additional, Yokoyama, Naoaki, additional, Zhou, Jinlin, additional, Suzuki, Hiroshi, additional, Igarashi, Ikuo, additional, and Xuan, Xuenan, additional

Published
2015
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50. Mechanisms of interferon-beta-induced inhibition of T oxoplasma gondii growth in murine macrophages and embryonic fibroblasts: role of immunity-related GTPase M1.

Author

Mahmoud, Motamed Elsayed, Ui, Fumiki, Salman, Doaa, Nishimura, Maki, and Nishikawa, Yoshifumi

Subjects
INTERFERON beta 1b, TOXOPLASMA gondii, IMMUNITY, MICROBIAL growth, MACROPHAGES, GUANOSINE triphosphatase, FIBROBLASTS
Abstract

The apical complex of T oxoplasma gondii enables it to invade virtually all nucleated cells in warm-blooded animals, including humans, making it a parasite of global importance. Anti- T . gondii cellular defence mechanisms depend largely on interferon ( IFN)-γ production by immune cells. However, the molecular mechanism of IFN-β-mediated defence remains largely unclear. Here, mouse peritoneal macrophages and murine embryonic fibroblasts ( MEFs) primed with recombinant IFN-β and IFN-γ showed different pathways of activation. Treatment of these cells with IFN-β or IFN-γ inhibited T. gondii (type II PLK strain) growth. Priming macrophages with IFN-β had no effect on inflammatory cytokine expression, inducible nitric oxide synthase or indoleamine 2,3-dioxygenase, nor did it have an effect on their metabolites, nitric oxide and kynurenine respectively. In contrast, IFN-γ stimulation was characterized by classical macrophage activation and T . gondii elimination. IFN-β activation recruited the immunity-related GTPase M1 ( IRGM1) to the parasitophorous vacuole in the macrophages and MEFs. Anti-toxoplasma activities induced by IFN-β were significantly reduced after IRGM1 knockdown in murine macrophages and in IRGM1-deficient MEFs. Thus, this study unravels an alternative pathway of macrophage activation by IFN-β and provides a mechanistic explanation for the contribution of IRGM1 induced by IFN-β to the elimination of T . gondii. [ABSTRACT FROM AUTHOR]

Published
2015
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