School of Veterinary Medicine

Masanori Kobayashi

  (小林 正典)

Profile Information

Affiliation
Faculty of Veterinary Science, Nippon Veterinary and Life Science University
Degree
博士(獣医学)(日本獣医生命科学大学)

J-GLOBAL ID
201601020659238874
researchmap Member ID
B000250975

Papers

 42
  • Tomokazu Nagashima, Masanori Kobayashi, Yoshiaki Kubo, Katsuya Nagaho, Kayoko Sugibayashi, Takahiro Saito, Yukino Machida, Masaki Michishita
    Journal of Comparative Pathology, 210 8-14, Apr, 2024  Peer-reviewedLead author
  • Masanori Kobayashi, Moe Onozawa, Shiho Watanabe, Tomokazu Nagashima, Kyoichi Tamura, Yoshiaki Kubo, Akiko Ikeda, Kazuhiko Ochiai, Masaki Michishita, Makoto Bonkobara, Masato Kobayashi, Tatsuya Hori, Eiichi Kawakami
    Veterinary and comparative oncology, 21(2) 221-230, Feb 6, 2023  Peer-reviewedLead authorCorresponding author
    Canine prostate cancer (cPCa) is a malignant neoplasm with no effective therapy. The BRAF V595E mutation, corresponding to the human BRAF V600E mutation, is found frequently in cPCa. Activating BRAF mutations are recognized as oncogenic drivers, and blockade of MAPK/ERK phosphorylation may be an effective therapeutic target against BRAF-mutated tumors. The aim of this study was to establish a novel cPCa cell line and to clarify the antitumor effects of MEK inhibitors on cPCa in vitro and in vivo. We established the novel CHP-2 cPCa cell line that was derived from the prostatic tissue of a cPCa patient. Sequencing of the canine BRAF gene in two cPCa cell lines revealed the presence of the BRAF V595E mutation. MEK inhibitors (trametinib, cobimetinib, and mirdametinib) strongly suppressed cell proliferation in vitro, and trametinib showed the highest efficacy against cPCa cells with minimal cytotoxicity to non-cancer COPK cells. Furthermore, we orally administered 0.3 or 1.0 mg/kg trametinib to CHP-2 xenografted mice and examined its antitumor effects in vivo. Trametinib reduced tumor volume, decreased phosphorylated ERK levels, and lowered Ki-67 expression in xenografts in a dose-dependent manner. Although no clear adverse events were observed with administration, trametinib-treated xenografts showed osteogenesis that was independent of dosage. Our results indicate that trametinib induces cell cycle arrest by inhibiting ERK activation, resulting in cPCa tumor regression in a dose-dependent manner. MEK inhibitors, in addition to BRAF inhibitors, may be a targeted agent option for cPCa with the BRAF V595E mutation. This article is protected by copyright. All rights reserved.
  • Akiko Ikeda, Masanori Kobayashi, Tatsuya Hori, Masaki Michishita, Masato Kobayashi, Eiichi Kawakami
    American Journal of Animal and Veterinary Sciences, 18(1) 47-51, Jan 1, 2023  Peer-reviewed
    Vitamin D Receptor (VDR) expression is implicated in human Prostatic Carcinoma (PC), but its role in canine PC is unclear. To investigate how VDR expression is affected by age and castration in healthy dogs and how it changes with PC, we evaluated prostates from 8-month-old (n = 5) or 6-year-old (n = 8) intact males, 1-8-year-old healthy castrated males (n = 4) and 8-15-year-old castrated males (n = 7) with PC, by performing histopathology, immunohistochemistry, and ELISA. The results showed that VDR expression in canine prostate increased in an age-dependent manner and decreased after castration compared with intact dogs at 6 years of age. Castrated dogs with PC showed increased VDR expression compared with healthy castrated dogs and VDR expression in PC differed according to the pattern of tumor proliferation. The findings suggest that prostatic VDR expression may be a useful prognostic marker and therapeutic target for canine PC.
  • Tatsuya Hori, Hideo Tajima, Shinichi Sasaki, Mizuki Karasawa, Madoka Yoshizawa, Takuya Kuribara, Hidemasa Hori, Fujio Yamamoto, Etsuo Narushima, Kiyoshi Nagai, Kazuaki Nippashi, Yurie Sataka, Masato Kobayashi, Masanori Kobayashi, Toshihiko Tsutsui
    The Journal of veterinary medical science, 85(1) 117-122, Nov 28, 2022  Peer-reviewed
    In this study, cauda epididymal sperm were collected from Amur leopard cats with various causes of death as well as Tsushima leopard cats that underwent castration surgery, and sperm quality was compared with that in domestic cats. A sufficient number of sperm similar to those in domestic cats could be collected from the cauda epididymis of Amur leopard cats. However, in old leopard cats, no or very few cauda epididymal sperm were recovered, although there were no differences in sperm motility and sperm abnormality. There were no significant differences in sperm quality immediately after collection and after freezing-thawing of cauda epididymal sperm compared with corresponding estimates in domestic cats.
  • Masato Kobayashi, Honami Sekine, Yushi Ogawa, Shin Toyama, Yuki Komukai, Moto Nakamura, Ryusuke Mitanda, Marina Hayashi, Masanori Kobayashi, Tatsuya Hori
    Journal of reproductive immunology, 155 103778-103778, Nov 26, 2022  Peer-reviewed
    Tolerance towards fetal alloantigens in the maternal immune system is essential for maintaining pregnancy. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their ability to suppress immune activity and maintain maternal-fetal immune tolerance. However, the mechanisms underlying MDSC induction have not been elucidated. Herein, we investigated the myeloid-derived suppressor cells (MDSCs) in the peripheral blood of pregnant canines and its induction mechanism. By analyzing the concentration of MDSCs in the peripheral blood of pregnant canines, elevation of MDSCs has been observed during pregnancy. In addition, MDSCs from pregnant canines inhibit T cell activation. These results suggest that the elevated MDSCs in canine pregnancy may contribute to reduces maternal immune activity. To clarify the cause of MDSCs elevation in canine pregnancy, we analyzed the relationship between pregnancy-related hormones (estradiol, progesterone, and relaxin) and MDSCs. Serum relaxin levels, but not estradiol and progesterone, were correlated with the ratio of monocyte MDSCs. Additionally, relaxin induced monocytic MDSCs as well as inhibited T cell activation in vitro. Therefore, relaxin contributes to the elevation of monocytic MDSCs in the peripheral blood of pregnant canines. Our findings highlight the novel role of relaxin in pregnancy and contribute to a better understanding of maternal-fetal immune tolerance.

Misc.

 22

Books and Other Publications

 20

Presentations

 25

Teaching Experience

 15

Research Projects

 5