Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2022.04

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  Now

  Sapporo Medical University Hospital   Division of Laboratory Diagnosis   副部長

• 2021.02

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  Now

  Sapporo Medical University   血液内科学   講師

• 2007

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  2021.02

  Sapporo Medical University   School of Medicine   助教

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Hematology and oncology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University Hospital   Division of Laboratory Diagnosis   副部長  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• シグナル伝達

• 分子標的

• 活性酸素

• 内科

• CD34陽性細胞

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series.

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D Kocsis, Osamu Honmou

  Journal of clinical medicine   13 ( 20 )  2024.10  [International journal]

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI PubMed

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M. Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D. Kocsis, Osamu Honmou

  Journal of Clinical Medicine   13 ( 20 )  2024.10

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI

• Novel method for assessing sinusoidal obstruction syndrome using four‐dimensional computed tomography

  Saori Shimoyama‐Ibuki, Satoshi Iyama, Yoshiya Ohashi, Kento Ono, Yusuke Sugama, Chisa Fujita, Akari Goto, Hiroto Horiguchi, Akihito Fujimi, Takeo Tanaka, Kohichi Takada, Koh‐Ichi Sakata, Masayoshi Kobune

  eJHaem ( Wiley )   2024.07

  　View Summary

  Abstract Introduction To diagnose sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four‐dimensional computed tomography (4D‐CT). A 42‐year‐old Japanese woman was diagnosed with late‐onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D‐CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters. Result We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction. Conclusion 4D‐CT may become a helpful tool to diagnose and follow up with SOS/VOD.

  DOI

• Intravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients

  Tomohiro Yamaki, Shinichi Oka, Satoshi Iyama, Masanori Sasaki, Rie Onodera, Yuko Kataoka-Sasaki, Takahiro Namioka, Ai Namioka, Masahito Nakazaki, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Misako Yamaguchi, Marina Fukino, Taro Takazawa, Megumi Hayasaka, Takamitsu Owaku, Mika Funakura, Shinji Onodera, Yoichi M. Ito, Masayoshi Kobune, Junji Kato, Sumio Ishiai, Jeffery D. Kocsis, Masaru Odaki, Yasuo Iwadate, Shigeki Kobayashi, Osamu Honmou

  Interdisciplinary Neurosurgery: Advanced Techniques and Case Management   36  2024.06

  　View Summary

  Objective: This study explores safety, feasibility, and potential improvement in functional status after intravenous infusion of mesenchymal stem cells (MSCs) in chronic severe brain injury (BI) patients. Methods: An intravenous infusion of autologous MSCs in autoserum cultured under Good Manufacturing Practice was delivered to four chronic patients with BI. In addition to assessing feasibility and safety, neurological function was evaluated using the National Institutes of Health Stroke Scale, Fugl-Meyer Assessment, Barthel Index, and cognitive-related behavioral assessment. Imaging studies with 18F-FDG-PETCT and 11C-methionine-PETCT (METPET) were carried out to evaluate brain metabolic activity. Results: No serious adverse events were recorded. None of the patients developed CNS tumors, abnormal cell growth, or neurological deterioration. While this initial case series was not blinded, gradual functional improvement was observed after MSC infusion. Serial 11C-METPETs displayed a statistically significant increase in methionine uptake, primarily in the thalamus and pons. Conclusion: We emphasize that this study was unblinded and did not exclude placebo effects, the contribution of endogenous recovery, or observer bias; however, our observations support feasibility and safety. No adverse events were observed. The data suggests improved quality of life after infused MSCs; however, a blinded, larger-scale study will be necessary to fully address this possibility.

  DOI

• Anti‐CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study

  Kazutaka Sunami, Shin‐ichi Fuchida, Kenshi Suzuki, Masaki Ri, Morio Matsumoto, Chihiro Shimazaki, Hideki Asaoku, Hirohiko Shibayama, Kenichi Ishizawa, Hiroyuki Takamatsu, Takashi Ikeda, Dai Maruyama, Kazunori Imada, Michihiro Uchiyama, Toru Kiguchi, Satoshi Iyama, Hirokazu Murakami, Reiko Onishi, Keisuke Tada, Shinsuke Iida

  Hematological Oncology ( Wiley )  41 ( 3 ) 442 - 452  2022.12

  　View Summary

  Abstract The primary analysis of the phase 1/2 ISLANDs study in Japanese individuals with relapsed/refractory multiple myeloma (RRMM) showed that isatuximab monotherapy was well tolerated and effective, even in participants with high‐risk cytogenetic abnormalities. Here, we report a prespecified second analysis conducted 20 months after the first dosing of the last participant (ClinicalTrials.gov identifier: NCT02812706). The primary objectives were to evaluate the safety and tolerability of isatuximab in phase 1 and to evaluate the efficacy of isatuximab, including assessment of overall response rate (ORR) at the recommended dose (RD), in phase 2. In phase 1, three participants received isatuximab 10 mg/kg every week (QW) for 4 weeks/cycle followed by every 2 weeks (Q2W) and five participants received 20 mg/kg QW/Q2W. Since no dose‐limiting toxicities occurred in phase 1, 20 mg/kg QW/Q2W was identified as the RD for the phase 2 study (n = 28). At the time of data cut‐off, three participants (one in phase 1 and two in phase 2) continued to receive isatuximab; disease progression and treatment‐related adverse events were the most common reasons for treatment discontinuation. The overall safety profile was consistent with the primary analysis. One death, not related to isatuximab treatment, was reported since the first analysis. The ORR and clinical benefit rate remained unchanged from the primary analysis at 36.4% (95% confidence interval [CI]: 20.4%–54.9%) and 54.5% (95% CI: 36.4%–71.9%), respectively. The median progression‐free survival (PFS) was 5.6 months, longer than the median PFS reported in the primary analysis (4.7 months), whereas median overall survival was not reached. Overall, isatuximab 20 mg/kg QW/Q2W had an acceptable safety and tolerability profile and showed promising antitumor activity in Japanese individuals with RRMM.

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome

  Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Tatsunori Goto, Akio Kohno, Kazutaka Ozeki, Yasushi Onishi, Noriko Fukuhara, Nobuharu Fujii, Hisayuki Yokoyama, Masanobu Kasai, Hiroatsu Iida, Nobuhiro Kanemura, Tomoyuki Endo, Hiroatsu Ago, Makoto Onizuka, Satoshi Iyama, Yuichiro Nawa, Mika Nakamae, Yasuyuki Nagata, Shingo Kurahashi, Yasuo Tomiya, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

  Bone Marrow Transplantation ( Springer Science and Business Media LLC )  55 ( 7 ) 1399 - 1409  2020.07  [Refereed]  [International journal]

  　View Summary

  A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.

  DOI PubMed

• Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood

  Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Tatsunori Goto, Akio Kohno, Kazutaka Ozeki, Yasushi Onishi, Noriko Fukuhara, Nobuharu Fujii, Hisayuki Yokoyama, Masanobu Kasai, Hiroatsu Iida, Nobuhiro Kanemura, Tomoyuki Endo, Hiroatsu Ago, Makoto Onizuka, Satoshi Iyama, Yuichiro Nawa, Mika Nakamae, Yasuyuki Nagata, Shingo Kurahashi, Yasuo Tomiya, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

  BLOOD ( AMER SOC HEMATOLOGY )  134  2019.11

  Research paper, summary (international conference)  

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  DOI

• 【悪性黒色腫】 播種性骨髄癌腫症を呈した悪性黒色腫の1例

  澤田 匡秀, 澄川 靖之, 佐藤 さゆり, 菅 裕司, 加藤 潤史, 肥田 時征, 山下 利春, 橋本 亜香利, 井山 諭

  皮膚科の臨床 ( 金原出版(株) )  59 ( 13 ) 1963 - 1966  2017.12

  　View Summary

  79歳女。約2年前に左第4趾に黒色結節を自覚し、徐々に増大した。全切除生検を施行し、病理組織学的所見より悪性黒色腫と診断した。全身検索で他臓器転移を認めず、足趾離断術とセンチネルリンパ節生検を施行した。摘出した4個のリンパ節全てに転移を認めたため、鼠径、外腸骨、閉鎖リンパ節郭清を追加した。郭清したリンパ節に転移はなかった。pT3bN3M0 Stage IIICと診断し、術後化学療法としてDAV-Feron療法を計6クール施行した。以後はフェロン局注療法を継続していたが、術後約3年3ヵ月で突然強い腰痛が出現した。各種画像所見、臨床検査所見、骨髄生検の病理組織所見より、悪性黒色腫による播種性骨髄癌腫症とした。化学療法を施行するも改善なく、入院から19日後に永眠された。

  DOI

• P53-RESTORING SMALL MOLECULE CP-31398 INDUCES APOPTOSIS VIA INDUCTION OF REACTIVE OXIDATIVE SPECIES IN HUMAN MULTIPLE MYELOMA

  Y. Arihara, K. Takada, Y. Kawano, N. Hayasaka, H. Nakamura, S. Kikuchi, Y. Kamihara, K. Murase, H. Ikeda, S. Iyama, T. Sato, K. Miyanishi, M. Kobune, J. Kato

  HAEMATOLOGICA ( FERRATA STORTI FOUNDATION )  102   498 - 498  2017.06

  Research paper, summary (international conference)  

• Next Generation Sequencing of CD138+Myeloma Cells Could Predict Response Rate and Appropriate Therapy at Diagnosis

  Hiroshi Ikeda, Yasushi Sasaki, Soushi Ibata, Masahiro Yoshida, Ayumi Tatekoshi, Satoshi Iyama, Kazuyuki Murase, Kohichi Takada, Shohei Kikuchi, Tsutomu Sato, Masayoshi Kobune, Junji Kato

  BLOOD ( AMER SOC HEMATOLOGY )  128 ( 22 )  2016.12

  Research paper, summary (international conference)  

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 小越章平記念 Best Paer in The Year 2021

  2022.05   Japanese Society for Clinical Nutrition and Metabolism   Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study.

  Winner： 井山 諭

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Development of new therapy for AML by targeting of neuropeptide-PTH2R system

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  小船 雅義, 井山 諭, 池田 博, 後藤 亜香利, 堀口 拓人

• Analysis of the development and pathogenesis of AML/MDS via extracellular vesicles

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

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  2022.03

   

  Kobune Masayoshi

  Authorship： Coinvestigator(s)

  　View Summary

  The analysis of exome in MDS and AML has revealed the multiple mutations involved in the pathogenesis of these disorders. On the other hand, it has been increasingly focused on the dysfunction of BM microenvironment in the MDS/AML. However, little is known how the dysfunction of BM microenvironment was induced. In this study, high level of miR-7977, miR-8073, and miR-4286 were identified in extracellular vesicles from AML cells. In particular, miR-7977 effect on BM MSCs to reduce the expression of PCBP1 and STK4, resulting in the reduction of multiple mRNA and Hippo signaling, suggesting that it could be involved in the alteration of BM microenvironment favorable to leukemia cell survival. In addition, the possibility of rejuvenation by extracellular vesicles derived from immature cells was investigated. Although the expression of β galactosidase was slightly decreased, no changes of other aging markers were detected. Other strategy may be required for rejuvenation of aging MSCs.

• Efficacy for treating MM with DPP8/9 inhibitor.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2015.04

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  2018.03

   

  Iyama Satoshi

  Authorship： Principal investigator

  　View Summary

  Recently, the prognosis of patients with multiple myeloma (MM) has considerably improved due to the use of autologous hematopoietic stem cell transplantation and the introduction of new agents such as the immunomodulatory drugs, proteasome inhibitors. However, no curable treatment is available. We have previously shown that the DPP8/9 inhibitor, 1G244, induced MM cells to cell death by apoptosis. Hence, we demonstrated efficacy for treating MM with DPP8/9 inhibitor.

• Novel strategy against GVHD using NB-UVB with expansion of Treg cells

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

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  2016.03

   

  Sato Tsutomu, Iyama Satoshi, Kawano Yutaka

  Authorship： Coinvestigator(s)

  　View Summary

  Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to GVHD, we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, were irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB.

• Establishment of iron chelation therapy to inhibit the development of MDS

  Grant-in-Aid for Challenging Exploratory Research

  Project Year :

  2012.04

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  2015.03

   

  KOBUNE Masayoshi, KIKUCHI Shohei, IYAMA Satoshi, KATO Junji

  Authorship： Coinvestigator(s)

  　View Summary

  Most MDS patients eventually require red RBC transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. We analyzed 8-OHdG levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator,deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.

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