博士, 札幌医科大学, Jan. 2021

Life Science, Clinical pharmacy

Bachelor's degree program, School of Dental Medicine

Doctoral (PhD) degree program, Graduate school of Dental Medicine

Prevalence and profiles of clinically diagnosed autoimmune cerebellar ataxia in a Japanese nationwide survey.
Shintaro Fujii; Hiroaki Yaguchi; Akihiko Kudo; Katsuki Eguchi; Taichi Nomura; Hiroshi Hayashi; Keiko Tanaka; Makoto Yoneda; Akio Kimura; Takayoshi Shimohata; Yuji Takahashi; Hidehiro Mizusawa; Ichiro Yabe; Japan Consortium of ACA(JAC-ACA) group
Journal of Neurology, 273, 215, 2026, [Peer-reviewed]
English

リン酸化プルラン-CaCl2-βTCP-BMP2複合体移植の歯槽提増大への有効性
辻村 大河; 菅谷 勉; 高橋 直紀; 堂 寛隆; 川上 紗也雅; 沼田 沙和; 町田 紗樹; 櫻井 直人; 兵藤 佑貢真; 赤坂 司; 吉田 靖弘; 中西 康; 林 宏至
日本歯周病学会会誌, 67, 秋季特別, 157, 157, (NPO)日本歯周病学会, Oct. 2025
Japanese

New future dental material: Antimicrobial material "cetylpyridinium chloride-montmorillonite" and implantable material "phosphorylated pullulan".
Ko Nakanishi; Tsukasa Akasaka; Yasuhiko Abe; Hiroshi Hayashi; Kumiko Yoshihara; Teppei Nakamura; Mariko Nakamura; Bart VAN Meerbeek; Yasuhiro Yoshida
Dental materials journal, 11 Jan. 2025, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, In dental practice, there are two major diseases: dental caries and periodontal disease. Although dental treatment techniques have advanced along with advances in dental materials, some diseases such as root surface caries and horizontal bone resorption have not yet achieved satisfactory treatment results. Since these diseases are infections caused by oral bacteria, we believe that materials with long-lasting antimicrobial properties would help control these diseases. In addition, materials that can adhere to wet hard tissues would contribute to treatment. In this review, new materials developed based on this idea, the antimicrobial material "cetylpyridinium chloride-montmorillonite" and the hard tissue adhesive implantable material "phosphorylated pullulan" was introduced.

From Tooth Adhesion to Bioadhesion: Development of Bioabsorbable Putty-like Artificial Bone with Adhesive to Bone Based on the New Material "Phosphorylated Pullulan".
Ko Nakanishi; Tsukasa Akasaka; Hiroshi Hayashi; Kumiko Yoshihara; Teppei Nakamura; Mariko Nakamura; Bart Van Meerbeek; Yasuhiro Yoshida
Materials (Basel, Switzerland), 17, 15, 25 Jul. 2024, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Bioabsorbable materials have a wide range of applications, such as scaffolds for regenerative medicine and cell transplantation therapy and carriers for drug delivery systems. Therefore, although many researchers are conducting their research and development, few of them have been used in clinical practice. In addition, existing bioabsorbable materials cannot bind to the body's tissues. If bioabsorbable materials with an adhesive ability to biological tissues can be made, they can ensure the mixture remains fixed to the affected area when mixed with artificial bone or other materials. In addition, if the filling material in the bone defect is soft and uncured, resorption is rapid, which is advantageous for bone regeneration. In this paper, the development and process of a new bioabsorbable material "Phosphorylated pullulan" and its capability as a bone replacement material were demonstrated. Phosphorylated pullulan, which was developed based on the tooth adhesion theory, is the only bioabsorbable material able to adhere to bone and teeth. The phosphorylated pullulan and β-TCP mixture is a non-hardening putty. It is useful as a new resorbable bone replacement material with an adhesive ability for bone defects around implants.

Investigation of a new implant surface modification using phosphorylated pullulan
Kanako Nagamoto; Ko Nakanishi; Tsukasa Akasaka; Shigeaki Abe; Kumiko Yoshihara; Mariko Nakamura; Hiroshi Hayashi; Shinji Takemoto; Masato Tamura; Yoshimasa Kitagawa; Bart Van Meerbeek; Yasuhiro Yoshida
Frontiers in Bioengineering and Biotechnology, 12, Frontiers Media SA, 22 May 2024, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
Scientific journal, Various implant surface treatment methods have been developed to achieve good osseointegration in implant treatment. However, some cases remain impossible to treat with implants because osseointegration is not obtained after implantation, and the implants fail. Thus, this study focused on phosphorylated pullulan because of its adhesiveness to titanium (Ti) and bone, high biocompatibility, and early replacement with bone. In this study, the response of bone-related cells to phosphorylated pullulan was evaluated to develop a new surface treatment method. Saos-2 (human osteosarcoma-derived osteoblast-like cells), MC3T3-E1 (mouse calvaria-derived osteoblast-like cells), and RAW264.7 (mouse macrophage-like cells) were used. In evaluating cellular responses, phosphorylated pullulan was added to the culture medium, and cell proliferation and calcification induction tests were performed. The proliferation and calcification of cells on the surface of Ti disks coated with phosphorylated pullulan were also evaluated. In addition, bone morphogenetic protein-2 (BMP-2), an osteogenic factor, was used to evaluate the role of phosphorylated pullulan as a drug carrier in inducing calcification on Ti disks. Phosphorylated pullulan tended to promote the proliferation of osteoblast-like cells and the formation of calcification on Ti disks coated with phosphorylated pullulan. Ti disks coated with phosphorylated pullulan loaded with BMP-2 enhanced calcification. Phosphorylated pullulan inhibited osteoclast-like cell formation. These results are due to the properties of phosphorylated pullulan, such as adhesiveness to titanium and drug-loading function. Therefore, phosphorylated pullulan effectively promotes bone regeneration when coated on titanium implants and is useful for developing a new surface treatment method.

Phase I Randomized Trial of 17 O-Labeled Water: Safety and Feasibility Study of Indirect Proton MRI for the Evaluation of Cerebral Water Dynamics.
Taisuke Harada; Kohsuke Kudo; Hiroyuki Kameda; Ryota Sato; Toru Shirai; Yoshitaka Bito; Noriyuki Fujima; Satonori Tsuneta; Toshifumi Nogawa; Kenichiro Maeda; Hiroshi Hayashi; Makoto Sasaki
Journal of magnetic resonance imaging : JMRI, 56, 6, 1874, 1882, Dec. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: 17 O-labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow. PURPOSE: To evaluate the safety and feasibility of PSO17. STUDY TYPE: Prospective study. SUBJECTS: A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (normal saline), PSO17 10%, and PSO17 20%. FIELD STRENGTH/SEQUENCE: Dynamic 3D fluid attenuated inversion recovery (FLAIR, fast spin echo with variable refocusing flip angle) scans of the brain were performed with 3-T MRI. ASSESSMENT: Contrast agents were injected 5 minutes after the start of a 10-minute scan. Any symptoms, vital signs, and blood and urine tests were evaluated at five timepoints from preinjection to 4 days after. Blood samples for pharmacokinetic analysis, including half-life (T1/2), maximum fraction (Cmax ), time-to-maximum fraction (Tmax ), and area under the curve (AUC), were collected at 13 timepoints from preinjection to 168 hours after. Regions of interest were set in the cerebral cortex (CC), basal ganglia/thalamus (BG/TM), and white matter (WM), and 17 O concentrations were calculated from signal changes and evaluated using Cmax . STATISTICAL TESTS: All items were compared among the three groups using Tukey-Kramer's honestly significant difference test. Statistical significance was defined as P < 0.5. RESULTS: No safety issues were noted with the intravenous administration of PSO17. The T1/2 was approximately 160 hours, and the AUCs were 1.77 ± 0.10 and 3.75 ± 0.36 in the PSO17 10% and 20% groups, respectively. 17 O fractions calculated from MRI signals were higher in the PSO17 20% group than in the 10% and placebo groups. Significant differences were noted between all pairs of groups in the CC and BG/TM, and between PSO17 20% and both placebo and 10% groups in the WM. DATA CONCLUSION: PSO17 might be considered safe as a contrast medium. Dynamic 3D-FLAIR might detect dose-dependent signal changes and estimate 17 O. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Osteoclast formation from mouse bone marrow cells on micro/nano-scale patterned surfaces.
Tsukasa Akasaka; Hiroshi Hayashi; Miho Tamai; Yoshitaka Yoshimura; Yoh-Ichi Tagawa; Hirofumi Miyaji; Ko Nakanishi; Yasuhiro Yoshida
Journal of oral biosciences, 64, 2, 237, 244, Jun. 2022, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, OBJECTIVES: Osteoclasts can sense the surface topography of materials. However, it is difficult to identify the structural factors that affect osteoclast formation and its function. Furthermore, we hypothesized that the type of osteoclast precursor cells also affects osteoclastogenesis in the materials. In this study, we investigated the effects of defined micro/nanoscale patterns on osteoclastogenesis from bone marrow cells (BMCs). METHODS: Various cyclo-olefin polymer (COP) patterns were prepared using nanoimprinting. The effects of shape, size, and height of the patterns, and the wettability of the patterned surfaces on osteoclastogenesis from BMCs were evaluated in vitro. RESULTS: Osteoclast formation was promoted on pillars (diameter, 1 μm or 500 nm; height, 500 nm). Notably, osteoclastogenesis from BMCs was better promoted on hydrophobic pillars than on hydrophilic pillars. In contrast, decreased osteoclast formation was observed on the nanopillars (diameter, 100 nm; height, 200 nm). CONCLUSIONS: We demonstrated the promotion of osteoclast formation from BMCs on hydrophobic pillars with diameters of 1 μm and 500 nm. Some cellular behaviors in the patterns were dependent on the type of osteoclast precursor cells. The designed patterns are useful for designing the surface of dental implants or bone replacement materials with a controllable balance between osteoblast and osteoclast activities.

Efficacy of bezafibrate for preventing myopathic attacks in patients with very long-chain acyl-CoA dehydrogenase deficiency.
Hideaki Shiraishi; Kenji Yamada; Kiyoshi Egawa; Mika Ishige; Fumihiro Ochi; Asami Watanabe; Sanae Kawakami; Kazuyo Kuzume; Kenji Watanabe; Koji Sameshima; Kiyotaka Nakamagoe; Akira Tamaoka; Naoko Asahina; Saki Yokoshiki; Keiko Kobayashi; Takashi Miyakoshi; Koji Oba; Toshiyuki Isoe; Hiroshi Hayashi; Seiji Yamaguchi; Norihiro Sato
Brain & development, 43, 2, 214, 219, Feb. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks. PATIENTS AND METHODS: We conducted an open-label, non-randomized, multi-center study into the effects of bezafibrate on five patients with VLCADD. Bezafibrate was administered for 4 years, and we analyzed the number of myopathic attacks requiring hospitalization and treatment infusions. RESULTS: The number of myopathic attacks requiring infusions of 24 h or longer significantly decreased during the study period. The patients' ability to conduct everyday activities was also improved by the treatment. CONCLUSION: Our findings show the potential long-term efficacy of bezafibrate in preventing myopathic attacks for patients with VLCADD.

Preparation of Standard Operating Procedures Reflected the Latest Information for Investigator‒initiated Clinical Trials
Hiroshi Hayashi; Koji Iwasaki; Izumi Kumagai; Saki Yokoshiki; Kayoko Kikuchi; Shinobu Shimizu; Mayumi Teramachi; Yuki Kagayama; Kotone Matsuyama; Hiroi Kasai; Makiko Uchiyama; Manabu Yamamoto
Jpn Pharmacol Ther, 47, suppl. 2, s134, s147, ライフサイエンス出版(株), Dec. 2019, [Peer-reviewed], [Lead author]
Japanese, Scientific journal

Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa.
Wakana Matsumura; Yasuyuki Fujita; Satoru Shinkuma; Shotaro Suzuki; Saki Yokoshiki; Hideki Goto; Hiroshi Hayashi; Kota Ono; Masukazu Inoie; Shota Takashima; Chihiro Nakayama; Toshifumi Nomura; Hideki Nakamura; Riichiro Abe; Norihiro Sato; Hiroshi Shimizu
The Journal of investigative dermatology, 139, 10, 2115, 2124, Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Inherited skin disorders have been reported recently to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism). We observed a case of recessive dystrophic epidermolysis bullosa treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with revertant mosaicism. Based on these findings, we conducted an investigator-initiated clinical trial of CEAs from clinically revertant skin for recessive dystrophic epidermolysis bullosa. The donor sites were analyzed by genetic analysis, immunofluorescence, electron microscopy, and quantification of the reverted mRNA with deep sequencing. The primary endpoint was the ulcer epithelization rate per patient at 4 weeks after the last CEA application. Three patients with recessive dystrophic epidermolysis bullosa with 8 ulcers were enrolled, and the epithelization rate for each patient at the primary endpoint was 87.7%, 100%, and 57.0%, respectively. The clinical effects were found to persist for at least 76 weeks after CEA transplantation. One of the three patients had apparent revertant mosaicism in the donor skin and in the post-transplanted area. CEAs from clinically normal skin are a potentially well-tolerated treatment for recessive dystrophic epidermolysis bullosa.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan; 2nd report QOL survey.
Hideaki Shiraishi; Kenji Yamada; Eishin Oki; Mika Ishige; Toshiyuki Fukao; Yusuke Hamada; Norio Sakai; Fumihiro Ochi; Asami Watanabe; Sanae Kawakami; Kazuyo Kuzume; Kenji Watanabe; Koji Sameshima; Kiyotaka Nakamagoe; Akira Tamaoka; Naoko Asahina; Saki Yokoshiki; Takashi Miyakoshi; Koji Oba; Toshiyuki Isoe; Hiroshi Hayashi; Seiji Yamaguchi; Norihiro Sato
Molecular genetics and metabolism reports, 20, 100496, 100496, Sep. 2019, [International Magazine]
English, Scientific journal, INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by a defective mitochondrial fatty acid oxidation (FAO) enzyme. We recently reported that bezafibrate improved patient quality of life (QOL) based on the SF-36 questionnaire score in patients with FAODs during a 50-week, open-label, clinical trial. Herein we conducted further survey assessments of the trial patients to define the long-term efficacy and safety of bezafibrate. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in five patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and one patient with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 15.9 years; range, 5.8-26.4 years). The bezafibrate administration was continued for a further 102-174 weeks after the 24-week treatment described in our previous study. QOL was quantitated using the 36-Item Short Form Health Survey (SF-36) questionnaire, which constitutes eight components: physical functioning (PF), role limitation due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. RESULTS: PF was elevated in all patients and continued to rise during the study, with the total QOL scores increased from baseline in five of the six cases. In particular, three patients older than 20 years showed treatment efficacy, and all subcategories of QOL were elevated in two of these cases. CONCLUSION: Our findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs.

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma.
Hiroaki Shima; Giichiro Tsurita; Satoshi Wada; Yoshihiko Hirohashi; Hiroshi Yasui; Hiroshi Hayashi; Takashi Miyakoshi; Kazue Watanabe; Aiko Murai; Hiroko Asanuma; Serina Tokita; Terufumi Kubo; Munehide Nakatsugawa; Takayuki Kanaseki; Tomohide Tsukahara; Yutaka Nakae; Osamu Sugita; Yoichi M Ito; Yasunori Ota; Yasutoshi Kimura; Goro Kutomi; Koichi Hirata; Toru Mizuguchi; Kohzoh Imai; Ichiro Takemasa; Noriyuki Sato; Toshihiko Torigoe
Cancer science, 110, 8, 2378, 2385, Aug. 2019, [International Magazine]
English, Scientific journal, The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-β (IFNβ); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNβ. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNβ (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNβ group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNβ in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNβ did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNβ vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).

Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial.
Kenichi Yamahara; Akiko Hamada; Toshihiro Soma; Rika Okamoto; Masaya Okada; Satoshi Yoshihara; Kyoko Yoshihara; Kazuhiro Ikegame; Hiroya Tamaki; Katsuji Kaida; Takayuki Inoue; Yuko Ohsugi; Hiroki Nishikawa; Hiroshi Hayashi; Yoichi M Ito; Hiroaki Iijima; Shunsuke Ohnishi; Daigo Hashimoto; Toshiyuki Isoe; Takanori Teshima; Hiroyasu Ogawa; Norihiro Sato; Yoshihiro Fujimori
BMJ open, 9, 7, e026403, 09 Jul. 2019, [International Magazine]
English, Scientific journal, INTRODUCTION: Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD. METHODS AND ANALYSIS: This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. ETHICS AND DISSEMINATION: The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029945.

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan.
Kenji Yamada; Hideaki Shiraishi; Eishin Oki; Mika Ishige; Toshiyuki Fukao; Yusuke Hamada; Norio Sakai; Fumihiro Ochi; Asami Watanabe; Sanae Kawakami; Kazuyo Kuzume; Kenji Watanabe; Koji Sameshima; Kiyotaka Nakamagoe; Akira Tamaoka; Naoko Asahina; Saki Yokoshiki; Takashi Miyakoshi; Kota Ono; Koji Oba; Toshiyuki Isoe; Hiroshi Hayashi; Seiji Yamaguchi; Norihiro Sato
Molecular genetics and metabolism reports, 15, 55, 63, Jun. 2018, [International Magazine]
English, Scientific journal, INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). RESULTS: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. CONCLUSION: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.

Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disease: study protocol for a phase I/II, dual-centre, open-label, uncontrolled, dose-response trial.
Shinsuke Otagiri; Shunsuke Ohnishi; Arisa Miura; Hiroshi Hayashi; Izumi Kumagai; Yoichi M Ito; Takehiko Katsurada; Shiro Nakamura; Rika Okamoto; Kenichi Yamahara; Kyu Yong Cho; Toshiyuki Isoe; Norihiro Sato; Naoya Sakamoto
BMJ open gastroenterology, 5, 1, e000206, 2018, [International Magazine]
English, Scientific journal, INTRODUCTION: The medical treatment options for patients with Crohn's disease (CD) are limited and patients resistant to those therapies are left requiring surgical operations that usually only achieve some symptomatic relief. Mesenchymal stem cells (MSC) have been shown to be effective for the treatment of CD, and we have demonstrated in animal experiments that human amnion-derived MSCs (AMSC) are a potential new therapeutic strategy. Therefore, we designed this study to investigate the safety and efficacy of AMSCs in patients with treatment-resistant CD. METHODS AND ANALYSIS: This is the protocol for an ongoing phase I/II, dual-centre, open-label, uncontrolled, dose-response study. The estimated enrolment is 6-12 patients with treatment-resistant, moderate CD. A dose of 1.0×106 cells/kg will be administered intravenously in the low-dose group at days 0 and 7. After confirming the safety of low-dose administration, a dose of 4.0×106 cells/kg will be administered intravenously in the high-dose group on days 0 and 7. The primary endpoint will measure the occurrence of adverse events related to acute infusion toxicity, and secondary endpoints will include long-term adverse events and efficacy of AMSC administration. ETHICS AND DISSEMINATION: The Institutional Review Board of Hokkaido University Hospital approved this study protocol (approval number H29-6). A report releasing study results will be submitted to an appropriate journal. DISCUSSION: This study is the first to investigate the safety and efficacy of AMSC use for CD treatment. Our results will advance studies on more efficient and convenient methods to overcome the limits of available CD treatments. TRIAL REGISTRATION NUMBER: UMIN000029841.

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?
Toru Mizuguchi; Toshihiko Torigoe; Fukino Satomi; Hiroaki Shima; Goro Kutomi; Shigenori Ota; Masayuki Ishii; Hiroshi Hayashi; Sumiyo Asakura; Yoshihiko Hirohashi; Makoto Meguro; Yasutoshi Kimura; Toshihiko Nishidate; Kenji Okita; Masaho Ishino; Atsushi Miyamoto; Masamitsu Hatakenaka; Noriyuki Sato; Koichi Hirata
Surgery today, 46, 2, 139, 48, Feb. 2016, [Domestic magazines]
English, Scientific journal, Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.

オンラインPRO情報システムによるがん手術患者の術創部感染症の危険因子と予後の検証
石貫智裕; 久冨五郎; 島宏彰; 和田朝香; 青木武士; 吉田寛; 渡邉学; 長田拓哉; 横尾英樹; 問山裕二; 大西浩文; 林宏至; 森脇健介; 大柳俊夫; 水口徹, 日本癌治療学会学術集会(Web), 61st, 2023

脊髄小脳失調症1型の自然歴調査研究
白井慎一; 林宏至; 岡田和史; 伊藤陽一; 佐々木秀直; 佐々木秀直; 矢部一郎, 日本神経学会学術大会プログラム・抄録集, 64th, 2023

医師主導治験における標準業務手順書の適切な作成と効率的な運用に向けた検討
林 宏至; 岩崎 幸司; 熊谷 いづみ; 横式 沙紀; 菊地 佳代子; 清水 忍; 寺町 真由美; 加賀山 祐樹; 松山 琴音; 笠井 宏委; 内山 麻希子; 山本 学, 薬理と治療, 47, Suppl.2, s134, s147, Dec. 2019, [Peer-reviewed]
ライフサイエンス出版(株), Japanese

Phase I study of ¹⁷O-labeled water: safety and feasibility study of indirect proton MRI for the evaluation of cerebral blood flow
原田太以佑; 工藤與亮; 亀田浩之; 佐藤良太; 白猪亨; 尾藤良孝; 藤間憲幸; 常田慧徳; 野川敏史; 前田憲一郎; 林宏至; 佐々木真理, 日本磁気共鳴医学会雑誌, 39, 2, 2019

AROにおける医療機器等の開発
林宏至, 薬理と治療, 47, 8, 2019

医療機器開発の実例
林宏至, 薬理と治療, 46, 9, 2018

AROにおける医療機器等の開発
林宏至, CRCと臨床試験のあり方を考える会議プログラム・抄録集, 18th, 2018

Quality by Designによる質の高い臨床研究実施計画書作成を志向するツール作成の試み
松山 琴音; 松嶋 由紀子; 林 宏至; 真田 昌爾; 須崎 友紀; 長尾 典明; 小澤 郷司; 吉田 浩輔; 岩崎 幸司; 山本 学; 山口 拓洋; 上村 尚人, 臨床薬理, 48, Suppl., S269, S269, Nov. 2017
(一社)日本臨床薬理学会, Japanese

脂肪酸代謝異常症に対するベザフィブラートのオープンラベル臨床治験結果
山田健治; 白石秀明; 朝比奈直子; 横式沙紀; 宮腰崇; 大野浩太; 磯江敏幸; 林宏至; 山口清次; 佐藤典宏, 日本先天代謝異常学会雑誌, 33, 164, 164, 12 Sep. 2017
日本先天代謝異常学会, Japanese

医療機器開発の実例
林宏至, CRCと臨床試験のあり方を考える会議プログラム・抄録集, 17th, 2017

進行膵臓がんを対象とした複合型CTLワクチン療法第2相試験
水口徹; 島宏彰; 九冨五郎; 木村康利; 竹政伊知朗; 鳥越俊彦; 廣橋良彦; 塚原智英; 金関貴幸; 釣田義一郎; 安井寛; 和田聡; 林宏至; 宮腰崇, 日本臨床外科学会雑誌, 78, 2017

臨床研究のクオリティマネジメント計画書作成の取り組み
須崎 友紀; 小居 秀紀; 岩崎 幸司; 吉田 浩輔; 浅野 健人; 久米 学; 上村 尚人; 笠井 祥子; 松山 琴音; 林 宏至; 稲田 実枝子; 山本 学; クオリティマネジメント計画書作成ワーキンググループ, 臨床薬理, 46, Suppl., S175, S175, Nov. 2015
(一社)日本臨床薬理学会, Japanese

医師主導臨床試験におけるモニタリング計画書テンプレート作成に関する取り組み
浅野健人; 林宏至; 高橋睦; 稲野彰洋; 伊藤久裕; 矢野岬; 安藤幸子; 須崎友紀; 丸山秋弘; 久米学; 稲田実枝子; 上村尚人, 臨床薬理, 45, Supplement, 2014

医師主導型治験として施行したSUCCESS試験(臨床第I相試験)の結果
水口徹; 島宏彰; 九冨五郎; 鳥越俊彦; 林宏至; 西舘敏彦; 沖田憲司; 川本雅樹; 佐藤昇志; 平田公一, 日本消化器外科学会雑誌(Web), 47, Supplement1, 2014

膵癌に対するサバイビン免疫療法の研究
釣田義一郎; 谷澤健太郎; 篠崎大; 安井寛; 今井浩三; 石井浩; 石井浩; 尾阪将人; 尾阪将人; 島宏彰; 水口徹; 林宏至; 鳥越俊彦; 佐藤昇志, 膵・胆道癌Frontier, 4, 2, 2014

動体追跡陽子線治療の先進医療認可取得
白土博樹; 白土博樹; 林宏至, 臨床評価, 41, 1, 2013

Survivin2Bペプチドを用いた進行再発消化器癌に対するSUCCESS試験の途中経過
水口徹; 島宏彰; 鳥越俊彦; 九冨五郎; 下館広慎; 島田圭規; 林宏至; 稲毛富士郎; 杉田修; 朝倉純代; 佐藤昇志; 平田公一, 日本外科系連合学会誌, 38, 3, 2013

実地調査・治験依頼者による監査を受けて-治験実施体制の改善と今後のあり方-
林宏至; 熊谷いづみ; 高橋栄; 松浦理恵; 柴波明男; 妻木良二, 臨床薬理, 38, Supplement, 2007

治験実施体制の整備とその評価について-症例実施率と達成速度の検証-
熊谷いづみ; 高橋栄; 林宏至; 小森均; 妻木良二, 臨床薬理, 37, Supplement, 2006

ルイス酸存在下におけるβ-ジアステレオ選択的ラジカル環化反応
西田まゆみ; 林宏至; 西田篤司; 川原徳夫; 米光宰, 日本薬学会年会要旨集, 115th, Pt 2, 1995

.BETA.-Diastereoselective Radical Cyclization in the Presence of Lewis Acid.
西田まゆみ; 林宏至; 山浦洋介; 柳沼映美; 米光宰, 反応と合成の進歩シンポジウム講演要旨集, 20th, 1994

ルイス酸存在下におけるジアステレオ選択的分子内ラジカル付化反応の検討 (2)
西田まゆみ; 林宏至; 上山英二; 山浦洋介; 柳沼映美; 米光宰; 西田篤司, 日本薬学会年会要旨集, 114th, Pt 2, 1994

ルイス酸存在下におけるα,β-不飽和エステルへのラジカル付加反応
西田まゆみ; 上山英二; 林宏至; 山浦洋介; 柳沼映美; 光米宰; 西田篤司, 日本薬学会年会要旨集, 114th, Pt 2, 1994

ルイス酸存在下におけるジアステレオ選択的分子内ラジカル付加反応の検討 (1)
西田まゆみ; 上山英二; 林宏至; 山浦洋介; 柳沼映美; 米光宰; 西田篤司, 日本薬学会年会要旨集, 114th, Pt 2, 1994

Enzymatic Preparation of Modified Oligosaccharides. Synthesis and Application of N-trifluoloaceyllactosamine Derivatives.
畑中保丸; 菊池徹; 川野弘毅; 林宏至; 川嶋真司, 反応と合成の進歩シンポジウム講演要旨集, 19th, 1993

〔主要な業績〕JSCTRスタディマネジャーテキストブック : だれでもわかる臨床試験のスタディマネジメント
日本臨床試験学会
じほう, Nov. 2023, 9784840755382, 174p, Japanese, [Joint work]

JSCTRスタディマネジャーテキストブック : だれでもわかる臨床試験のスタディマネジメント
日本臨床試験学会
じほう, Oct. 2023, 9784840755368, 186p, Japanese, [Joint work]

フロンティア基礎科目, 2024年, 学士課程, 歯学部

歯科口腔外科用途に最適化した生体吸収性ゲルの開発と臨床研究
科学研究費助成事業
01 Apr. 2026 - 31 Mar. 2029
林 宏至
日本学術振興会, 基盤研究(C), 北海道大学, 26K15637

パイロジェンフリー・生体吸収素材への組織接着性付与と薬事戦略を考慮した非臨床試験
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2026
林 宏至; 中西 康; 吉田 靖弘; 中村 真理子
日本学術振興会, 基盤研究(C), 北海道大学, 23K11842

Research on standard methods and data for evaluating the cost-effectiveness of particle therapy
Grants-in-Aid for Scientific Research
01 Apr. 2017 - 31 Mar. 2022
Moriwaki Kensuke
Standard methods for evaluating the cost-effectiveness of proton beam therapy (PBT) were organized and analyzed in liver cancer. A model was constructed based on the Advanced B trial, and the incremental cost-effectiveness ratio (ICER) of PBT compared to transarterial embolization (TACE) was estimated from the public payer's perspective: $18,102 in additional costs were incurred in the PBT group compared to the TACE group, with an incremental benefit of 0.307 QALYs, and an ICER was $59,006/QALY, below the threshold for cancer treatment of $75,000/QALY. While the sensitivity analysis estimated a 70.8% probability that PBT would be cost-effective, scenarios were identified in which PBT would be cost-effective poorly, mainly in the survival function setting.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 17H04099