著者

Masayuki YABUTA Fumihiko TAKESHITA Shizuko UENO Natsuki TANAKA Takahiro YANO Keiji OE Chie NIKAIDO Ken J. ISHII Masaki IMAI Yoshihiro KAWAOKA Toru TANZAWA

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.3, no.3, pp.118-119, 2021 (Released:2021-12-24)

参考文献数

2

著者

Yafei LIU Yukoh NAKAZAKI Hisashi ARASE

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.4, no.1, pp.1-4, 2022 (Released:2022-04-27)

参考文献数

11

被引用文献数

2

著者

Kazushige MAKI

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

pp.2020-010, (Released:2020-08-05)

参考文献数

19

被引用文献数

1

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The development of oligonucleotide therapeutics (ONTs) has advanced recently. Various ONTs (e.g., antisense oligonucleotides, small-interfering RNA, and microRNA) exert their pharmacological effects via hybridization with mRNA sequences, and they can also bind to unintended mRNA sequences owing to sequence homology. For this reason, the safety of ONTs should be evaluated by judging hybridization-dependent on- and off-target toxicity in preclinical studies. As the off-target toxicity is unique to ONTs, it is difficult to assess their safety with the current guidelines established for small molecules and biotechnology-derived pharmaceuticals; thus, several research groups, such as the Oligonucleotide Safety Working Group in the Drug Information Association (DIA), have proposed concepts for the preclinical safety evaluation of ONTs. Although there are currently no specific International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for ONTs, the ICH S6 guideline states that “the principles outlined in this guidance may also be applicable to oligonucleotide drugs.” Recently, a preclinical safety guideline for ONTs has been developed by a Japanese working group to address the issues associated with the ICH S6. Here, the preclinical safety assessments of mRNA-targeting ONTs are discussed based on this guidance.

著者

Ryutaro SHIMAZAKI Kohji KUSANO

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.3, no.3, pp.122-124, 2021 (Released:2021-12-24)

参考文献数

12

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Sendai virus (SeV) vectors are able to infect a diverse range of cells. They have a high affinity for epithelial cells in the respiratory tract, which provides advantageous properties for intranasal inoculation. Vaccination of the respiratory tract, the main route of infection for Coronavirus (COVID-19), can strongly induce mucosal immunity, which is difficult to induce through injected vaccines, in addition to systemic immunity in a manner similar to innate immunity. A SeV vector vaccine carrying part of the SARS-CoV-2 spike-protein gene showed high immunogenicity in pharmacological studies using intranasally inoculated rodents and is a promising next-generation vaccine.

著者

Marwa AKAO Joohyeon WOO Shingo IWAMI Shoya IWANAMI

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.3, no.3, pp.85-88, 2021 (Released:2021-12-24)

参考文献数

13

被引用文献数

1

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To evaluate the effects of antiviral drugs against coronavirus disease (COVID-19), we calculated the sample size needed to detect significant differences in daily viral load in randomized controlled trials. While calculating sample sizes, simulated viral loads that mimicked longitudinal clinical data were used. The sample size computed from the viral load was the smallest 2 to 4 days after trial participation, while the smallest sample size computed from the positive rate was 4 to 7 days after clinical trial participation.

著者

Kazuki Fujii Hinano Otofuji Yu Nakamura Yumie Koshidaka Mayumi Adachi Eri Sasakawa Mohamed Darwish Keizo Takao

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.1, no.2, pp.46-57, 2019 (Released:2019-11-30)

参考文献数

42

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Propofol, known as “milk of anesthesia”, is used for the induction and maintenance of anesthesia. Recently, propofol has attracted increasing concerns about its safety and abuse potential because of its psychostimulant effects such as euphoria and sexual hallucinations. Previous reports focused on the effects of postoperative and neonatal exposure to propofol. However, the lasting effects of repetitive propofol administration during adulthood have not been well investigated. It is conceivable that prolonged use of propofol affects brain function and the behavioral characteristics of the abused patient. Thus, we performed a comprehensive behavioral analysis of mice exposed to propofol. Adult male C57BL/6J mice were repeatedly administered with propofol (20 or 80 mg/kg/day i.p.), intralipos (vehicle control), or saline only once a day for seven days. We then performed a behavioral test battery to evaluate various behaviors. Afterwards, we resumed the propofol treatment for three days and subsequently conducted contextual and cued fear conditioning tests. In the three‐chamber social approach test, propofol treatment attenuated social novelty preference in mice. In the fear conditioning test, high dose-treated mice exhibited impaired long-term cued-dependent memory retention. In the rotarod test, propofol- and intralipos-treated mice tended to have decreased motor coordination than the saline-treated mice. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Additionally, the solvent itself might have effects different from that of propofol. Our findings provide basic data on the safe use and risk of propofol abuse. Highlights Propofol, known as “milk of anesthesia”, has attracted increasing concerns about its safety and abuse potential. The lasting effects of repetitive propofol administration during adulthood have not been well investigated. To clarify the effects of repetitive propofol use on brain function and behavioral characteristics, we performed a comprehensive behavioral analysis of mice exposed to propofol. In this study, propofol treatment attenuated the social novelty preference and the performance of the cued long-term memory task in mice. Additionally, treatment with propofol and intralipos tended to induce decreased motor coordination. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Furthermore, the solvent itself might have effects different from that of propofol. Our findings provide basic data for the safe use and risk of propofol abuse.

著者

Yoichi Kurebayashi

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.1, no.1, pp.1-3, 2019 (Released:2019-08-19)

参考文献数

10

被引用文献数

1

著者

Kosei SAKAI Yuri SHINOHARA Kenjiro KAJI Tomohiro YONEZAWA Yasuyuki MOMOI Shingo MAEDA

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.3, no.1, pp.1-8, 2021 (Released:2021-02-02)

参考文献数

36

被引用文献数

1 1

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Human epidermal growth factor receptor 2 (HER2) is a cell surface receptor tyrosine kinase that belongs to the HER family. HER2 overexpression in human prostate cancer has been frequently observed; however, there are no reports on HER2 expression in canine prostate carcinoma (PC). The purpose of this study was to investigate HER2 expression and the underlying molecular mechanisms in canine PC. Twenty-one formalin-fixed paraffin-embedded canine prostate gland tissues (13 carcinomas and 8 normal controls) were analyzed for HER2 expression using immunohistochemistry. Using a digital polymerase chain reaction assay, the HER2 copy number in 8 PC and 6 normal prostate gland tissues was determined. HER2 overexpression occurred in 8/13 (61.5%) PC cases, but not in the normal controls. There were no significant associations between HER2 overexpression and clinical characteristics of the PC cases, such as age, neuter status, lymph node involvement, distant metastasis, and overall survival. HER2 copy number gain (CNG) was detected in 3/8 (37.5%) PC cases, but not in the normal controls. All PC cases with HER2 CNG exhibited HER2 overexpression, suggesting that HER2 CNG may lead to HER2 overexpression. These findings provide new insights into the molecular pathogenesis of canine PC; these may be therapeutically relevant. Dogs with PC would be useful as a preclinical large animal model for the development of new therapy for HER2-overexpressing prostate cancer in humans.

著者

Kengo SONODA

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.3, no.3, pp.120-121, 2021 (Released:2021-12-24)

参考文献数

1

被引用文献数

2

著者

Hajime KOJIMA

出版者

Catalyst Unit

雑誌

Translational and Regulatory Sciences (ISSN:24344974)

巻号頁・発行日

vol.1, no.2, pp.66-72, 2019 (Released:2019-11-22)

参考文献数

34

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EU and US proposals for a paradigm shift in toxicity testing have brought about a worldwide evolution in the safety assessment of chemicals by means of novel approach methods (NAM) that do not use animals. In Japan, as well, despite the fact that there have been no changes in regulation of cosmetics, pharmaceuticals, and other chemical substances, a number of manufacturers have voluntarily discontinued the use of animal testing, and we must now give serious consideration to means for ensuring the safety of chemicals without the use of animal testing in accordance with the international harmonisation. The expanding use of non-animal test methods in the safety assessment of chemicals continues to merit close scrutiny.